Murder Essay Example | Topics and Well Written Essays - 750 words

Murder - Essay Example The novel starts with him dispatching a priest who had killed orphaned children. He is aware of his being inhuman, but he has grown in himself qualities which is human-like to conceal who and what he truly is. He can be very charming but there is no sincerity behind it. Dexter cannot control his desire; when the full moon is out, he is compelled by his passion to kill, urged by a hidden force he calls his Dark Passenger. He takes pleasure in his killings, obtaining delight from a perfectly executed murder, gradually filleting his victims when they are still breathing, no traces of blood after, but he leaves one drop of blood from his victims in order for him to feel again the excitement of the murder He is one of the most likable vigilante serial killers, deals with his eventual opponent, a frightening evil which scares away Dexter's inner monster, and almost weakens his sense of humor. His job as Miami crime scene investigator, Dexter is familiarized with observing evil acts specifically in some instances, wherein he is more willing to commit them himself. He was A horrible double homicide at a university campus changes everything for Dexter as he is called to the crime scene wherein Dexter should usually investigate with delight. But this crime scene, wherein two co-eds were burned ceremonially and beheaded, gives even the human vivisection, mysteriously vanishes the voice of the Dark Passenger inside Dexter's head. The burned and beheaded corpse count persists to increase, and Dexter recognizes that the power behind the killings is incredibly even more evil than his Dark Passenger. Dexter Dark Passenger senses something familiar, something absolutely frightening, and the Passenger, the mastermind of Dexter's homicidal ability, instantly disappear. Similarly disturbing, Dexter starts to understand that a touch of a very dark force is reaching out to him. (Lindsay 2004) Matt Fowler kills for revenge, as he suffers tremendously because of his son's, Frank, murder. The victim's murder was so distressing to his parents that Matt's heart was dying to kill his son's killer, Richard Strout. The endless imagination of Frank's murder destroyed Matt and his wife Ruth, until they carried out their vengeance on Strout and comforted their emotions. At the same time, the crime also reflects through the mind of Matt Fowler, how Strout loved ones would die inside by his murder. In this particular spot, it is portrayed that the emotions of families died on the deaths of their loved ones. At the back of Matt's mind, he presumes that Strout will only serve some years in prison and be given probation and he does not agree that he can deal with it if that will happen. Ruth suffers the idea of seeing Strout all over places and can not face the truth that Strout is out on bail after murdering her son Frank. Matt then was overpowered with the killing of his son and chooses to take action. Matt, from his own perspective, has no other option but to kill as his wife 3 is emotionally manipulating him into taking drastic action and in their mind, they will never achieve peace unless they take a desperate act of closure. Richard murders

Video performance viewing Essay Example | Topics and Well Written Essays - 250 words

Video performance viewing - Essay Example The movement of the dancers can be seen to reflect this mood, especially through my favorite dance move during the ‘Jellicle’ Song. My favorite dance move would be the one, where majority of the cats come rushing into the foreground from the background, that is of an elevated platform, while some cats still remain on that platform. The sudden movement is the exact of a cat, which has spotted a ball of yarn and is eager to play with it, and the dance movements that follow, such as the twirl and arm movements, exactly give the feeling of a cat extending its paws to tap the ball of yarn. Here, the performers are seen to use the maximum space in stage, as they cover up the foreground as well as the background. The characters have been well developed and portrayed, not only do they have great costumes, but they have been able to capture the essence of domestic felines to the best extent. The various dance moves, such as the short leaps represent the movement of real cats, such as when they pounce on their preys etc, thus communicating feelings of victory, happiness etc. Therefore, it becomes clear how dance is used to express or communicate feelings and thoughts through theatre, and moreover, the music or scores are seen to strengthen the portrayal of these thoughts and feelings, thus helping the audience to better grasp the storyline as well as the major

The opening sequence of the Simpsons Essay Example for Free

The opening sequence of the Simpsons Essay Analyse the opening sequence of the Simpsons. How does the opening sequence appeal to a variety of age groups? Is this a successful title sequence? Matt Groening changed television forever when he brought animation back to primetime with this immortal nuclear family. It was first screened on 14th January 1990 and it has become one of the worlds most famous cartoon as it always captured a regular audience of 24 million each week. It has also established itself as an award-winning international pop culture phenomenon. It is the longest-running sitcom of all time and it is also one of the most literate television programs on the air. It contains many references to subject matter and scholars from various academic fields. It also contains over a hundred instances of mathematic ranging from arithmetic to geometry to calculus. Most episodes of The Simpsons contain significant math that relates to material we normally cover in our classes. The programmer is also an ideal source of fun. The show is funny with bad language and offensive things! At the opening sequence the Simpsons appear out of clouds, and then it shows us Homer in the Nuclear Power Plant and after that throws the little piece of fuel out of the car on his way home. Secondly it shows us Bart writing on the skating board and when bill rings he jumps out of the school skating on air and then crosses the traffic. Thirdly it shows us the mother, Marge Simpson doing her shopping and it also shows us that Maggie got scanned. After that Lisa Simpson comes up in her music class playing her saxophone and also she got kicked out of the class. The sequence ends in a funny way as the whole family sets on sofa watching T.V. The town of Springfield is full of places that the Simpsons family go and which most of the scenes occur. The Nuclear Power Plant is where Homer Simpson works in as the safety inspector. The school where Bart Simpson does his detention and writes silly quotes on the board with the chalk, For example: No one wants to hear about my sciatica, I cant see dead people, I did not win the Nobel Fart Prize, I have neither been there nor done that, etc The music store is where Lisa goes and looks for some music equipment as she is fascinated by music equipments and musicians. She is also in the school music team and a saxophonist. T.V store in which Bart like to miss around as he is known as a naughty boy! The shopping centre which Marge Simpson goes with Maggie does her shopping for her family and buys food We learn that Homer works in a nuclear power station in which he makes radioactive metals. He drops it while he was on his way home which means that he is careless and stupid! He nearly got ran over by a car which means he is clumsy and got a slow reflex action. We also learn that he is a slacker who is completely unqualified for his job. We also learn that he is a pig when it comes to food!! Marge Simpson doesnt appear a lot in the opening sequence as she only appears twice. First time is when she was shopping with little Maggie and funnily Maggie got scanned. The second time she appeared was when the whole family gathered around the sofa to watch T.V. which means that she is a good mother and she is looking after her familys needs. Bart Simpson is simply a rule breaker, he always gets in trouble and he stays at school to do detention and he writes some silly words on the board, e.g. I will not encourage others to fly, I will not fake my way through life, I will not sell my kidney on eBay. He also appears when he was skating, and when he crossed the street and almost got hit by a car. He is a poor student who enjoys comic books and television and hates girls. Lisa Simpson only appeared once when she was playing her saxophone in the band and she didnt follow the note and so she got sent off. So she is kind of a role breaker as well but she is not as bad as her brother! She can be described as an excellent student who is completely the opposite of Bart except they both enjoy violent cartoons. The cartoon shows the family always gets in little arguments. It also shows that its impossible to be good all the time. E.g. when theyre eating at home they use no table manners and when they go to church they try to be like normal families. There are also times in the show when they change from comedy and give a meaningful message about family values, or friendship, etc.. There are also some funny situations where they cant take the correct action at the beginning of the problem but they manage to get through it by the end of the show. Here is a little description of each character of the Simpsons family: Homer Simpson is a man who can only be described in one word overachieving. For a man with no brain, athletic, logical, social, or any other kind of skills, he has done a lot, including having three successful kids, a loving wife, and a steady job as the safety inspector at the Springfield Nuclear Power Plant. He is also an alcoholic!!! Marge Simpson is the glue that holds the Simpsons together. Without her continuous cleaning, scrubbing, mopping, the family would fall apart. Marge is always there to keep her husband in check, motivate Bart, cheer up Lisa, and just keep Maggie satisfied. She is very proud of her husband and she also has strong relations with her sisters. Bart Simpson is, first and foremost, a rebel. He is well-known across the city as a troublemaker and an underachiever, calling in prank calls, working in burlesque houses, etc However he got a sense of humour as he always cracking jokes and always up for an adventure. Lisa Simpson is straight student, a brilliant saxophonist, and an amateur philosopher. She is full of great thoughts and talents. She is always happy with herself. She is only 8; however she cant wait for collage. Maggie Simpson is a silent staple in the Simpsons family. She is always seen with the family, never speaking, but always secretly thinking. Bart Simpson writes on the blackboard. The writing changes every title sequence and it actually shows us what Bart does in his everyday life. E.g. I will not sell my kidney on e-bay, this quote tells us that Bart tried to sell his kidney on the Internet. The opening sequence also tells us that Bart is usually misunderstood. Wrongly pegged as an underachiever and troublemaker as he is always in detention. It also tells us that he is careless and doesnt care about his life or doesnt look out for dangerous things such as when he crossed the road and almost got hit by a car, this is also tells us that he is a bit stupid!! Homer Simpson was doing his little experiment on the Nuclear Power Plant with the radioactive piece of fuel and then it went in his hood and then he throws it out of the car. This tells us that he only cares about food because when teatime came he left his job in a hurry and that piece of fuel went in his hood and then he didnt recognise that it was a radioactive thing when he threw it out of the car window which tells us that he is very careless. We also saw Lisa in the music class playing her saxophone and she the teacher sent her out because she didnt follow the note and went on playing her own note, the funny bit was when she kept on playing with the saxophone after the teacher sent her off. It sounded like she was just trying to get the teachers off. Another funny situation when Marge Simpson was shopping and Maggie wondered off and got scanned by the machine and then she suddenly appeared at one of the bags on the trolley. And finally when the whole family sat on the sofa watching T.V which shows us how important T.V is in their life. Its also funny when they were rushing to sit on the sofa and then they crashed and fell on the floor I think the opening sequence suits every age-group. E.g. when Bart Simpson was in detention and he was writing his quotes on the blackboard I will not sell my kidney on eBay, they are laughing at me, not with me, garlic gum is not funny, I will not Xerox my butt, I will not do that thing with my tongue all these things appeal to the teen-agers in which it grabs the people in my age group to watch The Simpsons. Another example, little kids like 3-6 years old might like Maggie Simpson as she does some funny moves, like when she wandered of her mum, or when she feeds the dog. She also wandered the town of Springfield all by herself, and shes shot Springfields richest man because he attempted to steal her lollipop!!! She also tries to walk without falling which the younger kids might like to see. Here comes the most interesting part of all, the Simpson cartoon was also very successful in grabbing the eldest attention. The Simpsons makes the family sit on the sofa together watching the Simpson which rarely happens in our lives as older people usually watch shows and films which younger children dont see. and they dont watch cartoons either. However Matt Groening had the ability to make a cartoon which parents like to watch. Families and older people like to watch the Simpsons because it discusses problems in our lives sometimes and it shows us the argument between the family and how they solve it. It also shows us the father telling something to his son like giving him advice; he is also very funny and sometimes cracks jokes and acts funnily. Also Mr. Groening was successful to make something to show that the mothers always play the most important part in the family. Therefore he created the perfect character of all, the mother, Marge Simpson; she is like the glue that holds the Simpsons together. Without her constant cleaning, scrubbing, mopping, and gentle nagging the family would fall apart. Marge always keeps her husband in check, motivate Bart, cheer up Lisa or keep Maggi satisfied. She stands up against cartoon violence and she can also be trusted in taking ethical decisions.

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

The Psychogenesis of a Case of Homosexuality in a Woman by Sigmund Freu

In "The Psychogenesis of a Case of Homosexuality in a Woman", Freud discusses a case of a young woman brought to him by her parents for treatment as a homosexual. Although he states that Psychoanalysis is not truly a tool for curing homosexuality, but one to help those with inner conflict in one particular area or another, he attempts to study the girl to see if Psychoanalysis could be of any help to her. Once he realized that the girl had a deep rooted bitterness towards men, he called off his study of her and told her parents that if they were to seek more psychoanalysis for her it should be sought from a woman. Prior to this discovery he found a few things of interest that may have attributed to her choice of sexual object. One of the first things Freud thought about was whether the patient was a homosexual from birth or whether she changed her object choice later in life. At the time it was thought that homosexuals had characteristics (physical a psychical) of the opposite sex. Though there were a few of these found in the girl, they were not strong enough to count for much. She was tall like her father and her features were sharper rather than soft and feminine, but she was still a beautiful and well developed girl. As far as psychical characteristics that were more masculine, he listed sharp comprehension, and objectivity in that her passion did not have complete control over her. Still there were women at the time who had traits such as these and were not homosexual. The characteristic the girl displayed that was the most manly, however, was the way she acted and thought in regards to the Lady she was in love with. The girl preferred to think of herself as the lover, not the beloved. Simply being allowed to... ... had been there for the birth of one of her brothers and it had not effected her. Yet when her second brother was born she completely switched her object choice. This could have been a coincidence, but I am of the school that says there are no coincidences. All things have reason behind them, somewhere. Though Freud had issues with women which shaped his views on cases such as this one somewhat differently, he remained rather objective throughout. His reasoning behind the events that brought the girl to him made sound, logical sense. Even his reason for dumping this case and suggesting they take it up with a different psychoanalysist made a lot of sense. It is definitely more logical than pushing ahead against and almost un-budge-able brick wall build up of bitterness and resentment of men. All in all I was pretty impressed by a man who many bad mouth today.

Edge Detection in Claud Classification

It is a certain number of gradient operators using small arrays of pixels were tested in this study, in order to check their capacity to properly detect significant boundaries between different CTT and eventually cloud types. This capacity is 14 visually tested against direct CTT images. Among the detectors applied are the Canny, Roberts, Sobel and Kayyali 15 SENW (to be named here SENW) edge detectors, and the Harris corner and edge detector. The Roberts edge detector employs mainly 2 pixels in a 2*2 matrix for each computing direction (horizontal and vertical). The test conducted show a lesser sensitivity to edges i.e. the variation range of gradients is limited compared to the other methods.The Canny 18 method uses a 5*5 pixel matrix, that undergoes preliminary filtering before the use of a smaller-array gradient detector, making the calculation procedure longer. The Sobel detector uses a 3*3 matrix where 6 pixels practically contribute to 20 the gradient. The SENW edge detector i s based on the Sobel approach for edge detection but employs mainly 4-corner 21 pixels (upper and lower left, and right) in a 3*3 pixel-matrix, the remaining 5 pixels between the corners are set to zero.  The Harris detector detects both edges and corners.

Image Of Pakistan Word Fmt

Mostly, we protest against the wrong image of Pakistan portrayed in the world and international media. But if we judge ourselves in the same balance as other holds, it will become clear, without any doubt, that the Image the world holds of us is actually the right one. We were not born the hatred. We our self are the true butchers and barbarians and our actions presents it well. We act than we think, I'm sorry I don't mean it, because we just act and act, why should we think when we know that our state is down enough, and can easily handle this havoc and loss. Oral think, we are just a crowd of illiterate avengers.And sorry to say, yes we are. Must mention one most tragic event here, A few months ago a short-film was released on internet which was said to be anti-lilacs, and it hurt the global community Of Muslims. I hate that movie as, much as any of a Muslim will, But what did our people did? They went violent on the streets of Pakistan. An anti;lilacs film, wonder how it justify b urning a cinema down to ashes in Appeaser. But then we came to know that it was released on internet, Thanks God internet is safe and can't b urn, other wise the world would be downloading ashes on their desktop.We starts a protest in peaceful manner. Butts said we starts, the way we end up with is extremely horrible. We are very precise in sealing all the roads and passages around. We love to barb all the public transport not only public but also private vehicles which are owned by someone Pakistani and most probably a Muslim. Its not done yet, we don't even spare our street lights and traffic signals, because street light wastes electricity and we already lack it, and for traffic signals every one knows we don't bother them. How can we defend our Prophet (PUB) by torching and firing our own homeland, what just happened?Damage to property and loss of life caused to the peoples who had just nothing to do with it, what about them? Did their sacrifice just save the day ? No, we need t o think of our self and our behavior. We are intended to do exactly opposite to the thing which it need to be done. For example if there is a signboard saying please don't look on the back of this board then every person will, no matter hoe busy he is will make some time to inspect the back side of the road. So, now some one can exactly guess our actions at any appeal. What exactly are we? Admit that we look exactly like Humans, but do we act like humans? Do we have humanity? Do we care if, what would any other nation will think about us? We must not blame our Government because a government is only a reflection of people. We must put ourselves into effort.