gebhart/patrepeval huggingface dataset:
Knowledge-assisted document retrieval: II. The retrieval process (1987)

This article presents our conceptual model of the retrieval process of a document-retrieval system. The retrieval mechanism input is an unambiguous intermediate form of a user query generated by the language processor using the method described previously. Our retrieval mechanism uses a two-step procedure. In the first step a list of documents pertinent to the query are obtained from the document database, and then an evidence-combination scheme is used to compute the degree of support between the query and individual documents. The second step uses a ranking procedure to obtain a final degree of support for each document chosen, as a function of individual degrees of support associated with one or more parts of the query. The end result is a set of document citations presented to the user in ranked order in response to the information request. Numerical examples are given to illustrate various facets of the overall system, which has been prototypically implemented in modular form to test system response to changes in model parameters. © 1987 John Wiley & Sons, Inc.
Disparity field and depth map coding for multiview image sequence compression (2002)

Methods are proposed for coding of the depth map and disparity fields for stereo or multiview image communication applications. Block-based and wireframe modeling techniques are examined for the coding of isolated depth map information and 2-D and 3-D motion compensation techniques for the coding of depth map sequences are evaluated.
Control of the Initiation of DNA Synthesis in 3T3 Cells: Serum Factors (1974)

The initiation of DNA synthesis in 3T3 cells can be controlled by a variety of different factors. Cells that are quiescent because of limited serum initiate DNA synthesis in response to the fibroblast growth factor of Gospodarowicz, to insulin, and to dexamethasone, as well as to other, unidentified biological materials. Interactions are seen between the effects of different factors.
Carbonic anhydrase (CA IX) expression, a potential new intrinsic marker of hypoxia: correlations with tumor oxygen measurements and prognosis in locally advanced carcinoma of the cervix. (2001)

There is increasing evidence that hypoxia-regulated gene expression influences tumor aggressiveness, contributing to the poorer outcome of patients with hypoxic tumors. The role of the transcriptional complex hypoxia-inducible factor-1 as an important mediator of hypoxia-regulated gene expression is one of the best documented pathways. Recently, it has emerged that certain tumor-associated carbonic anhydrases (CAs) can be added to the list of known hypoxia-inducible factor-responsive genes. Here we show that the immunohistochemical expression of the tumor-associated CA IX is correlated with the level of hypoxia in human cervical tumors. We performed a prospective study in 68 patients where needle electrodes were used to make direct measurements of tumor oxygenation levels. CA IX expression was evaluated immunohistochemically in pretreatment tumor biopsies. There was a significant positive correlation between the level of tumor hypoxia (HP5) and the extent of CA IX expression. A retrospective study of 130 squamous cell cervical carcinomas demonstrated that a semiquantitative immunohistochemical analysis of CA IX expression in tumor biopsies is a significant and independent prognostic indicator of overall survival and metastasis-free survival after radiation therapy. These studies provide clinical evidence that CA IX expression is up-regulated in hypoxic human cervical tumors and is associated with a poor prognosis. CA IX may act as an intrinsic marker of tumor hypoxia and poor outcome after radiation therapy. The level of CA IX expression may be used to aid in the selection of patients who would benefit most from hypoxia-modification therapies or bio-reductive drugs.
The roles of hyaluronic acid, collagen and elastin in the mechanical properties of connective tissues. (1980)

Biomechanical testing of connective tissue is usually done on whole tissue. Studies of the mechanical properties of each component of the tissue, however, are important for elucidating the connection between the functional properties and the molecular structure. Enzymic degradation of one component at a time followed by mechanical testing was employed. The specificity of enzymes used was ascertained with mechanical tests on collagen films from purified, reconstituted collagen after enzymic treatment. The study shows that collagen is the component which is mainly responsible for the tensile strength of skin and aorta, while the toe-part of the 'stress'-strain curve of aorta is determined by both elastin and collagen. The hyaluronic acid does not seem to play any role in the static mechanical properties of skin and aorta as evaluated by means of the present method.
Antioxidative galloyl esters as enzyme inhibitors of p‐hydroxybenzoate hydroxylase (2000)

Gallic acid and its esters were evaluated as enzyme inhibitors of recombinant p-hydroxybenzoate hydroxylase (PHBH), a NADPH-dependent flavin monooxygenase from Pseudomonas aeruginosa. n-Dodecyl gallate (DG) (IC(50)=16 microM) and (-)-epigallocatechin-3-O-gallate (EGCG) (IC(50)=16 microM), a major component of green tea polyphenols, showed the most potent inhibition, while product-like gallic acid did not inhibit the enzyme significantly (IC(50)>250 microM). Inhibition kinetics revealed that both DG and EGCG inhibited PHBH in a non-competitive manner (K(I)=18.1 and 14.0 microM, respectively). The enzyme inhibition was caused by specific binding of the antioxidative gallate to the enzyme, and by scavenging reactive oxygen species required for the monooxygenase reaction. Molecular modeling predicted that EGCG binds to the enzyme in the proximity of the FAD binding site via formation of three hydrogen bonds.
Cloning and expression of the multiple sugar metabolism (msm) operon of Streptococcus mutans in heterologous streptococcal hosts (1993)

The multiple sugar metabolism (msm) operon of Streptococcus mutans is responsible for the uptake and metabolism of a variety of sugars. In order to further characterize the substrate specificities of the transport system, a 12-kb region of DNA containing the entire msm operon was cloned, via a novel two-step integration strategy, into the chromosomes of two heterologous streptococcal strains, Streptococcus gordonii Challis and Streptococcus anginosus Is57, as well as the chromosome of a natural isolate of S. mutans with a deletion of the msm region. These strains are unable to transport or ferment melibiose, raffinose, or isomaltosaccharides, but the newly constructed recombinants gained the ability to ferment all of these sugars. The S. gordonii Challis construct containing msm was shown to transport radiolabelled melibiose, raffinose, isomaltotriose, and isomaltotetraose, and the transport function was also subjected to induction by raffinose, an inducer of the msm operon in S. mutans. The results confirm the role of the msm operon in the transport and metabolism of melibiose, raffinose, and isomaltosaccharides.
Resveratrol commonly displays hormesis: Occurrence and biomedical significance (2010)

Resveratrol induces hormetic dose responses in a wide range of biological models, affecting numerous endpoints of biomedical and therapeutic significance. These responses were reported for numerous human tumor cell lines affecting breast, prostate, colon, lung, uterine and leukemia. In such cases, low concentrations of resveratrol enhanced tumor cell proliferation whereas higher concentrations were inhibitory. Similar resveratrol-induced biphasic dose responses were seen with several parasitic diseases, including Leishmaniasis and trichinella. Hormetic effects were also reported in animal models for cardiovascular induced injury, gastric lesions, ischemic stroke, Alzheimer’s disease and osteoporosis. In these cases, there was often a protective effect at low doses but an adverse effect at higher doses, exacerbating the disease process/incidence. This analysis indicates that many effects induced by resveratrol are dependent on dose and that opposite effects occur at low and high doses, being indicative of a hormetic dose response. Despite consistent occurrence of hormetic dose responses of resveratrol in a wide range of biomedical models, epidemiologic and clinical trials are needed to assess the nature of its dose-response in humans.
SEISMIC PHASE UNWRAPPING: METHODS, RESULTS, PROBLEMS1 (1992)

A bstract Six known methods of seismic phase unwrapping (or phase restoration) are compared. All the methods tested unwrap the phase satisfactorily if the initial function is a simple theoretical wavelet. None of the methods restore the phase of a synthetic trace exactly. An initial validity test of the phase‐unwrapping method is that the sum of the restored wavelet phase spectrum and the restored pulse‐trace phase spectrum (assuming the convolutional model for the seismic trace) must be equal to the restored phase spectrum of the synthetic trace. Results show that none of the tested methods satisfy this test. Quantitative estimation of the phase‐unwrapping accuracy by correlation analysis of the phase deconvolution results separated these methods, according to their efficiency, into three groups. The first group consists of methods using a priori wavelet information. These methods make the wavelet phase estimation more effective than the minimum‐phase approach, if the wavelet is non‐minimum‐phase. The second group consists of methods using the phase increment Δø(Δω) between two adjacent frequencies. These methods help to decrease the time shift of the initial synthetic trace relative to the model of the medium. At the same time they degrade the trace correlation with the medium model. The third group consists of methods using an integration of the phase derivative. These methods do not lead to any improvement of the initial seismic trace. The main problem in the phase unwrapping of a seismic trace is the random character of the pulse trace. For this reason methods based on an analysis of the value of Δø(Δω) only, or using an adaptive approach (i.e. as Δω decreases) are not effective. In addition, methods based on integration of the phase derivative are unreliable, due to errors in numerical integration and differentiation.
Active site of the mRNA-capping enzyme guanylyltransferase from Saccharomyces cerevisiae: similarity to the nucleotidyl attachment motif of DNA and RNA ligases. (1994)

Nascent mRNA chains are capped at the 5' end by the addition of a guanylyl residue to form a G(5')ppp(5')N ... structure. During the capping reaction, the guanylyltransferase (GTP:mRNA guanylyltransferase, EC 2.7.7.50) is reversibly and covalently guanylylated. In this enzyme-GMP (E-GMP) intermediate, GMP is linked to the epsilon-amino group of a lysine residue via a phosphoamide bond. Lys-70 was identified as the GMP attachment site of the Saccharomyces cerevisiae guanylyltransferase (encoded by the CEG1 gene) by guanylylpeptide sequencing. CEG1 genes with substitutions at Lys-70 were unable to support viability in yeast and produced proteins that were not guanylylated in vitro. The CEG1 active site exhibits sequence similarity to the active sites of viral guanylyltransferases and polynucleotide ligases, suggesting similarity in the mechanisms of nucleotidyl transfer catalyzed by these enzymes.
Proliferative Responses to Platelet-Derived Growth Factor in Young and Old Rat Patellar Tendon (1995)

Musculoskeletal soft tissue repair is often a slow process that may be complicated by aging, thus we investigated the mitogenic response of young and old rat patellar tendon (PT) explants to platelet-derived growth factor-AB (PDGF-AB). Bilateral PT explants from young (4 months) and old (29 or 36 months) rats of two strains (Fisher 344 and Fisher-Brown-Norway) were cultured for 72 h in platelet-poor horse serum in the presence or absence of 100 ng/ml recombinant human PDGF-AB. The explants were radiolabelled with [3H]-TdR for the final 24 h in culture. Tendon cellularity and DNA synthesis data were analyzed by multiple factor ANOVA (age, strain, and side), Mann-Whitney t-test (cellularity and DNA synthesis), and a sign test (proliferative response to PDGF). Tendon cellularity declined significantly with age in both strains (p < 0.05), while both young and old patellar tendon fibroblasts in both strains had a significant (> 100%) increase in DNA synthesis with the addition of PDGF (p < 0.05). Although there was a trend to lower proliferative responses in older tendons, the differences were not significant. Autoradiographic analysis of labeling indices in F344 tendons showed a diminished responsiveness to PDGF (p < 0.04, ANOVA). Strain and side response on a per cell or tissue weight basis were not significant factors. Under appropriate experimental conditions, these two animal models of aging showed declines in responses to high levels of PDGF, suggesting that the PT reflects an age-dependent diminished capacity for wound repair.
Embryonic development of identified neurons: origin and transformation of the H cell (1981)

We describe the origin and the transformation of a single neuron, the H cell, which assumes two different roles during grasshopper embryogenesis. The H cell originates from the single cell division of midline precursor 3 (MP3). In the metathoracic (T3) segment, the H cell first appears as one of a pair of central pioneer fibers and later transforms into an unpaired identified neuron. During the course of its transformation, the H cell loses its original morphology and acquires new morphological and physiological properties. The H cell acquires many of the same phenotypes as the first progeny of the median neuroblast (MNB); the processes of the first MNB progeny contact the soma of the H cell and these cells are electrically coupled prior to the H cell transformation.
Identification, Design and Bio-Evaluation of Novel Hsp90 Inhibitors by Ligand-Based Virtual Screening (2013)

Heat shock protein 90 (Hsp90), whose inhibitors have shown promising activity in clinical trials, is an attractive anticancer target. In this work, we first explored the significant pharmacophore features needed for Hsp90 inhibitors by generating a 3D-QSAR pharmacophore model. It was then used to virtually screen the SPECS databases, identifying 17 hits. Compound S1 and S13 exhibited the most potent inhibitory activity against Hsp90, with IC50 value 1.61±0.28 μM and 2.83±0.67 μM, respectively. Binding patterns analysis of the two compounds with Hsp90 revealed reasonable interaction modes. Further evaluation showed that the compounds exhibited good anti-proliferative effects against a series of cancer cell lines with high expression level of Hsp90. Meanwhile, S13 induced cell apoptosis in a dose-dependent manner in different cell lines. Based on the consideration of binding affinities, physicochemical properties and toxicities, 24 derivatives of S13 were designed, leading to the more promising compound S40, which deserves further optimization.
Immunization of Stage IV Melanoma Patients with Melan-A/MART-1 and gp100 Peptides plus IFN-α Results in the Activation of Specific CD8+ T Cells and Monocyte/Dendritic Cell Precursors (2006)

The use of IFN-alpha in clinical oncology has generally been based on the rationale of exploiting its antiproliferative and antiangiogenic activities. However, IFN-alpha also exhibits enhancing effects on T-cell and dendritic cell functions, which may suggest a novel use as a vaccine adjuvant. We have carried out a pilot phase I-II trial to determine the effects of IFN-alpha, administered as an adjuvant of Melan-A/MART-1:26-35(27L) and gp100:209-217(210M) peptides, on immune responses in stage IV melanoma patients. In five of the seven evaluable patients, a consistent enhancement of CD8(+) T cells recognizing modified and native MART-1 and gp100 peptides and MART-1(+)gp100(+) melanoma cells was observed. Moreover, vaccination induced an increase in CD8(+) T-cell binding to HLA tetramers containing the relevant peptides and an increased frequency of CD45RA(+)CCR7(-) (terminally differentiated effectors) and CD45RA(-)CCR7(-) (effector memory) cells. In all patients, treatment augmented significantly the percentage of CD14(+) monocytes and particularly of the CD14(+)CD16(+) cell fraction. An increased expression of CD40 and CD86 costimulatory molecules in monocytes was also observed. Notably, postvaccination monocytes from two of the three patients showing stable disease or long disease-free survival showed an enhanced antigen-presenting cell function and capability to secrete IP10/CXCL10 when tested in mixed leukocyte reaction assays, associated to a boost of antigen and melanoma-specific CD8(+) T cells. Although further clinical studies are needed to show the adjuvant activity of IFN-alpha, the present data represent an important starting point for considering a new clinical use of IFN-alpha and new immunologic end points, potentially predictive of clinical response.
Influence of Glial Growth Factor and Schwann Cells in a Bioresorbable Guidance Channel on Peripheral Nerve Regeneration (2000)

Using an established rat peripheral nerve regeneration model, we investigated the role of glial growth factor (GGF) in nerve regeneration in combination with a novel bioresorbable poly(lactic-co-glycolic) acid (PLGA) guide in vivo. Schwann cells, established from a 1-cm segment of excised rat sciatic nerve, were isolated and seeded onto nerve guides with or without GGF (n = 24/group). Living nerve guides were re-established in these animals, and nerve regeneration was assessed over a period of 12 weeks. Histological studies revealed a reduction in the total axon count and the number of myelinated axons in the presence of exogenously added Schwann cells compared to saline controls. In contrast, the addition of GGF alone enhanced the total number of axons and significantly increased the number of blood vessels. Although combining GGF with Schwann cells negated the enhanced numbers of axons and blood vessels seen with GGF alone, this combination resulted in the highest myelination index and the fastest conduction velocities recorded. The PLGA guide material did not trigger any histologically detectable host response and was permissive for nerve regeneration in this animal model. The results from this study demonstrate the potential utility of this guide in vivo and establish a promotional role for GGF in nerve regeneration.
BindingDB Entry 50042006: Localization of organic anion transport protein 2 in the apical region of rat retinal pigment epithelium. (2013)

In rat retina, Oatp2 is localized at the interface between the pigment epithelium and the photoreceptor outer segments. A2E is a competitive inhibitor of Oatp2-mediated substrate transport, suggesting that A2E or A2E-like compounds and some retinoids may be substrates for Oatp2 transport.
Novel and effective routes to optically pure amino acids, dipeptides, and their derivatives viaβ-lactams obtained through asymmetric cycloaddition (1987)

Optically pure dipeptides bearing aromatic amino acid residues were synthesized via homochiral (optically pure)β-lactams which were obtained through asymmetric cycloadditions of homochiral ketenes to homochiral imines.
New Ordered Structure for the H-Saturated Si(100) Surface: The (3×1) Phase (1985)

High-resolution infrared data of Si(100) surfaces saturated with H at room temperature show that the so-called 1\ifmmode\times\else\texttimes\fi{}1 surface is in fact a disordered phase with roughly half the H bonded in monohydride (H-Si-Si-H) and half in dihydride (Si${\mathrm{H}}_{2}$) configurations. Upon saturation exposure at 380 K, the surface is ordered into a newly identified 3\ifmmode\times\else\texttimes\fi{}1 phase, as evidenced by LEED, involving repeated alternating monohydride and dihydride units.
TLR4 Ligands Augment Antigen-Specific CD8 + T Lymphocyte Responses Elicited by a Viral Vaccine Vector (2010)

Toll-like receptor (TLR) ligands are critical activators of innate immunity and are being developed as vaccine adjuvants. However, their utility in conjunction with viral vector-based vaccines remains unclear. In this study, we evaluated the impact of a variety of TLR ligands on antigen-specific CD8(+) T lymphocyte responses elicited by a recombinant adenovirus serotype 26 (rAd26) vector expressing simian immunodeficiency virus Gag in mice. The TLR3 ligand poly(I:C) suppressed Gag-specific cellular immune responses, whereas the TLR4 ligands lipopolysaccharide and monophosphoryl lipid A substantially augmented the magnitude and functionality of these responses by a MyD88- and TRIF-dependent mechanism. These data demonstrate that TLR ligands can modulate the immunogenicity of viral vaccine vectors both positively and negatively. Moreover, these findings suggest the potential utility of TLR4 ligands as adjuvants for rAd vector-based vaccines.
CAPTURE AND PROCESSING OF EXOGENOUS ANTIGENS FOR PRESENTATION ON MHC MOLECULES (1997)

Class I and class II MHC molecules bind peptides during their biosynthetic maturation and provide a continuously updated display of intracellular and environmental protein composition, respectively, for scrutiny by T cells. Receptor-mediated endocytosis, phagocytosis, and macropinocytosis all contribute to antigen uptake by class II MHC-positive antigen-presenting cells. Capture of antigenic peptides by class II MHC molecules is facilitated because antigen catabolism and class II MHC maturation take place in the same compartments or in communicating compartments of the endosome/lysosome system. These class II MHC-rich, multivesicular endosomes receive incoming antigen and can support not only antigen processing and class II MHC peptide loading but also the export of peptide/class II MHC complexes to the cell surface. A balance between production and destruction of antigenic peptides is achieved by the activity of local proteases and may be influenced by binding of antigen to other proteins both prior to the onset of processing (e.g. antibodies) and during antigen unfolding (e.g. MHC molecules). T cell determinants that can be released for MHC binding without a substantial processing requirement may be able to utilize a distinct minor population of cell surface class II MHC molecules that become available during peripheral recycling. Although peptides derived from exogenous protein sources are usually excluded from presentation on class I MHC molecules, recent evidence shows that this embargo may be lifted in certain professional antigen-presenting cells to increase the spectrum of antigens that may be displayed on class I MHC.
Sacituzumab Govitecan, a Novel Antibody–Drug Conjugate, in Patients With Metastatic Platinum-Resistant Urothelial Carcinoma (2015)

Patients with metastatic, platinum-resistant urothelial carcinoma (PRUC) have no Food and Drug Administration–approved therapies. The response rates to second-line chemotherapy have generally been < 20%, with a median overall survival of < 1 year. We report our experience with 6 heavily pretreated patients with advanced PRUC (ClinicalTrials.gov identifier NCT01631552) with the novel antibody–drug conjugate, sacituzumab govitecan (IMMU-132). This antibody–drug conjugate comprises the active metabolite of irinotecan, SN-38, conjugated to an anti-Trop-2 antibody. Trop-2 is widely expressed in ≤ 83% of urothelial carcinomas. Of the 6 patients, 3 had a clinically significant response (progression-free survival, 6.7 to 8.2 months; overall survival, 7.5+ to 11.4+ months). Sacituzumab govitecan was well tolerated. Because of these results, a phase II trial has been initiated. The present report highlights the promise of antibody–drug conjugates, such as sacituzumab govitecan, as a novel therapeutic strategy for the treatment of PRUC.