gebhart/patrepeval huggingface dataset:
Effect of erythrocyte transbilayer phospholipid distribution on fusion with vesicular stomatitis virus (1990)

To identify the specific component(s) in the target membrane involved in fusion of vesicular stomatitis virus (VSV), we examined the interaction of the virus with human erythrocyte membranes with asymmetric and symmetric bilayer distributions of phospholipids. Fusion was monitored spectrofluorometrically by the octadecylrhodamine dequenching assay. Fusion of VSV with lipid-symmetric erythrocyte ghosts was rapid at 37 degrees C and low pH, whereas little or no fusion was observed with lipid-asymmetric ghosts. Conversion of phosphatidylserine in the lipid-symmetric ghost membrane to phosphatidylethanolamine by means of the enzyme phosphatidylserine decarboxylase did not alter the target membrane's susceptibility to VSV fusion. Spin-labeled phospholipid analogues with phosphatidylserine, phosphatidylethanolamine, and phosphatidylcholine headgroups incorporated into the outer leaflet of lipid-asymmetric erythrocytes did not render those membranes fusogenic. Electron spin resonance spectra showed an increased mobility of a phosphatidylcholine spin-label incorporated into the outer leaflet of lipid-symmetric erythrocyte ghosts as compared to that of lipid-asymmetric ghosts. These results indicate that the susceptibility to VSV fusion is not dependent on any particular phospholipid but rather is related to packing characteristics of the target membrane.
Human metalloprotease/disintegrin-like (MDC) gene: exon-intron organization and alternative splicing (1995)

A recently identified gene encoding a metalloprotease-like, disintegrin-like, cysteine-rich protein (MDC) represents a candidate tumor suppressor gene for human breast cancer based on its location within a minimal region of chromosome 17q21 previously defined by tumor deletion mapping. The work reported here has shown that the MDC gene consists of 28 exons interrupted by relatively short introns, most of them 67 bp to 5 kb in length. We have identified two forms of transcripts generated by alternative splicing. The more abundant form encodes a protein of 769 amino acids; the other, a previously described cDNA, encodes 524 amino acids. Exons 1a, 1b, 1c, 1d, and 2-7 encode a proprotein domain; exons 7-13, a metalloprotease-like domain; exons 14-17, a disintegrin domain; exons 18-22, a cysteine-rich domain, including an epidermal growth factor (EGF)-like repeat domain within exons 21 and 22; exon 23, a transmembrane domain; and exons 24 and 25, a short cytoplasmic domain. These results show that human MDC contains a mosaic of exons capable of encoding several functional domains.
A Synthesis Methodology for Ternary Logic Circuits in Emerging Device Technologies (2017)

Automatic synthesis of digital circuits has played a key role in obtaining high-performance designs. While considerable work has been done in the past, emerging device technologies call for a need to re-examine the synthesis approaches, so that better circuits that harness the true power of these technologies can be developed. This paper presents a methodology for synthesis applicable to devices that support ternary logic. We present an algorithm for synthesis that combines a geometrical representation with unary operators of multivalued logic. The geometric representation facilitates scanning appropriately to obtain simple sum-of-products expressions in terms of unary operators. An implementation based on Python is described. The power of the approach lies in its applicability to a wide variety of circuits. The proposed approach leads to the savings of 26% and 22% in transistor-count, respectively, for a ternary full-adder and a ternary content-addressable memory (TCAM) over the best existing designs. Furthermore, the proposed approach requires, on an average, less than 10% of the number of the transistors in comparison with a recent decoder-based design for various ternary benchmark circuits. Extensive HSPICE simulation results show roughly 92% reduction in power-delay product (PDP) for a 12 ×12 TCAM and 60% reduction in PDP for a 24-ternary digit barrel shifter over recent designs.
Antibiotic resistance in Burkholderia cepacia at two regional cystic fibrosis centres in Northern Ireland: is there a need for synergy testing? (2001)

a population of 230 (3%), and all of these children have B. cepacia genomovar III. Antimicrobial susceptibility assays were performed on all recent BCC isolates employing a modified Stokes’ disc diffusion assay on DST agar (Oxoid Ltd, Basingstoke, UK) supplemented with 5% v/v defibrinated horse blood, with the following antibiotics (� g): ciprofloxacin (5), colistin (10), ceftazidime (30), azlocillin (75), aztreonam (30), imipenem (10), gentamicin (10), tobramycin (10), meropenem (10), amikacin (30), temicillin (30) and piperacillin/tazobactam (110). Antibiotic disc concentrations were similar for adults and children with the exception of colistin, which was 25 � g for testing with children. Susceptibility data are shown in the Table. Overall, the paediatric isolates were more susceptible to several antibiotics than the adult BCC organisms, and this may allow for an opportunity to attempt to eradicate the organism on first isolation from the lung, when the organism is still relatively susceptible. In addition, the B. multivorans isolates were more susceptible in the adult patients than B. cepacia genomovar III isolates. However, it was noted that 81% of the adults were infected with a pan-resistant genomovar III epidemic organism. With the emergence of pan-resistance in BCC organisms, in particular in B. cepacia genomovar III, clinicians are often compromised in choosing combinations of two or more agents in order to obtain a synergic effect, in the absence of any in vitro synergy data. Previous data from North America, where such synergy testing is available on request, have indicated various combinations with limited activity in vitro. 1 In this study, 47% of isolates demonstrated antagonism when a second antibiotic was added, and triple combinations of tobramycin, meropenem and an additional antibiotic were most effective and were bactericidal against 81‐93% of isolates tested. However, no data are available to indicate the in vitro efficacy of these combinations against UK isolates. Recently, Mackay et al. 4 examined a chequerboard method and time‐kill curves to examine antagonism and synergy in seven BCC isolates, and showed synergy by time‐kill curve with a combination of rifampicin and ceftazidime, but were unable to demonstrate antagonism in any of the combinations employed. In conclusion, antimicrobial management of BCC in CF remains a complex problem, and hence some form of synergy testing, especially testing to examine and prevent antagonism, should form a basis to help guide more efficacious combinations of agents used. Development of a UK reference laboratory for antagonism/synergy testing of isolates should be evaluated further to help guide optimal and appropriate therapy in such patients.
Compilation and analysis of 54-dependent promoter sequences (1999)

Promoters recognized by the RNA-polymerase with the alternative sigma factor sigma(54) (Esigma54) are unique in having conserved positions around -24 and -12 nucleotides upstream from the transcriptional start site, instead of the typical -35 and -10 boxes. Here we compile 186 -24/-12 promoter sequences reported in the literature and generate an updated and extended consensus sequence. The use of the extended consensus increases the probability of identifying genuine -24/-12 promoters. The effect of several reported mutations at the -24/-12 elements on RNA-polymerase binding and promoter strength is discussed in the light of the updated consensus.
Intracellular glutathione determines bortezomib cytotoxicity in multiple myeloma cells (2016)

Multiple myeloma (myeloma in short) is an incurable cancer of antibody-producing plasma cells that comprise 13% of all hematological malignancies. The proteasome inhibitor bortezomib has improved treatment significantly, but inherent and acquired resistance to the drug remains a problem. We here show that bortezomib-induced cytotoxicity was completely dampened when cells were supplemented with cysteine or its derivative, glutathione (GSH) in ANBL-6 and INA-6 myeloma cell lines. GSH is a major component of the antioxidative defense in eukaryotic cells. Increasing intracellular GSH levels fully abolished bortezomib-induced cytotoxicity and transcriptional changes. Elevated intracellular GSH levels blocked bortezomib-induced nuclear factor erythroid 2-related factor 2 (NFE2L2, NRF2)-associated stress responses, including upregulation of the xCT subunit of the Xc- cystine-glutamate antiporter. INA-6 cells conditioned to increasing bortezomib doses displayed reduced bortezomib sensitivity and elevated xCT levels. Inhibiting Xc- activity potentiated bortezomib-induced cytotoxicity in myeloma cell lines and primary cells, and re-established sensitivity to bortezomib in bortezomib-conditioned cells. We propose that intracellular GSH level is the main determinant of bortezomib-induced cytotoxicity in a subset of myeloma cells, and that combined targeting of the proteasome and the Xc- cystine-glutamate antiporter can circumvent bortezomib resistance.
Antithrombotic Effects of Naturally Derived Products on Coagulation and Platelet Function (2010)

To date, there have been few systematic studies of the antiplatelet and/or anticoagulant effects of natural products. According to the Natural Medicines Comprehensive Database, approximately 180 dietary supplements have the potential to interact with warfarin, and more than 120 may interact with aspirin, clopidogrel, and dipyridamole. These include anise and dong quai (anticoagulant effects); omega 3-fatty acids in fish oil, ajoene in garlic, ginger, ginko, and vitamin E (antiplatelet properties); fucus (heparin-like activity); danshen (antithrombin III-like activity and anticoagulant bioavailability); and St. John's Wort and American Ginseng (interference with drug metabolism). Other supplements, such as high doses of vitamin E (vitamin K antagonist activity), alfalfa (high-vitamin K content), and coenzyme Q10 (vitamin K-like activity), may affect blood clotting, which is dependent on vitamin K. Studies are needed to understand the role of various dietary supplements in thrombosis and their interactions with standard anticoagulants and antiplatelet drugs.
Learning to Hash with Binary Reconstructive Embeddings (2009)

Fast retrieval methods are increasingly critical for many large-scale analysis tasks, and there have been several recent methods that attempt to learn hash functions for fast and accurate nearest neighbor searches. In this paper, we develop an algorithm for learning hash functions based on explicitly minimizing the reconstruction error between the original distances and the Hamming distances of the corresponding binary embeddings. We develop a scalable coordinate-descent algorithm for our proposed hashing objective that is able to efficiently learn hash functions in a variety of settings. Unlike existing methods such as semantic hashing and spectral hashing, our method is easily kernelized and does not require restrictive assumptions about the underlying distribution of the data. We present results over several domains to demonstrate that our method outperforms existing state-of-the-art techniques. 1
N-cadherin localization in early heart development and polar expression of Na+, K+-ATPase, and integrin during pericardial coelom formation and epithelialization of the differentiating myocardium (1992)

N-cadherin, a Ca(2+)-dependent cell adhesion molecule, has been localized previously to the mesoderm during chick gastrulation and to adherens junctions in beating avian hearts. However, a systematic study of the dynamic nature of N-cadherin localization in the critical early stages of heart development is lacking. The presented work defines the changes in the spatial and temporal expression of N-cadherin during early stages of chick heart development, principally between Hamburger and Hamilton stages 5-8, 18-29 hr of development. During gastrulation N-cadherin appears evenly distributed in the heart forming region. As development proceeds to form the pericardial coelom (stages 6, 7, and 8, i.e., between 22 and 26 hr of development) N-cadherin localization becomes restricted to the more central areas of the mesoderm. The localization also shows a periodicity that correlates closely with the distance between foci of cavities that eventually coalesce to form the coelom. This distribution suggests that N-cadherin may have a function in the sorting out of somatic and splanchnic mesoderm cells to form the coelom. This separation of the mesoderm in the embryo for the first time physically delineates the precardiac mesoderm population. Concomitant with cell sorting during coelom formation, the precardiac cells change shape and show a distinct polarity as conveyed by (1) the apical expression of N-cadherin on precardiac cell surfaces lining the pericardial coelom, (2) the primarily lateral expression of Na+,K(+)-ATPase, and (3) an enrichment of integrin (beta 1 subunit) on basal cell surfaces. The somatic mesoderm cells apparently down-regulate N-cadherin expression. N-cadherin is also absent from the precardiac cells close to the endoderm. The latter cells eventually form the endocardium, i.e., the endothelial lining of the heart. By contrast, in the tubular, beating heart N-cadherin is found throughout the myocardium. In summary, immunolocalization patterns of N-cadherin during early cardiogenesis suggest that this cell adhesion molecule has a major role in the dynamics of pericardial coelom formation. Subsequently, its continued expression during cell differentiation of the cardiomyocyte to form the myocardium, but not endocardium, suggests N-cadherin is an essential morphoregulatory molecule in heart organogenesis.
The Nanoaquarium: A Platform for In Situ Transmission Electron Microscopy in Liquid Media (2010)

Transmission electron microscopes (TEMs) and scanning transmission electron microscopes (STEMs) are powerful tools for imaging on the nanoscale. These microscopes cannot be typically used to image processes taking place in liquid media because liquid simply evaporates in the high-vacuum environment of the microscope. In order to view a liquid sample, it is thus necessary to confine the liquid in a sealed vessel to prevent evaporation. Additionally, the liquid layer must be very thin to minimize electron scattering by the suspending medium. To address these issues, we have developed a flow cell with a height of tens of nanometers, sandwiched between two thin silicon nitride membranes. The cell is equipped with electrodes for actuation and sensing. The cell is thin enough to allow the transmission of electrons and the real-time imaging of nanoparticles suspended in liquid. This paper details the fabrication process, which relies on plasma-activated wafer bonding. Some of the advantages of our nanoaquarium include the thinnest observation chamber of any reported in situ TEM/STEM device, integrated electrodes for sensing and actuation, and wafer-scale processing that allows bulk device production. Device performance was demonstrated by STEM imaging of gold and polystyrene nanoparticles suspended in water with excellent resolution. Potential applications of the device include imaging of colloidal crystal formation, aggregation, nanowire growth, electrochemical deposition, and biological interactions.
Comparison of human adult and fetal expression and identification of 535 housekeeping/maintenance genes (2000)

Gene expression levels of about 7,000 genes were measured in 11 different human adult and fetal tissues using high-density oligonucleotide arrays to identify genes involved in cellular maintenance. The tissues share a set of 535 transcripts that are turned on early in fetal development and stay on throughout adulthood. Because our goal was to identify genes that are involved in maintaining cellular function in normal individuals, we minimized the effect of individual variation by screening mRNA pooled from many individuals. This information is useful for establishing average expression levels in normal individuals. Additionally, we identified transcripts uniquely expressed in each of the 11 tissues.
Natural antibodies against phosphorylcholine as potential protective factors in SLE (2008)

Low levels of anti-PC could be of importance in SLE. Anti-BSA and anti-PS and low levels of anti-PC could contribute to development of CVD in SLE.
Business cycle and monetary policy analysis with market rigidities and financial frictions (2013)

We describe a dynamic macroeconomic model that incorporates firm-level borrowing constraints, competitive CES loan production, and rigidities on both setting prices and wages. The external finance premium (interest-rate spread) is countercyclical with technology and financial shocks, and procyclical with consumption spending shocks. The real effects of financial shocks are significantly amplified when either considering greater rigidities for price/wage setting or a low elasticity of substitution in loan production (banking real rigidities). In the monetary policy analysis, a stabilizing Taylor (1983)-style rule performs slightly better when incorporating a positive and small response coefficient to the external finance premium.
Stromal Cell–Derived Factor-1α Is Cardioprotective After Myocardial Infarction (2008)

These findings suggest that SDF-1alpha may serve a tissue-protective and regenerative role for solid organs suffering a hypoxic insult.
N,N‐Diphospholylamines—A New Family of Ligands for Highly Active, Chromium‐Based, Selective Ethene Oligomerisation Catalysts (2013)

Abstract A series of new diphosphazane (PNP) ligands that contain 2,3,4,5‐tetraethylphosphole or dibenzophosphole moieties has been synthesised. The new compounds have been screened for chromium‐catalysed, selective ethene oligomerisation by in situ combination with CrCl 3 (thf) 3 and methylaluminoxane (MAO). The ligands derived from 2,3,4,5‐tetraethylphosphole produce highly active catalysts for ethene oligomerisation, which show excellent selectivity to C 6 and C 8 linear α‐olefins. Complexes of the form [Cr(CO) 4 L] were synthesised and studied by IR spectroscopy and single‐crystal XRD. Variable‐temperature NMR spectroscopy was used to investigate restricted PN rotation in compounds with bulky nitrogen substituents.
Isolation of the gene encoding the human T-lymphocyte differentiation antigen Leu-2 (T8) by gene transfer and cDNA subtraction. (1984)

We report the isolation of genomic and cDNA clones encoding the human T-lymphocyte cell-surface differentiation antigen, Leu-2 (T8), by use of a combination of transfection, fluorescence-activated cell-sorting, and subtractive cDNA hybridization. We constructed a cDNA library with mRNA from a mouse L-cell transfectant in which the human Leu-2 gene is expressed and amplified. We identified Leu-2 cDNA clones by screening with a selected cDNA probe from a second amplified Leu-2 transfectant. This probe contained cDNA species not removed by hybridization with L-cell mRNA. A Leu-2 cDNA clone was used to isolate a genomic clone. Transfection with DNA from this clone resulted in a high number of Leu-2 transfectants. This approach can be used to clone genes coding for other cell-surface molecules.
The Importance of Sodium Pyruvate in Assessing Damage Produced by Hydrogen Peroxide (1997)

Instability of hydrogen peroxide solutions was noted during the experimental exposure of human cells in culture to hydrogen peroxide in experiments designed to study the production and repair of DNA single-strand breaks. A hydrogen peroxide concentrate was diluted into culture medium, which was then added to experimental cell cultures at various times, with all cultures assessed for DNA damage at 2 h. Only cells treated by the first addition had observable DNA damage. This result was unexpected since these cells had had the maximum repair time. It was determined that the hydrogen peroxide had been eliminated by the culture medium. To determine the mechanism of this elimination, 200 microM hydrogen peroxide was added to various cell culture components, and the solutions were assayed for hydrogen peroxide after 1 h at 37 degrees C. Although most components (except the balanced salts) showed some hydrogen peroxide degradation, it was found that sodium pyruvate was most effective, by a wide margin, in eliminating hydrogen peroxide and its toxic effects. This was confirmed by addition of pyruvate to balanced salt solutions or buffers, and observing the same elimination of hydrogen peroxide. We subsequently found a few earlier reports describing the decarboxylation reaction between hydrogen peroxide and pyruvate, but no kinetic measurements have been published and there seems to be no general appreciation for the very high efficiency of this reaction. The present work presents a preliminary assessment of the importance of pyruvate in the study of hydrogen peroxide and other reactive oxygen species in mammalian cell culture.
Crystal Structures of HIV-1 Reverse Transcriptase with Picomolar Inhibitors Reveal Key Interactions for Drug Design (2012)

X-ray crystal structures at 2.9 Å resolution are reported for two complexes of catechol diethers with HIV-1 reverse transcriptase. The results help elucidate the structural origins of the extreme antiviral activity of the compounds. The possibility of halogen bonding between the inhibitors and Pro95 is addressed. Structural analysis reveals key interactions with conserved residues P95 and W229 of importance for design of inhibitors with high potency and favorable resistance profiles.
Inhibition of Double-Stranded RNA-Dependent Protein Kinase PKR by Vaccinia Virus E3: Role of Complex Formation and the E3 N-Terminal Domain (1998)

The human double-stranded RNA (dsRNA)-dependent protein kinase PKR inhibits protein synthesis by phosphorylating translation initiation factor 2alpha (eIF2alpha). Vaccinia virus E3L encodes a dsRNA binding protein that inhibits PKR in virus-infected cells, presumably by sequestering dsRNA activators. Expression of PKR in Saccharomyces cerevisiae inhibits protein synthesis by phosphorylation of eIF2alpha, dependent on its two dsRNA binding motifs (DRBMs). We found that expression of E3 in yeast overcomes the lethal effect of PKR in a manner requiring key residues (Lys-167 and Arg-168) needed for dsRNA binding by E3 in vitro. Unexpectedly, the N-terminal half of E3, and residue Trp-66 in particular, also is required for anti-PKR function. Because the E3 N-terminal region does not contribute to dsRNA binding in vitro, it appears that sequestering dsRNA is not the sole function of E3 needed for inhibition of PKR. This conclusion was supported by the fact that E3 activity was antagonized, not augmented, by overexpressing the catalytically defective PKR-K296R protein containing functional DRBMs. Coimmunoprecipitation experiments showed that a majority of PKR in yeast extracts was in a complex with E3, whose formation was completely dependent on the dsRNA binding activity of E3 and enhanced by the N-terminal half of E3. In yeast two-hybrid assays and in vitro protein binding experiments, segments of E3 and PKR containing their respective DRBMs interacted in a manner requiring E3 residues Lys-167 and Arg-168. We also detected interactions between PKR and the N-terminal half of E3 in the yeast two-hybrid and lambda repressor dimerization assays. In the latter case, the N-terminal half of E3 interacted with the kinase domain of PKR, dependent on E3 residue Trp-66. We propose that effective inhibition of PKR in yeast requires formation of an E3-PKR-dsRNA complex, in which the N-terminal half of E3 physically interacts with the protein kinase domain of PKR.