gebhart/patrepeval huggingface dataset:
The β-tail domain (βTD) regulates physiologic ligand binding to integrin CD11b/CD18 (2006)

Crystallographic and electron microscopy studies revealed genuflexed (bent) integrins in both unliganded (inactive) and physiologic ligandbound (active) states, suggesting that local conformational changes are sufficient for activation. Herein we have explored the role of local changes in the contact region between the membrane-proximal beta-tail domain (betaTD) and the ligand-binding betaA domain of the bent conformation in regulating interaction of integrin CD11b/CD18 (alphaMbeta2) with its physiologic ligand iC3b. We replaced the betaTD CD loop residues D658GMD of the CD18 (beta2) subunit with the equivalent D672SSG of the beta3 subunit, with AGAA or with NGTD, expressed the respective heterodimeric receptors either transiently in epithelial HEK293T cells or stably in leukocytes (K562), and measured their ability to bind iC3b and to conformation-sensitive mAbs. In the presence of the physiologic divalent cations Ca(2+) plus Mg(2+) (at 1 mM each), the modified integrins showed increased (in HEK293) or constitutive (in K562) binding to iC3b compared with wild-type receptors. K562 expressing the betaTD-modified integrins bound in Ca(2+)Mg(2+) to the betaA-directed high-affinity reporter mAb 24 but not to mAb KIM127, a reporter of the genu-straightened state. These data identify a role for the membrane proximal betaTD as an allosteric modulator of integrin activation.
Emerging Solution‐Processable Luminescent Nanomaterials in Hybrid Structures Offer New Solutions for Displays and Lighting (2017)

As the development of quantum dot and perovskite luminescent materials accelerates, it is expected that these materials will increasingly gain applications in display and lighting markets, particularly in hybrid structures with state‐of‐the‐art phosphor or OLED systems.
Involvement of lymphocyte function-associated antigen-1 (LFA-1) but not ICAM-1 in a radioactive leukocyte cell-mediated immunity (LA-CMI) assay. (1990)

A number of monoclonal antibodies (Mab) specific to human leukocyte adherence molecules were investigated for their possible function in LA-CMI assay. These data indicate that LFA-1 appears to be directly involved in LA-CMI of human peripheral blood leukocytes since both MAb H52, specific to LFA-1 beta and MAb MHM24, specific to LA-1 alpha inhibited LA-CMI that retained distinct functional characteristics normally exhibited in LFA-1-dependent adhesion steps. That is, binding of cells onto tube wall required the presence of bivalent cations and metabolic energy production; it could be stimulated by phytohemagglutinin (PHA) and was partially dependent on intact cytoskeleton and temperature. MAbs specific to other adherence molecules such as ICAM-1, CD2, CD58, CD4, CD8, CD11b and LAM-1 did not affect leukocyte adherence in this model.
The period gene encodes a predominantly nuclear protein in adult Drosophila (1992)

The period gene of Drosophila melanogaster (per) is important for the generation and maintenance of biological rhythms. Previous light microscopic observations indicated that per is expressed in a variety of tissues and cell types and suggested that the per protein (PER) may be present in different subcellular compartments. To understand how PER influences circadian rhythms, it is important to define its subcellular location, especially in adult flies where inducible promoter experiments suggested that it is most relevant to circadian locomotor activity rhythms. To this end, we report the results of an immunoelectron microscopic analysis of wild-type flies and per-beta-galactosidase (beta-gal) fusion gene transgenics using a polyclonal anti-PER antibody or an anti-beta-gal antibody, respectively. Most of the PER antigen and the fusion gene product were located within nuclei, suggesting that PER acts in that subcellular compartment to affect circadian rhythms. The results are discussed in terms of per's possible biochemical functions.
A large and accurate collection of peptidase cleavages in the MEROPS database (2009)

Peptidases are enzymes that hydrolyse peptide bonds in proteins and peptides. Peptidases are important in pathological conditions such as Alzheimer's disease, tumour and parasite invasion, and for processing viral polyproteins. The MEROPS database is an Internet resource containing information on peptidases, their substrates and inhibitors. The database now includes details of cleavage positions in substrates, both physiological and non-physiological, natural and synthetic. There are 39 118 cleavages in the collection; including 34 606 from a total of 10 513 different proteins and 2677 cleavages in synthetic substrates. The number of cleavages designated as 'physiological' is 13 307. The data are derived from 6095 publications. At least one substrate cleavage is known for 45% of the 2415 different peptidases recognized in the MEROPS database. The website now has three new displays: two showing peptidase specificity as a logo and a frequency matrix, the third showing a dynamically generated alignment between each protein substrate and its most closely related homologues. Many of the proteins described in the literature as peptidase substrates have been studied only in vitro. On the assumption that a physiologically relevant cleavage site would be conserved between species, the conservation of every site in terms of peptidase preference has been examined and a number have been identified that are not conserved. There are a number of cogent reasons why a site might not be conserved. Each poorly conserved site has been examined and a reason postulated. Some sites are identified that are very poorly conserved where cleavage is more likely to be fortuitous than of physiological relevance. This data-set is freely available via the Internet and is a useful training set for algorithms to predict substrates for peptidases and cleavage positions within those substrates. The data may also be useful for the design of inhibitors and for engineering novel specificities into peptidases.Database URL:http://merops.sanger.ac.uk.
Levels of plasma circulating cell free nuclear and mitochondrial DNA as potential biomarkers for breast tumors (2009)

Our data suggests that nuclear and mitochondrial ccf DNA have potential as biomarkers in breast tumor management. However, ccf nDNA shows greater promise regarding sensitivity and specificity.
CXCL10 (IFN-γ-Inducible Protein-10) Control of Encephalitogenic CD4+ T Cell Accumulation in the Central Nervous System During Experimental Autoimmune Encephalomyelitis (2001)

Experimental autoimmune encephalomyelitis (EAE) is a CD4(+) Th1-mediated demyelinating disease of the CNS that serves as a model for multiple sclerosis. A critical event in the pathogenesis of EAE is the entry of both Ag-specific and Ag-nonspecific T lymphocytes into the CNS. In the present report, we investigated the role of the CXC chemokine CXCL10 (IFN-gamma-inducible protein-10) in the pathogenesis of EAE. Production of CXCL10 in the CNS correlated with the development of clinical disease. Administration of anti-CXCL10 decreased clinical and histological disease incidence, severity, as well as infiltration of mononuclear cells into the CNS. Anti-CXCL10 specifically decreased the accumulation of encephalitogenic PLP(139-151) Ag-specific CD4+ T cells in the CNS compared with control-treated animals. Anti-CXCL10 administration did not affect the activation of encephalitogenic T cells as measured by Ag-specific proliferation and the ability to adoptively transfer EAE. These results demonstrate an important role for the CXC chemokine CXCL10 in the recruitment and accumulation of inflammatory mononuclear cells during the pathogenesis of EAE.
Skin Rejuvenation with Non-Invasive Pulsed Electric Fields (2015)

Degenerative skin diseases affect one third of individuals over the age of sixty. Current therapies use various physical and chemical methods to rejuvenate skin; but since the therapies affect many tissue components including cells and extracellular matrix, they may also induce significant side effects, such as scarring. Here we report on a new, non-invasive, non-thermal technique to rejuvenate skin with pulsed electric fields. The fields destroy cells while simultaneously completely preserving the extracellular matrix architecture and releasing multiple growth factors locally that induce new cells and tissue growth. We have identified the specific pulsed electric field parameters in rats that lead to prominent proliferation of the epidermis, formation of microvasculature, and secretion of new collagen at treated areas without scarring. Our results suggest that pulsed electric fields can improve skin function and thus can potentially serve as a novel non-invasive skin therapy for multiple degenerative skin diseases.
Superdrawn crystalline polymers: A new class of high‐strength fiber (1974)

Abstract A new kind of acetal fiber has been discovered which has a tensile strength of 1.7 GPa (250,000 psi) and an elastic modulus of 35 GPa (5 × 10 6 psi). This fiber is produced by a special two‐stage drawing process in the solid state which requires careful control of deformation rate and temperature. Previously known drawn fibers are reported to consist of folded‐chain blocks joined by a limited number of tie‐molecules. It is hypothesized that the second stage of the novel drawing process eliminates the lamella (block) surfaces which act as strength‐limiting stress concentrators. A new type of fiber is created in which any remaining chain‐folds are distributed as defects in a continuous crystal matrix. It is the continuity of the crystal matrix which is believed responsible for the remarkable properties of the fiber.
Expression of vascular endothelial growth factor in human hepatocellular carcinoma (1998)

Vascular endothelial growth factor (VEGF) is thought to take an important role in tumor angiogenesis. The present study examined VEGF expression immunohistochemically in hepatocellular carcinomas (HCCs) in various histological grades and sizes. In HCCs that were composed of cancerous tissues of single histological grade, VEGF expression was the highest in well-differentiated HCCs, followed by moderately differentiated HCCs, and then poorly differentiated HCCs. VEGF positivity gradually decreased with the increase in tumor size. In the nodules larger than 3.0 cm, 36.8% were VEGF-negative. In HCCs consisting of cancerous tissues of two different histological grades, the expression was less intensive in the higher-grade HCC component. VEGF was not expressed in sarcomatous areas, while VEGF was expressed in the surrounding HCC tissues. The expression was also remarkable in the noncancerous tissues in which inflammatory cell infiltration was apparent. VEGF expression was also examined in six HCC cell lines. In reverse-transcription polymerase chain reaction (RT-PCR) analysis, expressions of the two secretion types (VEGF121 and VEGF165) were the highest. Thus, VEGF protein in culture supernatant was measured by using enzyme-linked immunosorbent assay (ELISA) with or without inflammatory cytokines, i.e., interleukin (IL)-1beta, interferon (IFN)-alpha, IFN-gamma, and tumor necrosis factor (TNF)-alpha; and growth factors, i.e., epidermal growth factor (EGF), platelet-derived growth factor (PDGF)-BB, basic fibroblast growth factor (bFGF), and transforming growth factor (TGF)-alpha. As a result, secretion of VEGF from the cell lines was upregulated at various degrees. Based on these findings, VEGF expression in HCC tissues was thought to be related to the histological grade. The findings also indicate that various cytokines and growth factors could cooperatively act to enhance VEGF expressions in HCC.
Purification and characterization of a ferulic acid decarboxylase from Pseudomonas fluorescens (1994)

A ferulic acid decarboxylase enzyme which catalyzes the decarboxylation of ferulic acid to 4-hydroxy-3-methoxystyrene was purified from Pseudomonas fluorescens UI 670. The enzyme requires no cofactors and contains no prosthetic groups. Gel filtration estimated an apparent molecular mass of 40.4 (+/- 6%) kDa, whereas sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed a molecular mass of 20.4 kDa, indicating that ferulic acid decarboxylase is a homodimer in solution. The purified enzyme displayed an optimum temperature range of 27 to 30 degrees C, exhibited an optimum pH of 7.3 in potassium phosphate buffer, and had a Km of 7.9 mM for ferulic acid. This enzyme also decarboxylated 4-hydroxycinnamic acid but not 2- or 3-hydroxycinnamic acid, indicating that a hydroxy group para to the carboxylic acid-containing side chain is required for the enzymatic reaction. The enzyme was inactivated by Hg2+, Cu2+, p-chloromercuribenzoic acid, and N-ethylmaleimide, suggesting that sulfhydryl groups are necessary for enzyme activity. Diethyl pyrocarbonate, a histidine-specific inhibitor, did not affect enzyme activity.
L-trans-Epoxysuccinyl-leucylamido(4-guanidino)butane (E-64) and its analogues as inhibitors of cysteine proteinases including cathepsins B, H and L (1982)

1. L-trans-Epoxysuccinyl-leucylamido(4-guanidino)butane (E-64) at a concentration of 0.5 mM had no effect on the serine proteinases plasma kallikrein and leucocyte elastase or the metalloproteinases thermolysin and clostridial collagenase. In contrast, 10 muM-E-64 rapidly inactivated the cysteine proteinases cathepsins B, H and L and papain (t0.5 = 0.1-17.3s). The streptococcal cysteine proteinase reacted much more slowly, and there was no irreversible inactivation of clostripain. The cysteine-dependent exopeptidase dipeptidyl peptidase I was very slowly inactivated by E-64. 2. the active-site-directed nature of the interaction of cathepsin B and papain with E-64 was established by protection of the enzyme in the presence of the reversible competitive inhibitor leupeptin and by the stereospecificity for inhibition by the L as opposed to the D compound. 3. It was shown that the rapid stoichiometric reaction of the cysteine proteinases related to papain can be used to determine the operational molarity of solutions of the enzymes and thus to calibrate rate assays. 4. The apparent second-order rate constants for the inactivation of human cathepsins B and H and rat cathepsin L by a series of structural analogues of E-64 are reported, and compared with those for some other active-site-directed inhibitors of cysteine proteinases. 5. L-trans-Epoxysuccinyl-leucylamido(3-methyl)butane (Ep-475) was found to inhibit cathepsins B and L more rapidly than E-64. 6. Fumaryl-leucylamido(3-methyl)butane (Dc-11) was 100-fold less reactive than the corresponding epoxide, but was nevertheless about as effective as iodoacetate.
Retrofitting YACs for direct DNA transfer into plant cells (1997)

The utility of plant YAC libraries prepared in conventional YAC vectors would be dramatically increased if these YACs could be used directly for plant transformation. A pair of vectors that allow clones from YAC libraries to be modified (retrofitted) for plant transformation by direct DNA transfer methods, such as particle bombardment or electroporation, has been developed. Modification of the YAC is achieved in two sequential yeast transformation steps by taking advantage of the homologous recombination system in yeast. Using this approach, two plant-selectable marker genes and DNA sequence elements required for copy number amplification in yeast can be introduced into YACs present in yeast strain AB1380. The utility of these vectors is demonstrated by retrofitting YACs that contain inserts ranging in size from 80 to 700 kb. The 6- to 12-fold increase in copy number of these modified YACs facilitates the isolation of YAC DNA for direct DNA transformation methods. Retrofitted YACs were used for particle bombardment to examine the efficiency with which their large DNA inserts are transferred into plant cells. The availability of these retrofitting vectors should facilitate the transfer of YAC DNA inserts into plant cells and thus help bridge the gap between existing mapping techniques and plant transformation procedures.
Effect of a Monoclonal Antibody to PCSK9 on LDL Cholesterol (2012)

Gain-of-function mutations in a serine protease, proprotein convertase subtilisin/kexin 9 (PCSK9), have been associated with high plasma levels of low-density lipoprotein (LDL) cholesterol and an increased incidence of coronary heart disease. Previous studies showed that PCSK9 loss-of-function mutations in patients were associated with low levels of LDL cholesterol and a reduced incidence of coronary heart disease. This suggested that pharmacologic inhibition of PCSK9 could lower LDL cholesterol levels in patients with hypercholesterolemia. REGN727/SAR236553 (REGN727) is an investigational, fully human monoclonal antibody highly specific for human PCSK9. This antibody blocks the interaction of PCSK9 with LDL receptors. This report presents the results of 3 phase 1 studies of REGN727 in humans. The participants were healthy volunteers and patients with familial or nonfamilial hypercholesterolemia. Three separate clinical studies of REGN727 were conducted. The first two compared the effect of single doses of REGN727, administered either intravenously (n = 40) or subcutaneously (n = 32), in healthy volunteers and a placebo. After these 2 single-dose studies, a randomized, placebo-controlled multiple-dose trial that investigated the effect of REGN727in 3 separate cohorts with hypercholesterolemia was conducted. The first cohort was composed of 21 subjects with heterozygous familial hypercholesterolemia and the second cohort consisted of 30 subjects with nonfamilial hypercholesterolemia. All patients in these 2 cohorts were receiving atorvastatin therapy and had a baseline LDL cholesterol level greater than 100 mg/dL (2.6 mM). The third cohort was composed of 10 subjects with nonfamilial hypercholesterolemia who had a baseline LDL cholesterol level greater than 130 mg/dL (3.4 mM); these patients were treated only with a modified diet. Patients in the multiple-dose study were randomly assigned to receive subcutaneous REGN727 (50, 100, or 150 mg) or placebo administered on days 1, 29, and 43. The primary study outcome was the incidence of adverse events. The major secondary end point evaluated was the effect of REGN727 on the lipid profile. None of the subjects receiving REGN727 withdrew from the study early because of an adverse event. There was a significant reduction in levels of LDL cholesterol among patients receiving REGN727 in all studies. Levels of LDL in the multiple-dose study were as follows: REGN727 doses of 50, 100, and 150 mg reduced LDL levels in the combined atorvastatin-treated populations to 77.5 mg/dL (2.00 mL), 61.3 mg/dL (1.59 mL), and 53.8 mg/dL (1.39 mL), respectively; differences in the change from baseline with the 50-, 100-, and 150-mg doses were −39.2, −53.7, and −61.0 percentage points compared with placebo (P < 0.001 for all 3 comparisons). These phase 1 trials suggest a role for PCSK9 in the regulation of LDL cholesterol in humans.
``Was It Good? It Was Provocative.'' Learning the Meaning of Scalar Adjectives (2010)

Texts and dialogues often express information indirectly. For instance, speakers’ answers to yes/no questions do not always straightforwardly convey a ‘yes’ or ‘no ’ answer. The intended reply is clear in some cases (Was it good? It was great!) but uncertain in others (Was it acceptable? It was unprecedented.). In this paper, we present methods for interpreting the answers to questions like these which involve scalar modifiers. We show how to ground scalar modifier meaning based on data collected from the Web. We learn scales between modifiers and infer the extent to which a given answer conveys ‘yes ’ or ‘no’. To evaluate the methods, we collected examples of question–answer pairs involving scalar modifiers from CNN transcripts and the Dialog Act corpus and use response distributions from Mechanical Turk workers to assess the degree to which each answer conveys ‘yes ’ or ‘no’. Our experimental results closely match the Turkers ’ response data, demonstrating that meanings can be learned from Web data and that such meanings can drive pragmatic inference. 1
Phenotypic knockout of VEGF-R2 and Tie-2 with an intradiabody reduces tumor growth and angiogenesisin vivo (2005)

The endothelial cell receptor-tyrosine kinases, VEGF receptor 2 (VEGF-R2) and Tie-2, and their ligands, vascular endothelial growth factor (VEGF) and angiopoietins 1 and 2, respectively, play key roles in tumor angiogenesis. Several studies suggest that the VEGF receptor pathway and the Tie-2 pathway are independent and essential mediators of angiogenesis, leading to the hypothesis that simultaneous interference with both pathways should result in additive effects on tumor growth. In this study, a human melanoma xenograft model (M21) was used to analyze the effects of simultaneous intradiabody depletion of vascular endothelial growth receptor-R2 and Tie-2 on tumor angiogenesis and tumor xenograft growth. The intradiabodies were expressed from recombinant adenovirus delivered through subtumoral injection. Blockade of both VEGF-R2 and Tie-2 pathways simultaneously or the VEGF receptor pathway alone resulted in a significant inhibition of tumor growth and tumor angiogenesis (92.2% and 74.4%, respectively). In addition, immunohistochemical staining of intradiabody-treated tumors demonstrated a decreased number of tumor-associated blood vessels versus control treatment. Previous studies with intrabodies had demonstrated that the Tie-2 receptor pathway was essential for tumor growth. The simultaneous blockade of the VEGF and Tie-2 pathways resulted in effective inhibition of tumor growth and demonstrated the potential of simultaneous targeting of multiple pathways as a therapeutic strategy.
High frequency ultrasound imaging using an active optical detector (1998)

Optical detection of ultrasound has numerous advantages over traditional piezoelectric methods. These systems offer noncontact inspection, rapid scanning capabilities, fine spatial sampling, and large bandwidths. In addition, difficulties associated with conventional ultrasound imaging systems such as cross-talk between elements, electrical connections, and electromechanical resonances are greatly reduced or even eliminated. Because of this, high frequency phased arrays for ultrasound detection can be emulated by accurately positioning and focusing optical beams on a suitable surface, which defines array elements. However, optical systems have lower sensitivity than their piezoelectric counterparts, limiting their widespread use in ultrasound imaging. Active optical detection offers a solution. An active ultrasound detector consisting of a neodymium-doped glass waveguide laser with an optical demodulation system, was built demonstrating enhanced sensitivity while preserving the benefits of traditional passive optical detection.
Building an example application with the Unstructured Information Management Architecture (2004)

IBM's Unstructured Information Management Architecture (UIMA) is a software architecture for developing and deploying unstructured information management (UIM) applications. In this paper we provide a high-level overview of the architecture, introduce its basic components, and describe the set of tools that constitute a UIMA development framework. Then we take the reader through the steps involved in building a simple UIM application, thus highlighting the major UIMA concepts and techniques.