gebhart/patrepeval huggingface dataset:
Identification of a Novel Point Mutation in the RET Gene (Ala883Thr), Which Is Associated with Medullary Thyroid Carcinoma Phenotype Only in Homozygous Condition (2004)

The RET protooncogene mutations responsible for multiple endocrine neoplasia type 2 are inherited as autosomic dominant traits. We describe here a novel germline homozygous mutation in exon 15 of the RET gene that determines an amino acid substitution (Ala->Thr) at codon 883. The index case was a 51-yr-old patient with an apparently sporadic form of medullary thyroid cancer (MTC). RET gene mutations screening was performed in exons 10, 11, 13, 14, 15, and 16 by automatic sequence analysis. An unexpected homozygous GCT->ACT point mutation was found at codon 883 in exon 15 and confirmed by restriction analysis (Alu I). The presence of the two chromosomes 10 was confirmed by fluorescence in situ hybridization analysis on lymphocytes. As expected on the basis of the homozygosity of the index case, the parents were consanguineous (second-degree cousins). Eight relatives were further investigated: the mother, two sisters, and the son were positive for heterozygous RET mutation. The mother (82 yr old) showed a nodular goiter but was negative both for basal and pentagastrin stimulated calcitonin. The young son (15 yr old) and the two sisters (63 and 58 yr old) did not show any clinical and/or biochemical sign of MTC. One brother (59 yr old) was negative both for RET mutation and clinical/biochemical examination. The other brother, 56 yr of age, was positive for both homozygous RET mutation and serum calcitonin. When operated, the histological examination of the thyroid showed the presence of MTC and C cell hyperplasia. In conclusion, we identified a new germline RET gene mutation during a routine RET gene screening of an apparently sporadic MTC case. This mutation showed a very low transforming activity as demonstrated by the absence of MTC phenotype in heterozygous subjects. The possibility that the homozygous gene carriers were indeed carrying a germline loss of heterozygosity was excluded by fluorescence in situ hybridization analysis for RET gene performed on lymphocytes derived from one homozygous patient. The analysis of several RET polymorphisms also confirmed the presence of two mutated alleles in MTC affected patients and both mutated and wild-type allele in heterozygous subjects.
The Effect of Oral Dexmedetomidine Premedication on Preoperative Cooperation and Emergence Delirium in Children Undergoing Dental Procedures (2017)

Oral DEX administered at 1 <i>μ</i>g/kg provided satisfactory sedation levels, ease of parental separation, and mask acceptance in children but was not effective in preventing emergence delirium. The trial was registered (Protocol Registration Receipt NCT03174678) at clinicaltrials.gov.
The “Dead-End Elimination” Theorem: A New Approach to the Side-Chain Packing Problem (1994)

The prediction of a protein's tertiary structure is still computationally infeasible, mainly because of the huge number of a priori possible global conformations. The prediction of side-chain conformations that are attached to a given, fixed main-chain structure is considered as a less complex but still important subproblem with applications to, for instance, homology modeling (Lee and Subbiah, 1991). Nevertheless, the determination of the global minimum energy conformation (GMEC) of a set of protein side chains was up to now still limited to small, densely packed units (Ponder and Richards, 1987; Lee and Levitt, 1991).KeywordsSolvent AccessibilityAccessible Surface AreaPrediction ScorePotential Energy FunctionBovine Pancreatic Trypsin InhibitorThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Expression of an adenovirally encoded lymphotoxin-beta inhibitor prevents clearance of Listeria monocytogenes in mice. (1995)

The lymphotoxin (LT)-beta heterotrimer was recently identified as a molecule containing LT-alpha subunits, tethered to the cell through non-covalent association with an integral plasma membrane protein, derived from the LT-beta gene. Since knockout mutations of the LT-alpha gene yield animals that lack lymph nodes, whereas animals lacking either or both of the receptors for tumor necrosis factor (TNF) and LT-alpha homotrimers have normal lymph nodes, it has been inferred that the association between the LT-beta heterotrimer and its cognate receptor is required for lymph node ontogeny. Similarly, LT-beta and its receptor are thought to be important for development of the spleen. Since LT-alpha deficient mice lack lymph nodes, it is difficult to assess the extradevelopmental contribution of LT-beta to immune competence. To this end, we employed a strategy for the conditional blockade of LT-beta heteromer activity in normal mice. The interaction between LT-beta and its receptor is essential for the destruction of intracellular Listeria monocytogenes.
Evolution of Catabolic Pathways: Genomic Insights into Microbial s -Triazine Metabolism (2006)

In recent years, studies on the catabolism of organonitrogen compounds have accelerated due to the recognition that these compounds are widespread and significant environmentally. Nitrogen is the second most abundant macronutrient in cellular organisms, where it is found in major macromolecules (
Image Processing Architecture for Semiconductor Nanowire Based Fabrics (2008)

A new processing architecture for semiconductor nanowire grid fabrics is presented. The system consists of a large number of functionally identical units called cells. Cells are locally interconnected with nearest neighbors, with a limited number of global signals routed from supporting CMOS circuitry. One possible implementation of a digital cellular neural network (CNN) using this architecture is shown. The digital cellular design may be up to 27times denser than an equivalent 18 nm CMOS implementation. The system, based on a collective computation model, may also significantly alleviate manufacturing, since 100% fault-free components may not be necessary.
A Novel Dual Eigen-Analysis of Mouse Multi-Tissues’ Expression Profiles Unveils New Perspectives into Type 2 Diabetes (2017)

Type 2 diabetes (T2D) is a complex and polygenic disease yet in need of a complete picture of its development mechanisms. To better understand the mechanisms, we examined gene expression profiles of multi-tissues from outbred mice fed with a high-fat diet (HFD) or regular chow at weeks 1, 9, and 18. To analyze such complex data, we proposed a novel dual eigen-analysis, in which the sample- and gene-eigenvectors correspond respectively to the macro- and micro-biology information. The dual eigen-analysis identified the HFD eigenvectors as well as the endogenous eigenvectors for each tissue. The results imply that HFD influences the hepatic function or the pancreatic development as an exogenous factor, while in adipose HFD's impact roughly coincides with the endogenous eigenvector driven by aging. The enrichment analysis of the eigenvectors revealed diverse HFD impact on the three tissues over time. The diversity includes: inflammation, degradation of branched chain amino acids (BCAA), and regulation of peroxisome proliferator activated receptor gamma (PPARγ). We reported that in the pancreas remarkable up-regulation of angiogenesis as downstream of the HIF signaling pathway precedes hyperinsulinemia. The dual eigen-analysis and discoveries provide new evaluations/guidance in T2D prevention and therapy, and will also promote new thinking in biology and medicine.
Rapid mobilization of murine hematopoietic stem cells with enhanced engraftment properties and evaluation of hematopoietic progenitor cell mobilization in rhesus monkeys by a single injection of SB-251353, a specific truncated form of the human CXC chemokine GROβ (2001)

SB-251353 is an N-terminal truncated form of the human CXC chemokine GRObeta. Recombinant SB-251353 was profiled in murine and rhesus monkey peripheral blood stem cell mobilization and transplantation models. SB-251353 rapidly and transiently mobilized hematopoietic stem cells and neutrophils into the peripheral blood after a single subcutaneous injection. Transplantation of equivalent numbers of hematopoietic stem cells mobilized by SB-251353 into lethally irradiated mice resulted in faster neutrophil and platelet recovery than stem cells mobilized by granulocyte colony-stimulating factor (G-CSF). A single injection of SB-251353 in combination with 4 days of G-CSF administration resulted in augmented stem and progenitor cell mobilization 5-fold greater than G-CSF alone. Augmented stem cell mobilization could also be demonstrated in mice when a single injection of SB-251353 was administered with only one-day treatment with G-CSF. In addition, SB-251353, when used as a single agent or in combination with G-CSF, mobilized long-term repopulating stem cells capable of hematopoietic reconstitution of lethally irradiated mice. In rhesus monkeys, a single injection of SB-251353 induced rapid increases in peripheral blood hematopoietic progenitor cells at a 50-fold lower dose than in mice, which indicates a shift in potency. These studies provide evidence that the use of SB-251353 alone or in combination with G-CSF mobilizes hematopoietic stem cells with long-term repopulating ability. In addition, this treatment may (1) reduce the number of apheresis sessions and/or amount of G-CSF required to collect adequate numbers of hematopoietic stem cells for successful peripheral blood cell transplantation and (2) improve hematopoietic recovery after transplantation.
Bromine, Organic Compounds (2011)

Abstract This article focuses on organic bromine compounds with industrial application. The organic bromine compounds are prepared and produced either by substitutive or additive bromination. Organic bromine compounds, in which the bromine atom is retained in the final molecular structure, and where its presence contributes to the properties of the desired products, are the largest segment in terms of consumed volumes. This segment includes mainly flame retardants (50%), biocides (mostly for water treatment), gasoline additives, halons, bromobutyl rubber, pharmaceuticals, and dyes. New process developments resulted in new applications in ultraviolet (UV) sunscreens, high‐performance polymers, and others.
CD25+CD4+ Regulatory T Cells Prevent Graft Rejection: CTLA-4- and IL-10-Dependent Immunoregulation of Alloresponses (2002)

Specific and selective immunological unresponsiveness to donor alloantigens can be induced in vivo. We have shown previously that CD25+CD4+ T cells from mice exhibiting long-term operational tolerance to donor alloantigens can regulate rejection of allogeneic skin grafts mediated by CD45RB(high)CD4+ T cells. In this study, we wished to determine whether donor-specific regulatory cells can be generated during the induction phase of unresponsiveness, i.e., before transplantation. We provide evidence that pretreatment with anti-CD4 Ab plus a donor-specific transfusion generates donor-specific regulatory CD25+CD4+ T cells that can suppress rejection of skin grafts mediated by naive CD45RB(high)CD4+ T cells. Regulatory cells were contained only in the CD25+ fraction, as equivalent numbers of CD25-CD4+ T cells were unable to regulate rejection. This pretreatment strategy led to increased expression of CD122 by the CD25+CD4+ T cells. Blockade of both the IL-10 and CTLA-4 pathways abrogated immunoregulation mediated by CD25+ T cells, suggesting that IL-10 and CTLA-4 are required for the functional activity of this population of immunoregulatory T cells. In clinical transplantation, the generation of regulatory T cells that could provide dynamic control of rejection responses is a possible route to permanent graft survival without the need for long-term immunosuppression.
Prediction of Marginal Mass Required for Successful Islet Transplantation (2010)

Islet quality assessment methods for predicting diabetes reversal (DR) following transplantation are needed. We investigated two islet parameters, oxygen consumption rate (OCR) and OCR per DNA content, to predict transplantation outcome and explored the impact of islet quality on marginal islet mass for DR. Outcomes in immunosuppressed diabetic mice were evaluated by transplanting mixtures of healthy and purposely damaged rat islets for systematic variation of OCR/DNA over a wide range. The probability of DR increased with increasing transplanted OCR and OCR/DNA. On coordinates of OCR versus OCR/DNA, data fell into regions in which DR occurred in all, some, or none of the animals with a sharp threshold of around 150-nmol/min mg DNA. A model incorporating both parameters predicted transplantation outcome with sensitivity and specificity of 93% and 94%, respectively. Marginal mass was not constant, depended on OCR/DNA, and increased from 2,800 to over 100,000 islet equivalents/kg body weight as OCR/DNA decreased. We conclude that measurements of OCR and OCR/DNA are useful for predicting transplantation outcome in this model system, and OCR/DNA can be used to estimate the marginal mass required for reversing diabetes. Because human clinical islet preparations in a previous study had OCR/DNA.
Effect of correlation between subcarriers of an MCM/DSSS communication system (2002)

The analysis of a combined multicarrier modulation/direct-sequence spread-spectrum (DSSS) modem carried out by Kondo and Milstein (see IEEE Trans. on Commun., 1995) in delay spread multipath is extended to include the effect of correlation between the DSSS subcarriers due to an exponential power delay profile. Analytical and simulation results show that additional diversity gain can be achieved with more subcarriers, but at the expense of multiple access capability. Eventually, an irreducible bit error probability (BEP) is approached as more subcarriers are used.
Metabolites from the Induced Expression of Cryptic Single Operons Found in the Genome of Burkholderia pseudomallei (2011)

Bacterial genome sequencing projects routinely uncover gene clusters that are predicted to encode the biosynthesis of uncharacterized small molecules. A subset of these cryptic genetic elements appears as individual operons. Here we investigate potential single-operon biosynthetic systems found in the genome of the pathogenic bacterium Burkholderia pseudomallei . Placing these operons under the control of an inducible promoter led to the production of seven new metabolites. Among the molecules we identified are inhibitors of type-4 phosphodiesterases, suggesting that previously cryptic biosynthetic operons may encode metabolites that could contribute to microbial virulence by disrupting host signaling pathways.
A Principled Approach to Detecting Surprising Events in Video (2005)

Primates demonstrate unparalleled ability at rapidly orienting towards important events in complex dynamic environments. During rapid guidance of attention and gaze towards potential objects of interest or threats, often there is no time for detailed visual analysis. Thus, heuristic computations are necessary to locate the most interesting events in quasi real-time. We present a new theory of sensory surprise, which provides a principled and computable shortcut to important information. We develop a model that computes instantaneous low-level surprise at every location in video streams. The algorithm significantly correlates with eye movements of two humans watching complex video clips, including television programs (17,936 frames, 2,152 saccadic gaze shifts). The system allows more sophisticated and time-consuming image analysis to be efficiently focused onto the most surprising subsets of the incoming data.
Unexpected Anion Effect in the Alkoxylation of Alkynes Catalyzed by N‐Heterocyclic Carbene (NHC) Cationic Gold Complexes (2014)

Abstract The intermolecular alkoxylation of alkynes is the oldest application of cationic gold(I) catalysts; however, no systematic experimental data about the role of the anion are available. In this contribution, the role of the anion in this catalytic reaction as promoted by a N‐heterocyclic carbene‐based gold catalyst, [(NHC)AuX] (X=BARF − , BF 4 − , OTf − , OTs − , TFA − , or OAc − ) is analyzed, through a combined experimental (NMR spectroscopy) and theoretical (DFT calculation) approach. The most important factor seems to be the ability to abstract the proton from the methanol during the nucleophilic attack, and such ability is related to the anion basicity. On the other hand, too high coordination power or basicity of the anion worsens the catalytic performance by preventing alkyne coordination or by forming too much free methoxide in solution, which poisons the catalyst. The intermediate coordinating power and basicity of the OTs − anion provides the best compromise to achieve efficient catalysis.
In vitro receptor binding assays: general methods and considerations. (2008)

The development of receptor-targeting radiopharmaceuticals commonly involves the use of peptides, antibodies or small molecules. Resulting from the numerous modifications that can be made to these basic targeting agents, research in this field often generates a series of compounds as potential ligands for in vivo investigation. However, measuring each variant of a series in vivo can be both costly and time-consuming. Therefore, a number of in vitro assays, to study interactions between the targeted receptor and the ligands of interest, are frequently used to quickly and inexpensively narrow the field and identify a lead compound(s) for further investigation. For example, in saturation binding studies, the amount of radioligand required to saturate the receptors is measured and analyzed to determine the radioligand equilibrium dissociation constant (Kd), a useful gauge of the receptor binding affinity of a radioligand. In competitive binding experiments, a ligand of interest competes for available receptor sites with a standard radioligand of known high receptor affinity. Competition data are analyzed to yield another indicator of receptor affinity, called an IC50 value, which can be used to rank the relative receptor binding affinities for a series of ligands. In internalization and efflux studies, the rate and extent of receptor-mediated radioligand taken into and subsequently released from cells is measured, providing insight into cellular uptake and retention of the radioligand. Individually or taken together, these in vitro receptor binding assays are useful tools in radiopharmaceutical development.
p53-Independent Negative Regulation of p21/Cyclin-Dependent Kinase–Interacting Protein 1 by the Sonic Hedgehog-Glioma-Associated Oncogene 1 Pathway in Gastric Carcinoma Cells (2005)

The activation of Hedgehog (Hh) signaling has been implicated in the growth of various tumor types, including gastric carcinoma. However, the precise mechanisms of Hh activation and suppression of tumor growth by the blockade of Hh signaling in gastric carcinoma cells remain unknown. The aim of this study was to elucidate the mechanism of abnormal Hh signaling and the key molecules contributing to dysregulated growth of gastric carcinoma. The Sonic hedgehog (Shh) ligand and its receptor Patched were expressed in all five gastric carcinoma cell lines examined (MKN1, MKN7, MKN45, MKN74, and AGS cells). The blockade of Hh signaling with anti-Shh antibody inhibited the growth of all five gastric carcinoma cell lines. Shh was overexpressed (mean, 12.8-fold) in 8 of 14 (57.0%) cancerous tissue samples from patients with gastric carcinoma as compared with expression in the surrounding noncancerous tissues. The disruption of glioma-associated oncogene 1 (Gli1) by small interfering RNA induced an increase in p21/cyclin-dependent kinase-interacting protein 1 (CIP1), interfered with the G1-S transition, and suppressed cell proliferation. The stimulation or inhibition of Hh signaling did not affect p53 activity and the induction of p21/CIP1 expression and the G1 arrest by inhibition of Hh signaling were not affected by the p53 status. These findings suggest that the overexpression of Shh contributes to constitutive Hh activation and that this signaling pathway negatively regulates p21/CIP1 through a Gli1-dependent and p53-independent mechanism in gastric carcinoma cells.
Enhanced Development of Skeletal Myotubes from Porcine Induced Pluripotent Stem Cells (2017)

The pig is recognized as a valuable model in biomedical research in addition to its agricultural importance. Here we describe a means for generating skeletal muscle efficiently from porcine induced pluripotent stem cells (piPSC) in vitro thereby providing a versatile platform for applications ranging from regenerative biology to the ex vivo cultivation of meat. The GSK3B inhibitor, CHIR99021 was employed to suppress apoptosis, elicit WNT signaling events and drive naïve-type piPSC along the mesoderm lineage, and, in combination with the DNA methylation inhibitor 5-aza-cytidine, to activate an early skeletal muscle transcription program. Terminal differentiation was then induced by activation of an ectopically expressed MYOD1. Myotubes, characterized by myofibril development and both spontaneous and stimuli-elicited excitation-contraction coupling cycles appeared within 11 days. Efficient lineage-specific differentiation was confirmed by uniform NCAM1 and myosin heavy chain expression. These results provide an approach for generating skeletal muscle that is potentially applicable to other pluripotent cell lines and to generating other forms of muscle.
Synthesis and Preliminary Biological Evaluation of Novel Functionalised Poly(ethylene glycol)-block-poly(ester-carbonate) Copolymers as Biodegradable Polymeric Carriers (2001)

Polymer conjugates of anticancer drugs containing bound active moieties are used to improve pharmacokinetics by prolonging antitumour activity and decreasing protein immunogenicity. The first generation of polymer conjugates, N-(2-hydroxylpropyl)methacrylamide copolymer or poly(ethylene glycol) conjugates, cannot be considered optimised since their polymer chain lacks biodegradability. The polymeric system proposed here is based on high molecular weight water-soluble functionalised polyesters containing fumarate or maleate units linked by poly(ethylene glycol) segments by means of carbonate bonds. It shows the following features: a) high molecular weight; b) biodegradable backbone (rate of degradation was determined viscometrically in vitro, under conditions mimicking physiological conditions and c) water solubility. Also the biocompatibility of the polymer and its precursors were assessed using a B16F10 murine melanoma cell line and a haemolysis assay.
Effect of Polyethylene Glycol Linker Chain Length of Folate-Linked Microemulsions Loading Aclacinomycin A on Targeting Ability and Antitumor Effect In vitro and In vivo (2005)

These findings suggest that a folate-linked microemulsion is feasible for tumor-targeted ACM delivery. This study shows that folate modification with a sufficiently long PEG chain on emulsions is an effective way of targeting emulsion to tumor cells.
Experimental Studies of Transmission Bit-Rate for Teletext Signal in the 525-Line Television System (1979)

In order to investigate the optimum transmission bit-rate for teletext signals in the 525-line television system, laboratory and field tests were carried out using binary NRZ digital data signals of several bit-rates to 5.73 Mbit/s ( 364fH, 8/5fsc). In these tests, the bit-errors and eye-openings of PN signals were measured and subjective evaluation of teletext signals was also made under various receiving conditions. The results have indicated that a digital data signal of 5.73 Mbit/s could be utilized for teletext in the 525-line television system. The Japanese teletext system now being developed employs this bit-rate for transmitting and displaying the signals.
PSLpred: prediction of subcellular localization of bacterial proteins (2005)

PSLpred is available at http://www.imtech.res.in/raghava/pslpred/