Regulating Iron Metabolism

Regulating Iron Metabolism Introduction Iron is an essential nutrient for many organisms as it aids in numerous cellular processes such as oxygen transport and DNA synthesis. In overload, iron generates free radicals that damage both proteins and lipids. On the other hand, a deficiency of iron undermines cell proliferation. Iron metabolism: an outline An adult manages to take up around 1-3mg of iron a day, in order to make up for any losses through sweat, urine and dying red cells. Non-heme iron is taken up by red cells through bivalent metal transporters, also heme iron is taken up by red cells though an undefined mechanism. Regulation of iron metabolism Keeping a constant cellular iron content is important and therefore the body has developed precise mechanisms for the regulation of uptake storage and export of iron. The Iron-Responsive Element (IRE)/ Iron Regulatory Protein (IRP) regulatory mechanism consists of a mechanism responsible for regulating post-transcriptional gene expression to maintain iron homeostasis. It involves two RNA binding proteins Iron-regulatory protein 12 (IRP 1, IRP 2) and a regulatory RNA elements known as Iron Responsive Elements. IRE/IRP interactions control the expression of mRNA sequences that encode for proteins responsible for iron acquisition (divalent metal transporter 1 and transferrin receptor 1), storage of iron (H-ferritin and L-ferritin) iron utilization (erythroid 5-aminolevulinic acid synthase), energy (mitochondrial aconitase), and iron export (ferroportin) (Muckhentaler, et al., 2008). The processes responsible from binding IRP1 and IRP2 to IRE are regulated mainly by iron levels, although other stimuli do exist, such as hypoxia and nitric oxide. In cells which have high iron levels, the IRP/IRE binding activity is low as IRP 1 2 are incapable of binding to IRE. In such conditions, IRP1 would set up an iron-sulphur cluster (Fe-S) which in turn transforms into cytosolic aconitase, whereas IRP2 would become degraded through the action of the proteosome. This means that only in iron-depleted cells would the IRP proteins bind to IRE. Both IRP 1 2 hinder translation initiation when bound to the 5’Untranslated Region of IRE, by inhibiting the binding of the small ribosomal sub-unit to the mRNA sequence (Muckenthaler, et al., 1998). In addition, when IRP1 is bound to a cap proximal IRE, and hence the cap binding complex (eIF4F) is produced. At this point the small ribosomal sub-unit does not incorporate in the presence of IRP1 which hinders any interactions needed between the cap binding complex and the small ribosomal sub-unit. The association of IRP 1 with the 3’IRE of transferrin receptor 1 reduces its turnover by hindering the cleavage of a restriction site and eventually its mRNA degradation (Binder, et al., 1994). The mechanism that stabilizes IRP mRNA has not yet been well investigated for other 3’IRE containing mRNA’s like CDC14A and DMT1, which contain one 3’IRE site and could require other factors in order to be regulated. Therefore, it can be said that the binding of IR P 1 2 ensures iron balance and no over expression of target mRNA molecules. The IRP/IRE system was primarily described as a non-complex post-transcriptional gene expression which regulates the formation of ferritins and transferrin receptor 1. The discovery of other mRNA sequences associated with this system has increased the complexity and has enhanced the role of IRP proteins to connect different pathways, which are regulated by iron metabolism. Assessment of Iron Status Iron studies are a group of tests that are performed in order to evaluate the status of the iron stores as well as the concentration of iron in serum. Tests that are performed when an Iron profile is ordered may include: Serum iron Total Iron-Binding Capacity (TIBC) and/or Unsaturated Iron-Binding Capacity (UIBC) Transferrin Ferritin Transferrin receptor Transferrin Saturation Serum iron is a measure of the amount of iron present in blood and usually does not diminish until iron stores are depleted. It is ordered normally as a follow-up when low levels of haemoglobin and haematocrit are observed on a complete blood count. An increased level of iron can be due to ingestion of iron (e.g. food or medication) or ineffective erythropoiesis. On the other hand low iron levels might be the result of: infection, menstruation, inflammation, malignancy or iron deficiency. Total Iron-Binding Capacity (TIBC) is also used to measure the status of iron in blood. It can be either measured or else calculated based on the level of transferrin in the blood. TIBC and serum iron can then be used to calculate percentage transferrin saturation, which is a much better index for iron status than serum iron or TIBC alone, using the flowing calculation: The 26.1 value is used as a constant to convert Transferrin to an equivalent TIBC concentration. UIBC is normally used as an alternative to TIBC. Percentage transferrin saturation (TSAT) is a measurement of the amount of iron which is effectively bound to transferrin, therefore indicting the amount of iron which is available to sustain erythropoiesis. A low TSAT may be indicative of infection, erythropoiesis, inflammation or iron deficiency. Whereas, an elevate value might mean haemochromatosis, liver disease, ineffective erythropoiesis or recent ingestion of dietary iron. Transferrin is the plasma protein responsible for the transport of iron inside the body. It is also habitual to test for transferrin (apart from TIBC or UIBC) as this is a better indicator of the patient’s nutritional status and to some extent an indicator of liver function, since transferrin is produced in the liver. Low levels of transferrin can be observed with liver disease, however transferrin may also drop in malignant tumors and if not enough dietary protein is taken up. On the other hand, high levels can be observed with iron deficiency and during pregnancy. Iron can be stored intracellularly in the form of ferritin. Ferritin is a protein which stores iron in a non-toxic form. It is a sizeable molecule with a core of ferric hydroxide phosphate. It is considered to be the best indicator of iron stores in the body. Low levels of ferritin are normally indicative of iron deficiency or a response to therapy involving erythropoietin, whereas high levels might be due to inflammation, malignancy or infection. Soluble transferrin receptor (sTFR) does not necessarily feature in an iron panel; however it is worth mentioning since it helps distinguishing between iron deficiency anemia and anemia of chronic disease. It is normally ordered in the case that an iron panel does not give enough information to reach a conclusive diagnosis. Usually to evaluate the status of iron stores ferritin is the preferred indicator. However, it is an acute phase reactant, meaning that it can give a falsely elevated value with inflammation or chronic disease. Seeing a, sTFR is not an acute phase reactant, it can be used as an alternative in case chronic disease is suspected.

Comparing Women in House on Mango Street and Woman Hollering Creek Essa

Ethnic Identity of Women in House on Mango Street and Woman Hollering Creek  Ã‚      The novels The House on Mango Street (Cisneros 1984) and Woman Hollering Creek (Cisneros 1992) relate the new American through the eyes of Cisneros. The women in both novels are caught in the middle of their ethnic identity and their American identity, thus creating the "New American." Cisneros moved between Mexico and the United States often while growing up, thus making her feel "homeless and displaced" (Jones and Jorgenson 109). The House on Mango Street characterizes a community of girls and women restricted in their movements within the barrio. The roles of these girls and women are translated through the eyes of a child. When women in the barrio are confined, they can become a victim of abuse due to male domination. Women are confined to interior spaces in addition to their domestic roles as daughters, wives, and mothers. They live inside the barrio, but desire to escape and live outside the barrio. In addition, women can escape their restricted lifestyle by receiving an education. Esperanza, the child narrator is the only one who escapes this ethnic lifestyle (Mullen 6). In The House on Mango Street, the vignette "My Name," Esperanza was named after her great grandmother, desires a life outside her interior walls of the barrio. Esperanza’s name means hope in English, while it means sadness and waiting in Spanish. Her great grandmother was wild as a young lady, but was tamed by her Mexican husband. Cisneros states, "She looked out her window her whole life, the way so many women sit with sadness on an elbow . . . I have inherited her name, but I don’t want to inherit her place by the window" (11). Esperanza is proud of her namesake... ...il 1991. 22 Oct. 2000 False&origSearch=true&u=CA&u+CLC&u=DLB>. Mullen, Harryette. "A Silence Between Us Like a Language: The Untranslatability of Experience in Sandra Cisneros’s Woman Hollering Creek." Gale Literary Databases Summer, 1996. 22 Oct. 2000 Galenet.com/servlet/GLD/hit?c=1&secondary=false&orig SearchTrue&u=CA&u+CLC&u=DLB>. Olivares, Julian. "Sandra Cisneros’ The House on Mango Street and the Poetics of Space." Gale Literary Databases 1998. 14 Oct. 2000 <> Servlet/GLD/hits?c=6&secondary=false&origSearch=true& u=CA&†¦=>. "Sandra Cisneros." Contemporary Artists. Vol. 64. 1998. Wyatt, Jean. "On Not Being La Malinche: Border Negotiations of Gender in Sandra Cisneros’s Never Marry A Mexican and Woman Hollering Creek." Gale Literary Databases Fall 1995. 22 Oct. 2000 .    Comparing Women in House on Mango Street and Woman Hollering Creek Essa Ethnic Identity of Women in House on Mango Street and Woman Hollering Creek  Ã‚      The novels The House on Mango Street (Cisneros 1984) and Woman Hollering Creek (Cisneros 1992) relate the new American through the eyes of Cisneros. The women in both novels are caught in the middle of their ethnic identity and their American identity, thus creating the "New American." Cisneros moved between Mexico and the United States often while growing up, thus making her feel "homeless and displaced" (Jones and Jorgenson 109). The House on Mango Street characterizes a community of girls and women restricted in their movements within the barrio. The roles of these girls and women are translated through the eyes of a child. When women in the barrio are confined, they can become a victim of abuse due to male domination. Women are confined to interior spaces in addition to their domestic roles as daughters, wives, and mothers. They live inside the barrio, but desire to escape and live outside the barrio. In addition, women can escape their restricted lifestyle by receiving an education. Esperanza, the child narrator is the only one who escapes this ethnic lifestyle (Mullen 6). In The House on Mango Street, the vignette "My Name," Esperanza was named after her great grandmother, desires a life outside her interior walls of the barrio. Esperanza’s name means hope in English, while it means sadness and waiting in Spanish. Her great grandmother was wild as a young lady, but was tamed by her Mexican husband. Cisneros states, "She looked out her window her whole life, the way so many women sit with sadness on an elbow . . . I have inherited her name, but I don’t want to inherit her place by the window" (11). Esperanza is proud of her namesake... ...il 1991. 22 Oct. 2000 False&origSearch=true&u=CA&u+CLC&u=DLB>. Mullen, Harryette. "A Silence Between Us Like a Language: The Untranslatability of Experience in Sandra Cisneros’s Woman Hollering Creek." Gale Literary Databases Summer, 1996. 22 Oct. 2000 Galenet.com/servlet/GLD/hit?c=1&secondary=false&orig SearchTrue&u=CA&u+CLC&u=DLB>. Olivares, Julian. "Sandra Cisneros’ The House on Mango Street and the Poetics of Space." Gale Literary Databases 1998. 14 Oct. 2000 <> Servlet/GLD/hits?c=6&secondary=false&origSearch=true& u=CA&†¦=>. "Sandra Cisneros." Contemporary Artists. Vol. 64. 1998. Wyatt, Jean. "On Not Being La Malinche: Border Negotiations of Gender in Sandra Cisneros’s Never Marry A Mexican and Woman Hollering Creek." Gale Literary Databases Fall 1995. 22 Oct. 2000 .   

An Overview of Representative Problems

Krarup & Pruzan [27] have reviewed research on traditional facility location models that aim to minimize the sum of the fixed facility location and transportation costs by choosing the optimal facility locations among given probable sites to serve a set of customers. The objective function and constraints of these models are linear, but the resulting problems are NP-complete. Melo, Nickel and Saldahna [25] have reviewed facility location models in supply Chain and they focused more on integration of location decision along with other decision variables in the supply chain design. They noted that the role of facility location is decisive in supply chain network planning and this role is becoming more important with the increasing need for more comprehensive models that capture the real life constraint scenarios in detail. Leyla, Mark & Collette [29] in their recent publication claimed first work in the logistics literature that analyzes the potential savings that can be achieved by allowing a retailer to be sourced by more than one warehouse. They have proposed to leverage information technology to maximize the potential benefits. Huang et al. [30] paid attention to the opportunity of getting lower supplier prices by locating the warehouse correctly. In that theory, the optimal locations gravitate towards locations of the suppliers offering lower prices. However, if the price variability is high, the optimal location moves towards the demand's center of gravity. In those cases, it is beneficial for the organization to keep the location near that center of gravity and pay less attention to the supplier prices and supplier locations. The Research Problem: Many business managers are intending to answer following questions in the Post GST Scenario: â€Å"Will GST implementation enable supply chain network redesigning and Warehouse consolidation? Is it possible to create economic value and competitive advantage by altering the existing network to the more efficient one?† This project aims to study possible benefits of restructuring the warehouse network for a Food product company for their North India region in post GST set up.

International Treaties and Reservations to Them - Free Essay Example

Sample details Pages: 6 Words: 1808 Downloads: 8 Date added: 2017/06/26 Category Law Essay Type Analytical essay Level High school Did you like this example? Introduction Treaty is an international agreement between states or international organisations. Besides that, it is also one of the sources of international law because in a treaty parties can include rules and law on various aspects. In order to have a proper guidance on law regarding treaties, the Vienna Convention on Law of Treaties (VCLT) was formed and came into force on 27th January 1980. Don’t waste time! Our writers will create an original "International Treaties and Reservations to Them" essay for you Create order Thus, under the VCLT, it laid down the all the regulations from entering a treaty until end of a treaty. Nevertheless, the controversial issue in this research is on the rules on reservation. Even though reservation was allowed by the VCLT but in certain circumstance, such reservation is invalid. Hence, in this research, we will be looking into the reservation of treaties and what kind of reservation is deemed invalid. What is Reservation? The meaning of reservation is provided under Article 2(1)(d) of the VCLT[1]. It states that, Reservation means a unilateral statement, however phrased or named, made by a State, when signing, ratifying, accepting, approving or acceding to a treaty, whereby it purports to exclude or to modify the legal effect of certain provisions of the treaty in their application to that State. Therefore, by making a reservation to the treaty, the State can avoid itself from being bound by certain provisions of the treaty or it can change the legal effect of certain provisions. For instances, State A and B enter into a treaty on various agricultural trade between them but State A made a reservation not to trade on rubber because of certain reason. Hence, this will make other States not bound to State A on that clause. It is further provided in Article 19 of the VCLT on the circumstances whereby a reservation cannot be formulated if the treaty explicitly prohibits it or it is expressly stated in the treaty that only certain reservation can be made. Additionally, any reservation made but incompatible with the object and purpose of the treaty will fail. Therefore, a State can only make a reservation that is not prohibited by the treaty, reserve on the reservations specified in the treaty or the reservation made is consistent with the object and purpose of the treaty. Such reservations are vital because it promotes the give and take principle that able to persuade others to comply especially in a multilateral treaties situation. For instance, reservation on the Article 36(6) of the Statute of the International Court of Justice that allows court to determine which disputes fall within its jurisdiction. This clause maybe undesirable for many states but via reservation it was later on ratified by most countries. Additionally, Article 23 of the VCLT further laid down the procedure regarding the reservations. According to Article 23(1), a reservation have to be formulated in writing and communicated to the contracting states and other states who are parties to the treaty. If it were made upon simple signature, it would be regarded as mere declaratory. Therefore, writing is crucial. Article 23(2) further states that the reservation must also be formally confirmed by the reserving State when it express its consent to be bound by the treaty and the reservation will be regarded as having been made on the date of confirmation. Whereas Article 23(3) provides that an express acceptance of, or objection to, a reservation made previously to confirmation of the reservation does not itself require confirmation. Lastly, Article 23(4) further provides that the withdrawal of, or objection to, a reservation must also be formulated in writing. Thus, we can see that the VCLT generally recognised reservation on treaties but had set exception when reservation cannot be made. Nevertheless, the exceptions have been formulated too wide and at instances even parties to the treaties agreed that such provisions can be reserve but it was rejected because it affects the human rights. The United States reservation to international covenant on Civil and Political Rights (ICCPR) International Covenant on Civil and Political Rights (ICCPR)[2] is an early United Nations treaty that à ¢Ã¢â€š ¬Ã…“guarantees a broad spectrum of civil and political rights.à ¢Ã¢â€š ¬Ã‚ [3] President Carter signed the ICCPR on 5 October 1977 but was only ratified by the United States fifteen years later in 8th September 1992. T he United States has made five reservations[4] to ICCPR on the issue of prohibition of war propaganda,[5] capital punishment,[6] cruel, inhuman or degrading treatment,[7] criminal penalties[8] and juveniles.[9] Nevertheless, many countries objected to the second reservation made as Article 6 of the ICCPR stated that à ¢Ã¢â€š ¬Ã…“sentence of death may be imposed only for the most serious crimesà ¢Ã¢â€š ¬Ã‚ [10] and à ¢Ã¢â€š ¬Ã…“shall not be imposed for crimes committed by persons below eighteen years of age and shall not be carried out on pregnant women.à ¢Ã¢â€š ¬Ã‚ [11] Instead, the United States reserved the right to imposed death penalty on those below eighteen years of age. It is argued that the reservation made by The United States is against Article 4 of the ICCPR where it prohibits derogation from Articles 6, 7, 8 (paragraphs I and 2), 11, 15, 16 and 18. By reservation, the right to use death penalty to persons under the age of eighteen contravenes the major objec t and purpose of the covenant that provides for the right to life.[12] Article 19 of the Vienna Convention on the Law of Treaties stated that à ¢Ã¢â€š ¬Ã…“a State may, when signing, ratifying, accepting, approving or acceding to a treaty, formulate a reservation unlessà ¢Ã¢â€š ¬Ã‚ ¦ the reservation is incompatible with the object and purpose of the treaty. Therefore, as the reservation to inflict a cruel and inhumane punishment is against the object and purpose of the ICCPR to give adequate legal protection for human rights, the reservation by the United States would be invalid.[13] The Australia reservation on Convention on the rights of the child (CROC) Australia had made reservation on several treaties related to subject matter of human rights. One of them is Convention on the rights of the child (CROC) which came into force on 2nd September 1990.[14] The aim of CROC is to ensure a set of rights of child up to the age of eighteen are protected in the world. Example o f rights listed in CROC are right to education,[15] right to life,[16] right to express view[17] and right to be protected from neglect and abuse.[18] Australia became a party to this convention and ratified but with reservation on Article 37(c) on 1991.[19] Generally, reservation is allowed in multilateral treaties unless the treaty itself prohibits it.[20] CROC permits right of reservation under condition that it must compatible with the object and purpose of the Convention.[21] Therefore, reservation under Article 37(c) regarding right to detain children separately from adults will be invalid if it is incompatible with the object and purpose of CROC. There are several countries such as Japan, New Zealand and Switzerland also made reservation under Article 37(c) as they deem that it is unconditionally guaranteed. However, based on the Concluding Observations of the Committee on the Rights of the Child on Australiaà ¢Ã¢â€š ¬Ã¢â€ž ¢s report, the Committee opined that Australi aà ¢Ã¢â€š ¬Ã¢â€ž ¢s reservation was superfluous and should be withdrawn.[22] There is no inconsistency between the reason given by Australia and the provisions of Article 37(c) of the Convention.[23] The wording provided in Article 37(c) as every child deprived of liberty shall be separated from adults à ¢Ã¢â€š ¬Ã…“unless it is considered in the best interests of the child not to do soà ¢Ã¢â€š ¬Ã‚ . Therefore, it is not compulsory to do so if it violates the interests of the child and child shall have the right to maintain contact with his or her family. CROC guarantees the best interest of child therefore reservation made by Australia and others State parties found to be incompatible with the purpose of the convention and suggested to withdraw of its reservation. [1] Vienna Convention on the Law of Treaties 1969, (treaties.un.org) https://treaties.un.org/doc/Publication/UNTS/Volume 1155/volume-1155-I-18232-English.pdf ; last accessed 19th August 2014. [2] Adopted and opened for signature, ratification and accession by General Assembly resolution 2200A (XXI) of 16 December 1966 (entered into force 13 March 1976). [Hereinafter ICCPR.] [3] Senate Committee on Foreign Relations, Report on the International Convenant on Civil and Political Rights [4] (1) That Article 20 does not authorize or require legislation or other action by the United States that would restrict the right of free speech and association protected by the Constitution and laws of the United States.à ¢Ã¢â€š ¬Ã‚  à ¢Ã¢â€š ¬Ã…“(2) That the United States reserves the right, subject to its Constitutional constrains, to impose capital punishment on any person (other than a pregnant woman) duly convicted under existing or future laws permitting the imposition of capital punishment, including such punishment for crimes committed by persons below eighteen years of age.à ¢Ã¢â€š ¬Ã‚  (3) That the United States considers itself bound by Article 7 to the extent that `cruel, inhuman or degrading treatment or punishment means the cruel and unusual treatment or punishment prohibited by the Fifth, Eighth, and/or Fourteenth Amendments to the Constitution of the United States.à ¢Ã¢â€š ¬Ã‚  (4) That because U.S. law generally applies to an offender the penalty in force at the time the offense was committed, the United States does not adhere to the third clause of paragraph 1 of article 15.à ¢Ã¢â€š ¬Ã‚  (5) That the policy and practice of the United States are generally in compliance with and supportive of the Covenants provisions regarding treatment of juveniles in the criminal justice system. Nevertheless, the United States reserves the right, in exceptional circumstances, to treat juveniles as adults, notwithstanding paragraphs 2 (b) a nd 3 of Article 10 and paragraph 4 of Article 14. The United States further reserves to these provisions with respect to States with respect to individuals who volunteer for military service prior to age 18. [5] Reservation to Article 20 of the ICCPR [6] Reservation to Article 6 of the ICCPR [7] Reservation to Article 7 of the ICCPR [8] Reservation to Article 15 of the ICCPR [9] Reservation to Article 10 of the ICCPR [10] Article 6 paragraph 2 of ICCPR [11] Article 6 paragraph 5 of ICCPR [12] Kristina Ash, à ¢Ã¢â€š ¬Ã‹Å"U.S. Reservation to the International Covenant on Civil and Political Rights: Credibility Maximization and Global Influenceà ¢Ã¢â€š ¬Ã¢â€ž ¢, (2005), vol.3, Northwestern Journal of International Human Rights [13] Oliver de Frouville, à ¢Ã¢â€š ¬Ã‹Å"Practice by States in regard to reservations and declarationsà ¢Ã¢â€š ¬Ã¢â€ž ¢ Human Rights Dialogue between the European Union and China [14] à ¢Ã¢â€š ¬Ã‹Å"Australian Government-Departmen t of Foreign Affairs and Tradeà ¢Ã¢â€š ¬Ã¢â€ž ¢ (2007) lt;https://www.info.dfat.gov.au/Info/Treaties/treaties.nsf/AllDocIDs/E123F4F71DCAE3E7CA256B4F007F2905gt; accessed 14 March [15] Article 28 of CROC [16] Article 6 of CROC [17] Article 13 of CROC [18] Article 19 of CROC [19] Australia accepts the general principles of Article 37. In relation to the second sentence of paragraph (c), the obligation to separate children from adults in prison is accepted only to the extent that such imprisonment is considered by the responsible authorities to be feasible and consistent with the obligation that children be able to maintain contract with their families, having regard to the geography and demography of Australia. Australia, therefore, ratifies the Convention to the extent that it is unable to comply with the obligation imposed by article 37(c). [20] Article 19 (a) of VCLT [21] Article 51(2) of CROC [22] Consideration of reports submitted by States parties under a rticle 44 of the Convention (2012) [23] Ibid