Computerised Referral Service : a case study

Describes the attempt to develop a soft- ware package for computerised referral service taking Machine Tools as a case study. The system was developed ax DRTC using an ICL 1901 computer and the program was written in COBOL Language.The creation of the files and answering of queries are explained. Sample copies of output are attached

The role of clinical neurophysiology in the definition and assessment of fatigue and fatigability

Though a common symptom, fatigue is difficult to define and investigate, occurs in a wide variety of neurological and systemic disorders, with differing pathological causes. It is also often accompanied by a psychological component. As a symptom of long-term COVID-19 it has gained more attention. In this review, we begin by differentiating fatigue, a perception, from fatigability, quantifiable through biomarkers. Central and peripheral nervous system and muscle disorders associated with these are summarised. We provide a comprehensive and objective framework to help identify potential causes of fatigue and fatigability in a given disease condition. It also considers the effectiveness of neurophysiological tests as objective biomarkers for its assessment. Among these, twitch interpolation, motor cortex stimulation, electroencephalography and magnetencephalography, and readiness potentials will be described for the assessment of central fatigability, and surface and needle electromyography (EMG), single fibre EMG and nerve conduction studies for the assessment of peripheral fatigability. The purpose of this review is to guide clinicians in how to approach fatigue, and fatigability, and to suggest that neurophysiological tests may allow an understanding of their origin and interactions. In this way, their differing types and origins, and hence their possible differing treatments, may also be defined more clearly

Large-scale wind structures in OB supergiants: a search for rotationally modulated H\alpha variability

We present the results of a long-term monitoring campaign of the H\alpha line in a sample of bright OB-supergiants (O7.5-B9) that aims at detecting rotationally modulated changes potentially related to the existence of large-scale wind structures. A total of 22 objects were monitor ed during 36 nights spread over 6 months in 2001-2002. Coordinated broad-band photometric observations were also obtained for some targets. Conspicuous evidence for variability in H\alpha is found for the stars displaying a feature contaminated by wind emission. Most changes take place on a daily time-scale, although hourly variations are also occasionally detected. Convincing evidence for a cyclical pattern of variability in H\alpha has been found in 2 stars: HD 14134 and HD 42087 (periodic signals are also detected in other stars, but independent confirmation is required). Rotational modulation is suggested from the similarity between the observed recurrence time-scales (in the range 13-25 days) and estimated periods of stellar rotation. We call attention to the atypical case of HD 14134 which exhibits a clear 12.8-d periodicity both in the photometric and in the spectroscopic data sets. This places this object among a handful of early-type stars where one may observe a clear link between extended wind structures and photospheric disturbances. Further modelling may test the hypothesis that azimuthally-extended wind streams are responsible for the patterns of spectral variability in our target stars.Comment: 18 pages, accepted for publication in MNRA

Metabolic Syndrome: a challenging health Issue in highly urbanized Union Territory of north India

<p>Abstract</p> <p>Objectives</p> <p>1. To determine the prevalence of Metabolic Syndrome in adults aged 18 years and above in Chandigarh, India. 2. To determine the socio-demographic factors associated with MS. 3. To determine the agreement between IDF (International Diabetes federation definition) and ATP-III (National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults criteria).</p> <p>Methods</p> <p>In a community based cross-sectional study, total 605 subjects aged 18 yrs and above were studied using multistage random sampling.</p> <p>Results</p> <p>Prevalence of Metabolic Syndrome was estimated by using IDF and ATP-III criteria. By IDF, Metabolic Syndrome was found in 287 (47.4%) subjects and it was more prevalent among females 171 (59.6%) as compared to males 116 (40.4%). By applying ATP-III overall prevalence was less i.e. 233 (38.5%) but again its prevalence was more among females 141 (44.8%) than males 116 (39.5%). Higher socioeconomic status, sedentary occupation and high body mass index were significantly associated with Metabolic Syndrome.</p> <p>Conclusions</p> <p>Metabolic Syndrome is a major health problem in the region and proper emphasis should be given on its prevention and control.</p

Reward-Based Crowdfunding Research and Practice

publishedVersio

Epigenetic re-wiring of breast cancer by pharmacological targeting of C-terminal binding protein

The C-terminal binding protein (CtBP) is an NADH-dependent dimeric family of nuclear proteins that scaffold interactions between transcriptional regulators and chromatin-modifying complexes. Its association with poor survival in several cancers implicates CtBP as a promising target for pharmacological intervention. We employed computer-assisted drug design to search for CtBP inhibitors, using quantitative structure-activity relationship (QSAR) modeling and docking. Functional screening of these drugs identified 4 compounds with low toxicity and high water solubility. Micro molar concentrations of these CtBP inhibitors produces significant de-repression of epigenetically silenced pro-epithelial genes, preferentially in the triple-negative breast cancer cell line MDA-MB-231. This epigenetic reprogramming occurs through eviction of CtBP from gene promoters; disrupted recruitment of chromatin-modifying protein complexes containing LSD1, and HDAC1; and re-wiring of activating histone marks at targeted genes. In functional assays, CtBP inhibition disrupts CtBP dimerization, decreases cell migration, abolishes cellular invasion, and improves DNA repair. Combinatorial use of CtBP inhibitors with the LSD1 inhibitor pargyline has synergistic influence. Finally, integrated correlation of gene expression in breast cancer patients with nuclear levels of CtBP1 and LSD1, reveals new potential therapeutic vulnerabilities. These findings implicate a broad role for this class of compounds in strategies for epigenetically targeted therapeutic intervention

The Mechanism of Release of P-TEFb and HEXIM1 from the 7SK snRNP by Viral and Cellular Activators Includes a Conformational Change in 7SK

The positive transcription elongation factor, P-TEFb, is required for the production of mRNAs, however the majority of the factor is present in the 7SK snRNP where it is inactivated by HEXIM1. Expression of HIV-1 Tat leads to release of P-TEFb and HEXIM1 from the 7SK snRNP in vivo, but the release mechanisms are unclear.We developed an in vitro P-TEFb release assay in which the 7SK snRNP immunoprecipitated from HeLa cell lysates using antibodies to LARP7 was incubated with potential release factors. We found that P-TEFb was directly released from the 7SK snRNP by HIV-1 Tat or the P-TEFb binding region of the cellular activator Brd4. Glycerol gradient sedimentation analysis was used to demonstrate that the same Brd4 protein transfected into HeLa cells caused the release of P-TEFb and HEXIM1 from the 7SK snRNP in vivo. Although HEXIM1 binds tightly to 7SK RNA in vitro, release of P-TEFb from the 7SK snRNP is accompanied by the loss of HEXIM1. Using a chemical modification method, we determined that concomitant with the release of HEXIM1, 7SK underwent a major conformational change that blocks re-association of HEXIM1.Given that promoter proximally paused polymerases are present on most human genes, understanding how activators recruit P-TEFb to those genes is critical. Our findings reveal that the two tested activators can extract P-TEFb from the 7SK snRNP. Importantly, we found that after P-TEFb is extracted a dramatic conformational change occurred in 7SK concomitant with the ejection of HEXIM1. Based on our findings, we hypothesize that reincorporation of HEXIM1 into the 7SK snRNP is likely the regulated step of reassembly of the 7SK snRNP containing P-TEFb

What does the structure-function relationship of the HIV-1 Tat protein teach us about developing an AIDS vaccine?

The human immunodeficiency virus type 1 (HIV-1) trans-activator of transcription protein Tat is an important factor in viral pathogenesis. In addition to its function as the key trans-activator of viral transcription, Tat is also secreted by the infected cell and taken up by neighboring cells where it has an effect both on infected and uninfected cells. In this review we will focus on the relationship between the structure of the Tat protein and its function as a secreted factor. To this end we will summarize some of the exogenous functions of Tat that have been implicated in HIV-1 pathogenesis and the impact of structural variations and viral subtype variants of Tat on those functions. Finally, since in some patients the presence of Tat-specific antibodies or CTL frequencies are associated with slow or non-progression to AIDS, we will also discuss the role of Tat as a potential vaccine candidate, the advances made in this field, and the importance of using a Tat protein capable of eliciting a protective or therapeutic immune response to viral challenge