gebhart/patrepeval huggingface dataset:
Discovery of Potent and Practical Antiangiogenic Agents Inspired by Cortistatin A (2009)

The discovery that cortistatins A and J show noteworthy antiangiogenic activity prompted an investigation of the possibility that simpler and much more easily made compounds based on a steroid core might have useful bioactivity. These studies have led to the development of several potent, water-soluble compounds that may be suitable for local application to treat ocular wet macular degeneration, an important cause of blindness, as well as for treatment of various other angiogenesis-dependent diseases. One of these substances was tested in a mouse retinal angiogenesis model and found to inhibit angiogenesis at a locally administered dose of 500 pmol. Comparison of cell migration data for this and two other synthetic compounds with published data on cortistatin A indicate that they inhibit vascular endothelial growth factor-induced cell migration of human umbilical vein endothelial cells more strongly than cortistatin A.
Solvent Selection Strategies for Extractive Biocatalysis (1991)

This report follows the development of systematic solvent screening strategies for the identification of superior pure solvents and introduces techniques for the identification of effective coextractants. Specifically, methods to predict the biocompatibility and extractant capability of solvents are discussed. Biocompatibility is predicted by using heuristic data or the correlations between bioactivity and the logarithm of the partition coefficient of the solvent or the concentration of solvent in the cell membrane. A computer program, known as the extractant screening program or ESP, has been developed to effectively predict the behavior of virtually any product in any solvent/aqueous system. It is demonstrated that a biocompatible yet poor solvent can be mixed with a toxic solvent that has better extractant properties to yield a mixture with improved solvent characteristics that is still biocompatible. The fact that solvents do not mix in an ideal manner is exploited by using ESP to identify solvent mixtures that are still biocompatible at relatively high concentrations of toxic solvent.
Cardiomyocyte proliferation in mice expressing alpha-cardiac myosin heavy chain-SV40 T-antigen transgenes (1992)

To determine the proliferative potential of adult ventricular cardiomyocytes, we have generated transgenic mice that express the SV40 large T-antigen oncogene in the heart. A fusion gene comprised of the rat alpha-cardiac myosin heavy chain promoter and the SV40 early region was used to target oncogene expression to the myocardium. Expression of SV40 large T-antigen was observed in both atrial and ventricular cardiomyocytes in adult transgenic animals. T-antigen expression was associated with hyperplasia in the targeted cells. Immunohistological analysis indicated that the proliferating cells continued to express sarcomeric myosin. Electron microscopic examination demonstrated that cardiomyocytes in various stages of the cell cycle retained ultrastructural characteristics typical of mitotic cardiac muscle cells in vivo. Cardiomyocytes isolated from transgenic tumors were able to proliferate in culture and retained a differentiated phenotype, as evidenced by spontaneous contractile activity. Preliminary studies indicate that these cells can undergo a limited number of passages while retaining this differentiated phenotype. These studies demonstrate that both ventricular and atrial cardiomyocytes from transgenic mice proliferate in response to targeted T-antigen expression.
Molecular cloning of a human cDNA encoding a novel protein, DAD1, whose defect causes apoptotic cell death in hamster BHK21 cells. (1993)

The tsBN7 cell line, one of the mutant lines temperature sensitive for growth which have been isolated from the BHK21 cell line, was found to die by apoptosis following a shift to the nonpermissive temperature. The induced apoptosis was inhibited by a protein synthesis inhibitor, cycloheximide, but not by the bcl-2-encoded protein. By DNA-mediated gene transfer, we cloned a cDNA that complements the tsBN7 mutation. It encodes a novel hydrophobic protein, designated DAD1, which is well conserved (100% identical amino acids between humans and hamsters). By comparing the base sequences of the parental BHK21 and tsBN7 DAD1 cDNAs, we found that the DAD1-encoding gene is mutated in tsBN7 cells. The DAD1 protein disappeared in tsBN7 cells following a shift to the nonpermissive temperature, suggesting that loss of the DAD1 protein triggers apoptosis.
Role of exon-16-deleted HER2 in breast carcinomas (2006)

A splice variant of the human gene HER2, lacking exon-16 (DeltaHER2) which encodes a small extracellular region, has been described. This altered receptor forms disulfide bond-stabilized homodimers. We report here that the DeltaHER2 splice variant represents about 9% of the HER2 mRNA obtained from most of the 46 breast carcinoma samples with HER2 expression levels ranging from 3+ to 0 by HercepTest. Analysis of human cells transfected with DeltaHER2 or wild-type (WT) cDNA revealed no growth of WT cells in nude mice, whereas clones expressing 10-fold less DeltaHER2 were tumorigenic. Unlike WT transfectants, DeltaHER2-expressing cells showed low sensitivity to two new therapeutic drugs targeting receptors of the HER family (ZD1839 and Trastuzumab), whereas an inhibitor of the HER2 tyrosine kinase domain (Emodin) blocked activation of both DeltaHER2 and WT transfectants. Taken together, our findings indicate that the DeltaHER2 transcript encodes the transforming form of the oncoprotein. It is plausible that malignant transformation arises when a critical threshold of DeltaHER2 is reached in HER2-overexpressing tumors. Specific inhibitors of HER2 catalytic activity represent a promising approach to therapy of HER2-overexpressing tumors.
Effect of protective agents, freezing temperature, rehydration media on viability of malolactic bacteria subjected to freeze-drying (2005)

The viabilities of L. brevis and O. oeni after freeze-drying were shown to be strain specific and dependent on protective agents, rehydration media and freezing temperature.
Synthesis and absolute stereochemistry of the two diastereoisomers of P3-1-(2-nitrophenyl)ethyl adenosine triphosphate (‘caged’ ATP) (1992)

1 -(2-Nitrophenyl)ethanol was resolved by fractional crystallisation of its diastereoisomeric (1S)-cam-phanates. The absolute stereochemistry of the (S)-alcohol was determined using the Horeau kinetic resolution procedure, and subsequently confirmed by X-ray crystallography of its (1S)-camphanate ester. The resolved alcohols were converted to (R)- and (S)-1-(2-nitrophenyl)ethyl phosphates, each of which was condensed with adenosine diphosphate to give the (R)- and (S)-1-(2-nitro-phenyl)ethyl P3-esters of adenosine triphosphate.
Engineering InAsxP1-x/InP/ZnSe III−V Alloyed Core/Shell Quantum Dots for the Near-Infrared (2005)

Quantum dots with a core/shell/shell structure consisting of an alloyed core of InAs(x)P(1-x), an intermediate shell of InP, and an outer shell of ZnSe were developed. The InAs(x)P(1-x) alloyed core has a graded internal composition with increasing arsenic content from the center to the edge of the dots. This compositional gradient results from two apparent effects: (1) the faster reaction kinetics of the phosphorus precursor compared to the arsenic precursor, and (2) a post-growth arsenic-phosphorus exchange reaction that increases the arsenic content. The cores have a zinc blend structure for all compositions and show tunable emission in the near-infrared (NIR) region. A first shell of InP leads to a red-shift and an increase in quantum yield. The final shell of ZnSe serves to stabilize the dots for applications in aqueous environments, including NIR biomedical fluorescence imaging. These NIR-emitting core/shell/shell InAs(x)P(1-x)/InP/ZnSe were successfully used in a sentinel lymph node mapping experiment.
An Antibody Blocking Activin Type II Receptors Induces Strong Skeletal Muscle Hypertrophy and Protects from Atrophy (2013)

The myostatin/activin type II receptor (ActRII) pathway has been identified to be critical in regulating skeletal muscle size. Several other ligands, including GDF11 and the activins, signal through this pathway, suggesting that the ActRII receptors are major regulatory nodes in the regulation of muscle mass. We have developed a novel, human anti-ActRII antibody (bimagrumab, or BYM338) to prevent binding of ligands to the receptors and thus inhibit downstream signaling. BYM338 enhances differentiation of primary human skeletal myoblasts and counteracts the inhibition of differentiation induced by myostatin or activin A. BYM338 prevents myostatin- or activin A-induced atrophy through inhibition of Smad2/3 phosphorylation, thus sparing the myosin heavy chain from degradation. BYM338 dramatically increases skeletal muscle mass in mice, beyond sole inhibition of myostatin, detected by comparing the antibody with a myostatin inhibitor. A mouse version of the antibody induces enhanced muscle hypertrophy in myostatin mutant mice, further confirming a beneficial effect on muscle growth beyond myostatin inhibition alone through blockade of ActRII ligands. BYM338 protects muscles from glucocorticoid-induced atrophy and weakness via prevention of muscle and tetanic force losses. These data highlight the compelling therapeutic potential of BYM338 for the treatment of skeletal muscle atrophy and weakness in multiple settings.
Parallelizing local search for CNF satisfiability using vectorization and PVM (2002)

The purpose of this paper is to speed up the local search algorithm for the CNF Satisfiability problem. Our basic strategy is to run some 10 5 independent search paths simultaneously using PVM on a vector supercomputer VPP800, which consists of 40 vector processors. Using the above parallelization and vectorization together with some improvement of data structure, we obtained 600-times speedup in terms of the number of flips the local search can make per second, compared to the original GSAT by Selman and Kautz. We ran our parallel GSAT for benchmark instances and compared the running time with those of existing SAT programs. We could observe an apparent benefit of parallelization: Especially, we were able to solve two instances that have never been solved before this paper. We also tested parallel local search for the SAT encoding of the class scheduling problem. Again we were able to get almost the best answer in reasonable time.
CMOS Imager With 1024 SPADs and TDCs for Single-Photon Timing and 3-D Time-of-Flight (2014)

We present a CMOS imager consisting of 32×32 smart pixels, each one able to detect single photons in the 300-900 nm wavelength range and to perform both photon-counting and photon-timing operations on very fast optical events with faint intensities. In photon-counting mode, the imager provides photon-number (i.e, intensity) resolved movies of the scene under observation, up to 100 000 frames/s. In photon-timing, the imager provides photon arrival times with 312 ps resolution. The result are videos with either time-resolved (e.g., fluorescence) maps of a sample, or 3-D depth-resolved maps of a target scene. The imager is fabricated in a cost-effective 0.35-μm CMOS technology, automotive certified. Each pixel consists of a single-photon avalanche diode with 30 μm photoactive diameter, coupled to an in-pixel 10-bit time-to-digital converter with 320-ns full-scale range, an INL of 10% LSB and a DNL of 2% LSB. The chip operates in global shutter mode, with full frame times down to 10 μs and just 1-ns conversion time. The reconfigurable imager design enables a broad set of applications, like time-resolved spectroscopy, fluorescence lifetime imaging, diffusive optical tomography, molecular imaging, time-of-flight 3-D ranging and atmospheric layer sensing through LIDAR.
Titanium: Sapphire Laser as an Excitation Source in Two-Photon Spectroscopy (1997)

The passively mode-locked titanium: sapphire laser provides new opportunities for acquiring two-photon spectral data in the near-infrared, a region not commonly accessible to synchronously pumped dye lasers. This source generates pulses with peak powers near 100 kW at average powers over 1 W and is capable of yielding two-photon signals roughly two orders of magnitude larger than is possible with synchronously pumped dye lasers. However, the multimode output of this laser exhibits significant temporal and spectral pulse profile variations as the laser wavelength is tuned. As a consequence, peak powers of the titanium:sapphire laser can vary independently from average power across the tuning range. This wavelength dependence, coupled with the quadratic dependence of the two-photon signal upon the instantaneous power of the laser, precludes simple average power correction of nonlinear spectral band shapes. Here, we investigate the key properties of the titanium:sapphire laser as an excitation source for two-photon spectroscopy. We also identify a chemical reference suitable for obtaining source-corrected excitation spectra in the near-infrared using a double-beam, ratiometric approach; this is based on a source-in-dependent two-photon excitation spectrum for the laser dye coumarin-480 that has been obtained with a single-frequency titanium:sapphire laser. From these data, correction factors are generated for correction of multimode source data.
Development of Novel Protein Scaffolds as Alternatives to Whole Antibodies for Imaging and Therapy: Status on Discovery Research and Clinical Validation (2008)

Recent advances in combinatorial protein engineering have made it possible to develop antibody-based and non-Ig protein scaffolds that can potentially substitute for most whole antibody-associated properties. In theory, many different natural human protein backbones are suitable to be used as recombinant templates for engineering : antibody-derived scaffolds, carrier proteins that display a single binding interface, backbones that provide a rigid core structure suitable for grafting loops or protein scaffolds allowing the incorporation of variable loops in a favorable 3D configuration. In practice however, only a few have yielded the necessary properties to be translated into 'druggable Biologicals'. Amongst these properties, potential broad specificities towards any kind of target, ease of production, small size, good tolerability and low immunogenicity are essential and will be discussed in this review. Intellectual property is another key issue for the development of these protein scaffolds; although circumventing antibody-associated patents is often a major if not primary goal, clear advantages compared to whole antibodies must be presented to translate scaffold discovery into successful therapeutic drug candidates. In this review, a particular emphasis will be given to the most validated scaffolds that have reached the clinical development phase. Although the question of their immunogenicity is still open, preliminary clinical data do not point to any particular adverse immunogenic reactions although these are highly dependent on dosage, administration route and therapeutic indication. Finally, some of the emerging Biotechs developing protein scaffolds have been associated during the last two years with successful acquisitions by Big Pharmas and we will speak on the perspective positions of these proteins within the global Biologicals market.
Biosynthesis of human ficolin, an Escherichia coli‐binding protein, by monocytes: comparison with the synthesis of two macrophage‐specific proteins, C1q and the mannose receptor (1996)

Ficolin is characterized by the presence of both collagen-like and fibrinogen-like sequences, and potentially has a similar overall structure as the complement protein C1q and the collectins. Previous studies have reported the presence of human ficolin mRNA predominantly in peripheral blood leucocytes. In the present study, the cellular origin of human ficolin was investigated in further detail. Preliminary studies using reverse transcriptase-polymerase chain reaction (RT-PCR) showed that ficolin mRNA was synthesized by U937 cells, a human monocyte cell line. This finding suggested that blood monocytes also normally synthesize human ficolin. Peripheral blood monocytes from adult human donors were harvested at serial time-points (0-20 hr) after adhesion to tissue culture plates, and total RNA was isolated and assayed for ficolin mRNA by RT-PCR. Ficolin mRNA was highly expressed in monocytes throughout the first 20 hr of adhesion. In contrast, C1q and mannose receptor mRNA were not detectable during the first 8 hr of adhesion, but were highly expressed by 20 hr. Cells were harvested at longer time intervals (1, 2, 4, 6 and 8 days) to determine whether ficolin expression was temporally regulated at later stages of monocyte differentiation. Ficolin mRNA levels decreased sharply from day 1 to day 6. In contrast, the levels of both C1q and mannose receptor mRNA showed no changing trend. These results are consistent with the absence of ficolin expression in many macrophage-rich tissues previously reported. The origin of ficolin from monocytes, together with its structural similarity to C1q and the collectins, raises the possibility that ficolin may be another plasma protein capable of binding to surface structures of micro-organisms. Escherichia coli was therefore incubated with human serum, and bound proteins, after elution with sugars, were analysed by Western blotting using an antiserum raised against a synthetic ficolin peptide. The antiserum identified a polypeptide of approximately 42000 MW, which is similar in size to that of ficolin as predicted from its cDNA-derived sequence.
Phase I study of 24-hour continuous intravenous infusion of recombinant human tumor necrosis factor. (1988)

Sixteen patients with cancer were treated with a 24-h continuous intravenous infusion of recombinant human tumor necrosis factor (rHuTNF) to investigate the spectrum of side-effects, the maximum tolerated dose, the pharmacokinetics, and possible antitumor effects. Fever, chills, and flu-like symptoms were the most common side-effects. The maximum tolerated dose was 6 x 10(5) U/m2 (261 micrograms/m2). Severe hypotension, fluid retention, watery diarrhea, and central nervous deficits culminated in a profound prostration as the dose-limiting toxicity. No allergic reactions, positive skin tests, or antibodies against rHuTNF were observed. Plasma levels of rHuTNF were detected at doses of greater than or equal to 3 x 10(5) U/ml2. Maximal plasma levels were 19 U/ml (8.2 ng/ml). No objective tumor responses were observed.
Twist1 is a potential prognostic marker for colorectal cancer and associated with chemoresistance. (2015)

Twist1 is a highly conserved basic helix-loophelix transcription factor, and has been shown to play an important role in carcinogenesis of many tumors including colorectal cancer (CRC). Here we aimed to investigate the role of Twist1 in the clinical significance and chemoresistance in CRC. In this study, we examined the correlation between Twist1 expression and clinicopathological characteristics using immunohistochemistry in patients with CRC. The molecular mechanisms of Twist1 expression and its effects on chemosensitivity to 5-Fluorouracil and oxaliplatin were also explored by MTT assay, colony forming assay, flow cytometry assay. The results indicate that Twist1 is overexpressed in cancer tissue, and its positive expression are related to histological grade (P=0.004), T-stage (P=0.033), N-stage (P=0.000), M-stage (P=0.040), TNM stage (P=0.002) and recurrence (P=0.023). Moreover, positive Twist1 expression is correlated with poor overall survival in CRC patients (P<0.0001), and is a significant independent prognostic indicator. In addition, we show that knockdown of Twist1 inhibits proliferation, and increased the percentage of apoptotic cells of CRC cell lines. Our findings suggest that Twist1 promotes proliferation and chemoresistance of CRC cells. Twist1 may be a potential prognostic marker and a molecular target for therapies.
Compatibility of Autologous Fibrin Adhesive With Implant Materials (1988)

A safe, effective method for securing autologous and alloplastic implants would benefit modern surgery substantially. We studied the effects of a new autologous fibrin tissue adhesive with various alloplastic implants and ear cartilage. Twelve rabbits had Proplast (a woven combination of Teflon and organic fibers), Silastic, Supramid polyfilament surgical sheeting, and ear cartilage implanted. One side of each animal had implants secured with tissue adhesive. The other, control side had identical implants placed in "subcutaneous tunnels." The tissue adhesive was biodegradable and produced no apparent toxic reaction, infection, or foreign-body reaction. It did not adhere to Silastic, but bound to the other implants. Glued implants had no more clinical or histologic evidence of inflammation than controls. Autologous fibrin tissue adhesive seems to be promising as a safe, biologic bonding material for securing certain alloplastic and autologous implants.
Children's exposure to passive smoking in England since the 1980s: cotinine evidence from population surveys (2000)

Exposure to passive smoking among children in England has approximately halved since the late 1980s. This reduction is partly explained by the fall in the percentage of both mothers and fathers who smoke and is also likely to reflect reductions of smoking in public places. However, there is only limited evidence that children from smoking households have experienced a reduction in exposure through parents' avoidance of smoking in their presence.
Free Radicals and the Pathogenesis of Type 1 Diabetes (2003)

Free radical formation evoked by proinflammatory cytokines has been suggested to be involved in the destruction of beta-cells in the course of type 1 diabetes development. However, there is no direct evidence to support this hypothesis. In this study, we used electron paramagnetic resonance spectroscopy in conjunction with spin-trapping methodology to directly determine whether cytokines give rise to free radical formation in the islets. Our results demonstrate that direct, in vivo administration of tumor necrosis factor-alpha (1,000 units), interleukin-1beta (1,000 units), and interferon-gamma (2,000 units) into the rat pancreas through a bile duct cannula leads to the formation of lipid-derived free radicals in this tissue. These free radicals most likely are generated by the beta-cells because previous depletion of these cells by streptozotocin abolished the cytokine-induced free radical formation. Furthermore, macrophage depletion was found to decrease the production of free radicals. Inhibition of the enzyme inducible cyclooxygenase (COX-2) and the transcription factor nuclear factor-kappaB (NF-kappaB) significantly diminished the free radicals' signal intensity, implicating these factors in the formation of free radicals. We have also demonstrated that cytokine treatment leads to the activation of NF-kappaB in the pancreatic islets of the rats.