gebhart/patrepeval huggingface dataset:
Cardiac-Specific Ablation of the Na + -Ca 2+ Exchanger Confers Protection Against Ischemia/Reperfusion Injury (2005)

During ischemia and reperfusion, with an increase in intracellular Na+ and a depolarized membrane potential, Ca2+ may enter the myocyte in exchange for intracellular Na+ via reverse-mode Na+-Ca2+ exchange (NCX). To test the role of Ca2+ entry via NCX during ischemia and reperfusion, we studied mice with cardiac-specific ablation of NCX (NCX-KO) and demonstrated that reverse-mode Ca2+ influx is absent in the NCX-KO myocytes. Langendorff perfused hearts were subjected to 20 minutes of global ischemia followed by 2 hours of reperfusion, during which time we monitored high-energy phosphates using 31P-NMR and left-ventricular developed pressure. In another group of hearts, we monitored intracellular Na+ using 23Na-NMR. Consistent with Ca2+ entry via NCX during ischemia, we found that hearts lacking NCX exhibited less of a decline in ATP during ischemia, delayed ischemic contracture, and reduced maximum contracture. Furthermore, on reperfusion following ischemia, NCX-KO hearts had much less necrosis, better recovery of left-ventricular developed pressure, improved phosphocreatine recovery, and reduced Na+ overload. The improved recovery of function following ischemia in NCX-KO hearts was not attributable to the reduced preischemic contractility in NCX-KO hearts, because when the preischemic workload was matched by treatment with isoproterenol, NCX-KO hearts still exhibited improved postischemic function compared with wild-type hearts. Thus, NCX-KO hearts were significantly protected against ischemia-reperfusion injury, suggesting that Ca2+ entry via reverse-mode NCX is a major cause of ischemia/reperfusion injury.
Compact DC-60-GHz HJFET MMIC switches using ohmic electrode-sharing technology (1998)

Compact DC-60-GHz heterojunction field-effect transistor (HJFET) monolithic-microwave integrated-circuit (MMIC) switches have been demonstrated for millimeter-wave communications and radar systems. To reduce the MMIC chip size, a novel ohmic electrode-sharing technology (OEST) has been developed for MMIC switches with series-shunt FET configuration. Four FET's of the series-shunt single-pole double-throw (SPDT) MMIC switch were integrated into an area of approximately 0.018 mm/sup 2/. The developed MMIC switches have a high power-handling capability with low insertion loss (IL) and high isolation (Iso) at millimeter-wave frequencies. From DC to 60 GHz, the single-pole single-throw (SPST) MMIC switch achieved the IL and Iso of better than 1.64 and 20.6 dB, respectively. At 40 GHz, the IL increases by 1 dB at the input power of 21 dBm. A novel large-signal FET model for the switch circuit is presented. The simulated power-transfer performance shows the excellent agreement with the measured one. The developed MMIC switches will contribute to the low-cost and high-performance millimeter-wave communications and radar systems.
Comparative Metagenomics Revealed Commonly Enriched Gene Sets in Human Gut Microbiomes (2007)

Numerous microbes inhabit the human intestine, many of which are uncharacterized or uncultivable. They form a complex microbial community that deeply affects human physiology. To identify the genomic features common to all human gut microbiomes as well as those variable among them, we performed a large-scale comparative metagenomic analysis of fecal samples from 13 healthy individuals of various ages, including unweaned infants. We found that, while the gut microbiota from unweaned infants were simple and showed a high inter-individual variation in taxonomic and gene composition, those from adults and weaned children were more complex but showed a high functional uniformity regardless of age or sex. In searching for the genes over-represented in gut microbiomes, we identified 237 gene families commonly enriched in adult-type and 136 families in infant-type microbiomes, with a small overlap. An analysis of their predicted functions revealed various strategies employed by each type of microbiota to adapt to its intestinal environment, suggesting that these gene sets encode the core functions of adult and infant-type gut microbiota. By analysing the orphan genes, 647 new gene families were identified to be exclusively present in human intestinal microbiomes. In addition, we discovered a conjugative transposon family explosively amplified in human gut microbiomes, which strongly suggests that the intestine is a 'hot spot' for horizontal gene transfer between microbes.
IL-4 increases human endothelial cell adhesiveness for T cells but not for neutrophils. (1990)

The adhesion of leukocytes to vascular endothelium is the first step in their passage from the blood into inflammatory tissues. By modulating endothelial cell (EC) adhesiveness for leukocytes, cytokines may regulate leukocyte accumulation and hence the nature and progression of inflammatory responses. We have found that the T cell cytokine IL-4 increases the adhesion of T cells, but not neutrophils, to human umbilical vein EC monolayers. The increase in T cell adhesion induced by IL-4 was dose dependent (ED50 = 5 U/ml) and peaked around 33 U/ml. No increase in adhesion of neutrophils was observed at concentrations of IL-4 up to 1000 U/ml. The kinetic of the increase in T cell adhesion exhibited a steady rise peaking between 18 and 24 h before returning to basal levels by 72 h. The IL-4 specificity of the effect was confirmed by the ability of neutralizing anti-IL-4, but not anti-TNF, antibodies to abolish the effect. The increase in T cell-EC adhesion was due to an effect of IL-4 on EC inasmuch as preincubation of the T cells with IL-4 did not increase T cell binding. Furthermore, preincubation of A549 epithelial cell line monolayers with IL-4 caused no increase in T cell binding whereas A549 cells and EC showed a similarly enhanced adhesiveness for T cells after preincubation with IL-1, TNF, or IFN-gamma. EC treated with IL-4 retained their increased adhesiveness for T cells after light fixation, suggesting that IL-4 up-regulates binding by increasing the expression or accessibility of EC surface receptors for lymphocytes. Although antibodies to intercellular adhesion molecule-1 (CD54) and the beta-chain (CD18) of lymphocyte function-associated Ag-1 (CD11a/CD18) partially inhibited T cell adhesion to unstimulated EC, they did not affect the increase in adhesion due to IL-4 stimulation, indicating that the increased binding resulted from the generation of an alternative binding receptor(s) on the EC membrane. These findings suggest that IL-4 may play a role in the selective recruitment of T cells into sites of immune-mediated chronic inflammation.
Challenges in Enzyme Mechanism and Energetics (2003)

Since the discovery of enzymes as biological catalysts, study of their enormous catalytic power and exquisite specificity has been central to biochemistry. Nevertheless, there is no universally accepted comprehensive description. Rather, numerous proposals have been presented over the past half century. The difficulty in developing a comprehensive description for the catalytic power of enzymes derives from the highly cooperative nature of their energetics, which renders impossible a simple division of mechanistic features and an absolute partitioning of catalytic contributions into independent and energetically additive components. Site-directed mutagenesis has emerged as an enormously powerful approach to probe enzymatic catalysis, illuminating many basic features of enzyme function and behavior. The emphasis of site-directed mutagenesis on the role of individual residues has also, inadvertently, limited experimental and conceptual attention to the fundamentally cooperative nature of enzyme function and energetics. The first part of this review highlights the structural and functional interconnectivity central to enzymatic catalysis. In the second part we ask: What are the features of enzymes that distinguish them from simple chemical catalysts? The answers are presented in conceptual models that, while simplified, help illustrate the vast amount known about how enzymes achieve catalysis. In the last section, we highlight the molecular and energetic questions that remain for future investigation and describe experimental approaches that will be necessary to answer these questions. The promise of advancing and integrating cutting edge conceptual, experimental, and computational tools brings mechanistic enzymology to a new era, one poised for novel fundamental insights into biological catalysis.
Induction and apoptotic regression of lung adenocarcinomas by regulation of a K-Ras transgene in the presence and absence of tumor suppressor genes (2001)

To investigate the role of an activated K-Ras gene in the initiation and maintenance of lung adenocarcinomas, we developed transgenic mice that express murine K-Ras4b(G12D) under the control of doxycycline in type II pneumocytes. Focal proliferative lesions of alveolar type II pneumocytes were observed as early as seven days after induction with doxycycline; after two months of induction, the lungs contained adenomas and adenocarcinomas, with focal invasion of the pleura at later stages. Removal of doxycycline caused a rapid fall in levels of mutant K-Ras RNA and concomitant apoptotic regression of both the early proliferative lesions and the tumors. Tumor burden was dramatically decreased by three days after withdrawal, and tumors were undetectable after one month. When similar experiments were performed with animals deficient in either the p53 gene or the Ink4A/Arf locus, tumors arose more quickly (within one month of exposure to doxycycline) and displayed more obvious histological features of malignancy; nevertheless, these tumors also regressed rapidly when the inducer was removed, implying that continued production of mutant K-Ras is necessary to maintain the viability of tumor cells in the absence as well as the presence of tumor suppressor genes. We also show that the appearance and regression of these pulmonary tumors can be readily monitored in anesthetized transgenic animals by magnetic resonance imaging.
Situation analysis model of economic growth in Quang Nam (2015)

Model of economic growth in Quang Nam in the period 1997-2013 have been successful in terms of size , growth and raise living standards . However , this model only operates mainly in width , thus shifting the growth model to depth is necessary . The paper evaluates the current status of economic growth model in Quang Nam 1997-2013 period , thereby making policy implications and solutions oriented mainly to transform the economic growth model in Quang Nam next time.
Thermodynamic explanation to the enhanced diffusion of base dopant in AlGaAs-GaAs n p n bipolar transistors (1990)

A model is presented which accounts for the anomalous diffusion of the p-type base dopant during the growth of AlGaAs-GaAs npn bipolar transistors. The model is based upon Fermi level pinning at the crystal surface during epitaxial growth which leads to an increased concentration of column III interstitial defects in heavily n-type AlGaAs or GaAs. The excess column III interstitials generated in the n-type crystal flow into the p+ base region causing a transfer of the p-type impurity atoms from column III lattice sites to interstitial positions through a ‘‘kick-out’’ mechanism. Once in interstitial positions the impurity atoms are known to diffuse rapidly. The model is consistent with previously proposed mechanisms for both impurity diffusion and column III self-diffusion.
Thrombospondin promotes platelet aggregation (1988)

Abstract Thrombospondin (TSP), isolated from human platelets, promotes aggregation of both nonstimulated platelets and platelets stimulated with thrombin or ADP. The TSP-promoted aggregation is specific since a monoclonal antibody against TSP inhibits the effect of exogenously added TSP and inhibits thrombin-induced platelet aggregation in the absence of added TSP. Several lines of evidence suggest that TSP mediates its effect on aggregation of nonstimulated and stimulated platelets through different platelet-surface receptor systems. The TSP- promoted aggregation of nonstimulated platelets was inhibited by a monoclonal antibody to platelet glycoprotein IV (GPIV), but not by a monoclonal antibody to the fibrinogen receptor, GPIIb-IIIa. In contrast, the antibody to GPIIb-IIIa totally inhibited the TSP- potentiated aggregation of thrombin-stimulated platelets, whereas the antibody to GPIV has no effect. Thus, these studies suggest that TSP promotes platelet aggregation by at least two mechanisms--one dependent on and one independent of the platelet fibrinogen receptor system.
PD-1 and Tim-3 Regulate the Expansion of Tumor Antigen–Specific CD8+ T Cells Induced by Melanoma Vaccines (2013)

Although melanoma vaccines stimulate tumor antigen-specific CD8(+) T cells, objective clinical responses are rarely observed. To investigate this discrepancy, we evaluated the character of vaccine-induced CD8(+) T cells with regard to the inhibitory T-cell coreceptors PD-1 and Tim-3 in patients with metastatic melanoma who were administered tumor vaccines. The vaccines included incomplete Freund's adjuvant, CpG oligodeoxynucleotide (CpG), and the HLA-A2-restricted analog peptide NY-ESO-1 157-165V, either by itself or in combination with the pan-DR epitope NY-ESO-1 119-143. Both vaccines stimulated rapid tumor antigen-specific CD8(+) T-cell responses detected ex vivo, however, tumor antigen-specific CD8(+) T cells produced more IFN-γ and exhibited higher lytic function upon immunization with MHC class I and class II epitopes. Notably, the vast majority of vaccine-induced CD8(+) T cells upregulated PD-1 and a minority also upregulated Tim-3. Levels of PD-1 and Tim-3 expression by vaccine-induced CD8(+) T cells at the time of vaccine administration correlated inversely with their expansion in vivo. Dual blockade of PD-1 and Tim-3 enhanced the expansion and cytokine production of vaccine-induced CD8(+) T cells in vitro. Collectively, our findings support the use of PD-1 and Tim-3 blockades with cancer vaccines to stimulate potent antitumor T-cell responses and increase the likelihood of clinical responses in patients with advanced melanoma.
Spatiotemporal segmentation and tracking of objects in image sequences (1999)

In this paper a procedure is described for the segmentation of image sequences. For this purpose, we propose the novel procedure of K-Means with connectivity constraint algorithm as a general segmentation algorithm combining several types of information including intensity, motion and compactness. The algorithm is extended so as to separate and track objects appearing in consequent frames of an image sequence. In this algorithm, the use of spatiotemporal regions is introduced since a number of frames is analyzed simultaneously and as a result the same region is present in consequent frames. Experimental results demonstrate the usage and performance of the algorithm.
Longitudinal Modeling of Age-Related Memory Decline and theAPOEε4 Effect (2009)

Age-related memory decline in APOE epsilon4 carriers diverges from that of noncarriers before the age of 60 years, despite ongoing normal clinical status.
5-Methylcytosine DNA glycosylase activity is also present in the human MBD4 (G/T mismatch glycosylase) and in a related avian sequence (2000)

A 1468 bp cDNA coding for the chicken homolog of the human MBD4 G/T mismatch DNA glycosylase was isolated and sequenced. The derived amino acid sequence (416 amino acids) shows 46% identity with the human MBD4 and the conserved catalytic region at the C-terminal end (170 amino acids) has 90% identity. The non-conserved region of the avian protein has no consensus sequence for the methylated DNA binding domain. The recombinant proteins from human and chicken have G/T mismatch as well as 5-methylcytosine (5-MeC) DNA glycosylase activities. When tested by gel shift assays, human recombinant protein with or without the methylated DNA binding domain binds equally well to symmetrically, hemimethylated DNA and non-methylated DNA. However, the enzyme has only 5-MeC DNA glycosylase activity with the hemimethylated DNA. Footprinting of human MBD4 and of an N-terminal deletion mutant with partially depurinated and depyrimidinated substrate reveal a selective binding of the proteins to the modified substrate around the CpG. As for 5-MeC DNA glycosylase purified from chicken embryos, MBD4 does not use oligonucleotides containing mCpA, mCpT or mCpC as substrates. An mCpG within an A+T-rich oligonucleotide is a much better substrate than an A+T-poor sequence. The K:(m) of human MBD4 for hemimethylated DNA is approximately 10(-7) M with a V:(max) of approximately 10(-11) mol/h/microgram protein. Deletion mutations show that G/T mismatch and 5-MeC DNA glycosylase are located in the C-terminal conserved region. In sharp contrast to the 5-MeC DNA glycosylase isolated from the chicken embryo DNA demethylation complex, the two enzymatic activities of MBD4 are strongly inhibited by RNA. In situ hybridization with antisense RNA indicate that MBD4 is only located in dividing cells of differentiating embryonic tissues.
Pattern Recognition with Neural Networks in C++ (2021)

From the Publisher:
The addition of artificial neural network computing to traditionalpattern recognition has given rise to a new, different, and more powerful methodology that is presented in this interesting book. This is a practical guide to the application of artificial neural networks.
Geared toward the practitioner, Pattern Recognition with Neural Networks in C++ covers pattern classification and neural network approaches within the same framework. Through the book's presentation of underlying theory and numerous practical examples, readers gain an understanding that will allow them to make judicious design choices rendering neural application predictable and effective.
The book provides an intuitive explanation of each method for each network paradigm. This discussion is supported by a rigorous mathematical approach where necessary.
C++ has emerged as a rich and descriptive means by which concepts, models, or algorithms can be precisely described. For many of the neural network models discussed, C++ programs are presented for the actual implementation. Pictorial diagrams and in-depth discussions explain each topic. Necessary derivative steps for the mathematical models are included so that readers can incorporate new ideas into their programs as the field advances with new developments. For each approach, the authors clearly state the known theoretical results, the known tendencies of the approach, and their recommendations for getting the best results from the method.
The material covered in the book is accessible to working engineers with little or no explicit background in neural networks. However, the material is presented in sufficient depth so that those with prior knowledge will find this book beneficial. Pattern Recognition with Neural Networks in C++ is also suitable for courses in neural networks at an advanced undergraduate or graduate level. This book is valuable for academic as well as practical research.
Cloning and in situ localization of a brain-derived porin that constitutes a large-conductance anion channel in astrocytic plasma membranes. (1994)

We have cloned a protein from bovine brain, brain-derived voltage-dependent anion channel 1 (BR1-VDAC), that is identical to a recently sequenced plasmalemmal-bound porin from human lymphocytes. mRNA hybridization indicates that BR1-VDAC is widely distributed throughout nervous and nonnervous tissues. In situ localization substantiated that the BR1-VDAC is associated with the plasmalemma of astrocytes. A monoclonal antibody that recognizes the N terminus of the BR1-VDAC protein completely blocks an astrocytic high-conductance anion channel that has electrophysiological similarities with the mitochondrial VDAC. Since the high-conductance anion channel in astrocytes has been shown to respond to hypoosmotic solutions, its molecular identification provides the basis for a better understanding of volume regulation in brain tissue.
Peptidomimetic Probes and Molecular Modeling Suggest That Alzheimer's γ-Secretase Is an Intramembrane-Cleaving Aspartyl Protease (1999)

The amyloid beta-protein (Abeta), implicated in the pathogenesis of Alzheimer's disease (AD), is a proteolytic metabolite generated by the sequential action of beta- and gamma-secretases on the amyloid precursor protein (APP). The two main forms of Abeta are 40- and 42-amino acid C-terminal variants, Abeta40 and Abeta42. We recently described a difluoro ketone peptidomimetic (1) that blocks Abeta production at the gamma-secretase level [Wolfe, M. S., et al. (1998) J. Med. Chem. 41, 6-9]. Although designed to inhibit Abeta42 production, 1 also effectively blocked Abeta40 formation. Various amino acid changes in 1 still resulted in inhibition of Abeta40 and Abeta42 production, suggesting relatively loose sequence specificity by gamma-secretase. The alcohol counterparts of selected difluoro ketones also lowered Abeta levels, indicating that the ketone carbonyl is not essential for activity and suggesting that these compounds inhibit an aspartyl protease. Selected compounds inhibited the aspartyl protease cathepsin D but not the cysteine protease calpain, corroborating previous suggestions that gamma-secretase is an aspartyl protease with some properties similar to those of cathepsin D. Also, since the gamma-secretase cleavage sites on APP are within the transmembrane region, we consider the hypothesis that this region binds to gamma-secretase as an alpha-helix and discuss the implications of this model for the mechanism of certain forms of hereditary AD.
Heterogeneity and Lobularity of Pancreatic Pathology in Type 1 Diabetes during the Prediabetic Phase (2015)

Type 1 diabetes (T1D) is an autoimmune disease in which insulin-producing beta cells are destroyed in the islets of Langerhans. One of its main pathological manifestations is the hyper-expression of Major Histocompatibility Complex I (MHC-I) by beta cells, which was first described over 3 decades ago yet its cause remains unknown. It might not only be a sign of beta cell dysfunction but could also render the cells susceptible to autoimmune destruction; for example, by islet-infiltrating CD8 T cells. In this report, we studied pancreas tissue from a 22-year-old non-diabetic male cadaveric organ donor who had been at high risk of developing T1D, in which autoantibodies against GAD and IA-2 were detected. Pancreas sections were analyzed for signs of inflammation. Multiple insulin-containing islets were identified, which hyper-expressed MHC-I. However, islet density and MHC-I expression exhibited a highly lobular and heterogeneous pattern even within the same section. In addition, many islets with high expression of MHC-I presented higher levels of CD8 T cell infiltration than normal islets. These results demonstrate the heterogeneity of human pathology that occurs early during the pre-diabetic, autoantibody positive phase, and should contribute to the understanding of human T1D.