A study of accelerator driven sub critical system - material using the CASCADE code

In the existing situation of experimental data required for design and modeling of ADS and similar other applications, development and benchmarking of the simulation codes for providing reliable data has become essential. Amongst the intra nuclear cascade codes, CASCADE code which has been validated for the neutron production in proton collision with the high Z materials in the past, has been used to study nuclear behavior of some of the prominent ADS materials like, Th, U, Pb, Bi, W, Fe, Cr and Al in respect of reaction and production cross sections of isotopes and neutrons in a wide range of energy, 11 MeV to several GeV. Emphasis has been laid on the data of cross sections of (n, xn) reactions. It is found that their role is definite and effective in deciding fuel combinations. The code provides neutron cross section data which shows agreement with the existing experimental data and stresses need of further validation using precision data from the accelerators.За існуючого стану справ з експериментальними даними, які необхідні для проектування та моделювання АDS (accelerator driven systems) і для інших аналогічних застосувань, важливими стають розробка та еталонне тестування програм моделювання для забезпечення отримання надійних даних. Із програм, що існують для внутрішньоядерних каскадів, програма CASCADE, достовірність якої перевірялась для народження нейтронів при зіткненні протонів з матеріалами, що мали в минулому високий атомний номер Z, використовувалась для вивчення ядерної поведінки деяких відомих матеріалів ADS (Th, U, Pb, Bi, W, Fe, Cr, Al) у відношенні перетинів реакцій та перетинів народження ізотопів і нейтронів у широкому інтервалі енергій від 11 МеВ до кількох гігаелектронвольт. Особлива увага приділялась даним щодо перeтинів реакцій (n, xn). Встановлено, що вони грають визначну роль при виборі сполучень палива. Програма забезпечує дані щодо нейтронних перетинів, які узгоджуються з існуючими експериментальними даними, при цьому підкреслюється необхідність подальшої перевірки з використанням точних даних від прискорювача.При существующем положении дел с экспериментальными данными, требующимися для проектировки и моделирования ADS (accelerator driven systems) и для других аналогичных применений, становятся важными разработка и эталонное тестирование программ моделирования для обеспечения получения надежных данных. Из программ, существующих для внутриядерных каскадов, программа CASCADE, достоверность которой проверялась для рождения нейтронов при столкновениях протонов с материалами, имевшими в прошлом высокий атомный номер Z, использовалась для изучения ядерного поведения некоторых известных материалов ADS (Th, U, Pb, Bi, W, Fe, Cr и Al) в отношении сечений реакций и сечений рождения изотопов и нейтронов в широком интервале энергий от 11 МэВ до нескольких гигаэлектронвольт. Особое внимание уделялось данным о сечениях реакций (n, xn). Найдено, что они играют определяющую роль при выборе сочетаний топлива. Программа дает данные о нейтронных сечениях, которые находятся в согласии с существующими экспериментальными данными, при этом подчеркивается необходимость дальнейшей проверки с использованием точных данных от ускорителей

High-Affinity Inhibitors of Human NAD+-Dependent 15-Hydroxyprostaglandin Dehydrogenase: Mechanisms of Inhibition and Structure-Activity Relationships

BACKGROUND: 15-Hydroxyprostaglandin dehydrogenase (15-PGDH, EC 1.1.1.141) is the key enzyme for the inactivation of prostaglandins, regulating processes such as inflammation or proliferation. The anabolic pathways of prostaglandins, especially with respect to regulation of the cyclooxygenase (COX) enzymes have been studied in detail; however, little is known about downstream events including functional interaction of prostaglandin-processing and -metabolizing enzymes. High-affinity probes for 15-PGDH will, therefore, represent important tools for further studies. PRINCIPAL FINDINGS: To identify novel high-affinity inhibitors of 15-PGDH we performed a quantitative high-throughput screen (qHTS) by testing >160 thousand compounds in a concentration-response format and identified compounds that act as noncompetitive inhibitors as well as a competitive inhibitor, with nanomolar affinity. Both types of inhibitors caused strong thermal stabilization of the enzyme, with cofactor dependencies correlating with their mechanism of action. We solved the structure of human 15-PGDH and explored the binding modes of the inhibitors to the enzyme in silico. We found binding modes that are consistent with the observed mechanisms of action. CONCLUSIONS: Low cross-reactivity in screens of over 320 targets, including three other human dehydrogenases/reductases, suggest selectivity of the present inhibitors for 15-PGDH. The high potencies and different mechanisms of action of these chemotypes make them a useful set of complementary chemical probes for functional studies of prostaglandin-signaling pathways. ENHANCED VERSION: This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S2

Investigation into structural and functional relationships of short-chain dehydrogenases and reductases (SDRs) using a compound library

The short-chain dehydrogenases/reductases (SDR) protein family is one of the largest and most evolutionarily conserved protein superfamilies known to date. SDRs show a remarkable ability to accommodate hundreds of reactions/substrates by using the versatile nucleotide binding domain as their central scaffold. SDRs are implicated in many different disease pathways, and represent a ‘druggable’ enzyme class, which has generated extensive biotechnological and pharmaceutical interest. For 28 human SDR members, the three- dimensional structures have been determined. Despite this, almost 25 % of human SDR members still have unknown functions, and many members lack any chemical descriptors. To address the dearth of ligand knowledge, 28 SDRs were cloned, expressed and purified to further characterise members by the application of differential scanning fluorimetry (DSF). A family annotation through cofactor preference, substrate accommodation and subcellular localisation has shown a few distinctive traits within the SDR family. This in silico approach has led to the creation of a systematic flow chart, which provides a starting point to identify substrate classes for orphan SDRs. Cofactor and inhibitor screening of SDRs by DSF has shown Tm shifts that are in-line with previous experimental data. DSF screening showed the decryption of 6 cofactor preferences for orphan SDRs, five of which have been confirmed in crystal structures. In contrast, screening of substrates in DSF produce little thermal stability (15 % detection rate), rendering it difficult to distinguish specific substrates for orphan SDRs. However, over 70 % of SDRs screened in DSF with known enzyme activity produce thermal shifts with compounds that resemble their substrate structures. This can therefore infer substrate classes for orphan SDRs that compare well with those from computational predictions. DSF screening against a ligand library has led to the discovery of the first small molecule binders for Nmr-like family domain-conatining protein 1 (NMRAL1) and selective inhibitors for Hydroxyprostaglandin dehydrogenase (HPGD). The use of small molecule ligands identified from DSF has also contributed to the success of crystal formation in the case of Hydroxysteroid dehydrogenase-like protein 2 (HSDL2) and Dehydrogenase/reductase SDR family member 2 (DHRS2). Overall this study has provided a platform for ligand screening to further structurally characterise the SDR family

Determination of Opening Prices of Equities of the Day

Abstract Though past influences the present state, every day is a new day in the stock market. Hence, five forms of distributed lag model are used for analyzing data relating to opening prices of equities of 10 major companies for one year in BSE. This includes the analysis of day of the week effect. Equities of companies are not equally positioned in the market. So behavior of equity prices of no company can be generalized. Lags of daily opening prices explain the days of the influence of expectation built within the day. Influence of expectations of the day may be exhausted within a day or it lasts longer. It depends on the strengthening or weakening of expectations in subsequent days after the particular day. The paper focuses on differences, attributed to non-synchronous trading, between closing prices of preceding and opening prices of next days. Non-synchronous trading makes the market imperfect and oligopolistic in nature. Results show the length of lags of opening prices of equities of 7 companies to be 2 and 1 for 3 companies. Closing price of preceding day decisively influences current day"s opening price but day of the week effect is not significant. Opening prices display stability and convergence to equilibrium; oft repeated thesis of volatility is refuted. The time taken by the opening prices of different companies to move back into their band of stability differs between the companies JEL classification numbers: D630, G21

Primary cerebral rhabdomyosarcoma

Primary intracranial rhabdomyosarcomas are extremely rare tumors; those in the supratentorial location are commoner in adults. A 10 year old girl with primary cerebral rhabdomyosarcoma is presented

Validation of CASCADE code using the monitor reactions

Production cross-sections of monitor reaction 27Al(x, y)24Na for proton, neutron and deuteron projectiles have been estimated from the CASCADE code from tens of MeV/n to tens of GeV/n energy and compared them with the available experimental data. It has also been shown that using the CASCADE code production cross-section of 27Al(d, y2)24Na reaction can be obtained from the proton and neutron projectiles. Implicitly, this provides an alternative way of knowing production cross-section of 27Al(n, y 1)24Na reaction which may be used to monitor the neutron flux in a wide range of energy. However, in the paper need of experimental determination of cross-sections for neutron projectile has been stressed. Similarly, cross-section of other monitor reactions like 27Al(p, y ′)22Na and 27Al(n, y ′ 1)22Na are also calibrated as function of energy up to several GeV

Low Temperature-Enhanced Flavonol Synthesis Requires Light-Associated Regulatory Components in Arabidopsis thaliana

Plants are continuously exposed to a myriad of stresses, which lead to the formation of secondary metabolites including flavonoids. Studies suggest that low temperature exposure leads to enhanced flavonoid accumulation in Arabidopsis thaliana. In addition, flavonoid biosynthesis is regulated by light through various regulatory factors. Therefore, plants may possess the capability to integrate light and low temperature signals for survival under freezing conditions. However, the detailed molecular mechanism and the regulatory factors associated with light- and low temperature-responsive flavonoid biosynthesis remain largely unknown. Here, we report a strict requirement for light for the low temperature-enhanced flavonol biosynthesis. Low temperature-induced expression of biosynthetic genes as well as flavonol accumulation was hampered in ELONGATED HYPOCOTYL (hy5) and myb11myb111myb12 triple mutants as compared with the wild type in Arabidopsis. Overexpression of AtHY5 in the hy5 mutant restored induction of gene expression and flavonol accumulation in response to low temperature in light. Metabolite and gene expression analysis also suggests a negative role for CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1) in accumulation of flavonols in response to low temperature. Overexpression of AtMYB12 enhanced accumulation of flavonols under low temperature in a light- dependent manner. Together, our analysis suggests the requirement for HY5 and flavonol-specific MYB regulatory factors for low temperature-induced flavonol synthesis

Rearranged p53 gene with loss of normal allele in a low-grade nonrecurrent glioma

We are studying the p53 gene profile in primary glial tumors by seeking alterations in the hybridization pattern of the tumor DNA probed with a p53 gene probe. This report documents a rearranged p53 gene with loss of the normal allele in a low-grade mixed glioma which has not recurred during 4-year follow-up. The tumor had a low 5-bromodeoxyuridine (BrdU)-labeling index and low AgNOR count. The p53 protein was not detected on immunochemical staining. To our knowledge, this is the first report of an altered p53 gene in a low-grade nonrecurrent glial tumor and highlights the presence of further checks and balances on the control of cell proliferation and other malignancy-associated phenotypes, even in an already-established tumor

Congenital myopathies: A clinicopathological study of 25 cases

Objective: Congenital myopathies are rare. Through this article, the authors want to present a clinicopathological analysis of 25 new cases. Materials and methods: The clinical data of patients who were diagnosed with congenital myopathy between 2001 and 2006 was retrieved. Muscle biopsies were processed for H&E staining, enzyme histochemistry, and immunohistochemistry. Biopsies were also processed for ultrastructural analysis. Results: During a period of 6 years, 1.12% of the muscle biopsies were diagnosed as congenital myopathies. The most common congenital myopathy was central core disease followed by nemaline rod myopathy and multi-mini core disease. Clinically, they have variable features. The final diagnosis was made with the help of enzyme histochemistry and ultrastructural features. Conclusion: This study emphasizes the importance of enzyme histochemistry and electron microscopic examination in the diagnosis of congenital myopathies especially in the absence of genetic studies