968 resultados para Abnormal Subgroups


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Atmospheric perturbations due to the annular solar eclipse were monitored to understand its influence on the meteorological parameters from surface to the lower stratosphere. A strong inversion at 13 km and an abnormal warming in the upper troposphere were noticed on the eclipse day. A decrease in tropopause height associated with increase in temperature caused anomalous warming. Considerable attenuation of incoming solar radiation resulted in abrupt increase of air temperature during the next 24 h followed by sharp decrease in relative humidity. The time lag is attributed to the distance from the totality and the response time between tropopause and surface layer. (C) 2011 Elsevier Ltd. All rights reserved.

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Several studies on molecular profiling of oligodendrogliomas (OGs) in adults have shown a distinctive genetic pattern characterized by combined deletions of chromosome arms 1 p and 19q, O6-methylguanine-methyltransferase (MGMT) methylation, and isocitrate dehydrogenase 1 (IDH1) mutation, which have potential diagnostic, prognostic, and even therapeutic relevance. OGs in pediatric and young adult patients are rare and have been poorly characterized on a molecular and biological basis, and it remains uncertain whether markers with prognostic significance in adults also have predictive value in these patients. Fourteen cases of OGs in young patients (age, <= 25 years) who received a diagnosis over 7 years were selected (7 pediatric patients age <= 18 years and 7 young adults aged 19-25 years). The cases were evaluated for 1p/19q status, MGMT promoter methylation, p53 mutation, and IDH1 mutation. None of the pediatric cases showed 1p/19q deletion. In young adults, combined 1p/19q loss was observed in 57% and isolated 1p loss in 14% of cases. The majority of cases in both subgroups (71% in each) harbored MGMT gene promoter methylation. TP53 and IDH1 mutations were not seen in any of the cases in both the groups. To our knowledge, this is the first study to show that molecular profile of OGs in pediatric and young adult patients is distinct. Further large-scale studies are required to identify additional clinically relevant genetic alterations in this group of patients.

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A technique is proposed for classifying respiratory volume waveforms(RVW) into normal and abnormal categories of respiratory pathways. The proposed method transforms the temporal sequence into frequency domain by using an orthogonal transform, namely discrete cosine transform (DCT) and the transformed signal is pole-zero modelled. A Bayes classifier using model pole angles as the feature vector performed satisfactorily when a limited number of RVWs recorded under deep and rapid (DR) manoeuvre are classified.

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The use of Fourier shape descriptors for morphological studies of vectorcardio-grams (VCGs) is p resented . The FDs can effectively be used as features for classf-fication of VCGs of different clinical categories . In addition , they provide cli-nically significant qualitative shape information for use by the Cardiologist. The initial result sofanalysisof nwrmal and abnormal VCGs areencouraging.

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Arteries are heterogeneous, composite structures that undergo large cyclic deformations during blood transport. Presence, build-up and consequent rupture of blockages in blood vessels, called atherosclerotic plaques, lead to disruption in the blood flow that can eventually be fatal. Abnormal lipid profile and hypertension are the main risk factors for plaque progression. Treatments span from pharmacological methods, to minimally invasive balloon angioplasty and stent procedures, and finally to surgical alternatives. There is a need to understand arterial disease progression and devise methods to detect, control, treat and manage arterial disease through early intervention. Local delivery through drug eluting stents also provide an attractive option for maintaining vessel integrity and restoring blood flow while releasing controlled amount of drug to reduce and alleviate symptoms. Development of drug eluting stents is hence interesting albeit challenging because it requires an integration of knowledge of mechanical properties with material transport of drug through the arterial wall to produce a desired biochemical effect. Although experimental models are useful in studying such complex multivariate phenomena, numerical models of mass transport in the vessel have proved immensely useful to understand and delineate complex interactions between chemical species, physical parameters and biological variables. The goals of this review are to summarize literature based on studies of mass transport involving low density lipoproteins in the arterial wall. We also discuss numerical models of drug elution from stents in layered and porous arterial walls that provide a unique platform that can be exploited for the design of novel drug eluting stents.

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The regulation of cell proliferation in the external granular layer (EGL) of the developing cerebellum is important for its normal patterning. An important signal that regulates EGL cell proliferation is Sonic hedgehog (Shh). Shh is secreted by the Purkinje cells (PC) and has a mitogenic effect on the granule cell precursors of the EGL. Deregulation of Shh signaling has been associated with abnormal development, and been implicated in medulloblastomas, which are tumors that arise from the cerebellum. Given the importance of the Shh pathway in cerebellum development and disease, there has been no systematic study of its expression pattern during human cerebellum development. In this study, we describe the expression pattern of Shh, its receptor patched, smoothened, and its effectors that belong to the Gli family of transcription factors, during normal human cerebellum development from 10 weeks of gestational age, and in medulloblastomas that represents a case of abnormal cell proliferation in the cerebellum. This expression pattern is compared to equivalent stages in the normal development of cerebellum in mouse, as well as in tumors. Important differences between human and mouse that reflect differences in the normal developmental program between the 2 species are observed. First, in humans there appears to be a stage of Shh signaling within the EGL, when the PC are not yet the source of Shh. Second, unlike in the postnatal mouse cerebellum, expression of Shh in the PC in the postnatal human cerebellum is downregulated. Finally, medulloblastomas in the human but not in patched heterozygote mouse express Shh. These results highlight cross-species differences in the regulation of the Shh signaling pathway.

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The roles of myosin during muscle contraction are well studied, but how different domains of this protein are involved in myofibril assembly in vivo is far less understood. The indirect flight muscles (IFMs) of Drosophila melanogaster provide a good model for understanding muscle development and function in vivo. We show that two missense mutations in the rod region of the myosin heavy-chain gene, Mhc, give rise to IFM defects and abnormal myofibrils. These defects likely result from thick filament abnormalities that manifest during early sarcomere development or later by hypercontraction. The thick filament defects are accompanied by marked reduction in accumulation of flightin, a myosin binding protein, and its phosphorylated forms, which are required to stabilise thick filaments. We investigated with purified rod fragments whether the mutations affect the coiled-coil structure, rod aggregate size or rod stability. No significant changes in these parameters were detected, except for rod thermodynamic stability in one mutation. Molecular dynamics simulations suggest that these mutations may produce localised rod instabilities. We conclude that the aberrant myofibrils are a result of thick filament defects, but that these in vivo effects cannot be detected in vitro using the biophysical techniques employed. The in vivo investigation of these mutant phenotypes in IFM development and function provides a useful platform for studying myosin rod and thick filament formation generically, with application to the aetiology of human myosin rod myopathies. (C) 2012 Elsevier Ltd. All rights reserved.

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Three-dimensional numerical study of natural convection in a vertical channel with flush-mounted discrete heaters on opposite conductive substrate walls is carried out in the present work. Detailed flow and heat transfer characteristics are presented for various Grashof numbers. The heat transfer effects on one wall by the presence of heaters on its opposite wall is examined. It is found that heat transfer rates on one wall are increased by the presence of heaters on its opposite wall. The thermal boundary layers on the opposite walls complement each other for enhanced heat transfer. The effects of spacing between the heated walls, spacings between heaters and substrate conductivity on flow and heat transfer are examined. Existence of optimum spacings between the heated walls for maximum heat transfer and mass flow are observed. It is found that the heat transfer and fluid flow do not follow the same optimum spacings. Mass flow rate reaches maximum value at a wall spacing greater than the spacing for maximum heat transfer. This is because the interaction of thermal boundary layers on individual walls ceases at a lower spacing before the velocity boundary layers separate each other. It is found that increased spacings between heaters reduce individual heater temperatures provided the heaters close to exit on both substrates avail sufficient substrate potions on the exit side. Insufficient substrate portions between the exit heaters and the exit cause abnormal local temperature rise in the exit heaters which are the hottest ones among all the heaters. Optimal heater spacings exist for minimum hottest heater temperature rise. Correlations are presented for dimensionless mass flow rate, temperature maximum, and average Nusselt number.

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Examination of type material and new collections from Goa, southern Maharashtra and northern Karnataka, leads to the conclusion that Gegeneophis nadkarnii Bhatta & Prashanth, 2004 is a subjective junior synonym of Gegeneophis danieli Giri, Wilkinson & Gower, 2003. The purported differences between these species are very minor and attributable to normal individual variation, except for some features of the dentition that are peculiar to the exceptionally abnormal paratype of G. nadkarnii. This taxonomic revision extends the known geographic range of G. danieli and suggests it could be transferred from Data Deficient to Least Concern status in the IUCN Red List.

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Sudden cardiac death is often caused by cardiac arrhythmias. Recently, special attention has been given to a certain arrhythmogenic condition, the long-QT syndrome, which occurs as a result of genetic mutations or drug toxicity. The underlying mechanisms of arrhythmias, caused by the long-QT syndrome, are not fully understood. However, arrhythmias are often connected to special excitations of cardiac cells, called early afterdepolarizations (EADs), which are depolarizations during the repolarizing phase of the action potential. So far, EADs have been studied mainly in isolated cardiac cells. However, the question on how EADs at the single-cell level can result in fibrillation at the tissue level, especially in human cell models, has not been widely studied yet. In this paper, we study wave patterns that result from single-cell EAD dynamics in a mathematical model for human ventricular cardiac tissue. We induce EADs by modeling experimental conditions which have been shown to evoke EADs at a single-cell level: by an increase of L-type Ca currents and a decrease of the delayed rectifier potassium currents. We show that, at the tissue level and depending on these parameters, three types of abnormal wave patterns emerge. We classify them into two types of spiral fibrillation and one type of oscillatory dynamics. Moreover, we find that the emergent wave patterns can be driven by calcium or sodium currents and we find phase waves in the oscillatory excitation regime. From our simulations we predict that arrhythmias caused by EADs can occur during normal wave propagation and do not require tissue heterogeneities. Experimental verification of our results is possible for experiments at the cell-culture level, where EADs can be induced by an increase of the L-type calcium conductance and by the application of I-Kr blockers, and the properties of the emergent patterns can be studied by optical mapping of the voltage and calcium.

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This paper addresses the problem of localizing the sources of contaminants spread in the environment, and mapping the boundary of the affected region using an innovative swarm intelligence based technique. Unlike most work in this area the algorithm is capable of localizing multiple sources simultaneously while also mapping the boundary of the contaminant spread. At the same time the algorithm is suitable for implementation using a mobile robotic sensor network. Two types of agents, called the source localization agents (or S-agents) and boundary mapping agents (or B-agents) are used for this purpose. The paper uses the basic glowworm swarm optimization (GSO) algorithm, which has been used only for multiple signal source localization, and modifies it considerably to make it suitable for both these tasks. This requires the definition of new behaviour patterns for the agents based on their terminal performance as well as interactions between them that helps the swarm to split into subgroups easily and identify contaminant sources as well as spread along the boundary to map its full length. Simulations results are given to demonstrate the efficacy of the algorithm.

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Telomerases are an attractive drug target to develop new generation drugs against cancer. A telomere appears from the chromosomal termini and protects it from double-stranded DNA degradation. A short telomere promotes genomic instability, like end-to-end fusion and regulates the over-expression of the telomere repairing enzyme, telomerase. The telomerase maintains the telomere length, which may lead to genetically abnormal situations, leading to cancer. Thus, the design and synthesis of an efficient telomerase inhibitor is a viable strategy toward anticancer drugs development. Accordingly, small molecule induced stabilization of the G-quadruplex structure, formed by the human telomeric DNA, is an area of contemporary scientific art. Several such compounds efficiently stabilize the G-quadruplex forms of nucleic acids, which often leads to telomerase inhibition. This Feature article presents the discovery and development of the telomere structure, function and evolution in telomere targeted anticancer drug design and incorporates the recent advances in this area, in addition to discussing the advantages and disadvantages in the methods, and prospects for the future.

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The sensitivity of combustion phasing and combustion descriptors to ignition timing, load and mixture quality on fuelling a multi-cylinder natural gas engine with bio-derived H-2 and CO rich syngas is addressed. While the descriptors for conventional fuels are well established and are in use for closed loop engine control, presence of H-2 in syngas potentially alters the mixture properties and hence combustion phasing, necessitating the current study. The ability of the descriptors to predict abnormal combustion, hitherto missing in the literature, is also addressed. Results from experiments using multi-cylinder engines and numerical studies using zero dimensional Wiebe function based simulation models are reported. For syngas with 20% H-2 and CO and 2% CH4 (producer gas), an ignition retard of 5 +/- 1 degrees was required compared to natural gas ignition timing to achieve peak load of 72.8 kWe. It is found that, for syngas, whose flammability limits are 0.42-1.93, the optimal engine operation was at an equivalence ratio of 1.12. The same methodology is extended to a two cylinder engine towards addressing the influence of syngas composition, especially H-2 fraction (varying from 13% to 37%), on the combustion phasing. The study confirms the utility of pressure trace derived combustion descriptors, except for the pressure trace first derivative, in describing the MBT operating condition of the engine when fuelled with an alternative fuel. Both experiments and analysis suggest most of the combustion descriptors to be independent of the engine load and mixture quality. A near linear relationship with ignition angle is observed. The general trend(s) of the combustion descriptors for syngas fuelled operation are similar to those of conventional fuels; the differences in sensitivity of the descriptors for syngas fuelled engine operation requires re-calibration of control logic for MBT conditions. Copyright (C) 2014, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved.

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Drosophila melanogaster has served as an excellent model system for understanding the neuronal circuits and molecular mechanisms regulating complex behaviors. The Drosophila female reproductive circuits, in particular, are well studied and can be used as a tool to understand the role of novel genes in neuronal function in general and female reproduction in particular. In the present study, the role of Beadex, a transcription co-activator, in Drosophila female reproduction was assessed by generation of mutant and knock down studies. Null allele of Beadex was generated by transposase induced excision of P-element present within an intron of Beadex gene. The mutant showed highly compromised reproductive abilities as evaluated by reduced fecundity and fertility, abnormal oviposition and more importantly, the failure of sperm release from storage organs. However, no defect was found in the overall ovariole development. Tissue specific, targeted knock down of Beadex indicated that its function in neurons is important for efficient female reproduction, since its neuronal knock down led to compromised female reproductive abilities, similar to Beadex null females. Further, different neuronal class specific knock down studies revealed that Beadex function is required in motor neurons for normal fecundity and fertility of females. Thus, the present study attributes a novel and essential role for Beadex in female reproduction through neurons.

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Background. Pediatric glioblastoma multiforme (GBM) is rare, and there is a single study, a seminal discovery showing association of histone H3.3 and isocitrate dehydrogenase (IDH) 1 mutation with a DNA methylation signature. The present study aims to validate these findings in an independent cohort of pediatric GBM, compare it with adult GBM, and evaluate the involvement of important functionally altered pathways. Methods. Genome-wide methylation profiling of 21 pediatric GBM cases was done and compared with adult GBM data (GSE22867). We performed gene mutation analysis of IDH1 and H3 histone family 3A (H3F3A), status evaluation of glioma cytosine-phosphate-guanine island methylator phenotype (G-CIMP), and Gene Ontology analysis. Experimental evaluation of reactive oxygen species (ROS) association was also done. Results. Distinct differences were noted between methylomes of pediatric and adult GBM. Pediatric GBM was characterized by 94 hypermethylated and 1206 hypomethylated cytosine-phosphate-guanine (CpG) islands, with 3 distinct clusters, having a trend to prognostic correlation. Interestingly, none of the pediatric GBM cases showed G-CIMP/IDH1 mutation. Gene Ontology analysis identified ROS association in pediatric GBM, which was experimentally validated. H3F3A mutants (36.4%; all K27M) harbored distinct methylomes and showed enrichment of processes related to neuronal development, differentiation, and cell-fate commitment. Conclusions. Our study confirms that pediatric GBM has a distinct methylome compared with that of adults. Presence of distinct clusters and an H3F3A mutation-specific methylome indicate existence of epigenetic subgroups within pediatric GBM. Absence of IDH1/G-CIMP status further indicates that findings in adult GBM cannot be simply extrapolated to pediatric GBM and that there is a strong need for identification of separate prognostic markers. A possible role of ROS in pediatric GBM pathogenesis is demonstrated for the first time and needs further evaluation.