Saturday, August 31, 2019

Crime Rate in Centervale Essay

If one was to compare the crime in Centervale to that of Alaska or Alabama it would be clear that Centervale has the highest crime total. If one was to compare the crime rate it would be clear that Alabama has in fact the highest crime rate with Alaska and then Centervale sitting very close in numbers. Alabama has the highest population and Alaska has the lowest, but this would mean that Alabama would not be the safest place to live. In fact an individual would want to live in either Alaska or Centervale. Centervale has a lower aggravated assault rate than that of Alaska, but Alaska has a lower robbery rate that that of both Centervale and Alabama. When looking for a new place to locate its always a great decision to check out how a city, county, suburb, or state hold up against that of other similar places when it comes to crime. No one wants to live in a place where they are afraid to leave their homes. When looking at the actually numbers Centervale is the highest followed by Alabama and then Alaska, but if an individual was to look at the crime rate then it would appear that Alaska has the highest followed by Alabama and then Centervale, but both Alabama and Centervale are very close in rate percentage. Alaska has a problem with alcohol related crimes, whereas in other locations in the United States drugs and alcohol are secondary to the crime. Information Importance This kind of information is important due to the growing concern that most individuals and families have about the crime not only in their local neighborhoods, but also in places that they may be considering locating too. It’s also important to find out what programs are in place to keep the crime rate reduced. Each neighborhood has some sort of program in place to help keep children and adolescents occupied so they are less likely to go out and commit a crime, but crime doesn’t always involve children and adolescents. Crime can and is often committed by adults. Read more:  India Crime Rate Most communities have an early childhood development program in place. It’s been stated by Paul Leighton (2007), that children enrolled in this program have â€Å"half as many criminal arrests, less likelihood of going to jail, higher earnings and property wealth, and a greater commitment to family†. There are also drug treatment, recreation, gang- prevention, education, special curricula, job training, and the labor market (Leighton, 2007). When moving to a new community an individual can call around to find what programs have been put into place to reduce the crime rate and what else can be done to help reduce the crime. Parents with small children wish to make sure that they are bringing their children to a safe environment with programs set in place to help the children and adolescents occupied after school. Definitions of Crime Crime is defined as â€Å"the act or the commission of an act that is forbidden or the omission of a duty that is commanded by a public law and that makes the offender liable to punishment by that law† (Merriam-Webster, 2013). Alabama and Alaska differ when it comes to crime punishment. Alaska abolished its capital punishment in 1957, but has since then tried to reintroduce it to no avail. Alabama on the other hand does have capital punishment and certain crimes can lead to the death penalty. These crimes are capital murder charges, rape, robbery, and burglary. Alaska imprisons their convicted criminals for either short period of times to life. In both states children and adolescents are charged as juveniles unless found to have committed an adult crime such as murder (non-accidental), robbery that ends up with loss of life or assault or rape. Rape charges can be difficult to try depending on the age of the child or adolescents and how much understanding of the charges and their understanding of right and wrong. Charging children in an adult court can be difficult to do since their understanding and reasoning is far different and underdeveloped than that of an adult. Recommendations Recommendations to help reduce the crime rate would to beef up the police and special crime units to help get a grasp on the crime in the state. Have better programs put into place within the prisons/jails. This will give a positive opportunity and outlet for the prisoners so they will not wish to reoffend. Allow employers that wish to hire ex-convicts the opportunity to sit down with the convict prior to their release. This will give the individual something positive to look forward to and a better outlook on life. Have programs set up for ex-cons along with programs set up for those who may need a positive outlet. Ex-cons need the structure to help them adapt better to outside life than to be just â€Å"dumped† on the streets after their sentence with the hopes of not reoffending. Many individuals feel they have nothing â€Å"outside† so why even try. In many cases this is true, the individuals family and or friends have given up on them or they have a difficult time finding a job, so they do what they believe is the only thing left and this causes them to reoffend. Conclusion In conclusion crime is a scary thing for any family or individual, but with careful consideration and knowing the facts needed one can make the correct decision. Many criminals that are within the prison/jail system are those who have reoffended, but due to the unknown these individuals tend to end back up within the system. Families and friends of those ex-cons need to be there for the individual for emotional support. Those who don’t have the proper support feel alone and often believe they need to be back where they were. References Crime in the United States. U.S. Department of Justice (2009). Retrieved from http://www2.fbi.gov/ucr/cius2009/data/table_05.html What Every American Should Know About the Criminal Justice System. Leighton, Paul (2007). Stop Violence. Retrieved from http://stopviolence.com/cj-knowledge.htm Merriam-Webster. Crime (2013). Retrieved from http://www.merriam-webster.com/dictionary/crime

Aice Biology Nuclear Division

11/9/2011 AICE  Biology Ch  6  Jones;  Ch  10  RavenContent †¢Ã‚  Replication  and  division  of  nuclei  and  cells †¢Ã‚  Understanding  of  chromosome  behavior  in  mitosis Learning  Outcomes Candidates  should  be  able  to: (a)  explain  the  importance  of  mitosis  in  the  production  of  genetically   identical  cells,  growth,  repair  and  asexual  reproduction; (b)  [PA]  describe,  with  the  aid  of  diagrams,  the  behavior  of   ( )[ ] chromosomes  during  the  mitotic  cell  cycle  and  the  associated   behavior  of  the  nuclear  envelope,  cell  membrane,  centrioles and   spindle  (names  of  the  main  stages  are  expected); (c)  explain  how  uncontrolled  cell  division  can  result  in  cancer  and   identify  factors  that  can  increase  the  chances  of  cancerou s  growth; (d)  explain  the  meanings  of  the  terms  haploid  and  diploid  and  the  need  for   a  reduction  division  (meiosis)  prior  to  fertilization  in  sexual   reproduction; (e)  use  the  knowledge  gained  in  this  section  in  new  situations  or  to  solve   related  problems. ? Multicellular organisms  begin  as  a  single  cell ? Mitosis ? Cell  division ? Also  used  in  repair ? Asexual  reproduction p Cell Size ? Bacteria ? E. Coli  doubles  every  30  minutes ? Heart  &  nervous  system  cells  rarely  divide,  if  at  all ? Skin  cells  and  digestive  tract  cells  divide  throughout  life ? Some  every  6  hours ? Grow  to  a  certain  size  and  stop ? Controls  are  turned  on  and  off ? During  injury,  cells  are  stimulated  and  rapidly  divide  and  grow   †“ produces  new  cells,  Ã‚  . i. e. ealing ? After  healing,  cell  growth  slows  and  returns  to  normal ? Uncontrolled  cell  growth  results  in  cancer Surface Area (length x width x 6) Volume (length x width x height) Ratio of Surface Area to Volume ? Surface  area  and  volume  do  not  increase  at  the  same  rate ? Larger  cells  have  difficulty  exchanging  oxygen  and  waste  in and  out  of  the  cell ? Before  cell  becomes  too  large  it  undergoes  cellular  division   and  forms  2  daughter  cells 1 11/9/2011 Cell Cycle includes G1 phase Two  G  phases   and  S  phase   make  up   Interphase Interphase M phase (Mitosis) M phase S  phase is divided into is divided into G1 phase S phase G2 phase Prophase MetaphaseAnaphase Telophase G2 phase The  cell  has  several  systems  for  interrupting  the  cell  cycle   if  someth ing  goes  wrong†¦ ? Check  point  at  end  of  S  phase ? Monitor  for  presence  of  Okazaki  fragments  on  lagging  strand during  replication ? Cell  is  not  permitted  to  proceed  in  the  cell  cycle  until  fragments ? DNA  Overload ? must  be  enough  DNA  material  in  the  nucleus ? Larger  the  cell  =  information  crisis ? Materials  must  be  able  to  pass  through  the are  gone cytoplasm  quickly ? Speed  is  determined  by  size  of  cell ? Rate  at  which  food  and  oxygen  are  used  is ? DNA  Damage  checkpoints ? Sense  DNA  damage  before  cell  enters  S  phase  (G1 checkpoint) ? During  S  phase ? Read also Lab 2 BiologyAfter  DNA  replication  at  G2 checkpoint ? Spindle  Checkpoints ? Detect  any  failure  of  spindle  fibers ? Detect  improper  alignment  of  spindle  itself  and  block   cytokinesis ? Trigger  apoptosis  if  damage  is  irreparable determined  by  volume ? Volume  increases  faster  than  surface  area  as cell’s  size  increases ? Cell’s  DNA  no  longer  able  to  serve  the  increasing needs  of  the  growing  cell ? Cells  constantly divide ? Dead  cells  replaced   by  new  cells ? Cancer ? mistake  in  cell   cycle ? cancerous  cells   form  tumors   (masses  of  tissue) ? tumors  deprive   normal  cells  of   nutrients 2 11/9/2011 ? Mutagen ? A  factor  that  brings  about  a  mutation ? Genetic ? Mutations ? Oncogene Carcinogen ? Any  agent  that  causes  cancer ? Some  factors  whic h  can  increase  mutation  rates,  thus promoting  cancer ? Ionizing  Radiation:  Ã‚  Xrays,  gamma  rays  particles  from ? Environmental ? cigarette  smoke ? air  and  water  pollution ? UV  radiation  from  the  sun ? viral  infections ? Carcinogen ? Any  substance  that  can  induce  or  promote  cancer ? Most  carcinogens  are  mutagens  (change  in  genes) radioactive  decay? breakdown  of  DNA  strands ? Chemicals:  tobacco  smoke,  certain  dyes ? Virus  Infection:  Lymphoma,  Papilloma viruses ? Hereditary  predisposition  Ã¢â‚¬â€œ genetic  link ? Benign  Tumors  (tumours) ? Do  not  spread  from  their  site  of  origin  but  can  compress nd  displace  surrounding  tissues ? Warts,  ovarian  cysts,  some  brain  tumors ? Malignant ? Cancerous ? Dangerous  and  spread  throughout  the  body ? Invade  other  tissues  and  destroy  them ? Healthy ? Cancer  Ã¢â‚¬â€œ yellow  spots ? Staging  is  important  to  determine  if  the  patient  is potentially  in  a  curable  early  stage  or  otherwise: ? Stage  0  ? Cancer  in  Situ   ? Stage  I  ? Cancer  is  less  than  2  cm. ? Stage  II  ? Cancer  is  between  2  to  5  cm  with  or  without involvement  of  the  glands  in  the  armpit   i l    f   h    l d   i    h    i   ? Stage  III  ? Cancer  is  larger  than  5  cm  or  there  is  extensive involvement  of  the  glands  in  the  armpit ? Stage  IV  ? Cancer  has  spread  outside  the  breast  and nvolves  other  organs  in  the  body Cause  of  1  out  of  17  deaths  in  Britain  in  1990 1  in  13  deaths  in  men;  1  in  27  deaths  in  women ? Stage  I  &  II  are  consider ed  early  and  curable. ? Stage  IV  disease  is  not  curable. 3 11/9/2011 ? Chromosome ? two  identical  halves   connected  together  by  a   centromere ? Ch Chromatid tid ? half  of  one  chromosome ? Contains  one  complete  set   of  information ? Copies  itself  to  make  the   other  chromatid Centromere Two  chromatids,  each  made  of   identical  Ã‚  DNA  molecules ? The  karyotype of  a  normal human  female contains  23   pairs  of  homologous   chromosomes:   ? 22  pairs  of  autosomes ? 1  pair  of  X  chromosomes ? The  karyotype of  a  normal uman  male contains: ? the  same  22  pairs  of  autosomes ? Uncoiled  DNA  called  chromatin? between  cell  divisions ? Happens  during  cell  division ? DNA  wraps  tightly  around  proteins  called  histones ? one  X  chromosome   ? one  Y  chromosome 4 11/9/2011 Sex   chromosomes Spindle forming Centrioles Nuclear envelope Chromatin Centromere Chromosomes (paired chromatids) Centriole Interphase Cytokinesis Telophase Nuclear envelope reforming Prophase p Spindle Centriole Individual chromosomes Metaphase Anaphase ? Daughter  cells  genetically  identical  to  parent  nucleus ? Replacement  /  repair  of  tissues ? Skin ? Lining  of  gut A sample of cytoplasm is removed from a cell in mitosis.The sample is injected into a second cell in G2 of interphase. ? Basis  of  asexual reproduction As a result, the second cell enters mitosis. Cyclins  regulate  the  timing  of  the  cell  cycle  in  eukaryotic  cells 5 11/9/2011 Golgi apparatus produces vesicles ? haploid  (n)  and  diploid  (2n)  Ã‚  chromosomes Two  chromatids,  each  made  of   identical  Ã‚  DNA  molecules Centromere ? reduction  division  (meiosis)  prior  to  fertilization  in  sexual reproduc tion Chapter  Ã‚  17:  Ã‚  Meiosis,  genetics  and  gene  control  goes  into   more  detail Genetic  variation Crossing  over  in   Prophase  I 6 11/9/2011 Maternal set of chromosomes Possibility 1 Paternal set of chromosomes Possibility 2Two equally probable arrangements of chromosomes at metaphase I Metaphase II Prophase II Metaphase II Anaphase II Telophase II Meiosis II results in four haploid (N) daughter cells. Meiosis I results in two The chromosomes line up in a The sister chromatids haploid (N) daughter cells, similar way to the metaphase separate and move toward each with half the number of stage of mitosis. opposite ends of the cell. chromosomes as the original. Daughter cells Combination 1 Combination 2 Combination 3 Combination 4 Prophase I of meiosis Nonsister chromatids MITOSIS Parent cell (before chromosome replication) MEIOSIS Chiasma (site of crossing over) MEIOSIS I ProphaseProphase I Chromosome replication Chromosome replication 2n = 6 Tetrad Duplicated chromosome (two sister chromatids) Chiasma, site of crossing over Metaphase I Tetrad formed by synapsis of homologous chromosomes Metaphase Chromosomes positioned at the metaphase plate Tetrads positioned at the metaphase plate Metaphase I Metaphase II Anaphase Telophase Sister chromatids separate during anaphase Homologues separate during anaphase I; sister chromatids remain together Anaphase I Telophase I Haploid n=3 Daughter cells of meiosis I MEIOSIS II Daughter cells 2n Daughter cells of mitosis 2n n n n n Daughter cells of meiosis II Recombinant chromosomes Sister chromatids separate during anaphase IIGeneral Biology Ii Study Guide (Online Class)

Friday, August 30, 2019

Descriptive Essay House on Fire

descriptive essay house on fire The House on Fire That cold night of December 2004 had left behind a memory which will stay in my mind for a never ending period of time. That night was not the same as the rest of the days in my life. Instead of going to bed, that night I was standing in the middle of the road, in complete terror. My heartbeat was accelerating with fear and tears were rolling down my cheeks as I saw Emily taken away by the ambulance. The house, which I was standing in front of, was burning as fire engulfed it from all sides. There was fire everywhere.The roof was on fire, the doors and the windows were on fire, fire was even coming out of the house through various openings, looking like a fire-breathing dragon was inside the house, puffing fire. The flames burned deep red and amber, almost livid purple as I saw various firefighters trying to put out the fire. Nothing inside was likely to survive the fire. Flames were licking up in the air with the wind, trying to catc h something else on fire, and finding nothing but air, disappearing into the windy night, like disappointed flutters. Everything was happening too fast.During a minute or less, fire had spread across the entire landing. I was petrified by the sight of the fire, which crawled lizard like up the house. The house was exploding in yellow blue flames that quickly turned orange. I was trembling and whimpering softly as I saw Emily’s mother sitting on the ground, helplessly. She was crying out of despair. Her reaction had made me even more scared. I wanted someone to console me by telling me that nothing will happen to Emily. She was my best friend. We had spent seven years of our childhood together and I did not want to lose her.I was praying silently while Emily’s mother had lost all the hope of her survival. I had never felt so alone before. Even the thought of losing her, frightened me. I felt as if I was living through the worst nightmare. Grief is the worst feeling in t he world. You feel hopeless, scared, angry, frustrated, alone and afraid. Going through a phase in life when you have a feeling of losing someone is hard to accept and it is much harder for an eight years old child. You feel as if the world had stopped and you could never move on in life.It is very painful to accept that you will no longer be able to see someone who was very close to the heart. I was crying while looking at the crowd of people that had clustered around the house by that time. The voices of the people echoed in my ear hauntingly. Their screams and shouts gave rise to my fear. I was horrified by the siren of the ambulance, the police car and the firefighters, the ringing of the phones of the crowd, the yelling, the cries, the increasing roar of the fire; everything added chaos to that place and frightened me even more.Ghosts of smoke were drifting across the street. I smelled smoke. It was not heavy, but it had a pungent smell. I started to cough as the smoke enfolded me. The air surrounding me was becoming less breathable by the second. My mouth was filled with the bitter taste of the smoke. I wanted a draught of clean air to rinse out my polluted lungs. The cough had aggravated pain in my head. My eyes were becoming swollen and watery. Soon after, the fire got quite out of control as the whole house was on fire. The firefighters evacuated the street and told everyone to go inside their houses.I had no choice but to retreat to my room where I could see, feel, and hear Emily’s house burn down. In a few minutes, the house had been reduced to a pile of rubble, ashes, and smouldering wood and items. There was a rotting smell that took over the whole neighbourhood, like a bad barbeque party gone horribly wrong. The smell was so overpowering that it took almost a week to get it out of my nose. That horrifying night of December still reminds me how valuable a person is in our life. If the firefighters were even one minute late in rescuing Emily , I would have lost my best friend that day.

Thursday, August 29, 2019

Negotiations Journal Essay Example | Topics and Well Written Essays - 7500 words

Negotiations Journal - Essay Example The landlord was of course reticent to do this because he was not fond of the idea of spending more money in order to rent the apartment. From his perspective, other renters who were not so picky would take the apartment as is. However, having viewed several similar apartments that day, my friend and I were fully aware of the fact that for the same money that this particular apartment was renting for, it would be possible to rent a substitute. However, the issue was that we both loved the location, enjoyed the layout, neighborhood, and floor plan etc. Therefore, both of us were interested in trying to negotiate some type of satisfactory deal with the landlord. However, either as a result of our weak negotiating skills or the landlord’s refusal to give any leeway at all with regards to the price and/or condition of the current amenities, we were finally forced to take another apartment as our negations did not make any headway whatsoever. In the end, a host of factors contribut ed to this. These will be discussed in some greater detail and at length further in this worksheet. EXERCISE 2.1 Continued Creating and Claiming Value 2. Rate yourself from 1 to 10 on how well you created value in that negotiation, where 1 is "created little or no value" and 10 is "created a great deal of value." My effectiveness in creating value in my last negotiation was: ______4________. 3. Next, rate yourself from 1 to 10 on how well you claimed value in your last negotiation, where 1 represents "obtained little or no value for myself' and 10 represents "obtained a great deal of value for myself." My effectiveness in claiming value in my last negotiation was: ______1_________. The next step is to study how you create and claim value in your next three negotiations. This will help you determine your own pattern in creating and claiming value. To be an effective negotiator, you have to be good at both creating and claiming value. The following form has been designed to help you e xamine your own pattern of creating and claiming value. CREATING/CLAIMING VALUE FORM 1. Briefly summarize a second negotiation that you participated in on a separate sheet attached hereto as "Exercise 2.1: Attachment B." In the past, I was involved in quite a lengthy negotiation with my employer as how I might change my working hours so that they would be more amenable to my new schedule. This was a unique negotiation because it had varied interests involved in the mediation process. Firstly, and most obviously, there was the selfish interest that I had in order to make my work hours more convenient for me so that I could more easily enjoy my time, not have to wake up at an inconvenient hour, and spend more time concentrating on my studies etc. Likewise, from the employer’s perspective, the negotiation was centered around the fact that they could either deny the request and risk angering the employee (me) or grant it and work to find other personnel who could cover for the ti me gap that this would create. In order to facilitate the process of understanding and create value in the eyes of the employer, I worked to emphasize the many benefits that my employment brought to the company; as well as some of the many highlights of my career up until that point that were highly beneficial to the firm and their profit margin. Although it was a low paying job, my approach was to convince the employer, without appearing arrogant, that they would have a hard

Wednesday, August 28, 2019

Experience and Other Evidence Essay Example | Topics and Well Written Essays - 1000 words

Experience and Other Evidence - Essay Example (Ricks, 2006) Placing Ricks' findings and observations in Epicurean terms, I was able to synthesize the following argument: One could interpret America's continued occupation of Iraq as a manifestation of 'partiality', in this case toward so called national interest, which in turn translates into the interests of military contractors and oil corporations based in the country. The destruction of lives and resources on both sides is as a result of America 'troubling' itself and 'troubling' its distant and weak enemy in the form of Iraq. Further, consistent with the tenet, the invasion implies 'weakness' on part of the aggressor, more specifically a 'weakness' for material wealth (in this case fossil fuel). It is interesting to note that the wisdom of Epicurus, set out two millenniums ago, finds application in contemporary political actions as well as in an individual's personal life. In the case of the latter, I myself have been found falling short of being a 'blessed and indestructibl e being', for my occasional imprudent anger and partiality has gotten me into hot water a few times. One lingering memory in this respect is when I got into a verbal scuffle with a member of the audience during a college football game. I was slightly inebriated when my team was way behind in the game and the chance of winning was slim. At that point I over-reacted to a snide remark from a fan of the opposing team and got into a heated exchange. In retrospect I realized that though his remark was offensive it was not a defeat to my team and it did not mean anything significant. At that point I got the insight that my reaction is comparable to the way our government has conducted itself in the ongoing War on Terror... The researcher of this essay describes the element of his personal philosophy of life, regarding the dynamics of 'contentment'. Since the whole canon of Western Philosophy is centered on the causes, states and conditions of contentment, it is fair to say that contribution through this narrative is a minuscule one. Yet, the researcher would like to voice his assessment of this universal human concern and try to refine his theory through the responses it will elicit from the audience. The researcher has synthesized hispersonal experience with a larger political event and has studied them both in a philosophical framework. The researcher states that, in order for civilization to progress, parochialism and narrow-mindedness will have to be overcome by embracing principles of solidarity and compassion toward fellow humans. Bringing about this transformation at the level of nations is a highly challenging project, given the power and efficiency of propaganda systems in place. But transform ation at the individual level is more plausible. The researcher personally has endeavored to mould himself in the Epicurean fashion with reasonable success and he implores members of the audience to consider this path. By embracing this philosophy, that was discussed in the essay in details one can acquire a high degree of sophistication and refinement as a person. The researcher then concluds that it will also enable an individual to navigate challenging phases in life with equipoise, stoicism and mental tranquility.

Tuesday, August 27, 2019

War crime & crimes of aggression in international Essay

War crime & crimes of aggression in international - Essay Example Sometimes an enemy is dodged by waving a flag and then they are attacked, this also comes under war law violation. However, if an enemy is being deployed with the help of a parachute, then attacking them will not mean it is a war crime. However this rule is critical because in some areas it is not allowed to attack an enemy if they are being deployed from a damaged airplane. They cannot be attacked even if they have landed and are willing to surrender (ICRC, n.p, 1993)2. Genocide and mass murder also come under war crimes. If prisoners and civilians are ill treated then this is also considered as a violation of international war law. This ill treatment can also come under the crime against humanity. As the Nuremberg Trials and Tokyo trials, were held under the international humanitarian laws, there fore these have a significant impact on the war laws. "Wilful killing, torture or inhuman treatment, including... wilfully causing great suffering or serious injury to body or health, unlawful deportation or transfer or unlawful confinement of a protected person, compelling a protected person to serve in the forces of a hostile power, or wilfully depriving a protected person of the rights of fair and regular trial, ...taking of hostages and extensive destruction and appropriation of property, not justified by military necessity and carried out unlawfully and wantonly" (ICRC, n.p, 2005)3. It was after the World War... .taking of hostages and extensive destruction and appropriation of property, not justified by military necessity and carried out unlawfully and wantonly" (ICRC, n.p, 2005)3. It was after the World War II that people realized there should be some form of law that should stop violations against human rights. During the World War II the Nazis killed millions of people just because they were Jews. These people were killed very brutally. The Japanese also mistreated the prisoners during the Second World War. In 1945 and 1946 trials were held which lead to the execution of Nazi leaders. Several Japanese Commanders were also hanged in 1946 and 1948. The reasons for these trials were the war crimes these people did during the war (Smith, 1, n.d)4. Formerly, the international war laws addressed only the war crimes in an international conflict. Today an internal armed conflict can also have war crimes. The international human rights regime has changed over the last decade. Today, if anyone commits a war crime, even if it is a minor armed conflict within the country, the person can be subjected to a trial. Though war crimes have always existed yet formal war crime rules and regulations were established after the Second World War. Perfidy was one common and expected war crime for centuries. In 1899 and 1907, during The Hague Conventions, many rules and regulations were made clear. The Nuremberg Trials gave a new concept to war rules. It was published on August 8, 1945 in London. This has further clarified other forms of crimes done in a war (White, n.p. 2007)5. According to Article 22 of the Hague IV, "The right of belligerents to adopt means of

Monday, August 26, 2019

The Catholic Church and Sexuality Essay Example | Topics and Well Written Essays - 2250 words

The Catholic Church and Sexuality - Essay Example This is because the catholic still enjoins and enforces though in a subtle way complete obedience and docility on the principle of Roma locuta causa finite (Rome has spoken no more debate). The church has went ahead and imposed sanctions to members who have expressed divergent views on its dogmas and doctrines. In the recent times it has been observed that many Westerners, scholars, Catholic priests and nuns around the world have rejected the Catholic Church stand on sexual morality because of what they consider as lack of conformity with reality concerning sexual situations. Because in real situation if we go by the Catholic Church’s stand then incidences of unwanted pregnancies, procured abortions, sinkers and Sexually Transmitted Diseases (STDs) will spontaneously shoot to uncontrolled levels. Discussion The Catholic Church is considered as the most conservative force with respect to attitudes towards the accepted codes of social behavior. This requires that none of the Cat holic faithful goes against its doctrines. On the understanding of the Catholic Church that it is run by humans, some human traits can not trail it. Among them is the tendency to mask the freedom expression which curtails the freedom of those who want to give their views on sexual related issues like use of condoms to prevent spread of HIV virus, transgender persons and marriage. This is based on the fact that the Catholic Church loves and upholds absolute obedience as opposed to objection, contradiction, and independent opinion to those who oppose the views taken by the church. According to Abioye (4), basically the Catholic Church perceives that any form of sexual act outside marriage is a sin according to the doctrines therefore is excluded from sacramental communion. Besides, the church regards the usage of any form of artificial contraceptive equally as a sin. Though in contrast, the church insists that life must be respected and protected completely from the moment of concepti on. The church stipulates, â€Å"A person who procures an abortion a completed abortion incurs excommunication latae senteiae, by the very commission of the offence.† This stand taken by the church is supposed to be followed without too much questioning. Many scholars disagree with the Catholic stand on sex before marriage. This is because it lacks conformity with reality. St. Augustine of Hippo says on Church doctrines, â€Å"†¦..dramatizes the fear of sexual pleasure, equating pleasure with perdition in such a way that anyone who tries to follow his train of thought will have the sense of being trapped in a nightmare.† Their have been intensive research done and it has been observed by Hardon that, â€Å"neither the Jewish Talmund no the Moslem Quran and Hadith forbid polygamy, contraception or abortion.† The Catholic Church objects with zeal that the use of contraceptives and abortion. But on medical grounds abortion is allowed so as to save the life of the mother if it is in danger. According to Abioye (6), the ecclesiastical belief is that the use of contraceptives should not be encouraged because it creates room for sexual permissiveness. To some extent the statement is justifiable but

Sunday, August 25, 2019

Current Events (Spokane Mayor Jim West) Essay Example | Topics and Well Written Essays - 500 words

Current Events (Spokane Mayor Jim West) - Essay Example During the scandal the other facts of his private life also became publicly known to wide audience and to the City Council. Before this scandal West was involved in the accusations of child molestation. Three-year investigation and interviews with two felons who said West fondled them and forced them to perform sexual acts on him when they were Boy Scouts did not resulted in criminal responsibility because no evident had been found to accuse West. The anti-gay Mayor has been under scrutiny for allegedly molesting underage boys in the 70's and offering city jobs to young men he met on gay websites. Government officials suppose that the best way out for the city and Mayor Jim West is to resign. They say that many politicians are strong enough to overcome scandals and gossips, but in this case it will be impossible for public to "forget and forgive" it. It should be mentioned that some employees at Spokane City Hall were shocked by the accusations, others were trying to understand the implications. Organizers of an effort to remove Mayor Jim West were reviewing the wording of their recall petition after receiving an approval form a judge on one of the allegations in their ballot proposal.

Saturday, August 24, 2019

MODERN ORGANISATIONAL CONTEXT Essay Example | Topics and Well Written Essays - 1750 words

MODERN ORGANISATIONAL CONTEXT - Essay Example Moreover, I feel that the increase in the credit facilities coupled with decreasing interest broadened the market for the firm, as more people could not easily afford a car. As per Barney and Hesterly (2005), in addition to that, the working population has increased as more women have entered the working sector and many are working and studying simultaneously. This has increased the purchasing power of the customers and sales have increased because of it. However, I feel with the increasing working population, the demand has increased along with the competition (Gourlay, 2001, pp. 27-46). As per Ahrens (2010) this means that consumers have more choice and have become much more demanding. Moreover, in countries like India for instance the middle class expands every year by 30-40 million people, which in turn means more people now demand cars in these countries. Today, moreover, the consumers are being offered car loans on easy instalments, which make a positive impact on the sales of Toyota. Additionally, explain Berzon and Khan (2010), the prices of raw materials and petrol have increased which affects the price and thus the sales of Toyota products. These economic conditions play an important role in the increase of sales on Toyota. These conditions have of course affected the strategies of Toyota. With the economic crunch especially in the USA, the firm was proactive and aimed to increase its sales in developing China and India where the crunch was less prominent. The global strategy adopted by the firm worked positively. Additionally. When the economic conditions in the USA lowered the purchasing power of the consumers, the firm changed its strategy and started production of smaller and cheaper cars. Lastly, Jensen (2010) explains that with the increasing prices of the raw material, the firm resorted to the hybrid variety of cars, which reduced the prices increasing the sales. Thus I feel that Toyota altered its strategies very smartly as per the changing ec onomic conditions with the result that even with a global economic crunch, the firm had little effect on its sales (Kane, 2010). Berzon and Khan (2010) explain that the social aspects include the changing trends, the smarter consumer in terms of being more knowledgeable regarding product information. Kane (2010) adds that the customer can now use the internet to know about the number of Toyota recalls in any part of the world, the latest technology available, the new models, price comparisons, product features and much more. The consumer has become more knowledgeable and thus firms cannot fool them with smart and deceptive advertising. Also, Gourlay (2001, pp. 27-46) add that the consumers are becoming more demanding with globalisation, as there are many more products available in the global market. The consumer has now become more fashionable and seeks comfort. Thus Toyota needs to cater to both these social aspects. Ahrens (2010) adds that tradition, culture and the customers in t he respective markets have to be studied before the firm can design a car. Jensen (2010) explains that for instance, in India, the drivers are right hand drivers, thus the cars have to be designed differently for the market. In the US there are more left-hand drivers. Kane (2010) adds that colour preference, design and accessory preference varies from market to market and thus the firms have to cater differently to them. This means that Toyota has to change its traditional lean

Friday, August 23, 2019

History analytical paper (modern asia) Essay Example | Topics and Well Written Essays - 1250 words

History analytical paper (modern asia) - Essay Example The book ‘Under the Black Umbrella’ explains in a better away about how Koreans had complex and terrible lives under the colonization of Japan. The Japanese colonialism in Korea hovered like a cosmic umbrella the Peninsula; this caused a lot of distrust, uncertainty and fear over every life and every action. This left the Koreans with no option but to only bask in the shadow cast by their colonial rulers. Colonialism is crime against humanity, this is so because the colonized state loses its sovereignty right to another country (Hane, 23). The colonized citizens are exposed to brutal and hopeless life. Koreans were exposed to forced labor in their own country, it is true that civilization could be handled in a peaceful way without use of force or killing the people who opposed it, for everyone has the right of choice. Koreans who were rich before Japan invaded their country were forced to become poor while living in fear (Dudden, 12). Colonization of North Korea made its citizens to lose all they had to a foreign country who were only not satisfied with what they had in their backyard. Exposing people to fear in their own country can be very terrifying and this was the life Koreans were living under the colonization of Japan. ... Torture, forced labor and killing innocent people should never be used as a way of making people feel they are being developed, rather than being destroyed. Japan left orphans and widows in Korea; the destroyed families were only left in total darkness confused about life. It is true Korea as a country gained economically from Japan but the harm done to Koreans cannot be compared to those economic gains (Kang, 18-19). This is because Japan and other colonizers could have economically assisted the countries they colonized in a more diplomatic and peaceful way. The first method Japan used to colonize Korea, subjugation was a harsh way of leadership compared to the other two, cultural accommodation and assimilation (Kang, 20). The Blue Swallow film was aimed in showing how Japan had some positive impact on the Koreans. It is based on Park Kyung-won who was thought to be the first Korean pilot. The truth was revealed that all this story was about Kwon Ki-ok of the republic of the China A ir force, this forged story proved that what Japan did to Korea was only torture and freedom denial in their own country. Japan leaving Korea was not enough for they had affected the Koreans both socially and emotionally living with wounds due to lose of their loved ones (Matray,30). The movie Emperor explains more of how colonial rulers were only interested in subduing nations through torture. The movie has some images of unspeakable cruelty exercised on Koreans. It shows most of the inhuman activities which the Japanese government practiced in Korea. The movie shows men being burned alive and women who had been gang-raped and horribly mutilated. According to my opinion; what is the point of doing such wicked activities in the name of, you want to change their

General Beauregard and his early life leading up to the Civil War Essay

General Beauregard and his early life leading up to the Civil War - Essay Example During the first four years, after moving to New York, he learnt English as a second language, starting at the age of 12 years. After leaving school, he joined the US military academy at West Point, where he learnt a lot to do with the military and war (Eicher and Eicher 37-42). One of his instructors at the military academy was Robert Anderson, who was later appointed as the commander for Fort Sumter, and left the position for Beauregard after the start of the Civil War. While at the military academy, Beauregard dropped his first name, and started using Beauregard as his first name, and Tounant as his middle name. After his term at the military academy, he graduated at second position from the 1838 class, earning distinction as a military engineer and an artilleryman. Beauregard’s early years in Army career covered his service as an engineer under the command of General Scott, where he was appointed as the brevet captain, for the battles of Churubusco and Contreras; he was al so appointed as a major during the Chapultepec. He was among the first soldiers to move into Mexico City, but returned in 1848 (Eicher and Eicher 37-42). After his return, he spent 12 years he engaged in the Mississippi and Lake Defenses, while working on the construction of new and in the repair of forts along the Florida Coast and Alabama. Beauregard’s impact during the Civil War Beauregard’s presence and participation in the civil war was massive. His engagement started after he moved from New York to New Orleans, where he started offering advice on military operations to the local authorities of the area. The advice he offered included that on the need to strengthen different forts, which would secure the area from Mississippi attacks (Eicher and Eicher 37-42). After the appointment of Braxton Bragg as the commander, he was offered the post of a colonel, but preferred working as a private for the Orleans Guards. Later, he was appointed to head Charleston’s d efenses, and due to his qualifications as a military engineer and a leader, he was appointed as the first general officer in charge of the Confederate states. He also worked as a brigadier general with the transitional army of the Confederate states in 1861, and was later ousted to the post of a full general. While working at the different roles at the different areas, Beauregard facilitated the operations of the confederate states and also commanded major military activities. After his arrival at Charleston in 1861, he caused one of the most memorable victories, after his men made the first hits that marked the culmination of the civil war, forcing Anderson to surrender Fort Sumter on April 14. Following the successful attack, he received a heroic treatment, and for that matter, was placed in charge of Alexandria's line, to guard against the federal offensive that was expected from Brig’s forces. During the first Bull Run battle, he was working together with McDowell, and af ter the success of the multi-force excursions, he was acclaimed for his input and was recommended for promotion to the post of a full general. After the success of the attacks, he played a key role, together with William Miles in the creation of the Confederate Battle flag, which made the flag the confederation’s most popular symbol (Eicher and Eicher 37-42). Beauregard played a critical role in the planning of the surprise attack staged against Grant’s Army, nearly ending in victory. However, his planning

Thursday, August 22, 2019

Strategic Choice and Evalulation Essay Example for Free

Strategic Choice and Evalulation Essay In the strategic management process the company mission gives a general idea of what interests and goals the company has. These goals need a more specific target to evaluate the firm progress towards achieving that goal. The strategic management purpose is to define a general goal to sustain the corporate growth and to be profitable. There are different approaches to get there. Companies establish long-term objectives; usually over three to five years and by formulating grand strategies they achieve those long-term objectives. Following the value discipline model or Porter’s generic strategy model companies had successful achievements. As this paper will explain, the formulation of grand strategies that follow generic strategies to provide specific actions will help companies to maximize their competitive advantage. As an example, the company JetBlue Airways has implemented several of the strategies in their strategic management approach and the results show their continuous growth in the airline industry. The analysis of those value discipline, generic strategies and grand strategy alternatives will give a general idea of their importance for business growth. JetBlue Airways incorporates in their operations some these strategies at all levels which resulted on their rapid growth. JetBlue Grand Strategy, Generic Strategies and Value Discipline The definition of grand strategy refers to the means, how is going to be achieved the long term objectives. The principal responsibility of developing the strategies falls on the corporate managers and business managers. Grand strategy consists of the selection of different approaches, which executives understand is the best approach. Some of the grand strategies discussed in business are, growth, innovation, concentration and joint ventures (Pearce 2011). The selection of any of them or a mix of them should maximize the company profits. A combination of generic strategies will also support the company goals. Generic strategies are several â€Å"fundamental philosophical options for the design of strategies† (Pearce 2011). This type of strategies are based on two different philosophies on how to develop those strategies, following Michael Porter’s generic strategy idea or the Michael Treacy and Fred Wiersema alternative approach of value disciplines. Michael Porter, expressed the importance for the companies to develop strategies, he said, â€Å"strategy delineates a territory in which a company seeks to be unique† (Hammonds 2001). Porter generic strategies focus on cost leadership, differentiation and focus. Experts say this approach help the firms to produce above average returns for the organization and the starting point to get there is the grand strategy â€Å"the means by which objectives are achieved† (Pearce 2011). Michael Treacy and Fred Wiersema, business consultants, recommend a different method to generic strategy, they called it, value disciplines. They believe that strategies must center on â€Å"delivering superior customer value through one of three value disciplines: operational excellence, customer intimacy, or product leadership† (Pearce 2011). Even though there are similarities between the two models, their difference is that in the value discipline model â€Å"one discipline will be the focus of attention while the other two that are not selected must be maintained† (12 Manage 2013). Reviewing David Needleman’s decision to start JetBlue Airways constructed at New York’s JFK Airport it shows that from the beginning his business developed based on the strategy of concentrated growth. This grand strategy reflects the management decision to â€Å"direct the resources to profit on one single product, in a single market† (Pearce 2012). The company started by offering high quality customer service. As a result, they became a great competition to Southwest Airlines and American Airlines. JetBlue Airways used the low cost generic strategy to reduce cost and this gave them the advantage to charge lower prices for the same routes of competitor Southwest Airline. In a short period they gain market share and benefit from returns, as the 2001 annual report shows. When all other competitors showed financial reports with loss, JetBlue reported $38. 5 million in net income (JetBlue Annual Report 2002). In the case of JetBlue, concentrated growth is in fact a grand strategy. This firm placed all their investments to get profits out of a single product, airline service at low price to new routes. The goal of providing economical air service has been met by minimizing costs by installing more seats into the planes, selling tickets directly to customers no agent needed to complete this task (JetBlue 2013). Another area were they worked to minimize costs is by shortening ground delays. This discount airline is well-known by their new planes, the radio and satellite television on every seat and the leather sitting. JetBlue vision of product innovation and excellent service provides a low fare and low cost to passengers, it’s an airline that provides high quality customer services (JetBlue 2013). Differentiation is a business strategy that gives competitive advantage with its service. Being different from the competition also gave the company the distinction of being the airline with low cost with amenities for passengers. This was possible due their startup capital of $100 million (David 2011). The use of new planes, their leather seats, individual monitors with DIRECTV programming, was a few of the things they included on their low coast fare. They focused on service and that gave them the competitive advantage. The generic strategies of differentiation and low cost leadership at functional level produced the JetBlue Experience, network expansion, low fares, low operating expenses and investment in new and more efficient planes (JetBlue 2013). Another strategy JetBlue Airways use is focus to what they identified as the underserved but overpriced market (JetBlue 2002). They concentrated on U. S. cities from their main base New York that serves the largest travel market. They have grown from 1 route to serve almost 80 destinations across the US, Caribbean and Latin America (Nasdaq 2013). Pricing is another JetBlue strategy, that’s how they are winning new customers. By developing the image of low fare airline with high quality service, even though they offer only one class services, their high quality service create a new opportunity in the airline travel, including business travelers. Innovation is present in JetBlue company growth; they are the latest airline to give pilots IPads to cut back on paper manuals. The introduction to new technology will bring the capabilities to download weather images, also access updated flight documents (Sawers 2013). JetBlue Airways ability to perform tasks less expensive than competitors also keeps them as the top leaders. The airline fleet of, Airbus 320 and Embraer 190 permits them to offer lots of legroom, great entertainment and leather seats (JetBlue 2013). They keep maintenance and training costs down. For example, management can reinvest in growth opportunities, or commit to their employees training (Pearce 2011). JetBlue has focused on a strategy of serving customers how want low cost flights from place to place. That has been the consistent need of their clients. What JetBlue has done is assimilate new ideas to deliver that service, basically serving the same customers. Conclusion JetBlue competitive advantage is a combined strategy of cost leadership and differentiation. Their low cost position in relation to their competition supports the fact of their efficient operations. The introduction of new planes, allowed them to reduce their fuel costs and maintenance, and with large planes, there is more revenue for the company. They decided not to serve meals; this is another tactic that helped to reduce costs. Differentiation is another part of the combined strategy. Their strong image, TV entertainment, more legroom, and other amenities for the passengers, are evidence of the implementation of this strategy. This combined strategy, provides the company with excellent results, as they keep expanding their operation, partnering with other airlines, and starting new routes and destinations. Even in times of economic crisis and high fuel costs, â€Å"one of aviation’s most acute problems: the price of jet fuel†(Bachman 2012), they maintain their number one (1) ranking for nine consecutive years according to the 2013 North America Airline Satisfaction Study (JD Power 2013). This recognition confirms that all the efforts that JetBlue does by combining strategies to be a low cost airline with excellent customer service, are giving them the leadership in the airline market.

Wednesday, August 21, 2019

Strengths And Weaknesses In Terms Of Democratization Sociology Essay

Strengths And Weaknesses In Terms Of Democratization Sociology Essay In terms of potential harm and violence that ethnic nationalism and primordialism might bring, I have many things to say. First of all, let me clarify the perspective of ethnic nationalism and primordialism a bit more; these perspectives establish the identity (both ethnic and national) as fixed and non-changeable characteristics that are determined at birth and that does not change according to ones own beliefs or actions. As a result of these pre-determined ethnic and national identities, distinct identities are formed as counter groups such as others and us, whereas others are the evil and us is the good. Such a labeling does not leave any room for others since they are belong to different ethnicities. The roots of these fixed identities lie beneath primordialism because primordialism sees these identities as ancient and unchangeable. As a result of this formation of identities and labeling, which are nor changeable neither adaptable and which created others and us, fear arises. According to this view, others are different and bad and we (as us) have to protect ourselves from the possible violence that might come from the surroundings. This creates a vicious circle where every group fears the others and because the other is always us for another group, thus, every group is in fact afraid of every other group. Since the solution comes from the elimination of this fear by eliminating the others, things can go very violent. Many examples from the history can be given for the violence that ethnic nationalism and primordialism had so far caused; Rwanda Genocide of 1994, Nigerian Civil War of 1967 and genocide of Bosnian Muslims are just three examples. For example in Rwanda, the incompetence and failure of two groups to live together caused around 800,000 Africans to die. From this point of view, they are Hutus and Tut sis who were fighting and killing each other but on the other hand they share the same identity by being Africans. My motive for mentioning this is to exemplify the abstractness of the concept of being Hutu or Tutsi (or having an ethnic identity); the real murderer and butcher behind this violence was their approach to ethnic identities. The book (Heywood, 162) mentions the formation of these identities from the perspective of social constructivists. According to social constructivists critique on fixed ethnic and national identities of primordialism, sense of national belonging is constructed through political and social processes, thus, social constructivists suggest that nations in fact do not create nationalism, they say that nations themselves are actually fashioned by nationalism. Primordialist view generally leans over culture and linguistics and not on biological factors such as race because primordialists do not want to be seen as justifiers of violence arising from racial/ethnic differences. Considering that these supposedly logical theories and ideas had caused Holocaust, it is understandable that primordialists want to stay away from the biological elements. Another problem with primordialism is the paradox in defining ethnicity. If we accept the ethnicity to be really primordial then we also accept that we cannot change it but this is not correct. Through generations the ethnic identities may change. For example once-African people in America, now call themselves American or Afro-American. They accept both of these ethnic identities. It was possible for them to adapt to the culture and identity of America, thus their ethnic identity has changed. Also in certain parts of the world where the local cultures were changed by colonization and blended with the culture of colonizers to some extent and led to the creation of new ethnic identities. Primordialism cannot explain the specific transformations and the reasons of how some changes occur. Primordialism also fails to identify or explain the issue of multi-ethnic identities, such as in United States, Afro-Americans etc. There are people who say that they are multiracial and that they carry multiple ethnic identities. Furthermore, it is virtually impossible to determine whether or not the ethnic identities are primordial. According to socio-biologists, the sense of primordialism is derived from the common genes. If they were to be correct, then we can say that this primordial sense coming from the transfer of genes is the real reason underlying the ethnic identities. In this sense, we would have to assume that ethnic identities depend on senses and feelings (emotion) and that they are not really primordial. To a certain degree, one can have a patriotic view and at the same time a critical view of nationalism. One can suggest and support the protection/preservation of diversity in terms of culture, language and ethnicity because in a world in which even these diversities are globalized different perspectives and looks on the world would slowly fade away and a useless solidarity that would hinder or slow the pace of development would come into question. One can say that, these different things, diversities, should be practiced privately and not in public sphere. Well if we think the international arena as the public sphere then the area within the countries is a private sphere for the beliefs, culture and language etc. of the countries. I too believe that this area should be preserved no matter what. Difference and diversity is good in my opinion. I believe we can appreciate our own countries and cultures values in a defensive patriotic sense and at the same time be aware of the negative impacts of overly-patriotic behavior. In a sense, if I am overly patriotic, a fanatic, I may even want the world to belong to Turkey and to be Turkish. But then, if that ever happened, the world would be globalized and the diversities of the world would have vanished just as some people, for example some liberals would have wanted. 4. In a 1-3 page essay, please describe the liberal ideal of nationalism, and explain its strengths and weaknesses in terms of democratization (tolerance, open public sphere, diversity) and its power to command loyalty. Do you think Turkish nationalism tends more to civic nationalism or to ethnic nationalism? What are the reasons for your opinion?   Liberal ideal of nationalism is built around the view of nationalism as a liberating force. According to liberal ideal of nationalism, the important factor in formation of nations is shared political alliances. The perspective of this view suggests that nations are civic entities and nation-states are formed around political alliances. Contrary to the fixed identity of nations, which idea suggested by ethnic nationalists, liberal nationalists see the citizenship as open and volunteristic. Also, liberal nationalism is associated with civic nationalism. Liberal nationalists believe that having a world that consists of individual nation-states is really important as well as they pay very much importance on the existence of sovereign statehood. From the liberal ideal of nationalism, nationalism and internationalism are complementary ideologies as mentioned by Heywood. According to liberal view, in a world consisting of independent nation-states there would be concordance and peace. The r eason behind this belief of liberal nationalists lies beneath the belief that the respect paid by nation-states to the rights and freedom of others would be more, at such a degree that prevents wars. In terms of democratization, liberal view of nationalism suggests that the nationalism is consistent with tolerance, diversity and freedom. Liberal view argue that nationalism can be intolerant in nature only if the nation is described on the basis of ethnic and racial terms (in other words, by the values that are propounded by ethnic nationalists). On the other hand, counter arguments criticize every kind of nationalism for being intolerant in nature because nationalism fundamentally creates others and us. Critiques suggest that tolerance is not achievable in nationalism because there is a threat when there are others. In terms of diversity, liberals pay respect for ethnic differences and suggest that nationalism is consistent with diversity (at a certain degree). Liberals see that there is harmony between civic unity and diversity in the nation. However, they also suggest that the harmony is achievable if diversity is excluded from the public sphere. In other words, they believe th at diversity should be confined to the private sphere, meaning that cultural, moral and lifestyle differences should be within the private sphere. The public sphere is seen as a realm for integration. The unity in the public sphere is formed by shared political and civic allegiances. On the other hand, today, many nations are established around shared cultural, ethnic, regional values, common location and language. These values, which reflect the ethnic nationalism, are usually associated with deep sense of belonging to ones nation and culture. It is questionable if political and civic allegiances create a strong belonging to ones own nation. As is mentioned in the text, ethnicity, language and other cultural values are seen as values bounding people to their nation as well as each other. Therefore, political and civic allegiances might not establish the same connection in the society as much as shared history and ethnicity can establish. In terms of Turkish nationalism, I feel free to identify it as ethnic nationalism because it shares the same characteristics with ethnic nationalism. Ethnic nationalism is described basically by being deep-rooted in ethnic unity and deep sense of cultural and national belonging. When we think of Turkey, simply the people calling themselves as Turks, they identify themselves as people living in Turkey (certain location/territory), speaking Turkish (common language), and sharing same history (common descent). Given these characteristics of Turkish nationalism and because it has a fixed identity, Turkish nationalism tends towards ethnic nationalism. To exemplify how ethnic nationalism is supported in Turkey, I wrote the Turkish Oath (AndÄ ±mÄ ±z in Turkish) as an example.

Tuesday, August 20, 2019

Vitamin D Impact on the Liver and Kidney

Vitamin D Impact on the Liver and Kidney Revised vitamin D copy Sources and forms of vitamin D Vitamin D, also termed calciferol, is a fat-soluble secosteroid compound that is an essential regulatory factor for calcium and phosphate metabolism in humans and animals. Its biological functions involve a physiological action in bone formation and mineralization, muscle contraction, nerve signal modulation and transmission as well as many cellular metabolic effects in various organs. There are two forms of vitamin D that are metabolically important; vitamin D2 or ergocalciferol and vitamin D3 or cholecalciferol. The nutritional sources of both forms are limited to certain types of foods that naturally contain vitamin D and therefore it is added to some foods as a supplement. 1.1.1- Exogenous (Diet) Both forms of vitamin D (D2 and D3) are exogenously obtained in low quantities from some types of food in the diet. Vitamin D2 is rare as it is produced from fungal and plant sources such as mushrooms and cereals, as a result of irradiation, by ultraviolet photons, of the plant sterol ergosterol. When these foods are ingested, ergocalciferol is absorbed into the blood. Vitamin D3 , on the other hand, is available in very low amounts from animal sources including oily fish such as salmon and mackerel; other sources include meat, liver, cheese, cod liver oil, eggs and fortified foods such as margarine and milk (Holick, 2006; Engelsen et al., 2005; Nowson et al., 2004). Farmed salmon, for example, contains only 25% of the vitamin D levels present in wild salmon, however, the amount of vitamin D in canned food may affected by modern processing methods (Chen et al., 2007). 1.1.2- Endogenous In humans the principal precursor of vitamin D3 is cholesterol which is obtained from the diet. Cholesterol is initially converted to 7-dehydrocholesterol, provitamin D3, through the action of enzymes termed the mucosal dehydrogenase complex, present in the small intestine. Provitamin D3, is then incorporated within chylomicrons and transported to the skin where temperature dependent photoisomerisation processing of 7-dehydrocholesterol takes place in epidermal cells resulting in the production of D3. Within the epidermal cells, vitamin D3 undergoes photocoversion to its isomers 5,6-transvitamin D3 and suprasterol, a process which relies on the amount of ultraviolet radiation absorbed; inadequate sunlight exposure compromises this process (Holick, 2003; Iqbal, 1994). Sunlight exposure is therefore a crucial element in the regulation and enhancement of endogenous cholecalciferol production (Dusso, et al., 2005; Iqbal, 1994; Reichel, et al., 1989; Smith, 1988). Once photoconversion is completed, cholecalciferol binds to Vitamin D Binding Protein (VDBP) and transported to the liver for further metabolic processing. Vitamin D metabolism Both forms of vitamin D (D2 and D3) undergo similar metabolic activation in the liver and kidney respectively to produce the physiologically active form 1,25-dihydroxyvitamin D3. 1.2.1- Skin The skin is characterized by two layers, the outer epidermal region, consisting of several strata, and the inner dermal layer. Skin exposure to UVB rays in sunlight, characterized by a wavelength of 290 nm to 315 nm, allows the initial steps of vitamin D synthesis to occur using the substrate 7-dehydrocholesterol (7-DHC) as illustrated in step 1 of Figure 1. UVB absorption by 7-DHC is thought to occur actively in the stratum basale and stratum spinosum regions of the epidermal layer. The substrate 7-DHC is an important intermediate of cholesteryl ester biosynthesis from squalene. During the reaction, 7-DHC forms procholecalciferol through B ring opening of the steroid structure. This transition state is relatively unstable and can further undergo photocatalyzed reactions to form lumisterol and tachysterol (Wolpowitz and Gilchrest, 2006). Lumisterol and tachysterol have been shown to prevent vitamin D reaching intoxicating levels and do not have any direct vitamin D effects (Bouillon et al., 1998). In addition to this protective mechanism, previtamin D poisoning is also prevented because this is an equilibrium reaction that allows cholecalciferol to revert back to 7-DHC (Webb, 2006). Cholecalciferol (previtamin D3) is produced upon double bond rearrangement of procholecalciferol and remains in the extracellular space where it becomes bound to the ubiquitous VDBP (Holick, 2005). Figure1. Sources and steps of vitamin D synthesis in the three major sites: skin, liver and kidney (Figure obtained from Wolpowitz and Gilchrest, 2006). 1.2.2- Liver Cholecalciferol that has been transported to the liver undergoes the first step of its bioactivation, the hydroxylation of carbon 25 (Dusso, et al., 2005) by two hepatic enzymes; the microsomal and mitochomdrial 25-hydroxylases (Deluca et al., 1990). In hepatic cellular microsomes and mitochondria, vitamin D3 is hydroxylated at carbon 25 and transformed to 25-hydroxyvitamin D3 by both 25-hydroxylase enzymes. This enzyme complex requires the presence of essential catalytic cofactors including nicotinamide adenine dinucleotide phosphate (NAPDH), flavin adenine dinucleotide (FAD), ferredoxin and molecular oxygen for this reaction to proceed (Sahota and Hosking, 1999; Ohyama et al., 1997; Kumar, 1990). Recently, large numbers of hepatic cytochrome P-450 enzymes exhibiting 25-hydroxylase action have been identified in vitamin D activation pathways; these enzymes include CYP27A1, CYP3A4, CYP2D25 and CYP2R1 (Dusso, et al., 2005; Cheng et al., 2003; Sawada et al., 2000). However, CYP2R1 is b elieved to be the principal enzyme in the hepatic pathway and the presence of a genetic mutation in its gene may compromise the outcome of this process; both CYP27A1 and CYP2D25 demonstrate high capacity and low affinity features, therefore, their activity is considered insignificant in this pathway (Dusso, et al., 2005; Cheng et al., 2003; Sawada et al., 2000). This metabolic step is inefficiently regulated, i.e. the levels of 25-hydroxy vitamin D are elevated as dietary intake of vitamin D increases. Consequently, over 95% of 25-hydroxyvitamin D in serum circulates as 25-hydroxyvitamin D3 which has a half-life of approximately three weeks, and is therefore used in the assessment of vitamin D status (Dusso, et al., 2005; Reichel et al., 1989). The metabolically inert 25-hydroxyvitamin D3 is then transported to the kidney for the second step of its bioactivation. 1.2.3- Kidney The second step of vitamin D3 bioactivation takes place at the proximal convoluted tubule of the kidney. Hydroxylation occurs at C-1 of 25-hydroxyvitamin D3 whereby the highly active 25-hydroxyvitamin D3 1-ÃŽ ±-hydroxylase (CYP27B1) incorporates a hydroxyl group to Carbon-1 of the first ring to form the biologically active metabolite 1,25-dihydroxyvitamin D3 (Holick,2006; Dusso, et al., 2005; Deluca et al, 1990; Reichel, et al., 1989). The high activity of 1-ÃŽ ±-hydroxylase (CYP27B1) present in kidney is not unique to this organ and can also be found in some other organs (Bouillon, 1998). The renal hydroxylation of 25-hydroxyvitamin D3 is the rate-limiting step in the production of 1,25-dihydroxyvitamin D3 and is well regulated. An alternative pathway of hydroxylation of 25-hydroxyvitamin D3 within renal mitochondria takes place at Carbon-24 to form 24,25-dihydroxyvitamin D3 which is metabolically inert. This process is catalyzed by renal 24-ÃŽ ±-hydroxylase in response to 1-ÃŽ ±-hy droxylase suppression. However, 24-ÃŽ ±-hydroxylase not only initiates the attachment of the hydroxyl group at Carbon-24 but also enhances the dehydrogenation of 24,25-dihydroxyvitamin D3 and hydroxylation at Carbon 23 and 26 (Sahota and Hosking, 1999; Bouillon, 1998; Reichel, et al., 1989). Renal hydroxylases require the presence of catalytic cofactors that enhance their synthetic activities during this process. Figure 2 shows the details of vitamin synthesis including the enzymes and cofactors required for each step. Figure2. Enzymes, cofactor and intermediates compounds of vitamin D metabolism (Bouillon et al. 1998) 1.2.4- Regulation of vitamin D metabolism Numbers of factors have been demonstrated to be important in the regulation of vitamin D metabolism; particularly significant its regulation through renal production. The factors involved in this regulation comprise parathyroid hormone (PTH), calcitonin, dietary calcium and phosphate, insulin and insulin-like growth factor and 1,25-dihydroxyvitamin D3 itself (Holick,2006; Deluca, 2004; Sahota and Hosking, 1999). Key interactions of vitamin D with its receptor are known to initiate gene regulation. These mechanisms have been studied using vitamin D analogues which have revealed the mechanism of assembly of transcriptions factors and promotion of gene regulation by this molecule (Cheng et al., 2004; Wu et al., 2002). Figure 3 shows the effect of various regulators on vitamin D metabolism. Figure 3: Alternate pathway for vitamin D3 under different metabolic conditions of low mineral Ca and P levels, PTH concentration and secretion of GH / IGH (Figure obtained from Gomez, 2006). 1.2.4.1- Parathyroid Hormone Parathyroid hormone (PTH) is the primary regulator of renal 1,25-dihydroxyvitamin D3 formation (Holick, 2006; Dusso et al., 2005; Bouillon et al., 1998; Issa et al., 1998). PTH regulates 1,25-dihydroxyvitamin D3 production directly through enhancing 1-ÃŽ ±-hydroxylase activity within kidney cells and increasing the genetic transcription rate of renal proximal tubular 1-ÃŽ ±-hydroxylase both of which result in an increase in the renal 1,25-dihydroxyvitamin D3 production rate. High levels of 1,25-dihydroxyvitamin D3 suppress the enzyme transcription activity and PTH concentration. Thus, renal 1,25-dihydroxyvitamin D3 has a negative feedback response on PTH secretion, providing an efficient regulatory control of renal 1,25-dihydroxyvitamin D3 homeostasis (Dusso, et al., 2005; Holick,2003; Sahota and Hosking, 1999; Reichel, et al., 1989; Iqbal, 1994). 1.2.4.2- Calcium Dietary calcium exhibits a direct regulatory influence on renal 1-ÃŽ ±-hydroxylase activity via fluctuating serum calcium concentration and indirectly via its effect on serum PTH concentration. Calcium exerts its effect through calcium-sensing receptor (CaR) activation within the parathyroid gland and renal proximal tubules cells in response to low calcium concentration. Thus, the low intracellular calcium levels lead to increased production of 1,25-dihydroxyvitamin D3 within renal cells (Ramasamy, 2006; Bland et al., 1999; Chattopadhyay et al., 1996). On the other hand, it has been shown that high calcium concentrations markedly impair renal 1,25-dihydroxyvitamin D3 formation in human nephrotic cell cultures and in parathyroidectomised animals (Bland et al., 1999; Chattopadhyay et al., 1996). An increase in extracellular calcium indirectly suppresses 1,25-dihydroxyvitamin D3 production at the proximal convoluted tubule by inhibiting PTH release (Deluca, 2004; Carpenter, 1990). Howev er, the detailed mechanism of calcium-sensing receptors (CaR) activation is not yet fully understood (Dusso, et al., 2005; Hewison, et al., 2000). 1.2.4.3- Phosphate Dietary phosphate intake and serum phosphate concentrations exhibit regulatory effects on 1,25-dihydroxyvitamin D3 production in proximal renal tubules. This effect has been demonstrated in several studies which showed that a decrease in dietary phosphate accelerated renal formation of 1,25-dihydroxyvitamin D3, but did not directly affect 1, 25-dihydroxyvitamin D3 catabolism. Conversely, elevated serum phosphate and increased phosphate intake led to decreased production of 1, 25-dihydroxyvitamin D3 (Carpenter, 1989; Reichel et al., 1989). Several studies have shown that inorganic phosphate levels have no significant direct effect on mitochondrial 1-ÃŽ ±-hydroxylase activity in cultured renal cells in the short term, suggesting that the action of inorganic phosphate is not mediated via changes in PTH and Calcium concentrations and is possibly inducted by other hormones such as growth hormone, insulin and insulin-like growth factor (Khanal et al., 2006; Dusso et al., 2005; Carpenter, 1 989). In recent studies, fibroblast growth factor 23 (FGF-23), frizzled-related protein 4 (FRP-4) and matrix extracellular phosphoglycoprotein (MEPE) have all been identified as potent and key regulatory factors of 1-ÃŽ ±-hydroxylase activity in renal cells. These factors act through a biphasic mechanism on renal phosphate homeostasis and modulate the circulating levels of 1, 25-dihydroxyvitamin D3 produced by proximal renal tubules (Dusso et al., 2005; Inoue et al., 2005; Mirams et al., 2004). 1.2.4.4- Calcitonin Calcitonin belongs to a family of calcium regulating hormones that is produced in the parafollicular cells of the thyroid gland, also known as C cells. It is a short and linear polypeptide with a molecular weight of only 3.7 kD. It is characterized by 32 amino acids and a disulfide bridge in the N terminal portion of the peptide. Calcitonin is secreted in response to increased free Ca2+ in blood and acts on osteoclasts, the bone resorbing cells, as a suppressor of bone dissolution. Although calcitonin decreases Ca+2 and inorganic phosphate in blood, it also has the ability to recruit phosphorus into other cells. In addition to these metabolic functions, it is also involved in the upregualtion of CYP27B hydroxylase through the protein kinase C pathway (Yoshida et al., 1999) via a phosphorylation cascade that activates cAMP and induces the expression of hydroxylase thereby activating the transformation of 25(OH) D3 to 1,25(OH)2 D3. In addition to the significant role as a calcium regulating hormone, calcitonin is also known to stimulate the production of vitamin D in tandem with PTH (Yoshida et al., 1999; Wongsurawat and Armbrecht, 1991). Previous studies revealed that 1-ÃŽ ±-hydroxylase mRNA expression, 1-ÃŽ ±-hydroxylase activity and the production of 25(OH)D and 1,25(OH)2D3 all increased in rat kidney cells following the administration of calcitonin (Yoshida et al., 1999; Galante et al., 1972; Rasmussent et al., 1972). However, in cases of diabetes, it is postulated that the kidney becomes immune to the effect of this hormone in diabetic rats which lead to increase vitamin D production (Wongsurawat and Ambrecht, 1991). 1.2.4.5- Growth hormone, Insulin and Insulin-like growth factor-1 Growth hormone (GH) has many regulatory actions in various metabolic processes in humans and mammals and its effect on mineral homeostasis in target organs such as bone and renal cells is well documented. While the regulatory effects of GH on dietary calcium and phosphate metabolism in different tissues have been established, its effect on vitamin D metabolism remains controversial. However, many studies have shown that GH increases the expression of 1-ÃŽ ±-hydroxylase and 1, 25-dihydroxyvitamin D3 in cultured cells and experimental animals (Gomez, 2006). Wu and colleagues reported that serum1, 25-dihydroxyvitamin D3 increases after GH administration in hypophysectomized rats fed with a phosphate depleted diet. Short-term studies in healthy humans have shown that GH raises 1-ÃŽ ±-hydroxylase enzyme activity and promotes 1, 25-dihydroxyvitamin D3 synthesis without changes in PTH, calcium and phosphate concentrations, suggesting that the increasing circulating levels of 1, 25-dihydroxy vitamin D3 following GH administration is not mediated by PTH action (Wu et al., 1997; Bianda et al., 1997; Wright et al., 1996). GH has also been shown to lead to increased production and serum concentration of 1, 25-dihydroxyvitamin D3 in pigs and in renal impaired prepubescent children. These are thought to be a result of the direct and indirect effects of GH on 1-ÃŽ ±-hydroxylase expression, and on calcium and inorganic phosphate homeostasis in renal tubules cells (Strife and Hug, 1996; Denis et al., 1995). However, the action of GH on vitamin D metabolism in vitro remains uncertain and may involve other regulatory factors such as PTH and Insulin-like growth factor-1 (IGF-1). It has been shown that GH does not raise 1, 25-dihydroxyvitamin D3 levels directly in cultured cells obtained from aged-rats; yet it stimulates calcium absorption and the expression of calcium binding proteins in vitro indicating that the effect of GH is mediated through the action of other factors such as IGF-1 (Fleet et al., 1991). Insulin is another key factor with a role in vitamin D homeostasis. Insulin significantly decreases renal hydroxylase activity and renal synthetic capacity of 1, 25-dihydroxyvitamin D3 in insulin deficient patients or those receiving insulin therapy (Armbrecht et al., 1996). However, a study of different routes of therapeutic insulin administration in human diabetic subjects concluded that insulin induces the hepatic hydroxylation of 25-hydroxyvitamin D3. This effect is related to the fact that insulin is a potent inducer of the vast majority of liver hydroxylases enzymes (Colette et al., 1989). This study also showed that there was no significant difference in circulating levels of 1,25-dihydroxyvitamin D3 between different methods of insulin administration. Serum 1,25-dihydroxyvitamin D3 is maintained at normal concentrations in those subjects on long term insulin therapy; however, continuous intraperitioneal infusion procedure (CPII) may augment hepatic 25-hydroxlase activity (Col ette et al., 1989). Similarly insulin has shown a significant effect on stimulating 1,25-dihydroxyvitamin D3 production through 1,25-dihydroxyvitamin D3 and PTH stimulation with no concomitant action on 24-hydroxylase expression in rat osteoblast cells when these cells were cultured with known concentrations of 1,25-dihydroxyvitamin D3 and PTH (Armbrecht et al., 1996). Insulin-like growth factor-1 (IGF-1) is a relatively small peptide that is primarily expressed in hepatic cells and to a lesser extent in some other cells and tissues. It has been identified as one of the potent regulatory components of mineral metabolism in humans and mammals. Recent studies on the metabolic effect of IGF-1 revealed that the administration of IGF-1 to aged laboratory animals, fed on a calcium- and phosphate- deficient diet, can restore 1-ÃŽ ±-hydroxylase activity and enhance the production of 1,25-dihydroxyvitamin D3. In contrast, there was no significant effect of IGF-1 on enzyme activity and 1,25-dihydroxyvitamin D3 levels in adolescent or elderly rats fed on a calcium and phosphate fortified diet concluding that the expression of IGF-1 is not age related but related to the dietary calcium and phosphorus status. (Gomez, 2006; Wong et al., 1997; Wu et al., 1997). In healthy human subjects, a significant effect of IGF-1 on renal 1,25-dihydroxyvitamin D3 synthesis wa s observed after short term infusion with IGF-1. There was no noticeable alteration of the levels of circulating calcium, phosphate and PTH highlighting the role of IGF-1 in stimulating renal expression of 1-ÃŽ ±-hydroxylase and 1,25-dihydroxyvitamin D3 formation in conjunction with GH, independently from PTH (Bianda et al., 1997). In vitro studies have shown that IGF-1 influences the expression of 1-ÃŽ ±-hydroxylase and 1,25-dihydroxyvitamin D3 synthesis in cells cultured from non renal human tissues. Halhali and colleagues demonstrated that IGF-1 noticeably elevates both the enzyme activity and 1,25-dihydroxyvitamin D3 levels when added into cultured syncytiotrophoblast cells obtained from human placental sources. This study demonstrated that IGF-1 strongly enhances the ability of non renal cells to produce 1,25-dihydroxyvitamin D3 without involvement of GH and PTH (Halhali et al., 1997). 1.2.4.6- 1, 25-dihyroxy vitamin D3 The circulating levels of 1,25-dihydroxyvitamin D3 modulate its production by renal cells through an indirect negative feedback mechanism. This mechanism appears to reduce the likelihood of vitamin D toxicity by inhibiting 1,25-dihydroxyvitamin D3 synthesis by an indirect mechanism that controls the 1-ÃŽ ±-hydroxylase gene expression at the molecular level rather than inhibiting 1,25-dihydroxyvitamin D3 synthesis directly. However, the exact mechanism is not yet fully understood (Dusso et al., 2005; Deluca et al., 1990). A recent study examined the effect of 1,25-dihydroxyvitamin D3 on 1-ÃŽ ±-hydroxylase production by cultured human keratinocytes. Keratinocytes were cultured with labeled 25-hydroxyvitamin D3 and different concentrations of 1-ÃŽ ±-hydroxylase mRNA and 24-hydroxylase- suppressed proteins. The 1,25-dihydroxyvitamin D3 did not suppress either the 1-ÃŽ ±-hydroxylase activity or the rate of gene transcription. The study implied that metabolic regulation of 1,25-dihydroxyvi tamin D3 is related to the molecules biodegradation in response to augmented 24-hydroxylase activity rather than 1,25-dihydroxyvitamin D3 formation by 1-ÃŽ ±-hydroxylase (Xie et al., 2002). In addition, Wu and colleagues demonstrated a possible alternative mechanism of 1,25-dihydroxyvitamin D3 synthesis linked to the fact that both 24-hydroxylase and 1-ÃŽ ±-hydroxylase enzymes share equivalent metabolic capability and they proposed the possibility of protein- protein interaction between intracellular vitamin D binding protein and 1-ÃŽ ±-hydroxylase (Wu et al., 2002). 1.2.5- Vitamin D Transport, receptors and mechanism of action Vitamin D receptor (VDR), also known as calcitriol receptor, is a member of the steroid family and belongs to the nuclear receptor superfamily (NHR). Human VDR until recently was thought to comprises four functional units with a total of 427 amino acids residues with an estimated molecular weight of about 48 kDa. These units are the DNA binding domain (DBD) or C domain, the D domain and the ligand binding domain (LBD) or E domain. More recently, a carboxy-group with undefined function, known as the F region has been identified (Christakos et al., 2003; Aranda and Pascual, 2001; Rastinejad et al., 2000). These units as, shown in figure 4, are also known as A/B domain. The A/B region of VDR contains a low number of amino acids that participates in essential ligand-independent receptor stimulation (Aranda and Pascual, 2001; Issa et al., 1998). It is not yet clear if the deletion of A/B domain from VDR will compromise ligand binding, DNA binding or its transactivation features (Issa et a l., 1998). In contrast, the structure of the DNA binding domain or C region among NHRs comprises 40% unique amino acids sequences and a domain of more than 67 resemble amino acids residues (Rastinejad et al., 2000). Moreover, the core structure of DBD comprises between 22 and 114 amino acid residues, nine of them are cysteines. Eight of cysteine residues orchestrate with zinc atoms in tetrahedral fashion to form a dual â€Å"zinc-like finger† DNA binding configurations containing approximately 70 amino acids with a carboxy-terminal extension (CTE). This encloses T and A boxes in a dual helix molecule in which one helix is essential for definitive interaction with the main domain on DNA while the second helix takes a part in receptors structural properties (i.e. receptor dimerization) (Aranda and Pascual, 2001; Issa et al., 1998). However, the integration of the structural amino acids of the DBD ÃŽ ±-helix one, at the site of the first zinc atom, determines the selectivity and specificity of recognition of DBD and forms an area known as the â€Å"P Box†. Similarly; the integration of amino acids at the position of the second zinc atom modulates the formation of a configuration termed the â€Å"D Box† which forms a dimerization interface zone (Aranda and Pascual, 2001; Rastinejad et al., 2000; Issa et al., 1998). Furthermore the vast majority of DBD amino acid units are basic amino acids which enhance the non-covalent binding of the DNA helix at the negatively charged phosphate group (Issa et al., 1998). The ligand binding domain (LBD) or E domain has a spherical configuration with many functional regions composed of 12 cohered helix anchors defined as H1 to H12. LBD itself comprises a net of 427 amino acids which contribute to homodimerization and heterodimerization and the interaction of hormones and costimulaotors by a crucial transactivational mechanism (Aranda and Pascual, 2001; Weatherman et al., 2000; Issa et al., 1998). Crystallograp hic studies show that LBD have two cohered and integrated domains, the Ti or â€Å"signature motif† and the carboxy or C terminal AF-2 providing the self-ligand transcriptional properties; hence a higher degree of attraction of 1,25 dihydroxyvitamin D3 binding is observed at 382 to 402 of LBD amino acid sequence and any genetic aberration at this particular amino acids sequence will diminish the interaction capability of LBD (Aranda and Pascual, 2001; Issa et al., 1998). Figure 4: The primary structure of the vitamin D receptor (VDR) and the binding of retinoid X receptor (RXR)-VDR heterodimers to vitamin D response elements (VDREs) in the form of DR3 and ER6 motifs. (Figure from Lin and White, 2003) 1,25-dihydroxyvitamin D3, has been identified as steroid hormone with a mechanism of action similar to other steroid hormones, causing new protein expression in various target organs. Based on the nuclear receptors structural studies, calcitriol is known to exert its biological action through binding with VDR in the cell nucleus to mediate a cascade of transcriptional and translational processes resulting in either the regulation or inhibition of new protein expression in target tissues or the binding to plasma membrane receptors without stimulating new protein synthesis (Nezbedova and Brtko, 2004; Reichel and Norman, 1989). Two different receptors for 1,25-dihydroxyvitamin D3 have been recognized in different target cells; identified as genomic VDRnuc and typical VDRmem .These receptors provide the best dynamical conformational forms for calcitriol interaction and to evoke its genomic and non-genomic effects (Norman et al., 2002). The binding of 1,25-dihydroxyvitamin D3 to VDRnuc e nhances the interaction with an undistinguished protein known as the nuclear accessory factor (NAF) and to the caroxy-terminal of VDR. This interaction leads to a structural conversion pattern of the C-terminal of VDR allowing the AF-2 domain to attach with other transcriptional elements such as SCR-1, calcium binding protein (CBP) and P300. This promotes the binding of the heterodimer molecule with DNA at the vitamin D response sites (VDRE) and directs its transcriptional gene activity (Jones et al., 1998; Iqbal, 1994). In addition, these coactivators play a role in DNA configurational changes through histone acetyl transferase activation pathway of the core components of histones. This results in mechanical instability of the DNA structure and enhances the net binding capacity of the coactivators with their corresponding receptors at nucleosomal histone level and leads to the upregulation of these transcriptional coactivators which in trun, accelerate the net gene transcriptional rate to promote the synthesis of the analogous protein (Lipkin and Lamprech, 2006; Jones et al., 1998). Conversely, the non-genomic or classical effect of 1,25-dihydroxyvitamin D3 is modulated through its binding with the surface cellular membrane receptor known as mVDR which initiates an immediate response in various target tissues with no genomic transcriptional activity. Many studies demonstrate the rapid effect of calcitriol in rapidly increasing both the level of circulating calcium and its absorption rate in animal intestines, evoking phosphoinoisitide bioactivation, cyclic guanosine monophosphate (cGMP) elevation, activation of protein kinase C and triggering the mitogen activated protein kinase pathways and involving the chloride gates action potential in different organs (Dusso et al., 2005; Nezbedova and Brtko, 2004; Boyan and Schwartz, 2004; Norman et al., 2002). The entire mechanism, as shown in figure 5, for the rapid effect of calcitriol remains doubtful, however; the proposed mechanism is mediated through the interaction with mVDR leading to a series of intracellular sig naling events. Signaling is orchestrated by the activation of various metabolic pathways involving different transportation mechanisms of certain mineral components of target organs. (Pedrozo et al., 1999; Norman et al., 1999; Revelli et al., 1998). However, other studies reveal that the genomic effect of 1,25-dihydroxyvitamin D3 is independent of its non-genomic mechanism (Dusso et al., 2005). Figure 5: Cellular mechanism of action of 1,25(OH)2D3 (Figure from Horst et al., 1997) 1.3- Biological actions of Vitamin D on target tissues and Systems The active form of vitamin D, 1,25-dihydroxyvitamin D3 is well recognized as a member of steroid hormones that mediates several metabolic and non-metabolic processes in various organs in human and animals as shown in figure 6. 1.3.1- Intestine Mineral absorption in the intestines is increased in the presence of the hormone 1,25(OH) vitamin D. However without this, only 10 to 15% of dietary calcium and 60% of phosphorus is absorbed from the diet (De Luca, 2004). Ca2+ and HPO42- are also absorbed when intestinal cells interact with the vitamin D- VDR- RXR complex. The latter enhances the expression of the epithelial calcium channel and calcium-binding protein which recruits calcium and phosphorus (Holick, 2007). Knock out mice experiments studying the effect of VDR gene deletions also show that the size of the small intestines is related to the levels of calcitriol and dietary calcium availability. Vitamin D deficient mice fed with diets low in calcium exhibited the largest small intestine to large intestine ratio (Cantorna et al., 2004). VDR knock-out mice experiments also aid in the discovery of calcium channels, the route for Ca absorption, in the intestine (Peng et al., 1999). Calbindin is a potent calcium transporter in mammals which characterized by a high affinity for calcium ions. Therefore, the binding of vitamin D to VDR and RXR signals an increased production of calbindin which facilitates systemic Ca2+ ions transportation and prevent the occurrence of calcium toxicity in the intestines. Figure 6: Schematic diagram of the effects of Vitamin D on different tissues and organs (Figure from Holick, 2007). 1.3.2- Bone Takeda et al. (1999) studied the role of vitamin D and VDR in bone cells using knock out mice experiments. Their results showed that bone cells formation triggering mechanisms such as cell to cell interaction between osteoblast and osteoclast progenitors and stromal cells induced by 1,25(OH)2 vitamin D3 and provoke the formation of osteoclasts. In their capacity as bone resorbing cells, osteoclasts can be triggered by low serum calcium levels, to break down bone and free calcium back in to the blood thus redistributing calcium throughout the body. However, this does not occur without the expression of VDR and without vitamin D complexing with its receptor. This study emphasizes the important role of recognition sites on the VDR and the structural implications that the receptor-ligand binding has on VDREs and transcription initiation. Although the effects of PTH

Monday, August 19, 2019

Matewan: A 20th-century Form of Feudalism :: Economy Capitalism Freedom Essays

Matewan: A 20th-century Form of Feudalism Matewan, in which the action takes place in the 1920s in West Virginia, gives a clear and realistic picture of the economical situation of the given place and time. This has been a purpose and an idea which the director of the film, John Sales, has paid a particular attention to. The film elucidates a 20th-century conflict between two economical systems: feudalism and capitalism, with feudalism clearly dominating the economical status of the small town of Matewan, in spite of some outer characteristics (such as wages being paid) that imply capitalism. The main feature of capitalism is the free labor market and 'freedom' is the key concept: freedom in choosing an employer; freedom in deciding how and where to work in order to make the most reasonable living. In that sense it is indisputable that capitalism is not the economical process taking place in Matewan. It is very difficult, if not impossible, to live in this small town and not to work for the Stone Mountain Coal Company. It holds monopoly over most of the town, it owns and controls nearly everything: stores, buildings and so on. The miners are being underpaid and overcharged at the same time. Wages have gone down again, workers have to pay monopoly rents; besides, they are getting paid not in dollars but in company scrips that can be used at company stores only. Therefore, the contract the workers have signed with the company, in stead of giving them freedom and rights, puts restrictions on them and their way of life: they do not have the freedom to join in a union; they are not free to choose their employer, either. The working and the living conditions are beyond any criticism and are very far from what is needed in order to lead a normal life. However, this seems to be the only way for people there to make any living at all. The alternative is fleeing away in the mountains with no home and no money whatsoever, which is really not acceptable and can hardly even be considered as an 'alternative' therefore. In that sense, the geographical setting (i.e. the isolation of this small town) indirectly encourages the development of feudal relations in Matewan. The company leaves its workers with no choice and no freedom - a defining characteristic of feudalism, and that reinforces the feudal nature of the economical relations in Matewan.

Sunday, August 18, 2019

Sophocles Ajax - The Destruction of a Greek Hero Essay -- Sophocles A

Sophocles' Ajax - The Destruction of a Greek Hero Sophocles' Ajax, written around 440 B.C., deals with the destruction of the Greek hero Ajax, who is sometimes considered the greatest warrior of the Trojan War, second only to Achilles. Ajax, driven insane by the goddess Athena, slaughtered the Greek herds of cattle, thinking that they were Greeks, to avenge them for rewarding the armor of Achilles to Odysseus instead of him. Only after coming to his senses, he realized that he was disgraced and he committed suicide. The play moves on, however, to deal with his burial, in which Teucer, Ajax's half-brother, and Odysseus argue with two supreme kings, Agamemnon and Menelaus, that Ajax has the right to burial. Throughout the play until his death, Ajax is the central character, undergoing a grim change from a proud, insane lunatic to a sane, shamed man, whose only hope for honor is suicide. Opening the play, Ajax himself was a "powerful figure, towering over the others, but limited and essentially selfish" (xii). His madness brought on by Athena had left him utterly helpless, although he falsely believed that Athena had assisted him in slaughtering the Greeks. The mightiest of warriors, even Odysseus commented that he had seen no one who was equal in prowess, power, and bravery to that which Ajax had displayed. However, his eyes darkened with deadly delusions, he was at the hands of the gods, although he was so arrogant that he didn't even realize it. He did not know that, as Odysseus states, he was a "puppet" in their hands: I pity him, brought down to this, Caught in the grip of such a grievous fate-- ................ ...ur father was" (17). But in his words to the gods as he was dying, it was obvious that he had undergone a metamorphosis from the beginning of the play, in which he was excessively proud, forgetting that he could be controlled by fate, to his death, where he succumbed to the gods, fully knowing that fate rested in their hands. In conclusion, Ajax, I believe, was a noble character, although he did have a tragic flaw, his arrogance. Of course, everyone has a certain arrogance in some manner of life. Ajax, however, chose to display it, but he accepted the consequences of his actions nobly. He chose to end his life in what he believed was the honorable method, and to the end, he carried himself as a hero would have during his time. Works Cited Sophocles. Four Plays by Sophocles. Trans. Thomas H. Banks. New York: Oxford University Press, 1966.