gebhart/patrepeval huggingface dataset:
A New Approach to Assay Endo-Type Carbohydrases: Bifluorescent-Labeled Substrates for Glycoamidases and Ceramide Glycanases (1995)

Glycoamidases and ceramide glycanases are important "endo-type" enzymes for structural elucidations of glycoconjugates as well as for construction of neoglycoconjugates. The assay methods currently available for these enzymes are tedious and do not permit continual assay of the enzyme activities. We modified a desialylated biantennary glycopeptide with 2-naphthylacetic acid at the N-terminus and at the non-reducing terminal galactosyl residues with mono-N-dansylethylenediamine, via a specific oxidation of the C-6 hydroxyl group with galactose oxidase. In such a substrate, the naphthyl fluorescence (lambda em = 335 nm) is quenched due to absorption of its emitted light by the dansyl group, which in turn results in emission of fluorescence (lambda ex = 520 nm) by the latter. However, when the link between the two fluorophores is severed by glycoamidase (PNGase), the energy transfer ceases to occur. Consequently the emission of the dansyl fluorescence and the quenching of naphthyl fluorescence diminish or disappear. Likewise, the energy transfer between the fluorophores in an alkyl lactoside containing a dansyl group at the terminal position of aglycon and a 2-naphthylmethyl group on the galactosyl residue is also eliminated by the glycosidic cleavage by a ceramide glycanase from American leech, Macrobdella decora, resulting in enhancement of the naphthyl emission and decrease in the dansyl emission. The substrates presented here permit continuous fluorescent monitoring of the enzymatic reaction. This allows precise analyses of enzyme kinetics not possible with the conventional assay methods for the endo-type enzymes which usually require separation of reaction products.
Site-directed mutations in a highly conserved region of Bacillus thuringiensis delta-endotoxin affect inhibition of short circuit current across Bombyx mori midguts. (1993)

Bacillus thuringiensis delta-endotoxins (Cry toxins) are insecticidal proteins of approximately 65 kDa in the proteolytically processed and active form. The structure of one of these toxins, CryIIIA, has been determined by Li et al. [Li, J., Carroll, J. & Ellar, D. J. (1991) Nature (London) 353, 815-821] and contains three domains. It is believed that other delta-endotoxins adopt similar three-dimensional structure. Li et al. proposed that the first domain is the membrane pore-forming domain. Previous work from our laboratory has shown that the second domain is the receptor binding domain, but the function of the third domain is unclear. Site-directed mutagenesis was used to convert the "arginine face" of one of five highly conserved regions, QRYRVRIRYAS of CryIAa (residues 525-535), to selected other residues. This sequence corresponds to the beta-sheet 17 of CryIIIA in the third domain. Mutations in the second and third arginine positions resulted in structural alterations in the protein and were poorly expressed in Escherichia coli. Toxins from genes mutated to replace lysine for the first and fourth arginines were unaltered in expression and structure, as measured by trypsin activation, CD spectra, and receptor binding, but were substantially reduced in their insecticidal properties and inhibition of short circuit current across Bombyx mori midguts. It is proposed that this region plays a role in toxin function as an ion channel.
A Geodesic Framework for Fast Interactive Image and Video Segmentation and Matting (2007)

An interactive framework for soft segmentation and matting of natural images and videos is presented in this paper. The proposed technique is based on the optimal, linear time, computation of weighted geodesic distances to the user-provided scribbles, from which the whole data is automatically segmented. The weights are based on spatial and/or temporal gradients, without explicit optical flow or any advanced and often computationally expensive feature detectors. These could be naturally added to the proposed framework as well if desired, in the form of weights in the geodesic distances. A localized refinement step follows this fast segmentation in order to accurately compute the corresponding matte function. Additional constraints into the distance definition permit to efficiently handle occlusions such as people or objects crossing each other in a video sequence. The presentation of the framework is complemented with numerous and diverse examples, including extraction of moving foreground from dynamic background, and comparisons with the recent literature.
Activation of Triggering Receptor Expressed on Myeloid Cells-1 on Human Neutrophils by Marburg and Ebola Viruses (2006)

Marburg virus (MARV) and Ebola virus (EBOV), members of the viral family Filoviridae, cause fatal hemorrhagic fevers in humans and nonhuman primates. High viral burden is coincident with inadequate adaptive immune responses and robust inflammatory responses, and virus-mediated dysregulation of early host defenses has been proposed. Recently, a novel class of innate receptors called the triggering receptors expressed in myeloid cells (TREM) has been discovered and shown to play an important role in innate inflammatory responses and sepsis. Here, we report that MARV and EBOV activate TREM-1 on human neutrophils, resulting in DAP12 phosphorylation, TREM-1 shedding, mobilization of intracellular calcium, secretion of proinflammatory cytokines, and phenotypic changes. A peptide specific to TREM-1 diminished the release of tumor necrosis factor alpha by filovirus-activated human neutrophils in vitro, and a soluble recombinant TREM-1 competitively inhibited the loss of cell surface TREM-1 that otherwise occurred on neutrophils exposed to filoviruses. These data imply direct activation of TREM-1 by filoviruses and also indicate that neutrophils may play a prominent role in the immune and inflammatory responses to filovirus infections.
Murine B7 antigen provides an efficient costimulatory signal for activation of murine T lymphocytes via the T-cell receptor/CD3 complex. (1992)

We demonstrate that the murine B7 (mB7) protein is a potent costimulatory molecule for the activation of resting murine CD4+ T cells through the T-cell receptor (TCR)/CD3 complex. Stable mB7-transfected Chinese hamster ovary cells, but not vector-transfected controls, synergize with anti-CD3 monoclonal antibody and Con A-induced T-cell activation, resulting ultimately in proliferation. mB7 exerted its effect by inducing production of interleukin 2 and expression of the interleukin 2 receptor. Thus, mB7 costimulates T-cell activation through the TCR/CD3 complex by positively modulating the normal pathway of T-cell expansion. In contrast to the pronounced effect of mB7 on the activation of T cells through the TCR/CD3 complex, the mB7-transfected CHO cell line costimulated T-cell activation via the glycosylphosphatidylinositol-anchored proteins Thy-1 and Ly-6A.2 only inefficiently. Finally, the combination of a calcium ionophore and mB7 is not sufficient to cause T-cell proliferation, while the combination of a calcium ionophore and phorbol 12-myristate 13-acetate (PMA) stimulates T cells efficiently. The signals that mB7 and PMA provide for murine T lymphocyte activation are therefore not interchangeable, although both costimulate activation through the TCR/CD3 complex.
Fern phylogeny inferred from 400 leptosporangiate species and three plastid genes (2007)

In an effort to obtain a solid and balanced approximation of global fern phylogeny to serve as a tool for addressing large‐scale evolutionary questions, we assembled and analyzed the most inclusive molecular dataset for leptosporangiate ferns to date. Three plastid genes ( rbcL, atpB, atpA ), totaling more than 4,000 bp, were sequenced for each of 400 leptosporangiate fern species (selected using a proportional sampling approach) and five outgroups. Maximum likelihood analysis of these data yielded an especially robust phylogeny: 80% of the nodes were supported by a maximum likelihood bootstrap percentage ≥ 70. The scope of our analysis provides unprecedented insight into overall fern relationships, not only delivering additional support for the deepest leptosporangiate divergences, but also uncovering the composition of more recently emerging clades and their relationships to one another.
Effects of overproduction of the catalytic domain of 3-hydroxy-3-methylglutaryl coenzyme A reductase on squalene synthesis in Saccharomyces cerevisiae (1997)

The enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMG-R) is the major rate-limiting enzyme of the mevalonate pathway in many organisms, including yeasts. In the yeast Saccharomyces cerevisiae, there are two isoenzymes of HMG-R (Hmg1p and Hmg2p). Both consist of an anchoring transmembrane domain and a catalytic domain. We have removed the known controlling features of HMG-R by overproducing the catalytic domain of Hmg1p. This overproduction leads to an enhancement of squalene production, implying that HMG-R has been deregulated. The enhancement is apparent under semianaerobic and aerobic conditions. Despite the increase in squalene production, the amount of ergosterol produced by the HMG-R-overproducing yeast was not increased. This result suggests the presence of another regulatory step between squalene and ergosterol formation. Squalene levels generated by cells overproducing the catalytic domain of HMG-R were estimated to be up to 10 times those produced by wild-type cells. The enhancement in squalene production coincided with a reduction in growth rate. This reduction may be a direct consequence of the buildup of high concentrations of squalene and presqualene intermediates of the pathway.
Fundamental study on improvement of piezoelectricity of poly(ι-lactic acid) and its application to film actuators (2013)

We designed a new film actuator, whose driving force is generated by a surface wave, which induces rotational motion. Its performance is similar to that of a rotation motor even though the new film actuator has no complex mechanical parts. To realize the film actuator, we used a poly(l-lactic acid) (PLLA) film with improved piezoelectricity. First, we theoretically investigated the necessary conditions for a surface wave to be generated on the end face of a PLLA film by the fusion of its shear piezoelectricity and resonance, and then experimentally realized this. Using the actuator made using the PLLA film, we demonstrated that the clockwise and counterclockwise rotation of an object placed on the end face of the PLLA film actuator could be freely controlled by changing the frequency of the ac voltage applied to the actuator.
Clinical implications of angiogenesis in cancers (2006)

Angiogenesis plays an important role in the growth and progression of cancer. The regulation of tumor angiogenesis depends on a net balance of angiogenic factors and antiangiogenic factors, which are secreted by both tumor cells and host-infiltrating cells. Numerous studies have indicated that assessment of angiogenic activity by either microvessel density or expression of angiogenic factors in cancer can provide prognostic information independent of conventional clinicopathological factors such as tumor staging. Some studies also suggested that assessment of tumor angiogenesis may predict cancer response to chemotherapy or radiotherapy. However, the most important clinical implication of tumor angiogenesis is the development of a novel strategy of anticancer therapy targeting tumor vessels instead of cancer cells. Antiangiogenic therapy aims to inhibit the growth of tumor, and current evidence suggests that it works best in combination with conventional cytotoxic chemotherapy. Recently, a monoclonal antibody against vascular endothelial growth factor, which is one of the most potent angiogenic factors, has been approved for clinical use in colorectal cancer patients after a clinical trial confirmed that combining the antibody with standard chemotherapy regimen could prolong patient survival. The clinical implications of angiogenesis in cancer are reviewed in this article.
Survival signals within the tumour microenvironment suppress drug-induced apoptosis: lessons learned from B lymphomas. (1999)

The suppression of apoptosis is one mechanism by which tumours become drug resitant. Extracellular signals from the germinal centre (GC) of secondary lymphoid tissue can rescue B cells from physiological- and chemotherapy-induced apoptosis. Such survival signals include CD40 receptor ligation, interleukin-4 (IL-4) receptor stimulation and the interaction of the integrin ligand VCAM-1 with its receptor. The GC environment was modelled in vitro by providing B lymphoma cells with these survival signals. JLP119 B lymphoma cells underwent apoptosis after exposure to the topisomerase II inhibitor etoposide and this was dramatically reduced when the cells were cultured in the GC system. CD40 receptor ligation resulted in increased levels of Bcl-XL. Etoposide diminished the binding between Bax and Bcl-XL but this was restored by IL-4 and VCAM-1 triggered signals. These data demonstrate combined effects of three microenvironmental signals on the Bcl-2 family and illustrate the potential importance of such signalling pathways in drug resistance of tumour cells.
High-Accuracy HLA Type Inference from Whole-Genome Sequencing Data Using Population Reference Graphs (2016)

Genetic variation at the Human Leucocyte Antigen (HLA) genes is associated with many autoimmune and infectious disease phenotypes, is an important element of the immunological distinction between self and non-self, and shapes immune epitope repertoires. Determining the allelic state of the HLA genes (HLA typing) as a by-product of standard whole-genome sequencing data would therefore be highly desirable and enable the immunogenetic characterization of samples in currently ongoing population sequencing projects. Extensive hyperpolymorphism and sequence similarity between the HLA genes, however, pose problems for accurate read mapping and make HLA type inference from whole-genome sequencing data a challenging problem. We describe how to address these challenges in a Population Reference Graph (PRG) framework. First, we construct a PRG for 46 (mostly HLA) genes and pseudogenes, their genomic context and their characterized sequence variants, integrating a database of over 10,000 known allele sequences. Second, we present a sequence-to-PRG paired-end read mapping algorithm that enables accurate read mapping for the HLA genes. Third, we infer the most likely pair of underlying alleles at G group resolution from the IMGT/HLA database at each locus, employing a simple likelihood framework. We show that HLA*PRG, our algorithm, outperforms existing methods by a wide margin. We evaluate HLA*PRG on six classical class I and class II HLA genes (HLA-A, -B, -C, -DQA1, -DQB1, -DRB1) and on a set of 14 samples (3 samples with 2 x 100bp, 11 samples with 2 x 250bp Illumina HiSeq data). Of 158 alleles tested, we correctly infer 157 alleles (99.4%). We also identify and re-type two erroneous alleles in the original validation data. We conclude that HLA*PRG for the first time achieves accuracies comparable to gold-standard reference methods from standard whole-genome sequencing data, though high computational demands (currently ~30-250 CPU hours per sample) remain a significant challenge to practical application.
Wavelength tunable source of subpicosecond pulses from CW passively mode-locked two-section multiple-quantum-well laser (1993)

A wavelength-tunable passively-mode-locked semiconductor laser source of subpicosecond pulses is demonstrated. The system includes a two-section multiple-quantum-well laser which is coupled to an external grating for tuning and is followed by an external grating pair for pulse compression. A tuning range of 16 nm round 846 nm is obtained, resulting in compressed pulse widths as short as 260 fs and pulse widths shorter than 600 fs for all wavelength values within this tuning range. Time-bandwidth products are one to two times the transform limit.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Very high-efficiency green organic light-emitting devices based on electrophosphorescence (1999)

We describe the performance of an organic light-emitting device employing the green electrophosphorescent material, fac tris(2-phenylpyridine) iridium [Ir(ppy)3] doped into a 4,4′-N,N′-dicarbazole-biphenyl host. These devices exhibit peak external quantum and power efficiencies of 8.0% (28 cd/A) and 31 lm/W, respectively. At 100 cd/m2, the external quantum and power efficiencies are 7.5% (26 cd/A) and 19 lm/W at an operating voltage of 4.3 V. This performance can be explained by efficient transfer of both singlet and triplet excited states in the host to Ir(ppy)3, leading to a high internal efficiency. In addition, the short phosphorescent decay time of Ir(ppy)3 (&amp;lt;1 μs) reduces saturation of the phosphor at high drive currents, yielding a peak luminance of 100 000 cd/m2.
Expression of CD44 Variant Exons 8–10 in Colorectal Cancer and Its Relationship to Metastasis (1995)

Splice variants of CD44 are overexpressed in human lung, breast, and colon carcinoma cell lines. This study was conducted to clarify the association between the expression of CD44 variant exons 8-10 and metastatic potential in human colorectal cancer. We found that the expression of a CD44 splice variant containing exons v8-10 was increased in all of 60 colorectal cancer specimens examined compared with matched normal colerectal mucosa, as determined by Northern blotting. Expression of CD44 variant exons 8-10 did not significantly correlate with histological type, depth of tumor invasion, lymphatic invasion, venous invasion, or lymph node metastasis. However, the level of CD44 variant exon 8-10 expression was significantly higher in carcinomas associated with liver metastasis than in those without liver metastasis. In addition, expression of CD44 variant exons 8-10 in the liver metastases was more intense than that in the primary colorectal cancers. These findings indicated that this domain of the CD44 glycoprotein encoded by exons v8-10 may play an important role in tumor hematogenous metastasis of human colorectal cancer.
Exploiting latent semantic information in statistical language modeling (2000)

Statistical language models used in large-vocabulary speech recognition must properly encapsulate the various constraints, both local and global, present in the language. While local constraints are readily captured through n-gram modeling, global constraints, such as long-term semantic dependencies, have been more difficult to handle within a data-driven formalism. This paper focuses on the use of latent semantic analysis, a paradigm that automatically uncovers the salient semantic relationships between words and documents in a given corpus. In this approach, (discrete) words and documents are mapped onto a (continuous) semantic vector space, in which familiar clustering techniques can be applied. This leads to the specification of a powerful framework for automatic semantic classification, as well as the derivation of several language model families with various smoothing properties. Because of their large-span nature, these language models are well suited to complement conventional n-grams. An integrative formulation is proposed for harnessing this synergy, in which the latent semantic information is used to adjust the standard n-gram probability. Such hybrid language modeling compares favorably with the corresponding n-gram baseline: experiments conducted on the Wall Street Journal domain show a reduction in average word error rate of over 20%. This paper concludes with a discussion of intrinsic tradeoffs, such as the influence of training data selection on the resulting performance.
Live HTTP streaming of video and subtitles within a browser (2013)

Video streaming has become a very popular application on the web, with rich player interfaces and subtitle integration. Additionally, live streaming solutions are deployed based on HTTP Streaming technologies. However, the integration of video and subtitles in live streaming solutions still poses some problems. This paper describes a demonstration of live streaming of video and subtitle data using the MPEG-DASH technology and its synchronous playback in a web browser. It presents the formats, architecture and technical choices made for this demonstration and shows that it is feasible with upcoming browsers, paving the way for richer web video applications.
Biochemical markers and the FDA Critical Path: How biomarkers may contribute to the understanding of pathophysiology and provide unique and necessary tools for drug development (2009)

The aim of this review is to discuss the potential usefulness of a novel class of biochemical markers, neoepitopes, in the context of the US Food and Drug Administration (FDA) Critical Path Initiative, which emphasizes biomarkers of safety and efficacy as areas of pivotal interest. Examples of protein degradation fragments--neoepitopes--that have proven useful for research on bone and cartilage are collagen type I and collagen type II degradation products, respectively. These markers have utility in the translational approach, as they can be used to estimate safety and efficacy in both preclinical models and clinical settings. Biochemical markers of tissue degradation may provide optimal tools, which in combination with other techniques, prove essential to drug discovery and development.
Alteration of Cell Cycle-dependent Histone Phosphorylations by Okadaic Acid (1996)

Effects of okadaic acid (OA), a protein phosphatase inhibitor, on chromatin structure and phosphorylation of histones were examined using HeLa and N18 cells. The chromatin condensation in HeLa cells was mild and resemble prometaphase nuclei, while the condensation in N18 cells was extensive and chromatin became a compact body. H2A in HeLa cells was extensively and consistently phosphorylated at the same site throughout the cell cycle, and H3 was demonstrated to be phosphorylated at the mitosis-specific site Ser10. In contrast, H1 phosphorylation was rapidly decreased in most sites within 3 h. The reduction of H1 phosphorylation was accompanied by a quantitative change in the set of H1 phosphopeptides. During the early phase of the OA treatment, H1 phosphorylation was transiently elevated in tandem, whereas H3 phosphorylation reached a maximum somewhat later. The results suggest that mitosis-specific events (cdc2/H1 kinase activation, H1 superphosphorylation, mitosis-specific H3 phosphorylation and chromatin condensation) induced by OA are sequentially associated. The changes appear to reflect a molecular mechanism similar to that operating in normal mitosis.
Recent developments in tissue engineering and regenerative medicine (2006)

Increasingly, scientists in the fields of regenerative medicine and tissue engineering have applied the principles of cell transplantation, material science and bioengineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues.
Evolutionary conservation in the untranslated regions of actin mRNAs: DNA sequence of a human beta-actin cDNA (1984)

We report the complete nucleotide sequence of a human beta actin cDNA. Both the 5' and 3' untranslated regions of the sequence are similar (greater than 80%) to the analogous regions of the rat beta-actin gene reported by Nudel et al (1983). When a segment of the 3' untranslated region is used as a radiolabelled probe, strong hybridization to chick beta actin mRNA is seen. This conservation of sequences suggests that strong selective pressures operate on non-translated segments of beta actin mRNA.