gebhart/patrepeval huggingface dataset:
Sequestration of tau by granulovacuolar degeneration in Alzheimer's disease. (1991)

Antibodies directed against three regions of tau have been used in a histologic study of granulovacuolar degeneration (GVD) in Alzheimer's disease (AD). Granulovascular degeneration complexes, consisting of a dense granule in a less-dense vacuole, were found in hippocampal pyramidal neurons in all patients studied. Anti-tau antibodies directed against the N-and C-termini, and the repeat region of tau, were found to immunolabel the granule of the GVD complex. Intracellular neurofibrillary tangles also were labeled by these antibodies. In particular, MAb6.423, which recognizes tau protein sequestered in paired helical filaments (PHF) in AD, but not the normal tau proteins so far described in human brain, labeled GVD granules. Contrarily, a generic tau marker (MAb7.51), which immunolabels all known isoforms of isolated and expressed tau protein, including PHF-tau, did not label the GVD granule. These findings demonstrate that the entire tau molecule is sequestered within the GVD granule, and that the tau protein found in GVD complexes is antigenically related to that found in PHFs. There is, however, a difference in the way in which the repeat region of tau is incorporated into the two structures, making the MAb7.51 epitope unavailable in the GVD complex. These findings suggest that the formation of GVD complexes in hippocampal pyramidal neurons vulnerable to neurofibrillary degeneration may represent an alternative pathway for dealing with an aberrant molecular complex, which contributes to the formation of GVD granules and neurofibrillary tangles in AD.
A quantum annealing architecture with all-to-all connectivity from local interactions (2015)

Quantum annealers are physical devices that aim at solving NP-complete optimization problems by exploiting quantum mechanics. The basic principle of quantum annealing is to encode the optimization problem in Ising interactions between quantum bits (qubits). A fundamental challenge in building a fully programmable quantum annealer is the competing requirements of full controllable all-to-all connectivity and the quasi-locality of the interactions between physical qubits. We present a scalable architecture with full connectivity, which can be implemented with local interactions only. The input of the optimization problem is encoded in local fields acting on an extended set of physical qubits. The output is-in the spirit of topological quantum memories-redundantly encoded in the physical qubits, resulting in an intrinsic fault tolerance. Our model can be understood as a lattice gauge theory, where long-range interactions are mediated by gauge constraints. The architecture can be realized on various platforms with local controllability, including superconducting qubits, NV-centers, quantum dots, and atomic systems.
Polymeric Nanonozzle Array Fabricated by Sacrificial Template Imprinting (2005)

Polymer nanonozzle arrays are fabricated using a sacrificial template imprinting (STI) approach (see Figure). Polymer sacrificial templates, which can be easily removed after molding, are used in place of rigid masters. This approach avoids generation of structural damage or defects during demolding. The diameter of the sharp end of each nanonozzle is as small as 80 nm, and can be further reduced by silica synthesis on the inner channel surface.
A Comparison of Acute Toxicity of Biodiesel, Biodiesel Blends, and Diesel on Aquatic Organisms (2007)

The increased demand of alternative energy sources has created interest in biodiesel and biodiesel blends; biodiesel is promoted as a diesel substitute that is safer, produces less harmful combustion emissions, and biodegrades more easily. Like diesel spills, biodiesel can have deleterious effects on the aquatic environments. The effect of neat biodiesel, biodiesel blends, and diesel on Oncorhynchus mykiss and Daphnia magna was evaluated using acute toxicity testing. Static nonrenewal bioassays of freshwater organisms containing B100, B50, B20, B5, and conventional diesel fuel were used to compare the acute effects of biodiesel to diesel. Mortality was the significant end point measured in this study; percent mortality and lethal concentration (LC50) at different exposure times were determined from the acute toxicity tests performed. Trials were considered valid if the controls exhibited > 90% survival. Based on percentage of mortality and LC50 values, a toxicity ranking of fuels was developed.
cDNA sequence analysis of a 29-kDa cysteine-rich surface antigen of pathogenic Entamoeba histolytica. (1990)

A gamma gt11 cDNA library was constructed from poly(U)-Sepharose-selected Entamoeba histolytica trophozoite RNA in order to clone and identify surface antigens. The library was screened with rabbit polyclonal anti-E. histolytica serum. A 700-base-pair cDNA insert was isolated and the nucleotide sequence was determined. The deduced amino acid sequence of the cDNA revealed a cysteine-rich protein. DNA hybridizations showed that the gene was specific to E. histolytica since the cDNA probe reacted with DNA from four axenic strains of E. histolytica but did not react with DNA from Entamoeba invadens, Acanthamoeba castellanii, or Trichomonas vaginalis. The insert was subcloned into the expression vector pGEX-1 and the protein was expressed as a fusion with the C terminus of glutathione S-transferase. Purified fusion protein was used to generate 22 monoclonal antibodies (mAbs) and a mouse polyclonal antiserum specific for the E. histolytica portion of the fusion protein. A 29-kDa protein was identified as a surface antigen when mAbs were used to immunoprecipitate the antigen from metabolically 35S-labeled live trophozoites. The surface location of the antigen was corroborated by mAb immunoprecipitation of a 29-kDa protein from surface-125I-labeled whole trophozoites as well as by the reaction of mAbs with live trophozoites in an indirect immunofluorescence assay performed at 4 degrees C. Immunoblotting with mAbs demonstrated that the antigen was present on four axenic isolates tested. mAbs recognized epitopes on the 29-kDa native antigen on some but not all clinical isolates tested.
Tuberculosis and opportunistic infections: relevance to biologic agents. (2005)

With the expanding use of biologic agents, in particular TNF inhibitors, tuberculosis and other opportunistic infections have become an important and growing concern in rheumatology. Clinicians using these therapies should have an understanding of the scope of the problem, the underlying scientific rationale, as well as the optimal approaches to screening, monitoring and treatment.
Amino acid sequence of the first constant region domain and the hinge region of the delta heavy chain of human IgD. (1981)

We have determined the amino acid sequence of the first constant (C) region domain (C delta 1) and the hinge region of the delta heavy chain of human IgD WAH and also the sequence of the adjacent COOH-terminal portion of the variable (V) region, including the JH region. Together with the sequence of the Fc fragment already reported, this establishes the complete amino acid sequence of the C region of the human delta chain and confirms the presence of three C region domains in human IgD. Although the CH1 domains of the five classes of human heavy chains have the expected degree of homology (approximately 30%), the homology of the C delta 1 domains of the human and mouse chains is less than that exhibited by the CH1 domains of other pairs of human and mouse heavy chains. The hinge region of the human delta chain has an unusual structure; the NH2-terminal half has four (or five) GalN oligosaccharides attached, whereas the COOH-terminal half lacks carbohydrate, is dissimilar in sequence, and has a high charge. A computer search verified that the GalN-rich segment has a high degree of identity in sequence with the middle portion of the human C mu 2 domain and that the high-charge segment is related to the same sequence. We propose that the two segments of the human delta hinge have a common evolutionary origin and arose by duplication and independent mutation of a hinge exon derived from the ancestral gene for the C mu 2 domain.
Rituximab for reduction of anti-HLA antibodies in patients awaiting renal transplantation: 1. Safety, pharmacodynamics, and pharmacokinetics1 (2004)

RTX can be safely administered and may be an effective agent to reduce high-titer anti-HLA Abs in subjects awaiting kidney transplantation.
Polycondensed heterocycles. I. Synthesis of 11‐oxo‐5H, 11H‐pyrrolo[2,1‐c][1,4]benzothiazepine, Derivative of a novel ring system (1985)

Abstract The synthesis of the title compound 4 by cyclization of 1‐(2‐ethoxycarbonylthiobenzyl)pyrrole 9 , prepared by treating with ethyl chloroformate the 1‐(2‐mercaptobenzyl)pyrrole 7 previously obtained by debenzylation of 1‐(2‐benzylthiobenzyl)pyrrrole 6 , failed. On the other hand 4 was successfully synthesized by intramolecular cyclization of 1‐(2‐mercaptobenzyl)pyrrole‐2‐carboxylic acid 15 by DMAP ‐catalyzed DCC method. The pyrrole 6 and 1‐(2‐benzylthiobenzyl)pyrrole‐2‐carboxaldehyde 11 were useful as starting materials to obtain 1‐(2‐benzylthiobenzyl)pyrrole‐2‐carbonitrile 13 , which was hydrolyzed to corresponding amide 16 . Debenzylation of 16 afforded 1‐(2‐mercaptobenzyl)pyrrole‐2‐carboxyamide 17 , whose hydrolysis led to required acid 15 .
Secretory IgA Specific for a Conserved Epitope on gp41 Envelope Glycoprotein Inhibits Epithelial Transcytosis of HIV-1 (2001)

As one of the initial mucosal transmission pathways of HIV (HIV-1), epithelial cells translocate HIV-1 from apical to basolateral surface by nondegradative transcytosis. Transcytosis is initiated when HIV-1 envelope glycoproteins bind to the epithelial cell membrane. Here we show that the transmembrane gp41 subunit of the viral envelope binds to the epithelial glycosphingolipid galactosyl ceramide (Gal Cer), an alternative receptor for HIV-1, at a site involving the conserved ELDKWA epitope. Disrupting the raft organization of the Gal Cer-containing microdomains at the apical surface inhibited HIV-1 transcytosis. Immunological studies confirmed the critical role of the conserved ELDKWA hexapeptide in HIV-1 transcytosis. Mucosal IgA, but not IgG, from seropositive subjects targeted the conserved peptide, neutralized gp41 binding to Gal Cer, and blocked HIV-1 transcytosis. These results underscore the important role of secretory IgA in designing strategies for mucosal protection against HIV-1 infection.
Divergent Results Using Clinic and Ambulatory Blood Pressures (2010)

Patients with resistant hypertension are at increased risk for cardiovascular events. The addition of new treatments to existing therapies will help achieve blood pressure (BP) goals in more resistant hypertension patients. In the current trial, 849 patients with resistant hypertension receiving ≥3 antihypertensive drugs, including a diuretic, at optimized doses were randomized to the selective endothelin A receptor antagonist darusentan, placebo, or the central α-2 agonist guanfacine. The coprimary end points of the study were changes from baseline to week 14 in trough, sitting systolic BP, and diastolic BP measured in the clinic. Decreases from baseline to week 14 in systolic BP for darusentan (-15±14 mm Hg) were greater than for guanfacine (-12±13 mm Hg; P<0.05) but not greater than placebo (-14±14 mm Hg). Darusentan, however, reduced mean 24-hour systolic BP (-9±12 mm Hg) more than placebo (-2±12 mm Hg) or guanfacine (-4±12 mm Hg) after 14 weeks of treatment (P<0.001 for each comparison). The most frequent adverse event associated with darusentan was fluid retention/edema at 28% versus 12% in each of the other groups. More patients withdrew because of adverse events on darusentan as compared with placebo or guanfacine. We conclude that darusentan provided greater reduction in systolic BP in resistant hypertension patients as assessed by ambulatory BP monitoring, in spite of not meeting its coprimary end points. The results of this trial highlight the importance of ambulatory BP monitoring in the design of hypertension clinical studies.
STAT3 inhibitor, cucurbitacin I, is a novel therapeutic agent for osteosarcoma (2016)

The development of clinical agents remains a costly and time-consuming process. Although identification of new uses of existing drugs has been recognized as a more efficient approach for drug discovery than development of novel drugs, little screening of drugs that might be used for a rare malignant tumor such as osteosarcoma (OS) has been performed. In this study, we attempted to identify new molecular targeted agents for OS by employing Screening Committee of Anticancer Drugs (SCADS) kits. To screen compounds for OS treatment, their effect on cell viability of the OS cell lines 143B, MG63, HOS, SAOS-2, and HUO9 were evaluated. Candidate drugs were narrowed down based on a global anti-proliferative effect against these five OS cell lines. After excluding cytotoxic compounds and compounds unsuitable for in vivo administration, cucurbitacin I was extracted. Cucurbitacin I has been found to have cytotoxic and anti-proliferative properties against several tumors through inhibition of signal transducer and activator of transcription 3 (STAT3) activation. Cucurbitacin I dose- and time-dependently inhibited the proliferation of all five OS cell lines. Following cucurbitacin I treatment, STAT3 was inactivated and analysis of Mcl-1, cleaved PARP and caspase-3 indicated apoptosis induction. Expression of cell cycle regulator proteins, such as phospho-cyclin D1, c-Myc and survivin, were suppressed. Finally, cucurbitacin I potently inhibited the tumor growth of human OS 143B cells in nude mice. Our in vitro and in vivo results suggest that STAT3 inhibition by cucurbitacin I will be an effective and new approach for the treatment of OS.
New Technologies for Analysis of Extracellular Vesicles (2018)

Extracellular vesicles (EVs) are diverse, nanoscale membrane vesicles actively released by cells. Similar-sized vesicles can be further classified (e.g., exosomes, microvesicles) based on their biogenesis, size, and biophysical properties. Although initially thought to be cellular debris, and thus under-appreciated, EVs are now increasingly recognized as important vehicles of intercellular communication and circulating biomarkers for disease diagnoses and prognosis. Despite their clinical potential, the lack of sensitive preparatory and analytical technologies for EVs poses a barrier to clinical translation. New analytical platforms including molecular ones are thus actively being developed to address these challenges. Recent advances in the field are expected to have far-reaching impact in both basic and translational studies. This article aims to present a comprehensive and critical overview of emerging analytical technologies for EV detection and their clinical applications.
Murine pregnancy leads to reduced proliferation of maternal thymocytes and decreased thymic emigration (2007)

During mammalian pregnancy the maternal thymus undergoes significant involution, and then recovers in size after birth. The mechanism behind this involution is not known, but it has been suggested that elevated levels of hormones during pregnancy induce the involution. We have recently shown that injection of 17beta-oestradiol into mice causes loss of early thymocyte precursors and inhibits proliferation of developing thymocytes. This suggests that elevated oestrogen in pregnancy may contribute to thymic involution. We have investigated this idea by examining the fate of thymocytes during mouse pregnancy in much greater detail than has been previously reported. Looking over a broad time-course, we find that pregnancy does not affect thymocyte precursor populations in the bone marrow, but induces a profound loss of early thymic progenitors in the thymus as early as day 12 x 5 of pregnancy. This loss is accompanied by decreased thymocyte proliferation, which returns to normal 2-4 days postpartum. No enhancement of apoptosis is detectable at any stage of pregnancy. We also find that there is a reduction in recent thymic emigrants after oestrogen treatment and at day 17 x 5 of pregnancy, suggesting that thymic involution during pregnancy influences the peripheral T-cell repertoire. The similarities between oestrogen-mediated involution and pregnancy-mediated involution suggest that oestrogen is a significant contributor to loss of thymocyte cellularity during pregnancy, and probably functions primarily by reducing thymocyte proliferation.
Cleaving DNA with DNA (1998)

A DNA structure is described that can cleave single-stranded DNA oligonucleotides in the presence of ionic copper. This "deoxyribozyme" can self-cleave or can operate as a bimolecular complex that simultaneously makes use of duplex and triplex interactions to bind and cleave separate DNA substrates. Bimolecular deoxyribozyme-mediated strand scission proceeds with a kobs of 0.2 min-1, whereas the corresponding uncatalyzed reaction could not be detected. The duplex and triplex recognition domains can be altered, making possible the targeted cleavage of single-stranded DNAs with different nucleotide sequences. Several small synthetic DNAs were made to function as simple "restriction enzymes" for the site-specific cleavage of single-stranded DNA.
Molecular characterization of acute myeloid leukemia and its impact on treatment (2007)

We review the molecular heterogeneity within already established categories of acute myeloid leukemia and discuss how these data may translate into prognostic, molecular-based therapy stratification to improve patient outcome.
Inhibitors of Raf Kinase Activity Block Growth of Thyroid Cancer Cells with RET/PTC or BRAF Mutations In vitro and In vivo (2006)

Compounds that inhibit kinase activity are effective growth inhibitors for poorly differentiated thyroid cancer cell lines with either RET or RAF mutations, and hold promise for treatment of most forms of papillary thyroid carcinoma.
Bindings between names and objects in a persistent system (2003)

The paper addresses the issues of uniformity and simplicity in the area of the bindings between user object references (names) and system object references in persistent systems. Uniform treatment of these entities will allow simplification of the mechanisms which handle them. The authors propose a design, following an object-based approach, in which user environments are structured as collections of bindings. All objects which a user may access have a corresponding binding in the user's environment. All bindings are handled by the same mechanisms. There are no special cases-all data structures in the system (or the objects used to contain the data structures) are regarded as conceptually equivalent for purposes of storage, retrieval and activation. This ensures uniformity across the name space.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
High-Level Expression and Characterization of a Purified 142-Residue Polypeptide of the Prion Protein (1996)

The major, and possible only, component of the infectious prion is the scrapie prion protein (PrPSc); the protease resistant core of PrPSc is PrP 27-30, a protein of approximately 142 amino acids. PrPSc is derived from the cellular PrP isoform (PrPC) by a post-transliatonal process in which a profound conformational change occurs. Syrian hamster (SHa) PrP genes of varying length ranging from the N- and C- terminally truncated 90-228 up to the full-length mature protein 23-231 were inserted into various secretion and intracellular expression vectors that were transformed into Escherichia coli deficient for proteases. Maximum expression was obtained for a truncated SHaPrP containing residues 90-231, which correspond to the sequence of PrP 27-30; disruption of the bacteria using a microfluidizer produced the highest yields of this protein designated rPrP. After solubilization of rPrP in 8 M GdnHC1, it was purified by size exclusion chromatography and reversed phase chromatography. During purification the recovery was approximately 50%, and from each liter of E. coli culture, approximately 50 mg of purified rPrP was obtained. Expression of the longer species containing the basic N-terminal region was less successful and was not pursued further. The primary structure of rPrP was verified by Edman sequencing and mass spectrometry, and secondary structure determined by circular dichroism and Fourier transform infrared spectroscopy. When rPrP was purified under reducing conditions, it had a high beta-sheet content and relatively low solubility similar to PrPSc, particularly at pH values > 7. Refolding of rPrP by oxidation to form a disulfide bond between the two Cys residues of this polypeptide produced a soluble protein with a high alpha-helical content similar to PrPC. These multiple conformations of rPrP are reminiscent of the structural plurality that characterizes the naturally occurring PrP isoforms. The high levels of purified rPrP which can now be obtained should facilitate determination of the multiple tertiary structures that Prp can adopt.
Isolation of Halotolerant, Thermotolerant, Facultative Polymer-Producing Bacteria and Characterization of the Exopolymer (1986)

Over 200 bacterial strains were selected for anaerobic growth at 50 degrees C and extracellular polysaccharide production in a sucrose-mineral salts medium with NaNO(3) and up to 10% NaCl. The predominant cell type was an encapsulated gram-positive, motile, facultative sporeforming rod similar to Bacillus species. Strain SP018 grew and produced the polysaccharide on a variety of substrates at salinities up to 12% NaCl. Good polymer production only occurred anaerobically and was optimal between 4 and 10% NaCl. The ethanol-precipitated SP018 polymer was a charged heteropolysaccharide that contained glucose, mannose, arabinose, ribose, and low levels of allose and glucosamine. The SP018 polymer showed pseudoplastic behavior, was resistant to shearing, and had a higher viscosity at dilute concentrations and at elevated temperatures than xanthan gum. High-ionic-strength solutions reversibly decreased the viscosity of SP018 polymer solutions. The bacterium and the associated polymer have many properties that make them potentially useful for in situ microbially enhanced oil recovery processes.
Regulatory mutations in Sin recombinase support a structure‐based model of the synaptosome (2009)

The resolvase Sin regulates DNA strand exchange by assembling an elaborate interwound synaptosome containing catalytic and regulatory Sin tetramers, and an architectural DNA-bending protein. The crystal structure of the regulatory tetramer was recently solved, providing new insights into the structural basis for regulation. Here we describe the selection and characterization of two classes of Sin mutations that, respectively, bypass or disrupt the functions of the regulatory tetramer. Activating mutations, which allow the catalytic tetramer to assemble and function independently at site I (the crossover site), were found at approximately 20% of residues in the N-terminal domain. The most strongly activating mutation (Q115R) stabilized a catalytically active synaptic tetramer in vitro. The positions of these mutations suggest that they act by destabilizing the conformation of the ground-state site I-bound dimers, or by stabilizing the altered conformation of the active catalytic tetramer. Mutations that block activation by the regulatory tetramer mapped to just two residues, F52 and R54, supporting a functional role for a previously reported crystallographic dimer-dimer interface. We suggest how F52/R54 contacts between regulatory and catalytic subunits might promote assembly of the active catalytic tetramer within the synaptosome.
Elevation of Plasma High-Density Lipoprotein Concentration Reduces Interleukin-1–Induced Expression of E-Selectin in an In Vivo Model of Acute Inflammation (2001)

These observations demonstrate the potential anti-inflammatory action of HDLs and provide support for the further investigation of the mechanisms underlying the inhibitory effects of HDLs on endothelial cell activation.