Jammu and Kashmir Academy of Art, Culture and Languages

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    Elucidation of Etiology of Colorectal Cancer: A Study on Silencing of MGMT Gene by Promoter Hypermethylation

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    Prevalence of Promoterhypermethylation of MGMT Gene in Colorectal Cancer Patients of Kashmir Valley. Colorectal cancer, one of the most aggressive cancers, occurs with a high incidence in most countries. Colorectal cancer (CRC) is one of the leading malignancies worldwide. Cancer development and progression is dictated by series of alterations in genes such as tumor suppressor genes, DNA repair genes, oncogenes and others. In this study, efforts were made to identify promoter hypermethylation of CpG islands of MGMT gene in CRC patients among the Kashmiri population. Methylation status of CpG islands in the promoter region of MGMT gene in colorectal cancers and normal corresponding colonic mucosa was analysed. Fresh tissue samples were obtained from 50 patients (age of 21 to 81 years) undergoing resective surgery for CRC with primary colorectal adenocarcinonia and corresponding histopathologically normal tissues. Methylation-specific polymerase chain reaction (MSP) was used for analysis of the promoter methylation status of MGMT gene. The male to female ratio of the disease came out to be 1.38. The epigenetic analysis of the cases and controls revealed that unlike other high risk regions, Kashmiri population has a different hypermethylation profile of MGMT gene promoter hypermethylation. The frequency of cases with MGMT promoter hypermethylation was more as compared to controls (54% vs. 20%) and was statistically significant (O.R = 4.69, 95% C.I = 1.37 – 16.05, P = 0.015) using χ2 test with Odds Ratio. It was also found that the frequency of male cases with promoter hypermethylation of MGMT gene was more as seen against male controls (72.41% vs. 30%), which also showed statistically significant results (O.R = 6.13, 95% C.I = 1.26 – 29.71, P = 0.026) using Fisher’s Exact test, though the frequency of promoter hypermethylation of MGMT gene of female cases was more as compared to female controls (28.57% vs. 10%), the data was found not to be statistically significant (O.R = 3.6, 95% C.I = 0.37 – 34.93, P = 0.37) using Fisher’s Exact. While for the male verses female cases of promoter hypermethylation of MGMT gene the results were statistically significant (O.R = 6.563, 95% C.I = 1.882 - 22.82, P = 0.0037) using Fisher’s Exact Test. In this study it was concluded that male gender is generally associated with higher methylation levels for most CpG islands hypermethylation of MGMT gene in normal as well as cancerous colonic mucosa. The results indicate that MGMT aberrant methylation may play an important role in colorectal cancer. This study clearly demonstrates that promoter hypermethylation of MGMT gene can be designated as epigenetic biomarker for early diagnosis and better prognosis of the disease

    Trends of Crime in the Kashmir Valley: A Sociological Study of Srinagar City

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    Crime is essentially concerned with the social order. It is well known fact that man's interests are best protected as a member of the society or community. Everyone owes certain duties to his fellowmen and at the same time certain rights and privileges which he accepts others to ensure for him. This sense of mutual respect and trust for the rights of others regulate the conduct of the members of the society inter-se. Although most people believe in “Live and Let Live policy”. Yet there are a few who for some reason or the other deviate from this normal behavioral pattern and associate themselves with anti-social elements. This obviously imposes an obligation on the state to maintain normalcy in society. This arduous task of protecting the law abiding citizens and punishing the law breakers vests with the state which performs it through the instrumentality of law. It is for this reason that Salmond has defined law as a 'rule of action' regulating the conduct of individuals in society [1]. The conducts which are prohibited by the existing law at a given time and place are known as wrongful acts or crimes where as those which are permissible under the law are treated as lawful. The wrongdoers committing crime are punished to their guilt under the law of land

    A Study on Methylation Changes in Mismatch Repair Gene (hMLH1) in Esophageal Cancer Patients of Kashmir Valley

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    The Study was a Case Control undertaken to understand the etiology of esophageal cancer in the population of Kashmiri origin. This case control study was designed to assess the relationship of promoter hypermethylation of Mismatch Repair Gene MutL homolog 1 (hMLH1) with esophageal cancer. Also further an association of hypermethylation of hMLH1 gene with esophageal cancer in relation to clinicopathological features of Gender and Age was evaluated. Esophageal cancers are one of the most fatal cancers in the world and are considered to be the eighth most common malignancy. The prognosis of Esophageal Cancer is poor as its symptoms appear in the late stage of the disease. This cancer is one of the most prevalent cancers in Jammu and Kashmir region of India and has multi-factorial etiology involving dietary habits, genetic factors, and gene environmental interactions. Genetic abnormalities of proto-oncogenes, tumor suppressor genes and mis-match repair genes have been demonstrated to be involved frequently in esophageal carcinogenesis; chronic inflammation leading to malignancy in the esophagus may be due to errors in mismatch repair (MMR) genes such as hMLH1. Inactivation of the hMLH1 gene expression by aberrant promoter methylation plays an important role in the progression of esophageal carcinoma. In the present study the role of hMLH1 promoter methylation in 50 histopathologically confirmed esophageal cancer tissues and compared it with corresponding histopathologically confirmed Normal adjacent tissues was studied by methylation-specific polymerase chain reaction (MS-PCR). For evaluating the status of hMLH1 promoter hypermethylation and its association with Esophageal Cancer, a methylation specific polymerase chain reaction (MS-PCR) was used. DNA was extracted and treated with sodium bisulfite which converts unmethylated cytosines to uracil and does not affect methylated cytosines. The modified DNA was amplified in MS-PCR reaction by applying methylated and unmethylated promoter specific primers. Universally methylated DNA was used as positive control and DNA from normal lymphocytes used as negative control. The MS-PCR products were run on 3% agarose and bands were visualized under UV light. It was found that the frequency of promoter region hypermethylation of mismatch repair gene (hMLH1) in esophageal cancer cases was 56% (28 out of 50) and in histopathologically confirmed normals it was 15% (03 out of 20).Statistically the association of promoter region hypermethylation of mismatch repair gene (hMLH1) with esophageal cancer was evaluated using χ2-test (chi-square test) with odds ratio and was found significant and the p0.05.From the data it was concluded that The Frequency of MutL homolog 1 (hMLH1) gene promoter region hypermethylation was found high in Esophageal Cancer Cases of above 40 years of age (56%) and in controls (16%) and was significant as p0.05 and was evaluated by Fishers exact test. Observing similar level of hMLH1 promoter hypermethylation in patients with Esophageal Cancer in this high risk region and comparing it with other parts of the world could support the hypothesis that a common molecular mechanism might be involved in tumorigenesis of Esophageal Cancer. As regards promoter hypermethylation status of mismatch repair gene hMLH1 shows a significant increase in promoter region hypermethylation of esophageal cancer patients of Kashmiri origin as compared to controls was observed. This became more apparent when the data for hypermethylation was interpreted taking Gender into consideration here it was seen that Males shows higher frequency of promoter region hypermethylation as compared to females which was earlier reported in literature and also patients of above 40 years of age shows high frequency compared to below 40 years of age

    Afghan Rule in Kashmir (A Critical Review of Source Material)

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    Kashmir is a land of fabled beauty and eternal romance. It is blessed by nature with beauteous scenery, wondrous fertility and salubrious climate. Writer described it as “one of the finest countries upon which the sun shines” and “the sub-Alpine region of Asia‟s Italy” and unsurpassed land for its scenery, Kashmir is verily “the terrestrial paradise of the Indies. A fairy land, where each curve presents a grand picture and every horizon a new scene, each leaf a distinct lesson and each flower a new book. The poets have described Kashmir as garden land of picturesque scenery, lovely landscapes, unrivalled vistas, majestic forests, green pastures, shimming waters of vast silent and transparent lakes and rivers, perennial snows, mighty chinars of snow-clad mountains rumbling cataracts and roaring waterfal

    Document Image Classification: A Cognitive Approach

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    The economic feasibility of creating a large database of documentimage has left a tremendous need for robust ways to access theinformation. Printed documents are scanned for archiving or in anattempt to move towards a paperless office and are stored asimages. Analysis of document images for information extraction has become very prominent in recentpast. Wide variety of information, which has been conventionally stored on paper, is now beingconverted into electronic form for better storage and intelligent processing. This needs processingof documents using image analysis algorithms.Despite immense developments in Information & Communication Technology in automating the routine office processes, the printed documents still continue to be the main source of Data exchange in organizations. These documents include many common types: business letters, forms, engineering drawing & maps, text books, technical manual, music notations & other symbolic data. Though paper was the exclusive medium in past, many documents now originate on the computers & often reside exclusively in electronic form.Inspite of this it is unclear whether the computer has decreased/increased the amount of paper document produced, as these are printed out for reading,dissemination,markup predictions of paperless offices made so frequently during the early 1980 has given way to the realization that the objective is not elimination of paper but the ability to deal with the flow of electronic & paper document in effective & integrated way. Document processing is an important step in the office automation and has emerged as one of the potential research and commercial activity in the field of Computer Sciences. Extensive research has been going on since the past two decades in order to develop a robust document processing system and one of the products of the said activity which has become popular is in the form of an Optical character Recognition System (OCR). Although earlier generally research on paper document processing has focused on optical character recognition (OCR), in the last decade, it has been widely recognized that text acquisition by means of OCR is only one of the step of document processing. The field of Document Image Analysis aids in this objective through the use of image processing, pattern recognization techniques that are applied to various documents. A document image may contain any or all text, graphics & pictures. Optical character recognition (OCR) is used to recognize the characters of text in a document. Document Image Analysis improves availability& archival quality of context through developing reflow able image format. It needs to provide the tools to make this as intuitive & easy for users as possible. In all of the applications, the major goal is to extract the information contained in the document & to store them in computerized format. This is the motivation of electronic Document image Analysis system. Document image classification is an important step in Office Automation, Digital Libraries, and other document image analysis applications. The objective of document classification is to reduce the detail and diversity of data and the resulting information overload by grouping similar documents together. The classification of documents being processed is required for their efficient recognition as it reduces the number of searches and also reduces the chances of error at different stages. The document image may contain text only or text as well as tables and images. The key objective of this work is to explore efficient methods, in terms of resources and time of various methods of document analysis and document classification. These methods extracting features from documents and based on that classify them using a cognition based approach. Document Image analysis technologies interpret human thinking patterns based on cognitive science

    Phytochemical Investigation of Rhododendron Lepidotum

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    Throughout the ages, humans have relied on Nature for their basic needs for the production of food-stuffs, shelters, clothing, means of transportation, fertilizers, flavours and fragrances, and, not the least, medicines. Plants have formed the basis of sophisticated traditional medicine systems that have been in existence for thousands of years and continue to provide mankind with new remedies. Although some of the therapeutic properties attributed to plants have proven to be erroneous, medicinal plant therapy is based on the empirical findings of hundreds and thousands of years. The first records, written on clay tablets in cuneiform, are from Mesopotamia and date from about 2600 BC; among the substances that were used were oils of Cedrus species (Cedar) and Cupressus sempervirens (Cypress), Glycyrrhiza glabra (Licorice), Commiphora species (Myrrh) and Papaver somniferum (Poppy juice), all of which are still in use today for the treatment of ailments ranging from coughs and colds to parasitic infections and inflammation

    Relative Incidence and Molecular Analysis of Breast Cancer in Kashmiri population

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    Breast cancer is the third most common tumor in the world and represents 9% of global cancer burden. In India, breast cancer is the second common cancer in women after cervical cancer and has of late replaced cervical cancer as the leading site of cancer among women in Indian cities. Preliminary indications point towards an increasing trend in the occurrence of breast cancer amongst Kashmiri population. However, authentic data with regard to prevalence is almost non-existent in the state of Jammu and Kashmir. To our knowledge, this is the first attempt to examine the epidemiological distribution of different cancer typ es with particular emphasis on breast cancer in the wh ole valley. The source of our data include cancer registry in the Department of Radiation Oncology, Sheri -Kashmir Institute of Medical Sciences, Srinagar, and Department of Radiation Oncology, SMHS, Srina gar during Jan 2002 to Dec 2006 . A total of 6943 cas es registered between 1st January 2002 to 31st December 2006 comprised of 4345 males and 2598 females. The age standardized incidence rates were 34.9 per 100,000 for males an d 24.8 per 100,000 for females. Oesophagus was the leading site of cancer in both the sexes (male ASR 11.2; female ASR 8.3) followed by lung (ASR 6.5), brain (ASR 2.2), head and neck (ASR 2.2) in males and breast (ASR 5.2), skin (ASR 1.6) and rectum (ASR 0.95) in females. The incidence of cervical cancer turned out to be surprisingly lo w in Kashmir i women as compared to other Indian Registries quite contrary to the pattern in rest of the country. Our studies imply that cancer incidence was significantly lower and cancer patterns were markedly different in Kashmir. The observed cancer pattern indicates that awareness campaigns, life style and dietary habit changes, tobacco -control measures and early detection of breast cancer are very important for cancer control in this cohort of population. Abstract 2 Section II Abstract Environmental and genetic factors are attributed to explain the spectrum of geographical and ethnic variations in the development and pathogenesis of disease. The genesis of disease has been further complexed by involvement of number of genes with small effe cts and above all by population heterogeneity. Accordingly variations in genes like Brca1/Brca2 that have been strongly associated with breast cancer phenotype present a scattered mutational pattern in different populations. This study attempts to analyze the frequently mutated exons of BRCA2 for sequence variations in surgically resected breast cancer tissue samples, from a high risk ethnic Kashmiri population. PCR followed b y direct sequencing revealed presence of five variations, with four somatic mutat ions located on exon 11 and one germline variation located in UTR region of exon 2 at contig position 13870572 (rs1799943). All the four somatic mutations comprised of substitutions; two representing missense mutations leading to amino -acid substitution at codon positions 868 (novel) and 991 whereas other two were silent mutations at codon positions 846 and 1131. Codons for amino-acid positions 846 (TCC/TCA) and 868 (CCT/ACT) were seen to be present in heterozygous state in normal breast tissue samples and the heterozygous nature of both the codons was seen to be lost i n associated tumor samples in 44 out of 50 patients. Incidentally these two mutations were always found to be linked.No sequence variations were observed in exons 9, 18, 20 and 25. Gap -junction gene C onnexin 43, which codes fo r a 43 -kd gap -junction protein is a predominantly expressed gap junction protein in normal breast tissue and plays an important role in normal mammogenesis, lactogenesis and involution. Studies have shown down- re gulation of connexin 43 gap -junction protein is involved in primary tumor formation as well as metastasis in breast cancer patients and restoration of gap-junction intercellular communication by up-regulation of Abstract 3 connexins has been shown to restore normal phenotypes in vitro and reduce tumor growth in vivo . However the molecular mechanisms behind these processes remain elusive and a better understanding of the key events is necessary to gain information relevant to the designing of anti -cancer treatment models against breast cancer. In this study, coding sequence of C onnexin 43 was analyzed for polymorphic changes to establish its role (if any) in breast cancer in this cohort of population. After sequence analysis, none of the screened samples reveal ed any kind of variations in early or advanced stage of the disease. The findings from this study add to the body of knowledge about mutation prevalence and nature of different breast cancer pre -disposing genes in ethnic Kashmiri population, and may inform strategies for genetic cancer risk assessment. Our studies also imply that mutational deactivation does not play any role in the down regulation of Connexin 43 expression in Kashmiri breast cancer patients. Instead, some other regulatory mechanism like hypermethylation or mutati on of the promoter region of thegene may be involved. Additionally increased understanding of breast carcinoma pathways may enhance our ability to device targeted approaches to the preve ntion of diseas

    Rights of Women in Post-Soviet Uzbekistan

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    The 7th century witnessed glaring change with the coming of Islam in the region. Since, then Islam as a religion influenced the socio-religious conditions of a great majority of the indigenous population of Central Asia including Uzbekistan. After the Arab invasion new type of came into being in Central Asia. An absolutely new religious ideology which influenced and fashioned their private life. Inorder to have a meaningful discourse on the subject, interdisciplinary approach has been followed taking insight from history, geography, cultural anthropology, economics, political science and philosophy.The comparative methods were also employed for the understanding of different issues related to the subject. Since the study is based on theoretical and historical study as such all sources of information, books, official records, journals, periodicals, newspapers, etc were taken into account. Although enough of literature on the rights of women in Post Soviet Uzbekistan is not available, an attempt has been made to evaluate the available data with an objective analysis. There is hardly any compact research work which has been carried out on women or referred to the gender issues in Uzbekistan, even the little studies related to Uzbek women cover only disjoint and limited areas touching mainly general information. The present study therefore aims at filling up these gaps to the extent possible and to present an objective analysis of the rights of women in Post Soviet Uzbekistan

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