gebhart/patrepeval huggingface dataset:
The N-terminal and C-terminal domains of a receptor tyrosine phosphatase are associated by non-covalent linkage. (1992)

We have cloned the rat homolog of the human leukocyte common antigen-related gene (LAR), which encodes a transmembrane receptor phosphotyrosine phosphatase, and raised antibodies against its protein product. We present evidence here for a processing event resulting in a two-chain structure of the mature receptor on the cell surface. The LAR protein is synthesized as a 190-kDa precursor which is subsequently cleaved into 145-kDa and 85-kDa fragments. The 145-kDa fragment, representing the amino terminus of the protein, is exclusively extracellular and is modified by N-linked glycosylation. The 85-kDa component, derived from the C-terminus of the protein, contains the transmembrane region and intracellular phosphotyrosine phosphatase domains. The two products, associated in a non-covalent manner, comprise the functional LAR cell-surface receptor.
Nitric Oxide-Releasing Quaternary Ammonium-Modified Poly(amidoamine) Dendrimers as Dual Action Antibacterial Agents (2014)

Herein we describe the synthesis of nitric oxide (NO)-releasing quaternary ammonium (QA)-functionalized generation 1 (G1) and generation 4 (G4) poly(amidoamine) (PAMAM) dendrimers. Dendrimers were modified with QA moieties of different alkyl chain lengths (i.e., methyl, butyl, octyl, dodecyl) via a ring-opening reaction. The resultant secondary amines were then modified with N-diazeniumdiolate NO donors to yield NO-releasing QA-modified PAMAM dendrimers capable of spontaneous NO release (payloads of ~0.75 μmol/mg over 4 h). The bactericidal efficacy of individual (i.e., non-NO-releasing) and dual action (i.e., NO-releasing) QA-modified PAMAM dendrimers was evaluated against Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa bacteria. Bactericidal activity was found to be dependent on dendrimer generation, QA alkyl chain length, and bacterial Gram class for both systems. Shorter alkyl chains (i.e., methylQA, butylQA) demonstrated increased bactericidal activity against P. aeruginosa versus S. aureus for both generations, with NO release markedly enhancing overall killing.
Type 1 and 2 Immunity Following Vaccination Is Influenced by Nanoparticle Size:  Formulation of a Model Vaccine for Respiratory Syncytial Virus (2006)

Previous studies compared uptake by dendritic cells (DC) of 20, 40, 100, 200, 500, 1000, and 2000 nm beads in vivo. When beads were used as antigen carriers, bead size influenced antibody responses and induction of IFN-gamma-producing CD4 and CD8 T cells. Beads of 40-50 nm were taken up preferentially by DC and induced particularly strong immunity. Herein, we examine immunity induced by minute differences in nanobead size, specifically within a narrow viral-sized range (20, 40, 49, 67, 93, 101, and 123 nm), to see if bead carrier size influenced the induction of type 1 or type 2 cells as demonstrated by the production of IFN-gamma or IL-4. In vivo uptake by DC was assessed for selected sizes in this range. Responses to whole ovalbumin (OVA) or the OVA-derived CD8 T cell peptide epitope (SIINFEKL) were tested. After one immunization with beads-OVA, IFN-gamma responses to both OVA and SIINFEKL were significantly better with 40 and 49 nm beads than other sizes, while, in contrast, IL-4 responses to OVA were higher after immunization with OVA conjugated to larger beads (93, 101, and 123 nm). Thus IFN-gamma induction from CD8 T cells was limited to 40-49 nm beads, while CD4 T cell activation and IL-4 were induced by 93-123 nm beads-OVA. After two immunizations, there were comparable high levels of IFN-gamma produced with 40 and 49 beads and IL-4 reactivity was still higher for larger beads (93, 101, 123 nm). Production of IgG1 was seen across the full range of bead sizes, increasing after two immunizations. Since protection against respiratory syncytial virus (RSV) depends on strong IFN responses, while IL-4 responses are reported to cause asthma-like symptoms, immunization with RSV antigens on the 49 nm carrier beads could provide the basis for a suitable vaccine. When the 49 nm beads were conjugated to RSV proteins G88 (surface) or M2.1 (internal capsid), one immunization with G88 induced high levels of IFN-gamma and low levels of IL-4. IL-4 increased with two immunizations. Beads-M2.1 induced only moderate levels of IFN-gamma and low titer antibody after two immunizations. Mice vaccinated once with G88-conjugated 49 nm beads and challenged intranasally with RSV strain A2 subtype showed reduced viral titers and recovered from weight loss more rapidly than mice immunized with M2.1-conjugated 49 nm beads or naive control mice. These results show that precise selection of nanobead size for vaccination can influence the type 1/type 2 cytokine balance after one immunization, and this will be useful in the development of effective vaccines against common human pathogens such as RSV.
Antibody Isotypes for Tumor Immunotherapy (2017)

Compared to the evolutionary diversity of antibody isotypes, the spectrum of currently approved therapeutic antibodies is biased to the human IgG1 isotype. Detailed studies into the different structures and functions of human isotypes have suggested that other isotypes than IgG1 may be advantageous for specific indications - depending on the complex interplay between the targeted antigen or epitope, the desired mode of action, the pharmacokinetic properties, and the biopharmaceutical considerations. Thus, it may be speculated that with the increasing number of antibodies becoming available against a broadening spectrum of target antigens, identification of the optimal antibody isotype for particular therapeutic applications may become critical for the therapeutic success of individual antibodies. Thus, investments into this rather unexplored area of antibody immunotherapy may provide opportunities for distinction in the increasingly busy 'antibody space'. Therefore, IgG, IgA, IgE as well as IgM isotypes will be discussed in this review.
Just-Enough-Time (JET): a high speed protocol for bursty traffic in optical networks (2002)

We investigate a high speed protocol called Just-Enough-Time (JET) based on a tell-and-go (TAG) protocol. It is suitable for bursty traffic where the duration of each burst is neither long enough to warrant circuit switching nor short enough to fit in a packet. The proposed JET protocol can efficiently utilize the bandwidth, reduce the latency and provide data transparency.
A rat retinal damage model predicts for potential clinical visual disturbances induced by Hsp90 inhibitors (2013)

In human trials certain heat shock protein 90 (Hsp90) inhibitors, including 17-DMAG and NVP-AUY922, have caused visual disorders indicative of retinal dysfunction; others such as 17-AAG and ganetespib have not. To understand these safety profile differences we evaluated histopathological changes and exposure profiles of four Hsp90 inhibitors, with or without clinical reports of adverse ocular effects, using a rat retinal model. Retinal morphology, Hsp70 expression (a surrogate marker of Hsp90 inhibition), apoptotic induction and pharmacokinetic drug exposure analysis were examined in rats treated with the ansamycins 17-DMAG and 17-AAG, or with the second-generation compounds NVP-AUY922 and ganetespib. Both 17-DMAG and NVP-AUY922 induced strong yet restricted retinal Hsp70 up-regulation and promoted marked photoreceptor cell death 24h after the final dose. In contrast, neither 17-AAG nor ganetespib elicited photoreceptor injury. When the relationship between drug distribution and photoreceptor degeneration was examined, 17-DMAG and NVP-AUY922 showed substantial retinal accumulation, with high retina/plasma (R/P) ratios and slow elimination rates, such that 51% of 17-DMAG and 65% of NVP-AUY922 present at 30 min post-injection were retained in the retina 6h post-dose. For 17-AAG and ganetespib, retinal elimination was rapid (90% and 70% of drugs eliminated from the retina at 6h, respectively) which correlated with lower R/P ratios. These findings indicate that prolonged inhibition of Hsp90 activity in the eye results in photoreceptor cell death. Moreover, the results suggest that the retina/plasma exposure ratio and retinal elimination rate profiles of Hsp90 inhibitors, irrespective of their chemical class, may predict for ocular toxicity potential.
Solubilization and characterization of diacylglycerol acyltransferase from microspore-derived cultures of oilseed rape (1994)

Particulate fractions prepared from microspore-derived (MD) embryos of oilseed rape (Brassica napus L. cv. Reston) and an embryogenic MD cell suspension culture of oilseed rape (B. napus L. cv. Jet Neuf) were used as a source of diacylglycerol acyltransferase (DGAT, EC 2.3.1.20) for enzyme characterization and development of a solubilization procedure. DGAT activity in the 1500-100,000 g fraction from MD embryos was stimulated 4-5-fold by 3 to 4 mg of BSA/ml of reaction mixture. DGAT activity from MD embryos was stimulated 2-3-fold by fluoride salts and 1.4-fold by NaCl, whereas iodide salts caused substantial inhibition of enzyme activity. The effect of the various 1:1 electrolytes on enzyme activity appeared to be related more to their differential effects on solution structure rather than ionic strength. DGAT was solubilized from membranes of MD embryos and the cell suspension culture by about 80 and 50% respectively, using 2 M NaCl in 1% (w/v) octanoyl-N-methyl-glucamide (MEGA-8) (pH 8.0 buffer) at a detergent to protein ratio of 2:1. The specific activity of solubilized DGAT was about 2-fold greater than that of the particulate enzyme. The mechanism of solubilization appeared to be related to the lowering of the critical micellar concentration of MEGA-8 in the presence of NaCl. DGAT, solubilized from MD embryos, eluted with an M(r) of about 2 x 10(6) during gel-filtration chromatography on a Superose 6 column equilibrated in buffer containing 0.1% (w/v) MEGA-8. The solubilized enzyme exhibited optimal activity at pH 7. At concentrations above 2 microM acyl-CoA, the specificity of solubilized DGAT for oleoyl-CoA and palmitoyl-CoA was considerably greater than for stearoyl-CoA.
Recycling Polyurethane Materials: A Comparison of Polyol from Glycolysis with Micronized Polyurethane Powder in Particleboard Applications (2014)

Three different types of recycled polyurethane (PUR) material, two in powder form from a pulverizing process (one < 50 µm and one < 250 µm) and one in polyol form from a glycolysis process, were used as substitutes for polymeric methylene diphenyl diisocyanate (pMDI) resin at 5%, 15%, and 30% ratio, respectively, to replace the pMDI resin for particleboard manufacturing at 8% resin loading. The reactions between pMDI resin and recycled PUR powder and polyol were investigated with Fourier transform infrared (FT-IR) spectroscopy. It was found that 5% substitution of pMDI with recycled PU powder of < 50 µm resulted in significantly higher panel internal bonding (IB) strength than pure pMDI resin, which also tended to increase panel modulus of rupture (MOR), and modulus of elasticity (MOE). Polyol did not show advantages over PUR powder in particleboard application. Increasing the size of recycled PUR powder from < 50 µm to < 250 µm decreased the panel IB, which also tended to decrease MOR and MOE. Recycling PUR materials in either powder or polyol form in particleboard manufacturing did not improve panel thickness swelling, but did appear to improve panel water absorption.
Static benchmarking of membrane helix predictions (2003)

Prediction of trans-membrane helices continues to be a difficult task with a few prediction methods clearly taking the lead; none of these is clearly best on all accounts. Recently, we have carefully set up protocols for benchmarking the most relevant aspects of prediction accuracy and have applied it to >30 prediction methods. Here, we present the extension of that analysis to the level of an automatic web server evaluating new methods (http://cubic.bioc.columbia.edu/services/tmh_benchmark/). The most important achievements of the tool are: (i) any new method is compared to the battery of well-established tools; (ii) the battery of measures explored allows spotting strengths in methods that may not be 'best' overall. In particular, we report per-residue and per-segment scores for accuracy and the error-rates for confusing membrane helices with globular proteins or signal peptides. An additional feature is that developers can directly investigate any hydrophobicity scale for its potential in predicting membrane helices.
Myristoylation negative msbB-mutants of probiotic E. coli Nissle 1917 retain tumor specific colonization properties but show less side effects in immunocompetent mice (2010)

Specific colonization of solid tumors by bacteria opens the way to novel approaches in both tumor diagnosis and therapy. However, even non-pathogenic bacteria induce responses by the immune system, which could be devastating for a tumor bearing patient. As such effects are caused e.g., by the lipid A moiety of the lipopolysaccharide, a msbB-mutant of the probiotic E. coli Nissle 1917 strain was investigated. Bacteria of the mutant strain did not show any growth defects in culture media when compared to wild-type E. coli Nissle 1917 but were unable to myristoylate lipid A, had less toxic effects on immunocompetent BALB/c mice, and were still able to specifically colonize tumors. Therefore, the modification of lipid A could result in bacterial strains that might be better suited for diagnosis and therapy of tumors than the corresponding wild-type strains, even if those are not considered pathogenic or are of probiotic background.
Functional Consequences of the Ser334→Pro Mutation in a Human Factor X Variant (Factor XMarseille) (1995)

A factor X molecular variant was identified in a 55-year-old woman at a routine preoperative coagulation screening. Plasma factor X antigen was normal, whereas factor X activity was decreased when factor X was activated by either the extrinsic pathway (21%), the intrinsic pathway (21%) or the factor X activator from Russell viper venom, RVV-X (26%). Factor XMarseille was isolated from plasma by immunoaffinity chromatography and compared with normal factor X purified by the same method. Activation of factor XMarseille by factor IXa or by RVV-X in a purified system showed that the rate of cleavage was decreased, whereas once produced, factor XaMarseille had a normal catalytic efficiency for either the peptide substrate S-2765 (D-Arg-Gly-Arg-NH-Np) or prothrombin. The rate of inhibition of factor XaMarseille by antithrombin III was also normal. Defective proteolysis of factor XMarseille by factor IXa or by RVV-X was the consequence of a threefold decrease in the kcat for the activation of factor XMarseille while the Km of RVV-X or factor IXa for factor X was normal. We have determined the molecular basis of the defect in the factor XMarseille gene by amplification of all eight exons, single-strand conformational polymorphism analysis of the amplified exons and subsequent sequence analysis. The patient was homozygous for a T-->C mutation in exon VIII, resulting in the substitution of Ser334 by proline. From comparison of three-dimensional models of various serine proteases, it appears that Ser334 is located within a surface-exposed variable region of factor X. This observation suggests that the Ser334-->Pro mutation either is responsible for a misalignment of the active sites of specific factor X activators in close proximity to the cleavage site, or that the Ser-->Pro mutation alters the spatial orientation of the cleavage site by nonlocal modifications of factor X structure.
Fibronectin profiles in normal and chronic wound fluid. (1990)

Fibronectin, an adhesion protein found in blood and tissues, is an important factor in wound repair. Recently, we began studies using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting to compare fibronectin in the fluid of normal and chronic wounds. We found similar fibronectin profiles in suction blister fluid (2 normal volunteers) and mastectomy fluid (5 patients). There was primarily an intact 250 kilodalton fibronectin subunit and in addition some higher molecular mass fibronectin-containing complexes. On the other hand, fibronectin in diabetic ulcer wound fluid (2 patients) was partially degraded, and there was no intact fibronectin in stasis ulcer wound fluid (2 patients). The most prominent degradation products were 93 and 125 kilodalton polypeptides. When intact fibronectin was added back to stasis ulcer wound fluid, fragmentation occurred within 15 minutes at 37 degrees C indicating the presence of protease activity in the wound fluid.
MicroRNAs as Oncogenes and Tumor Suppressors (2005)

Recent discoveries related to microRNAs, RNA interference, small interfering RNAs (siRNAs), and small modulatory RNAs have revealed a new class of mechanisms of gene regulation that are mediated by small, noncoding RNAs. Among these small RNAs are the microRNAs. These are thought to control gene expression at the post-transcriptional level by degrading or repressing target messenger RNAs (mRNAs). Surprisingly simple and elegant, microRNA-mediated gene regulation is guided by the base-pairing rules of Watson and Crick.MicroRNAs are individually encoded by their own set of genes and are an integral component of the genetic program. Some are located in noncoding regions . . .
A Protein from Tetrahymena thermophila That Specifically Binds Parallel-Stranded G4-DNA (1994)

G4-DNA is a parallel, four-stranded structure mediated by tetrads of hydrogen-bonded guanines (G-quartets). An abundant protein called Tetrahymena G4 binding protein (TGP) that binds to an intermolecular, quadruplex form of d(TTGGGGTTGGGGTTGGGGTTGGGG) under physiological salt conditions has been identified in cellular extracts from the ciliated protozoan Tetrahymena thermophila. In binding competition experiments, molecules capable of forming G4 structures compete for binding to TGP, but non-G4-forming molecules and r(U2G4)4 do not. TGP binding also requires a single-stranded region adjacent to the G4 structure. During the course of this study, it was determined that Mg2+ facilitates the formation of parallel-stranded G4-DNA structures and that high oligonucleotide concentrations are not required to drive formation of these structures. In addition, G4-DNA and TGP/G4-DNA complexes form readily under physiological salt conditions. These data support the proposal that G4-DNA structures exist in vivo.
Increased SPARC expression promotes U87 glioblastoma invasion in vitro (1999)

Our recent studies have focused on identifying invasion-promoting genes that are expressed early in brain tumor progression. We identified and characterized SPARC (secreted protein acidic and rich in cysteine) as a potential candidate. To determine whether increased SPARC expression functionally promotes brain tumor invasion, SPARC was transfected into U87MG glioblastoma cells using the tetracycline-off gene expression system. The parental cell line (U87MG), the parental transactivator-transfected clone (U87T2) and three selected U87T2-SPARC-transfected clones (A2bi, A2b2 and C2a4) were characterized for endogenous and transfected SPARC expression. In comparison to the parental or U87T2 cell lines, the SPARC-transfected clones demonstrated: (1) morphological changes, (2) increased SPARC transcript and protein abundances that were down-regulated by the tetracycline analog doxycycline, (3) perinuclear localization of the transfected SPARC (consistent with reported localization of SPARC in normal cells in culture) and (4) altered adhesion and increased invasion as assessed by the spheroid confrontation assay. These data indicate that increased SPARC expression contributes to U87 glioblastoma tumor invasion in vitro and that these cell lines will serve as useful reagents to investigate the mechanism(s) by which SPARC promotes this phenotype in vitro and in vivo.
An Operand-Optimized Asynchronous IEEE 754 Double-Precision Floating-Point Adder (2010)

We present the design and implementation of an asynchronous high-performance IEEE 754 compliant double precision floating-point adder (FPA). We provide a detailed breakdown of the power consumption of the FPA datapath, and use it to motivate a number of different data-dependent optimizations for energy-efficiency. Our baseline asynchronous FPA has a throughput of 2.15 GHz while consuming 69.3 pJ per operation in a 65 nm bulk process. For the same set of nonzero operands, our optimizations improve the FPA's energy-efficiency to 30.2 pJ per operation while preserving average throughput, a 56.7% reduction in energy relative to the baseline design. To our knowledge, this is the first detailed design of a high-performance asynchronous double-precision floating-point adder.
Complementation of a Threonine Dehydratase-Deficient Nicotiana plumbaginifolia Mutant after Agrobacterium Tumefaciens-Mediated Transfer of the Saccharomyces cerevisiae ILV1 Gene (1987)

The Saccharomyces cerevisiae ILV1 gene, encoding threonine dehydratase (EC 4.2.1.16) was fused to the transferred DNA nopaline synthase promoter and the 3' noncoding region of the octopine synthase gene. It was introduced, by Agrobacterium tumefaciens-mediated gene transfer, into an isoleucine-requiring Nicotiana plumbaginifolia auxotroph deficient in threonine dehydratase. Functional complementation by the ILV1 gene product was demonstrated by the selection of several transformed lines on a medium without isoleucine and by the identification in these lines of the yeast threonine dehydratase activity. This is the first example illustrating the complementation of a plant auxotroph by transfection with a cloned gene.
Alpharadin, a 223Ra-based alpha-particle-emitting pharmaceutical for the treatment of bone metastases in patients with cancer. (2009)

Bone metastases occur in many patients with different forms of solid malignant tumors, particularly in advanced stages of prostate and breast cancer, and are commonly associated with increased morbidity and mortality. The resulting bone pain interferes with quality of life and thus requires effective treatment. However, various non-radiotherapeutic modalities such as analgesics, hormone therapy, orchidectomy, cytostatic and cytotoxic drugs, bisphosphonates and surgery are not universally effective. External-beam radiotherapy is suitable only for well-defined localized bone metastases, and extended field radiation is often accompanied by serious side effects. Therefore, systemic radionuclide therapy must be considered as a valuable and effective method of treatment in patients with widespread skeletal metastases. The alpha-emitter 223Ra-based Alpharadin is a new radiopharmaceutical under development by Algeta ASA in collaboration with Bayer Schering Pharma AG. Early clinical data demonstrated a significant decrease in bone-alkaline phosphatase levels following therapy with Alpharadin compared with placebo. Median time to PSA progression, median survival and pain relief were also superior to placebo, and no dose-limiting hematological toxicity was observed. A phase III trial for Alpharadin was ongoing at the time of publication.