gebhart/patrepeval huggingface dataset:
Hurler Syndrome: II. Outcome of HLA-Genotypically Identical Sibling and HLA-Haploidentical Related Donor Bone Marrow Transplantation in Fifty-Four Children (1998)

Untreated patients with Hurler syndrome (MPSIH) experience progressive neurologic deterioration and early death. Allogeneic bone marrow transplantation (BMT) ameliorates or halts this course. The Storage Disease Collaborative Study Group was formed to evaluate the effectiveness and toxicity of BMT. Effectiveness was defined as engrafted survival with continuing cognitive development. Fifty-four patients deficient in leukocyte alpha-L-iduronidase enzyme activity (median age, 1.8 years; range, 0.4 to 7.9) received high-dose chemotherapy with or without irradiation and BMT from HLA-genotypically identical sibling (GIS) or HLA-haploidentical related (HIR) donors between September 16, 1983 and July 14, 1995; all children were included in this report. Thirty-nine of 54 patients (72%) engrafted following the first BMT. The probability of grade II to IV acute graft-versus-host disease (GVHD) at 100 days was 32% for GIS and 55% for HIR patients. The probability of extensive chronic GVHD was 0% for GIS and 24% for HIR patients. The actuarial probability of survival at 5 years was 64% for all patients, 75% for GIS patients, 53% for HIR patients, and 53% for patients with donor marrow engraftment. The baseline Mental Developmental Index (MDI) was examined both for children less than and greater than 24 months of age at BMT. Children transplanted before 24 months had a mean baseline MDI of 78, while those transplanted after 24 months had a mean baseline MDI of 63 (P = . 0002). Both baseline and post-BMT neuropsychologic data were available for 26 of 30 engrafted survivors. Of 14 patients transplanted before 24 months of age, nine demonstrated developmental trajectories that were normal or somewhat slower than normal. In contrast, of 12 patients transplanted after 24 months of age, only three showed developmental trajectories that were normal or somewhat slower than normal (P = .01). For children with a baseline MDI greater than 70, there was a significant correlation between the MDI at follow-up study and leukocyte alpha-L-iduronidase enzyme activity (P = .02). Children were more likely to maintain normal cognitive development if they were fully engrafted following BMT from a donor with homozygous normal leukocyte alpha-L-iduronidase enzyme activity. Children who developed acute GVHD of grade II or worse had significantly poorer cognitive outcomes (P < .009). No difference in the post-BMT MDI was observed between patients whose preparative therapies did (n = 10; radiation dose, 300 to 1,400 cGy) or did not (n = 16) include radiation. We conclude that MPSIH patients, particularly those less than 24 months of age with a baseline MDI greater than 70, can achieve a favorable long-term outcome with continuing cognitive development and prolonged survival after successful BMT from a related donor with homozygous normal enzyme activity.
Dynamic Modeling and Transient Simulation for VSC based HVDC in Multi-Machine System (2006)

Voltage source converter (VSC) based high voltage direct current (HVDC) technology, abbreviated as VSC-HVDC, is a new and attractive transmission technology. With switch device having turn-on and turn-off capability, such as IGBT, VSC-HVDC has special characteristics comparing to conventional HVDC. Some of these characteristics are: passive ac load can be supplied; active and reactive power can be controlled separately and simultaneously; no requirement for fast communication between VSC stations. Based on the method of current injection at the ac bus of voltage source converter, the detailed dynamic model for VSC- HVCD is developed. This model includes three parts, i.e. the quasi-steady model for the ac side of voltage source converter, the dynamic model for VSC-HVDC inner dc system and the model for VSC-HVDC control system. With the help of User Program Interface function provided by Power System Analysis Software Package (PSASP/UPI), the transient simulation algorithm for VSC-HVDC is designed. Simulation results for multi-machine system with VSC-HVDC has verified the developed VSC-HVDC dynamic model and the designed transient simulation algorithm. Simulation results also show that with the active and reactive power control capability, not only the steady-state power flow can be controlled, but the system damping characteristic of low-frequency oscillation can be improved.
MIR16, a putative membrane glycerophosphodiester phosphodiesterase, interacts with RGS16 (2000)

We have identified the protein MIR16 (for Membrane Interacting protein of RGS16) from a yeast two-hybrid screen by using RGS16 as bait. MIR16 shares strong homology with bacterial glycerophosphodiester phosphodiesterases. It interacts with RGS16 and, more weakly, with several other selected RGS proteins. Analysis of deletion mutants showed that the N-terminal region of the RGS domain in RGS16 is required for its interaction with MIR16. MIR16 is an integral membrane glycoprotein, because it remained associated with membrane fractions after alkaline treatment and because, in some cells, it is sensitive to digestion with endoglycosidase H. By immunofluorescence and immunoelectron microscopy, MIR16 was localized on the plasma membrane in liver and kidney and on intracellular membranes in rat pituitary and cultured pituitary cells. MIR16 represents the only integral membrane protein identified thus far to interact with an RGS domain and, to our knowledge, is the only mammalian glycerophosphodiester phosphodiesterase that has been cloned. The putative enzymatic activity of MIR16 and its interaction with RGS16 suggest that it may play important roles in lipid metabolism and in G protein signaling.
Plasma lipopolysaccharide (LPS)-binding protein. A key component in macrophage recognition of gram-negative LPS (1992)

LPS-binding protein (LBP) binds with high affinity (Kd approximately equal to 10(-9) M) to lipid A of LPS isolated from rough (R)- or smooth (S)-form Gram-negative bacteria as well as to lipid A partial structures such as precursor IVA. To define the role of LBP in regulating responses to LPS we have examined TNF release in rabbit peritoneal exudate macrophages (M phi) stimulated with LPS or with complete or partial lipid A preparations in the presence or absence of LBP. In the presence of LBP, M phi showed increased sensitivity to S- and R-form LPS as well as synthetic lipid A. Compared with LPS or lipid A, up to 1000-fold greater concentrations of partial lipid A structures were required to induce TNF production. However, consistent with our previous observations that these structures bind to LBP, TNF production was increased in the presence of LBP. In contrast, LBP did not enhance or inhibit TNF production produced by heat-killed Staphylococcus aureus, peptidoglycan isolated from S. aureus cell walls, or PMA. Potentiated M phi responsiveness to LPS was observed with as little as 1 ng LBP/ml. Heat-denatured LBP (which no longer binds LPS), BPI (an homologous LPS-binding protein isolated from neutrophils), or other serum proteins were without effect. LBP-treated M phi also showed a more rapid induction of cytokine mRNA (TNF and IL-1 beta), higher steady-state mRNA levels and increased TNF mRNA stability. These data provide additional evidence that LBP is part of a highly specific recognition system controlling M phi responses to LPS. The effects of LBP are lipid A dependent and importantly, extend to LPS preparations isolated from bacteria of R- and S-form phenotype.
Hepatitis C virus: The major causative agent of viral non-A, non-B hepatitis (1990)

A 'blind' recombinant immunoscreening approach, of general application to studies of infectious diseases, was used to clone and identify the genome of the previously uncharacterized non-A, non-B hepatitis (NANB) virus. This agent is a positive-stranded RNA virus that appears to be distantly related to the flaviviridae family. A recombinant viral antigen (C100-3) was used to develop a capture assay for circulating antibody. Data obtained using this assay indicate that this agent, termed the hepatitis C virus (HCV), is the major cause of post-transfusion, community-acquired and cryptogenic, NANB. Anti-C100-3 antibody appears to be directed towards dominant, non-structural viral epitopes. It is a non-neutralising antibody that develops generally late in infection and is a particularly good marker of chronic, persistent viraemia. Many asymptomatic but infectious blood donors can now be detected using this antibody assay. HCV is associated with the development of hepatocellular carcinoma and possibly, other liver diseases.
Template-Directed Assembly of Receptor Signaling Complexes (2003)

Transmembrane receptors in the signaling pathways of bacterial chemotaxis systems influence cell motility by forming noncovalent complexes with the cytoplasmic signaling proteins to regulate their activity. The requirements for receptor-mediated activation of CheA, the principal kinase of the Escherichia coli chemotaxis signaling pathway, were investigated using self-assembled clusters of a receptor fragment (CF) derived from the cytoplasmic domain of the aspartate receptor, Tar. Histidine-tagged Tar CF was assembled on the surface of sonicated unilamellar vesicles via a lipid containing the nickel-nitrilotriacetic acid moiety as a headgroup. In the presence of the adaptor protein CheW, CheA bound to and was activated approximately 180-fold by vesicle-bound CF. The extent of CheA activation was found to be independent of the level of covalent modification on the CF. Instead, the stability of the complex increased significantly as the level of covalent modification increased. Surface-assembled CF was also found to serve as a substrate for receptor methylation in a reaction catalyzed by the receptor methyltransferase, CheR. Since neither CheA activation nor CF methylation was observed in comparable samples in the absence of vesicles, it is concluded that surface templating generates the organization among CF subunits required for biochemical activity.
High‐Performance Perovskite–Graphene Hybrid Photodetector (2014)

A high-performance novel photodetector is demonstrated, which consists of graphene and CH3 NH3 PbI3 perovskite layers. The resulting hybrid photodetector exhibits a dramatically enhanced photo responsivity (180 A/W) and effective quantum efficiency (5× 10(4) %) over a broad bandwidth within the UV and visible ranges.
Stereoselective Synthesis of the Halaven C14–C26 Fragment from D‐Quinic Acid: Crystallization‐Induced Diastereoselective Transformation of an α‐Methyl Nitrile (2015)

Crystallization-induced diastereoselective transformation (CIDT) of an α-methyl nitrile completes an entirely non-chromatographic synthesis of the halichondrin B C14-C26 stereochemical array. The requisite α-methyl nitrile substrate is derived from D-quinic acid through a series of substrate-controlled stereoselective reactions via a number of crystalline intermediates that benefit from a rigid polycyclic template. Therefore, all four stereogenic centers in the Halaven C14-C26 fragment were derived from the single chiral source D-quinic acid.
In vivo Toxicity of a Synthetic Dodecapeptide from a Gliadin in Patients with Coeliac Disease (1991)

A single dose of a synthetic peptide of A gliadin (residues 206-217) sharing homology with the E1b protein of adenovirus 12 was instilled intraduodenally in two treated coeliac patients. Biopsy specimens were taken before and repeatedly up to 24 h after the instillation by means of a Quinton hydraulic multiple biopsy instrument and processed for histology, morphometry (intraepithelial lymphocyte counts, crypt-to-villus ratio), immunocytochemistry, electron microscopy, and disaccharidase assays. Two subjects with irritable bowel syndrome served as controls. In the coeliac group disaccharidase activities decreased at 24 h, and abnormalities were seen on light and electron microscopy and in morphometric measurements. The lamina propria became infiltrated with mononuclear cells after 2 h, and there was also a rise in IgA-containing cells in one patient. No such abnormalities were seen in the control group. The serum concentrations of C3, C4, and C1 esterase inhibitor remained unchanged. Thus, the dodecapeptide may be one epitope of gliadin mediating the pathogenesis of coeliac disease.
[Gene therapy and its applications]. (1998)

Gene therapy consists in the introduction of genes in cells of the human organism. It allows the treatment of not only monogenic diseases (those in which one gene is altered, such as rare enzymatic diseases), but also of diseases in which there is an acquired gene alteration such as AIDS and cancer, and diseases in which several genes and the environment interact, such as diabetes and coronary artery disease. In the few years of development of this therapy several clinical trials have been approved, that, along with experiment of this therapy several clinical trials have been approved, that, along with experimental research, are offering promising results. In this new field of modern medicine, specially in experiments related to genetic manipulation of germinal cells, ethical aspects have great importance.
Isolation of a novel human gene, APCDD1, as a direct target of the beta-Catenin/T-cell factor 4 complex with probable involvement in colorectal carcinogenesis. (2002)

To clarify the molecular mechanisms of human carcinogenesis associated with abnormal beta-catenin/T-cell factor (Tcf) signaling, we have been using cDNA microarrays to search for genes whose expression is significantly altered after introduction of wild-type APC into SW480 colon cancer cells. These experiments identified a novel human gene, termed APCDD1, that was down-regulated in the cancer cells by exogenous wild-type APC; its expression was also reduced in response to transduction of AXIN1. Moreover, we documented elevated expression of APCDD1 in 18 of 27 primary colon cancer tissues compared with corresponding noncancerous mucosae. A reporter gene assay using the 5'-flanking region of APCDD1 indicated that transfection of beta-catenin together with wild-type Tcf4 into HeLa cells increased the reporter activity through two putative Tcf/lymphoid enhancer factor-binding motifs upstream of the transcription start site, indicating that APCDD1 is one of the direct targets of this transcription complex. Exogenous APCDD1 promoted growth of colon cancer cells both in vitro and in vivo, whereas transfection with antisense S-oligodeoxynucleotides decreased cell/tumor growth. These data suggest that APCDD1 is directly regulated by the beta-catenin/Tcf complex and that its elevated expression is likely to contribute to colorectal tumorigenesis.
Five year safety and immunogenicity of GlaxoSmithKline's candidate malaria vaccine RTS,S/AS02 following administration to semi-immune adult men living in a malaria-endemic region of The Gambia (2009)

RTS,S is a pre-erythrocytic malaria vaccine candidate antigen based on the circumsporozoite surface protein of Plasmodium falciparum fused to HBsAg, incorporating a novel Adjuvant System (AS02). The first field efficacy of RTS,S/AS02 against infection was demonstrated in a trial initiated in The Gambia in 1998. This paper presents the five-year safety and immunogenicity follow up of the 306 men who were enrolled in the original trial. In the primary study men aged 18 to 45 years were randomized to receive either RTS,S/AS02 or rabies vaccine at 0, 1, 5 months followed by a booster dose at month 19. The subjects were observed for long term safety and immunogenicity continuously until month 58. Of the 153 subjects in each group at enrollment, 80 (52%) subjects in the RTS,S/AS02 group and 83 (54%) subjects in the rabies group returned for the final long-term follow-up visit at month 58. The main reason for non-attendance at month 58 was migration (76% of all drop-outs). Nine subjects in the RTS,S/AS02 group and seven in the rabies group experienced serious adverse events (SAEs) over the 58 month surveillance period, of which seven had a fatal outcome (five RTS,S/AS02 and two rabies group). None of the SAEs with fatal outcome were attributed to the study vaccine. Anti-CS antibody persistence compared to control was observed for five years, although titres had waned from post-booster levels; similar responses in anti-HBs antibody persistence were observed in initially HBsAg seronegative subjects. This study provides the first indication of the long-term safety and persistence of anti-CS and anti-HBs antibodies of the RTS,S vaccine candidate in combination with the novel AS02 Adjuvant System.
Structure and motion from line segments in multiple images (2003)

An approach for recovering the structure of a rigid scene composed of straight line segments and the pose of moving camera from multiple images under perspective projection is presented. Recovery is formulated as minimizing the total squared image distance between measured segments and the projection of the reconstructed infinite lines with respect to structural and motion parameters. An efficient algorithm for minimizing this nonlinear objective function is presented. The approach can be directly used for accurately locating correspondences in multieyed stereo, as well as for pose estimation from landmarks. Its effectiveness is demonstrated quantitatively through simulation and qualitatively with a real image sequence.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
DenseCap: Fully Convolutional Localization Networks for Dense Captioning (2015)

We introduce the dense captioning task, which requires a computer vision system to both localize and describe salient regions in images in natural language. The dense captioning task generalizes object detection when the descriptions consist of a single word, and Image Captioning when one predicted region covers the full image. To address the localization and description task jointly we propose a Fully Convolutional Localization Network (FCLN) architecture that processes an image with a single, efficient forward pass, requires no external regions proposals, and can be trained end-to-end with a single round of optimization. The architecture is composed of a Convolutional Network, a novel dense localization layer, and Recurrent Neural Network language model that generates the label sequences. We evaluate our network on the Visual Genome dataset, which comprises 94,000 images and 4,100,000 region-grounded captions. We observe both speed and accuracy improvements over baselines based on current state of the art approaches in both generation and retrieval settings.
HMM-based audio-visual speech recognition integrating geometric- and appearance-based visual features (2002)

A good front end for visual feature extraction is an important element of audio-visual speech recognition systems. We propose a new visual feature representation that combines both geometric- and pixel-based features. Using our previously developed contour-based lip-tracking algorithm, geometric features including the height and width of the lips are automatically extracted. Lip boundary tracking allows accurate determination of a region of interest from which we construct pixel-based features that are robust to variation in scale and translation. Motivated by computational considerations, we selected a subset of the pixels in the center of the inner mouth area that was found to capture sufficient details of the appearance of the teeth and tongue for assisting in the discrimination of spoken words. We show the advantage of the combination of these visual features for visual-only and audio-visual speech recognition of isolated digits.
Characterization of a mutant E-cadherin protein encoded by a mutant gene frequently seen in diffuse-type human gastric carcinoma (2000)

The cell-cell adhesion molecule E-cadherin plays an essential role in the maintenance and function of epithelial tissues. Altered expression of E-cadherin has been implicated in tumor invasion. Analysis of mutations of the human E-cadherin gene in gastric carcinoma of the diffuse type has revealed that deletion of exon 8 or 9 in its cDNA appears to be predominant. In this study, we carried out structural and functional analyses of a mutant form of E-cadherin in a cell line, HSC45-M2, established from a human signet ring-cell carcinoma. Although immunohistochemical analysis showed that the mutant cadherin was localized at cell-cell contact sites as usually seen with the wild type, these cells did not form compact colonies. HSC45-M2 cells expressed aberrant E-cadherin with an m.w. larger than that of the wild type. In these cells, we found deletion of the exon 9-intron 9 boundary including the splicing donor site in E-cadherin genomic DNA. RT-PCR indicated 2 transcripts, which appeared to be caused by the splicing defect. Northern blotting, however, showed that the transcript lacking exon 9 was predominantly detected in these cells. The electrophoretic mobilities on SDS-PAGE of the mutant E-cadherin protein in HSC45-M2 cells and the protein expressed from cDNA lacking exon 9 appeared identical. Analysis of the amino-terminal region of the mutant E-cadherin protein revealed that the cadherin was capable of becoming a mature form by removal of its amino-terminal peptide. However, the mutant E-cadherin was susceptible to trypsinization in the presence of Ca(2+), which is not the case for wild-type E-cadherin, suggesting that the mutant E-cadherin frequently found in diffuse-type gastric carcinoma may have lost its Ca(2+)-binding ability, leading to disruption of the tight cell-cell association.
Inhibition of endothelial cell movement by pericytes and smooth muscle cells: activation of a latent transforming growth factor-beta 1-like molecule by plasmin during co-culture. (1989)

When a confluent monolayer of bovine aortic endothelial (BAE) cells is wounded with a razor blade, endothelial cells (ECs) spontaneously move into the denuded area. If bovine pericytes or smooth muscle cells (SMCs) are plated into the denuded area at low density, they block the movement of the ECs. This effect is dependent upon the number of cells plated into the wound area and contact between ECs and the plated cells. Antibodies to transforming growth factor-beta 1 (TGF-beta 1) abrogate the inhibition of BAE cell movement by pericytes or SMCs. TGF-beta 1, if added to wounded BAE cell monolayers, also inhibits cell movement. When cultured separately, BAE cells, pericytes, and SMCs each produce an inactive TGF-beta 1-like molecule which is activated in BAE cell-pericyte or BAE cell-SMC co-cultures. The activation appears to be mediated by plasmin as the inhibitory effect on cell movement in co-cultures of BAE cells and pericytes is blocked by the inclusion of inhibitors of plasmin in the culture medium.