gebhart/patrepeval huggingface dataset:
Adenoviral VEGF‐C overexpression induces blood vessel enlargement, tortuosity, and leakiness but no sprouting angiogenesis in the skin or mucous membranes (2002)

Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are important regulators of blood and lymphatic vessel growth and vascular permeability. The VEGF-C/VEGFR-3 signaling pathway is crucial for lymphangiogenesis, and heterozygous inactivating missense mutations of the VEGFR-3 gene are associated with hereditary lymphedema. However, VEGF-C can have potent effects on blood vessels because its receptor VEGFR-3 is expressed in certain blood vessels and because the fully processed form of VEGF-C also binds to the VEGFR-2 of blood vessels. To characterize the in vivo effects of VEGF-C on blood and lymphatic vessels, we have overexpressed VEGF-C via adenovirus- and adeno-associated virus-mediated transfection in the skin and respiratory tract of athymic nude mice. This resulted in dose-dependent enlargement and tortuosity of veins, which, along with the collecting lymphatic vessels were found to express VEGFR-2. Expression of angiopoietin 1 blocked the increased leakiness of the blood vessels induced by VEGF-C whereas vessel enlargement and lymphangiogenesis were not affected. However, angiogenic sprouting of new blood vessels was not observed in response to AdVEGF-C or AAV-VEGF-C. These results show that virally produced VEGF-C induces blood vessel changes, including vascular leak, but its angiogenic potency is much reduced compared with VEGF in normal skin.
Comparison of Three Fluid Solutions for Resuscitation in Dengue Shock Syndrome (2005)

Initial resuscitation with Ringer's lactate is indicated for children with moderately severe dengue shock syndrome. Dextran 70 and 6 percent hydroxyethyl starch perform similarly in children with severe shock, but given the adverse reactions associated with the use of dextran, starch may be preferable for this group.
A universal algorithm for fast and automated charge state deconvolution of electrospray mass-to-charge ratio spectra (1998)

This article describes a new algorithm for charge state determination and deconvolution of electrospray ionization (ESI) mass-to-charge ratio spectra. The algorithm (ZSCORE) is based on a charge scoring scheme that incorporates all above-threshold members of a family of charge states or isotopic components, and deconvolves both low- and high-resolution mass-to-charge ratio spectra, with or without a peak list (stick plot). A scoring weight factor, log (I/I0), in which I is the signal magnitude at a calculated mass-to-charge ratio, and I0 is the signal threshold near that mass-to-charge ratio, was used in most cases. For high-resolution mass-to-charge ratio spectra in which all isotopic peaks are resolved, the algorithm can deconvolve overlapped isotopic multiplets of the same or different charge state. Compared to other deconvolution techniques, the algorithm is robust, rapid, and fully automated (i.e., no user input during the deconvolution process). It eliminates artifact peaks without introducing peak distortions. Its performance is demonstrated for experimental ESI Fourier transform ion cyclotron resonance mass-to-charge ratio spectra (both low and high resolution). Charge state deconvolution to yield a "zero-charge" mass spectrum should prove particularly useful for interpreting spectra of complex mixtures, identifying contaminants, noncovalent adducts, fragments (N-terminal, C-terminal, internal), and chemical modifications of electrosprayed biomacromolecules.
A first-in-human phase 1 study of anticancer stem cell agent OMP-54F28 (FZD8-Fc), decoy receptor for WNT ligands, in patients with advanced solid tumors. (2014)

2505 Background: The WNT/FZD signaling pathway is implicated in tumor cell de-differentiation and cancer stem cell (CSC) function in numerous cancer types. As a first-in-class recombinant fusion protein, OMP-54F28 binds WNT ligands and blocks WNT signaling through its domain of an extracellular part of human Frizzled 8 receptor (fused to a human IgG1 Fc fragment). In patient-derived xenograft models, OMP-54F28 inhibits growth and CSC frequency, promotes differentiation of tumor cells, and synergizes with chemotherapy in a broad spectrum of malignancies. Methods: A 3+3 design was used; OMP-54F28 was given intravenously every 3 weeks. Objectives were determination of maximum tolerated dose (MTD), safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy. Results: 25 patients were treated in 7 dose-escalation cohorts (0.5, 1, 2.5, 5, 10, 15 and 20 mg/kg). No further dose escalation was pursued as animal data and PK modeling indicated 10 mg/kg as the target efficacious dose. Most common related Grade 1 and 2 adverse events (AEs; ≥20% of patients) were dysgeusia, decreased appetite, fatigue, muscle spasms, nausea, and vomiting. No related Grade ≥3 AEs were reported. OMP-54F28 had a half-life of ~4 days at ≥10 mg/kg. Consistent with WNT pathway inhibition in bone, 5 patients had doubling from baseline of bone turnover marker β-C-terminal telopeptide (β-CTX), an event that was reversible (β-CTX return to baseline) upon treatment with a single dose of zoledronic acid. PD modulation of WNT pathway genes was shown in hair follicles at ≥2.5 mg/kg. Two desmoid tumor patients have experienced stable disease (SD) for >6 months. 4 of 4 patients at 20 mg/kg with ≥1 on-study tumor assessment continue on study with SD. Conclusions: OMP-54F28 is well tolerated up to 20 mg/kg, double the target efficacious dose. PD modulation in bone and hair follicles was observed. Several patients experienced prolonged SD. Dose escalation is completed, and 3 Phase 1b studies are ongoing (pancreas cancer with nab-paclitaxel and gemcitabine, ovarian cancer with carboplatin and paclitaxel, and hepatocellular cancer with sorafenib). Detailed efficacy, safety, PK and PD results will be presented. Clinical trial information: NCT01608867.
Combinatorial Administration of Molecules That Simultaneously Inhibit Angiogenesis and Invasion Leads to Increased Therapeutic Efficacy in Mouse Models of Malignant Glioma (2004)

This supports the concept that prolonged glioma growth inhibition can be achieved by simultaneous delivery of molecules that target both tumor and endothelial cells and acting by separate mechanisms.
Dual Role for Phospholipid:Diacylglycerol Acyltransferase: Enhancing Fatty Acid Synthesis and Diverting Fatty Acids from Membrane Lipids to Triacylglycerol in Arabidopsis Leaves (2013)

There is growing interest in engineering green biomass to expand the production of plant oils as feed and biofuels. Here, we show that phospholipid:diacylglycerol acyltransferase1 (PDAT1) is a critical enzyme involved in triacylglycerol (TAG) synthesis in leaves. Overexpression of PDAT1 increases leaf TAG accumulation, leading to oil droplet overexpansion through fusion. Ectopic expression of oleosin promotes the clustering of small oil droplets. Coexpression of PDAT1 with oleosin boosts leaf TAG content by up to 6.4% of the dry weight without affecting membrane lipid composition and plant growth. PDAT1 overexpression stimulates fatty acid synthesis (FAS) and increases fatty acid flux toward the prokaryotic glycerolipid pathway. In the trigalactosyldiacylglycerol1-1 mutant, which is defective in eukaryotic thylakoid lipid synthesis, the combined overexpression of PDAT1 with oleosin increases leaf TAG content to 8.6% of the dry weight and total leaf lipid by fourfold. In the plastidic glycerol-3-phosphate acyltransferase1 mutant, which is defective in the prokaryotic glycerolipid pathway, PDAT1 overexpression enhances TAG content at the expense of thylakoid membrane lipids, leading to defects in chloroplast division and thylakoid biogenesis. Collectively, these results reveal a dual role for PDAT1 in enhancing fatty acid and TAG synthesis in leaves and suggest that increasing FAS is the key to engineering high levels of TAG accumulation in green biomass.
Perfluorocyclobutyl Copolymers for Microphotonics (2002)

The copolymerization of aryl bis- and tris-trifluorovinyl ether monomers yields aromatic perfluorocyclobutyl (PFCB) polymers, via thermally initiated step-growth cycloaddition chemistry. PFCB polymers and their copolymers enjoy a unique combination of attributes well suited for applications in photonic technologies, such as broad tailorability of refractive indices and thermo-optic coefficients, low transmission losses at 1300 and 1550 nm, high thermal, mechanical, and optical stability, and excellent melt and solution processability. Planar PFCB structures can be processed by direct micro-transfer molding, which is a first step towards rapid soft-lithographic fabrication of polymer planar lightwave circuits. Copolymerization chemistry and processing parameters and characterization, including thermal (Tg = 120–350 °C) and optical properties (refractive indices from 1.443 to 1.508 at 1550 nm; thermo-optic coefficients dn/dT = –7×10–5 K–1 to –1.5 × 10–4 K–1), birefringence (< 0.003), and temporal stability of refractive index, are described.
The Intermediate S1′ Pocket of the Endometase/Matrilysin-2 Active Site Revealed by Enzyme Inhibition Kinetic Studies, Protein Sequence Analyses, and Homology Modeling (2003)

Human matrix metalloproteinase-26 (MMP-26/endometase/matrilysin-2) is a newly identified MMP and its structure has not been reported. The enzyme active site S1' pocket in MMPs is a well defined substrate P1' amino acid residue-binding site with variable depth. To explore MMP-26 active site structure-activity, a series of new potent mercaptosulfide MMP inhibitors (MMPIs) with Leu or homophenylalanine (Homophe) side chains at the P1' site were selected. The Homephe side chain is designed to probe deep S1' pocket MMPs. These inhibitors were tested against MMP-26 and several MMPs with known x-ray crystal structures to distinguish shallow, intermediate, and deep S1' pocket characteristics. MMP-26 has an inhibition profile most similar to those of MMPs with intermediate S1' pockets. Investigations with hydroxamate MMPIs, including those designed for deep pocket MMPs, also indicated the presence of an intermediate pocket. Protein sequence analysis and homology modeling further verified that MMP-26 has an intermediate S1' pocket formed by Leu-204, His-208, and Tyr-230. Moreover, residue 233 may influence the depth of an MMP S1' pocket. The residue at the equivalent position of MMP-26 residue 233 is hydrophilic in intermediate-pocket MMPs (e.g. MMP-2, -8, and -9) and hydrophobic in deep-pocket MMPs (e.g. MMP-3, -12, and -14). MMP-26 contains a His-233 that renders the S1' pocket to an intermediate size. This study suggests that MMPIs, protein sequence analyses, and molecular modeling are useful tools to understand structure-activity relationships and provides new insight for rational inhibitor design that may distinguish MMPs with deep versus intermediate S1' pockets.
Diameter‐Controlled Growth of Single‐Crystalline In2O3 Nanowires and Their Electronic Properties (2003)

Single‐crystalline In 2 O 3 nanowires have been synthesized using a laser ablation approach. Precise control over the nanowire diameter was achieved by using monodispersed gold clusters as the catalyst. Extensive material characterization has been carried out to determine the lattice structure (see Figure) and dimensions of these nanowires. Individual In 2 O 3 nanowires have been utilized to construct field‐effect transistors with on/off ratios up to 1000.
Automated Spectrophotometric Analysis of Mitochondrial Respiratory Chain Complex Enzyme Activities in Cultured Skin Fibroblasts (2005)

With this automated method, a panel of RCC enzyme activities can be determined in <2 h. In addition, an immunoblot assay using monoclonal antibodies against specific subunits of RCC enzyme complexes can be informative in cases of borderline enzyme activity. Our results suggest that in vitro diagnosis of RCC enzyme deficiencies in skin fibroblasts is an effective alternative to invasive muscle biopsy.
Carbohydrate Microarrays: Survey of Fabrication Techniques (2006)

Carbohydrate microarrays are being developed in order to decipher the information content of the glycome. This postgenomic activity is necessary because of the complexity of protein biosynthesis and post-translational modifications that cannot currently be detected at the genome level. This review looks, in detail, at the experimental approaches that have been taken in the fabrication and preparation of carbohydrate microarrays, glycan arrays and glyco-chips. Tether structures, glycan solution preparation, detection methods and applications have been gathered together in a tabular format.
Striatal Versus Hippocampal Representations During Win-Stay Maze Performance (2009)

The striatum and hippocampus are widely held to be components of distinct memory systems that can guide competing behavioral strategies. However, some electrophysiological studies have suggested that neurons in both structures encode spatial information and may therefore make similar contributions to behavior. In rats well trained to perform a win-stay radial maze task, we recorded simultaneously from dorsal hippocampus and from multiple striatal subregions, including both lateral areas implicated in motor responses to cues and medial areas that work cooperatively with hippocampus in cognitive operations. In each brain region, movement through the maze was accompanied by the continuous sequential activation of sets of projection neurons. Hippocampal neurons overwhelmingly were active at a single spatial location (place cells). Striatal projection neurons were active at discrete points within the progression of every trial-especially during choices or following reward delivery-regardless of spatial position. Place-cell-type firing was not observed even for medial striatal cells entrained to the hippocampal theta rhythm. We also examined neural coding in earlier training sessions, when rats made use of spatial working memory to guide choices, and again found that striatal cells did not show place-cell-type firing. Prospective or retrospective encoding of trajectory was not observed in either hippocampus or striatum, at either training stage. Our results indicate that, at least in this task, dorsal hippocampus uses a spatial foundation for information processing that is not substantially modulated by spatial working memory demands. By contrast, striatal cells do not use such a spatial foundation, even in medial subregions that cooperate with hippocampus in the selection of spatial strategies. The progressive dominance of a striatum-dependent strategy does not appear to be accompanied by large changes in striatal or hippocampal single-cell representations, suggesting that the conflict between strategies may be resolved elsewhere.
Purification of the major protein-tyrosine-phosphatases of human placenta. (1988)

This report describes the purification of the major protein-tyrosine-phosphatases from human placenta. Enzyme activity was followed with a novel artificial substrate, namely reduced, carboxamidomethylated, and maleylated lysozyme, phosphorylated on tyrosine by a partially purified preparation of insulin and epidermal growth factor receptor kinases, also from human placenta. The key step in the purification of the protein-tyrosine-phosphatases was affinity chromatography on a column of thiophosphorylated, reduced, carboxamidomethylated, and maleylated lysozyme-Sepharose. Purification was carried out separately from both the soluble and particulate fractions. Whereas multiple and distinct enzyme forms were obtained from each of these, little difference could be detected between the behavior of the "soluble" enzyme subtypes and their "particulate" counterparts. The major subtypes were purified to apparent homogeneity with an approximately 23,000-fold enrichment and 10% yield from the soluble fraction and a 4,300-fold enrichment and 13% yield from the particulate fraction. Both samples migrated as bands of 35 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and had specific activities of approximately 45,000 nmol of Pi released min-1 mg-1, at least 2-3-fold higher than that of the type 1 and 2A serine/threonine phosphatases. The level of protein-tyrosine-phosphatases in the soluble fraction of human placenta (2,000 units/g of protein) was approximately the same as protein-serine/threonine-phosphatases 1 and 2A in skeletal muscle.
The biochemistry of programmed cell death (1995)

Programmed cell death (PCD) is involved in the removal of superfluous and damaged cells in most organ systems. The induction phase of PCD or apoptosis is characterized by an extreme heterogeneity of potential PCD-triggering signal transduction pathways. During the subsequent effector phase, the numerous PCD-inducing stimuli converge into a few stereotypical pathways and cells pass a point of no return, thus becoming irreversibly committed to death. It is only during the successive degradation phase that vital structures and functions are destroyed, giving rise to the full-blown phenotype of PCD. Evidence is accumulating that cytoplasmic structures, including mitochondria, participate in the critical effector stage and that alterations commonly considered to define PCD (apoptotic morphology of the nucleus and regular, oligonucleosomal chromatin fragmentation) have to be ascribed to the late degradation phase. The decision as to whether a cell will undergo PCD or not may be expected to be regulated by "switches" that, once activated, trigger self-amplificatory metabolic pathways. One of these switches may reside in a perturbation of mitochondrial function. Thus, a decrease in mitochondrial transmembrane potential, followed by mitochondrial uncoupling and generation of reactive oxygen species, precedes nuclear alterations. It appears that molecules that participate in apoptotic decision-making also exert functions that are vital for normal cell proliferation and intermediate metabolism.
Photon detection with high gain avalanche photodiode arrays (1998)

The detection of light emitted in fast scintillating fibers and Cerenkov radiators used for fiber calorimetry and tracking applications in high energy colliders, requires fast detector arrays with high sensitivity to short wavelength photons. Photomultiplier tubes, the traditional imaging detectors for short wavelength optical radiation, have limited spatial resolution and require expensive anti-magnetic shielding. We report on short wavelength sensitivity improvement and detection efficiency performance for a novel p-n junction planar structure silicon avalanche photodiode (APD) array, operated in Geiger mode. The APD array provides a high sensitivity detector for applications requiring the detection of light spatial distributions with single photon sensitivity.
Identification and characterization of an aspartyl protease from Cryptococcus neoformans (2007)

Cryptococcosis, caused by Cryptococcus neoformans, is an invasive infection often occurring in AIDS patients. Potent therapy against HIV, which includes protease inhibitors (PIs), has beneficial effects also on opportunistic infections by pathogens such as C. neoformans and C. albicans. PIs inhibit growth of C. albicans by affecting the activity of its aspartyl proteases. We identified, cloned and sequenced a cDNA from C. neoformans encoding for a putative aspartyl protease (CnAP1), and the corresponding genomic region. The gene cnap1 codifies for a protein of 505 aa, with a canonical aspartyl protease structure. We purified the recombinant protein and analyzed its activity in the presence of PIs (Indinavir, Lopinavir, Ritonavir), but did not evidence any inhibition of protease activity. The transcriptional level of cnap1 in C. neoformans is constant in different media. The absence of any inhibition activity by PIs suggests that other targets for PIs might exist in C. neoformans.
BindingDB Entry 4838: Risperidone: a novel antipsychotic with balanced serotonin-dopamine antagonism, receptor occupancy profile, and pharmacologic activity. (2011)

The interaction of risperidone, 9-hydroxyrisperidone (the principal active metabolite), and clozapine with neurotransmitter receptors was investigated in vitro using animal brain tissue homogenates and cloned human receptors expressed in cells and ex vivo using quantitative receptor autoradiography in rat and guinea pig brain sections. In vitro, risperidone and 9-hydroxyrisperidone had similar binding profiles, and their highest affinity was for 5-HT2A receptors (cloned human, Ki 0.4 nM); affinities for other 5-HT-receptor subtypes were at least 100 times lower. Risperidone bound to 5-HT2A receptors with 20 times greater affinity than clozapine and 170 times greater affinity than haloperidol. Clozapine primarily bound to histamine H1 receptors and haloperidol to dopamine D2 receptors. The binding affinity of risperidone and 9-hydroxyrisperidone for the D2 family of receptors (D2L, D2S, D3, D4) was one order of magnitude lower than their affinity for 5-HT2A receptors. Risperidone bound to D2 and D3 receptors with 50 and 20 times greater affinity than clozapine and was only 2 to 3 times less potent than haloperidol. All compounds bound with similar affinities to D4 receptors (Ki 5-9 nM), and their affinities for D1 receptors were 100 times lower than for D4 receptors. The ex vivo receptor occupancy profile of the compounds matched the in vitro receptor binding profile. A conspicuous property of risperidone, not seen for the other compounds, was the shallow occupancy curve at D2 receptors in the striatum and mesolimbic brain area. Moreover, it was observed that antagonism of strong D2-receptor stimulation by apomorphine in rats was achieved at less than 50% D2 occupancy by the antipsychotics.(ABSTRACT TRUNCATED AT 250 WORDS)
A peptide mimic of E-selectin ligand inhibits sialyl Lewis X-dependent lung colonization of tumor cells. (2000)

Selectins bind to carbohydrate ligands in a calcium-dependent manner and play critical roles in host defense and possibly in tumor metastasis. To isolate peptides that mimic E-selectin ligands, we screened a phage peptide library using E-selectin as a target molecule. This attempt unexpectedly failed, probably because the binding affinity of E-selectin to its ligand is low. We then took an approach that is analogous to the isolation of anti-idiotype antibodies and were able to isolate peptides that bound to anticarbohydrate antibodies recognizing E-selectin ligands. These peptides, enriched for their binding to anti-Lewis A antibody, were found to bind to E-, P- and L-selectins in a calcium-dependent manner. Phage harboring the identified peptide IELLQAR and synthetic peptides having the same sequence inhibited the binding of sialyl Lewis X or sialyl Lewis A oligosaccharides to E-selectin. The adhesion of HL-60 and B16 melanoma cells expressing sialyl Lewis X to E-selectin was also inhibited by the phage-displaying IELLQAR peptide. Moreover, i.v. injected IELLQAR peptide inhibited the lung colonization of mouse B16 melanoma and human lung tumor cells expressing sialyl Lewis X. These results demonstrate that it is possible to isolate peptides mimicking carbohydrate ligands by screening the peptides for binding to anticarbohydrate antibodies and then using them to inhibit carbohydrate-dependent experimental tumor metastasis.
The Efficacy and Safety of Subcutaneous Clazakizumab in Patients With Moderate‐to‐Severe Rheumatoid Arthritis and an Inadequate Response to Methotrexate: Results From a Multinational, Phase IIb, Randomized, Double‐Blind, Placebo/Active‐Controlled, Dose‐Ranging Study (2015)

In patients with RA and an inadequate response to MTX, treatment with clazakizumab in combination with MTX or clazakizumab monotherapy was well tolerated, and patients achieved significant improvements in disease activity, including higher rates of remission, as compared with patients receiving MTX alone.
Subtitling using teletext service — technical and editorial aspects (1979)

This paper describes both the technical implementation on the ITCA Oracle teletext system of a subtitling facility and also reviews the editorial constraints and research by various public and private bodies.