gebhart/patrepeval huggingface dataset:
In Vivo Liver Regeneration Potential of Human Induced Pluripotent Stem Cells from Diverse Origins (2011)

Human induced pluripotent stem cells (iPSCs) are a potential source of hepatocytes for liver transplantation to treat end-stage liver disease. In vitro differentiation of human iPSCs into hepatic cells has been achieved using a multistage differentiation protocol, but whether these cells are functional and capable of engrafting and regenerating diseased liver tissue is not clear. We show that human iPSC-derived hepatic cells at various differentiation stages can engraft the liver in a mouse transplantation model. Using the same differentiation and transplantation protocols, we also assessed the ability of human iPSCs derived from each of the three developmental germ layer tissues (that is, ectoderm, mesoderm, and endoderm) to regenerate mouse liver. These iPSC lines, with similar but distinct global DNA methylation patterns, differentiated into multistage hepatic cells with an efficiency similar to that of human embryonic stem cells. Human hepatic cells at various differentiation stages derived from iPSC lines of different origins successfully repopulated the liver tissue of mice with liver cirrhosis. They also secreted human-specific liver proteins into mouse blood at concentrations comparable to that of proteins secreted by human primary hepatocytes. Our results demonstrate the engraftment and liver regenerative capabilities of human iPSC-derived multistage hepatic cells in vivo and suggest that human iPSCs of distinct origins and regardless of their parental epigenetic memory can efficiently differentiate along the hepatic lineage.
Clostridial Neurotoxins and Substrate Proteolysis in Intact Neurons (1996)

Clostridial neurotoxins are zinc endopeptidases that block neurotransmission and have been shown to cleave, in vitro, specific proteins involved in synaptic vesicle docking and/or fusion. We have used immunohistochemistry and immunoblotting to demonstrate alterations in toxin substrates in intact neurons under conditions of toxin-induced blockade of neurotransmitter release. Vesicle-associated membrane protein, which colocalizes with synaptophysin, is not detectable in tetanus toxin-blocked cultures. Syntaxin, also concentrated in synaptic sites, is cleaved by botulinum neurotoxin C. Similarly, the carboxyl terminus of the synaptosomal-associated protein of 25 kDa (SNAP-25) is not detectable in botulinum neurotoxin A-treated cultures. Unexpectedly, tetanus toxin exposure causes an increase in SNAP-25 immunofluorescence, reflecting increased accessibility of antibodies to antigenic sites rather than increased expression of the protein. Furthermore, botulinum neurotoxin C causes a marked loss of the carboxyl terminus of SNAP-25 when the toxin is added to living cultures, whereas it has no action on SNAP-25 in vitro preparations. This study is the first to demonstrate in functioning neurons that the physiologic response to these toxins is correlated with the proteolysis of their respective substrates. Furthermore, the data demonstrate that botulinum neurotoxin C, in addition to cleaving syntaxin, exerts a secondary effect on SNAP-25.
Support for Radiolabeling of a Glycine Recognition Domain on the N‐Methyl‐d‐Aspartate Receptor Ionophore Complex by 5,7‐[3H]Dichlorokynurenate in Rat Brain (1993)

Pretreatment with Triton X-100 more than doubled the binding of radiolabeled 5,7-dichlorokynurenic acid (DCKA), a proposed antagonist at a glycine (Gly) recognition domain on the N-methyl-D-aspartate (NMDA) receptor ionophore complex, in rat brain synaptic membranes. The binding exhibited an inverse temperature dependency, reversibility, and saturability, the binding sites consisting of a single component with a high affinity (27.5 nM) and a relatively low density (2.87 pmol/mg of protein). The binding of both [3H]DCKA and [3H]Gly was similarly displaced by numerous putative agonists and antagonists at the Gly domain in a concentration-dependent manner at a concentration range of 100 nM to 0.1 mM. Among the 24 putative ligands tested, DCKA was the second most potent displacer of the binding of both radioligands with no intrinsic affinity for the binding of [3H]kainic acid and alpha-amino-3-hydroxy-5- [3H]methylisoxazole-4-propionic acid (AMPA) to the non-NMDA receptors. In contrast, the other proposed potent Gly antagonist, 5,7-dinitroquinoxaline-2,3-dione, was active in displacing the binding of [3H]glutamic ([3H]Glu) and D,L-(E)-2-amino-4-[3H]propyl-5-phosphono-3-pentenoic acids to the NMDA recognition domain with a relatively high affinity for the non-NMDA receptors. In addition, the proposed antagonist at the AMPA-sensitive receptor, 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline, not only displaced weakly the binding of both [3H]-Gly and [3H]DCKA, but also inhibited the binding of (+)-5-[3H]methyl-10,11- dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine ([3H]MK-801) to an ion channel associated with the NMDA-sensitive receptor in the presence of added Glu alone in a manner sensitive to antagonism by further added Gly. Clear correlations were seen between potencies of the displacers to displace [3H]DCKA binding and [3H]Gly binding, in addition to between the potencies to displace [3H]-DCKA or [3H]Gly binding and to potentiate or inhibit [3H]MK-801 binding. All quinoxalines tested were invariably more potent displacers of [3H]DCKA binding than [3H]Gly binding, whereas kynurenines were similarly effective in displacing the binding of both [3H]Gly and [3H]DCKA. These results undoubtedly give support to the proposal that [3H]DCKA is one useful radioligand available in terms of its high selectivity and affinity for the Gly domain in the brain. Possible multiplicity of the Gly domain is suggested by the differential pharmacological profiles between the binding of [3H]Gly and [3H]DCKA.
Expression of Globo‐series Gangliosides in Human Renal Cell Carcinoma (1997)

Gangliosides have been shown to be involved in development, differentiation, oncogenesis, and cancer progression. We investigated immunohistochemical expression of globo-series gangliosides in human renal cell carcinoma (RCC) and whether their expression is related to the clinical course. The expression of globo-series gangliosides was evaluated in fresh-frozen sections of 55 primary renal tumors and 8 metastatic deposits using monoclonal antibodies RM1 and RM2, which define monosialosyl and disialosyl galactosylgloboside, respectively. The immunoreactivity of primary tumors to RM1 and/or RM2 was correlated with the clinicopathological data. Cumulative incidence of metastasis detected at initial diagnosis and during the follow-up period was significantly higher in the cases whose primary tumors were RM1/RM2-positive (RM1 and/or RM2-positive) than in the RM1/ RM2-negative (neither RM1 nor RM2-positive) cases (P < 0.05). During the follow-up period, metastasis developed in none of the RM1/RM2-negative cases which had not shown metastasis at initial diagnosis. High nuclear grade was observed only in the RM1/RM2-positive cases. The RM1/RM2-positive rate of the metastatic deposits was higher than that of the primary tumors. Furthermore, a metastatic deposit obtained from one of the cases whose primary tumors were equivocal for RM1/ RM2 was extensively stained by RM1 and RM2. These results indicate that globo-series gangliosides may be one of the biochemical indicators related to the metastatic potential of human RCC.
A novel DNA-binding motif in MarA: The first structure for an AraC family transcriptional activator (1998)

A crystal structure for a member of the AraC prokaryotic transcriptional activator family, MarA, in complex with its cognate DNA-binding site is described. MarA consists of two similar subdomains, each containing a helix-turn-helix DNA-binding motif. The two recognition helices of the motifs are inserted into adjacent major groove segments on the same face of the DNA but are separated by only 27 A thereby bending the DNA by approximately 35 degrees. Extensive interactions between the recognition helices and the DNA major groove provide the sequence specificity.
Protein Phosphatase Type 1 Regulates Ion Homeostasis in Saccharomyces cerevisiae (2002)

Protein phosphatase type 1 (PP1) is encoded by the essential gene GLC7 in Saccharomyces cerevisiae. glc7-109 (K259A, R260A) has a dominant, hyperglycogen defect and a recessive, ion and drug sensitivity. Surprisingly, the hyperglycogen phenotype is partially retained in null mutants of GAC1, GIP2, and PIG1, which encode potential glycogen-targeting subunits of Glc7. The R260A substitution in GLC7 is responsible for the dominant and recessive traits of glc7-109. Another mutation at this residue, glc7-R260P, confers only salt sensitivity, indicating that the glycogen and salt traits of glc7-109 are due to defects in distinct physiological pathways. The glc7-109 mutant is sensitive to cations, aminoglycosides, and alkaline pH and exhibits increased rates of l-leucine and 3,3'-dihexyloxacarbocyanine iodide uptake, but it is resistant to molar concentrations of sorbitol or KCl, indicating that it has normal osmoregulation. KCl suppresses the ion and drug sensitivities of the glc7-109 mutant. The CsCl sensitivity of this mutant is suppressed by recessive mutations in PMA1, which encodes the essential plasma membrane H(+)ATPase. Together, these results indicate that Glc7 regulates ion homeostasis by controlling ion transport and/or plasma membrane potential, a new role for Glc7 in budding yeast.
Interleukin 2 activated tumor inhibition in vivo depends on the systemic involvement of host immunoreactivity. (1987)

Daily local administration at the tumor challenge site of 10 injections of 10 U of recombinant interleukin 2 (IL 2) obtained from different factories induces a consistent, though limited inhibition of the growth of CE-2, a poorly immunogenic methylcholanthrene-induced tumor. By contrast, almost complete tumor inhibition is observed when these injections are performed in mice challenged with tumor cells admixed at 1:5 cell ration with nylon wool column purified lymphocytes obtained from tumor-bearing animals. The host immune system plays a fundamental role in this lymphokine-activated tumor inhibition (LATI), which is derived from the local combination of IL 2 and nonreactive lymphocytes. When the host is sublethally irradiated, or the reactivity of L3T4 and Asialo GM1 lymphocytes is suppressed by in vivo antibody treatment, in fact, LATI no longer takes place. Daily injections of antibody to murine interferon-gamma or cyclosporin A have the same effect, indicating that lymphokine release plays an important role in the recruitment of host reactivity. The morphological data show that when LATI is taking place the tumor challenge area becomes infiltrated by mononuclear cells and granulocytes (mostly eosinophils), which establish close contacts with each other and with tumor cells as determined at ultrastructural analysis. Tumor draining lymph nodes display marked expansion of cortical and paracortical areas. Lymphocyte proliferation, interferon-gamma release and cytotoxicity against CE-2 and YAC-1 target cells are greatly enhanced during LATI. Contralateral lymph nodes and the spleen also show a slight increment of these functions. In mice challenged with CE-2 tumor cells only and receiving daily IL 2 injections, these reaction functions (with the exception of interferon-gamma secretion) are also enhanced, though to a lesser extent than during LATI and only in tumor-draining lymph nodes. Last, the growth of a second contralateral tumor challenge is significantly impaired during or after LATI, showing that a persistent and effective systemic reactivity can be quickly induced in this way.
Formin mDia1 Mediates Vascular Remodeling via Integration of Oxidative and Signal Transduction Pathways (2012)

We conclude that mDia1 integrates oxidative and signal transduction pathways triggered, at least in part, by receptor for advanced glycation endproducts ligands, thereby regulating pathological neointimal expansion.
Novel current‐conducting composite substrates for exposing osteoblasts to alternating current stimulation (2001)

The present study demonstrates that novel nanocomposites consisting of blends of polylactic acid and carbon nanotubes effectively can be used to expose cells to electrical stimulation. When osteoblasts cultured on the surfaces of these nanocomposites were exposed to electric stimulation (10 microA at 10 Hz) for 6 h/day for various periods of time, there was a 46% increase in cell proliferation after 2 days, a 307% increase in the concentration of extracellular calcium after 21 consecutive days, and upregulation of mRNA expression for collagen type-I after both 1 and 21 consecutive days. These results provide evidence that electrical stimulation delivered through novel, current-conducting polymer/nanophase composites promotes osteoblast functions that are responsible for the chemical composition of the organic and inorganic phases of bone. Furthermore, this evidence elucidates aspects of the cellular/molecular-level mechanisms involved in new bone formation under electrical stimulation.
Multi modal multi-semantic image retrieval (2010)

viii ACKNOLWEDGEMENTS x ABBREVIATIONS xi CHAPTER 1 INTRODUCTION 1 1.1 Motivation 2 1.1.1 Representing Visual Content and Classifying Images 3 1.1.2 Ambiguity of Natural Language in Text Captions 4 1.1.3 Use of Hybrid Visual and Textual Metadata Models 5 1.2 Research Objectives 6 1.3 Structure of this Thesis 8 CHAPTER 2 FUNDAMENTALS 10 2.1 Main Processes for IMR 10 2.2 Content-Based Image Retrieval (CBIR) 13 2.2.1 Global Features 14 2.2.2 Local Features 15 2.3 Semantic-Based Image Retrieval (SBIR) 16 2.3.1 Knowledge (Ontology-based) Representation Techniques 18 2.3.2 Advantages of Using Ontologies for IR 21 2.4 MPEG-7 and Ontology-based KB 21 2.5 Summary 25 CHAPTER 3 SURVEY AND ANALYSIS OF THE STATE-OF-THE-ART FRAMEWORKS 26 3.1 Problem Analysis of the Image Retrieval Systems 26 3.2 Formal Requirements of Image Retrieval Systems 28 3.3 Survey of State of the Art Frameworks 29 3.3.1 Ontology-Based KB Frameworks for IMR 29 3.3.2 Visual Features-Based Frameworks for Visual Content Representation 34 3.4 Discussion 39 3.5 Summary 42
Asymmetric Fabry-Perot device arrays with low insertion loss and high uniformity (1992)

The authors report on arrays of normally on asymmetric Fabry-Perot modulator (AFPM) devices which exhibit a high degree of uniformity between devices, with a thickness variation across an array of 0.07%. The devices in one array have a mean insertion loss of 1.8 dB and have off reflectivities of less than 3%, giving a mean contrast ratio of 22:1. These characteristics are measured at a single operating wavelength of 857 nm. The spatial light modulators show promise for the use of AFPM devices in optical processing.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Identification of a conformationally distinct form of plasminogen activator inhibitor-1, acting as a noninhibitory substrate for tissue-type plasminogen activator. (1992)

Plasminogen activator inhibitor-1 (PAI-1), the primary physiological inhibitor of tissue-type plasminogen activator (t-PA) in plasma, is a serine proteinase inhibitor (serpin) that forms a 1:1 stoichiometric complex with its target proteinase leading to the formation of a stable inactive complex. The active, inhibitory form of PAI-1 spontaneously converts to a latent form that can be reactivated by protein denaturants. In the present study we have isolated another molecular form of intact PAI-1 that, in contrast with active PAI-1, does not form stable complexes with t-PA but is cleaved at the P1-P1' bond (Arg346-Met347). Other serine proteinases, e.g. urokinase-type plasminogen activator and thrombin, also cleaved this "substrate" form of PAI-1. Fluorescence spectroscopy revealed conformational differences between the latent, active, and substrate forms of PAI-1. This observation confirms our hypothesis that the three functionally different forms of PAI-1 are the consequence of conformational transitions. Thus PAI-1 may occur in three interconvertible conformations: latent, inhibitor, and substrate PAI-1. The identification of two distinct conformations of PAI-1 which interact with their target protease either as an inhibitor or as a substrate is a previously unrecognized phenomenon among the serpins. Conversion of substrate PAI-1 to its inactive degradation product may constitute a pathway for the physiological regulation of PAI-1 activity.
Developmental regulation of tropoelastin isoforms. (1988)

The production of tropoelastin isoforms was examined by cell-free translation of nuchal ligament RNA from cows of various ages ranging from 110 days of gestation to adult. Tropoelastin polypeptides synthesized in vitro were immunoprecipitated with a specific monoclonal antibody and separated by high resolution sodium dodecyl sulfate-polyacrylamide gel electrophoresis. From these experiments three distinct tropoelastin isoform patterns were detected at different developmental periods. 1) The fetal period was characterized by three polypeptides of about 67, 65, and 63 kDa produced in a ratio of 1:3:2. 2) In neonatal tissue, the same molecular mass forms were detected; however, the relative isoform ratio changed to 2:3:1. 3) From adult ligament RNA, only the 67- and 65-kDa forms of tropoelastin were detected, and these were produced in equal amounts. The pattern of tropoelastin isoforms produced from RNA isolated from other fetal elastic tissues was the same as for fetal ligament. Additional studies demonstrated that the relative amount of functional tropoelastin mRNA correlated with steady state levels of mRNA consistent with transcriptional regulation of tropoelastin synthesis. Although the significance of developmental switching of individual tropoelastin isoforms is unknown, it is likely that this process is required for proper assembly and, thus, function of elastic tissue.
Detection of Novel Genomic Markers for Predicting Prognosis in Hepatocellular Carcinoma Patients by Integrative Analysis of Copy Number Aberrations and Gene Expression Profiles: Results from a Long-Term Follow-Up (2015)

The aim of this study was to explore novel genomic biomarkers predicting hepatocellular carcinoma (HCC) prognosis by integrative analysis of DNA copy number aberrations (CNAs) and gene expression profiles. Array comparative genomic hybridization and expression array were performed on 45 and 31 HCC samples, respectively. To identify functionally important genes, concordant results of DNA copy number and gene expression were retrieved by integrative analysis. Cox regression analysis indicated that the CNAs in 192 genomic regions were significantly associated with overall survival (OS; p < 0.05). Integrative analysis capturing concordant results demonstrated that the low expression of TLE4 (p = 0.041) and XPA (p = 0.006) was associated with poor OS. In the analysis of tumor recurrence, 514 genomic regions with CNAs were associated with recurrence. Integrative analysis revealed that the overexpression of 16 genes, including FGR (p = 0.003), RELA (p = 0.049), LTBP3 (p = 0.050), and RIN1 (p = 0.023), was significantly associated with shorter time to tumor recurrence. On multivariate analysis, FGR and XPA were independent risk factors of early recurrence and poor OS, respectively. Integrated analysis of CNAs and gene expression profiles correlated with long-term follow-up data successfully identified potential prognostic markers predicting survival and tumor recurrence in patients with HCC who underwent surgical resection.
Motion vector coding techniques for HEVC (2011)

High Efficiency Video Coding (HEVC) is a new international video coding standard that has been developed by the Joint Collaborative Team on Video Coding (JCT-VC). In this paper, an overview of the motion vector coding techniques for HEVC is presented. Our three proposed coding tools for the motion vector predictor (MVP) in the Inter, Skip and Merge modes of HEVC are also presented, which includes a new location of the temporal MVP, a priority-based derivation method of spatial MVPs, and a derivation method of temporal MVPs. A combination of these three tools can achieve on average 1.3%, 1.8%, 1.2% and 2.2% bit rate reductions for high efficiency random access, low complexity random access, high efficiency low delay, and low complexity low delay, respectively.
Interactions Between Compression and Prefetching in Chip Multiprocessors (2007)

In chip multiprocessors (CMPs), multiple cores compete for shared resources such as on-chip caches and off-chip pin bandwidth. Stride-based hardware prefetching increases demand for these resources, causing contention that can degrade performance (up to 35% for one of our benchmarks). In this paper, we first show that cache and link (off-chip interconnect) compression can increase the effective cache capacity (thereby reducing off-chip misses) and increase the effective off-chip bandwidth (reducing contention). On an 8-processor CMP with no prefetching, compression improves performance by up to 18% for commercial workloads. Second, we propose a simple adaptive prefetching mechanism that uses cache compressions extra tags to detect useless and harmful prefetches. Furthermore, in the central result of this paper, we show that compression and prefetching interact in a strong positive way, resulting in combined performance improvement of 10-51% for seven of our eight workloads
Drug therapy of reflux oesophagitis: an update. (1989)

The various therapeutic approaches for reflux oesophagitis are to enhance oesophageal clearance, to coat damaged tissue, to increase the competence of the reflux barrier, to reduce the volume and pH of gastric contents, and to improve gastric emptying and pyloric sphincter competence. Unfortunately, drug therapy of reflux oesophagitis is not yet ideal. Of the prokinetic agents, cisapride is the only drug with proven benefit. Single-agent therapy with the H2-receptor antagonists or sucralfate results in similar degrees of symptom relief and healing. Rapid symptom relief and healing are achieved by omeprazole; however, the significance of sustained achlorhydria remains to be established. Dinnertime dosing of cimetidine appears to be a rational method of suppressing late-evening gastric acidity. Patients with severe or recalcitrant disease should not be treated with conventional therapy alone; the results of controlled studies of combination therapy with the H2-receptor antagonists and sucralfate or cisapride will be viewed with interest.