gebhart/patrepeval huggingface dataset:
Ranibizumab, a mAb against VEGF-A for the potential treatment of age-related macular degeneration and other ocular complications. (2007)

Genentech Inc and Novartis Ophthalmics AG have developed and launched the humanized anti-VEGF antibody fragment ranibizumab, a 48-kDa humanized antibody fragment that inhibits all forms of biologically active VEGF-A, for the treatment of age-related macular degeneration by intravitreal administration. Phase I to III clinical trials to confirm the role of ranibizumab in the treatment of choroidal neovascularization (phase II and III), diabetic macular edema (phase II and III), retinal venous occlusion (phase II and III), telangiectasia (phase I and II), central serous chorioretinopathy (phase I), polypoidal choroidal vasculopathy (phase I/II), conjunctival neoplasms (phase I) and von Hippel-Lindau syndrome (phase I) are ongoing.
Sequential Regulation of the Small GTPase Rap1 in Human Platelets (2000)

Rap1, a small GTPase of the Ras family, is ubiquitously expressed and particularly abundant in platelets. Previously we have shown that Rap1 is rapidly activated after stimulation of human platelets with alpha-thrombin. For this activation, a phospholipase C-mediated increase in intracellular calcium is necessary and sufficient. Here we show that thrombin induces a second phase of Rap1 activation, which is mediated by protein kinase C (PKC). Indeed, the PKC activator phorbol 12-myristate 13-acetate induced Rap1 activation, whereas the PKC-inhibitor bisindolylmaleimide inhibited the second, but not the first, phase of Rap1 activation. Activation of the integrin alpha(IIb)beta(3), a downstream target of PKC, with monoclonal antibody LIBS-6 also induced Rap1 activation. However, studies with alpha(IIb)beta(3)-deficient platelets from patients with Glanzmann's thrombasthenia type 1 show that alpha(IIb)beta(3) is not essential for Rap1 activation. Interestingly, induction of platelet aggregation by thrombin resulted in the inhibition of Rap1 activation. This downregulation correlated with the translocation of Rap1 to the Triton X-100-insoluble, cytoskeletal fraction. We conclude that in platelets, alpha-thrombin induces Rap1 activation first by a calcium-mediated pathway independently of PKC and then by a second activation phase mediated by PKC and, in part, integrin alpha(IIb)beta(3). Inactivation of Rap1 is mediated by an aggregation-dependent process that correlates with the translocation of Rap1 to the cytoskeletal fraction.
Influence of Interfacial Structure Development on the Fracture Mechanism and Bond Strength of Aluminum/Copper Bimetal Plate (2006)

The aim of this article is to study the influence of interfacial structure development at interface on the fracture mechanism and the bond strength of cold roll bonded Al/Cu bimetal plate. The Al/Cu bimetal plates are produced by cold roll bonding and then sintered at different conditions. The bond strength of the Al/Cu bimetal plate increases generally to maximum values and then decreases to low values with increasing sintering temperature and time. Interfacial structures develop with increasing sintering temperature and time. The main interfacial layers are Al2Cu, AlCu, Al3Cu4 and Al4Cu9. The formation and thickening of those intermetallic compounds promotes cracks propagation and weakens the bond strength of the bimetal plates. The fracture mechanism transforms from ductile to brittle cleavage with the development of interfacial structures. While the bond strength of the material starts to decrease, no obvious Kirkendall effect of void formation is observed in the present study.
Hepatitis C Virus Therapies: Current Treatments, Targets and Future Perspectives (2003)

Chronic hepatitis C virus (HCV) infection is the cause of an emerging global epidemic of chronic liver disease. Current combination therapies are at best 80% efficacious and are often poorly tolerated. Strategies to improve the therapeutic response include the development of novel interferons, nucleoside analogues with reduced haemolysis compared with ribavirin and inosine 5'-monophosphate dehydrogenase inhibitors. Compounds in preclinical or early clinical trials include small molecules that inhibit virus-specific enzymes (such as the serine proteases, RNA polymerase and helicase) or interfere with translation (including anti-sense molecules, iRNA and ribozymes). Advances in understanding HCV replication, obtaining a sub-genomic replicon and contriving potential small animal models, in addition to solving crystallographic structures for the replication enzymes, have improved prospects for developing novel therapies. This review summarizes current and evolving treatments for chronic hepatitis C infection. In addition, progress in HCV targets and drug discovery tools valuable in the search for novel anti-HCV agents is detailed.
N-glycosylation and microtubule integrity are involved in apical targeting of prostate-specific membrane antigen: implications for immunotherapy (2005)

Prostate-specific membrane antigen (PSMA) is an important biomarker expressed in prostate cancer cells with levels proportional to tumor grade. The membrane association and correlation with disease stage portend a promising role for PSMA as an antigenic target for antibody-based therapies. Successful application of such modalities necessitates a detailed knowledge of the subcellular localization and trafficking of target antigen. In this study, we show that PSMA is expressed predominantly in the apical plasma membrane in epithelial cells of the prostate gland and in well-differentiated Madin-Darby canine kidney cells. We show that PSMA is targeted directly to the apical surface and that sorting into appropriate post-Golgi vesicles is dependent upon N-glycosylation of the protein. Integrity of the microtubule cytoskeleton is also essential for delivery and retention of PSMA at the apical plasma membrane domain, as destabilization of microtubules with nocodazole or commonly used chemotherapeutic Vinca alkaloids resulted in the basolateral expression of PSMA and increased the uptake of anti-PSMA antibody from the basolateral domain. These results may have important relevance to PSMA-based immunotherapy and imaging strategies, as prostate cancer cells can maintain a well-differentiated morphology even after metastasis to distal sites. In contrast to antigens on the basolateral surface, apical antigens are separated from the circulation by tight junctions that restrict transport of molecules across the epithelium. Thus, antigens expressed on the apical plasma membrane are not exposed to intravenously administered agents. The ability to reverse the polarity of PSMA from apical to basolateral could have significant implications for the use of PSMA as a therapeutic target.
Gene Silencing by Double‐Stranded RNA (Nobel Lecture) (2007)

Abstract I would like to thank the Nobel Assembly of the Karolinska Institute for the opportunity to describe some recent work on RNA‐triggered gene silencing. First a few disclaimers, however. Telling the full story of gene silencing would be a mammoth enterprise that would take me many years to write and would take you well into the night to read. So we'll need to abbreviate the story more than a little. Second (and as you will see) we are only in the dawn of our knowledge; so consider the following to be primer …︁ the best we could do as of December 8th 2006. And third, please understand that the story that I am telling represents the work of several generations of biologists, chemists, and many shades in between. I'm pleased and proud that work from my laboratory has contributed to the field, and that this has led to my being chosen as one of the messengers to relay the story in this forum. At the same time, I hope that there will be no confusion of equating our modest contributions with those of the much grander RNAi enterprise.
Matriptase-2- and Proprotein Convertase-cleaved Forms of Hemojuvelin Have Different Roles in the Down-regulation of Hepcidin Expression (2010)

Hemojuvelin (HJV) is an important regulator of iron metabolism. Membrane-anchored HJV up-regulates expression of the iron regulatory hormone, hepcidin, through the bone morphogenic protein (BMP) signaling pathway by acting as a BMP co-receptor. HJV can be cleaved by the furin family of proprotein convertases, which releases a soluble form of HJV that suppresses BMP signaling and hepcidin expression by acting as a decoy that competes with membrane HJV for BMP ligands. Recent studies indicate that matriptase-2 binds and degrades HJV, leading to a decrease in cell surface HJV. In the present work, we show that matriptase-2 cleaves HJV at Arg(288), which produces one major soluble form of HJV. This shed form of HJV has decreased ability to bind BMP6 and does not suppress BMP6-induced hepcidin expression. These results suggest that the matriptase-2 and proprotein convertase-cleavage products have different roles in the regulation of hepcidin expression.
Lysine 2,3-Aminomutase (1970)

Abstract The enzyme lysine 2,3-aminomutase from Clostridium SB4 which catalyzes the conversion of l-lysine to l-β-lysine has been studied. A satisfactory radiochemical assay has been developed. Although the enzyme is inactivated rapidly by exposure to oxygen, it can be fully activated by anaerobic incubation with a sulfhydryl compound for 1 hour at 37°. Optimal activation occurs when 0.9 mm ferrous ion is present; evidence is presented that enzyme-bound ferrous ion is required for activity. The enzyme is moderately stable and has been purified 53-fold in 10% yield to a specific activity of 6.4 units per mg. The best preparations appear to be at least 95% homogeneous on the basis of disc gel electrophoresis and gel filtration. A molecular weight of 285,000 has been estimated by two different procedures. The sedimentation coefficient is 10.0 S. The addition of S-adenosylmethionine stimulated activity; near maximal activity was achieved when 3.7 moles of S-adenosylmethionine per mole of enzyme were added to the assay. The apparent Km for S-adenosylmethionine is 2.8 x 10-8 m. S-Adenosylhomocysteine inhibits competitively with S-adenosylmethionine. The enzyme is stereospecific for l-lysine; the apparent Km is 6.6 mm. S-Aminoethylcysteine is a competitive inhibitor (Ki = 56 µm). The aminomutase reaction is reversible; the equilibrium constant (K = (l-β-lysine)/(l-lysine)) at 37° is 6.7. The absorption spectrum of the enzyme has a peak at 420 mµ and is similar to that of some pyridoxal phosphate enzymes. The activity and the absorbance peak are decreased by treatment with cysteine, hydroxylamine, or isonicotinic acid hydrazide. Analytical data show that the enzyme contains at least 1.7 moles of protein-bound vitamin B6 per mole. Experiments with D2O and T2O show that little or no exchange between solvent hydrogen and lysine or β-lysine occurs during the aminomutase reaction.
Isolated working rat heart perfusion with perfluorochemical emulsion Fluosol-43 (1982)

Isolated working rat hearts were perfused with the perfluorochemical emulsion Fluosol-43 to determine whether it would support prolonged, stable cardiac function. The perfluorochemical emulsion provides a controlled perfusate composition, relatively high oxygen capacity, and a colloid osmotic pressure that is similar to that of plasma. Electrically paced (325 beats/min) hearts were perfused for 6 h at 35 degrees C in a recirculating system. Hemodynamic and mechanical function of seven Krebs-Henseleit-perfused hearts declined significantly more than that of seven Fluosol-43-perfused hearts over the 6-h period. The percent of initial function remaining at 6 h for Krebs-Henseleit-perfused vs. Fluosol-43-perfused hearts was 70.3 +/- 5.0 vs. 95.4 +/- 1.1% (P less than 0.001) for left ventricular peak systolic pressure; 55.6 +/- 7.7 vs. 97.5 +/- 2.4% (P less than 0.001) for dP/dtmax; 27.1 +/- 7.2 vs. 60.6 +/- 5.2% (P less than 0.005) for cardiac output; 11.0 +/- 6.3 vs. 67.2 +/- 3.4% (P less than 0.001) for external work efficiency; and 17.4 +/- 8.4 vs. 67.7 +/- 4.5% (P less than 0.001) for stroke rhythmic than Fluosol-43-perfused hearts during the last 3 h of perfusion. Perfusate lactate concentration was 4.5-fold higher in the Krebs-Henseleit perfusate than in the Fluosol-43 perfusate at 6 h, reflecting greater anaerobic metabolism in the Krebs-Henseleit-perfused hearts. Thus isolated rat hearts perfused with Fluosol-43 have greater maintenance of hemodynamic and mechanical function over a longer time period than hearts perfused with Krebs-Henseleit bicarbonate buffer.
Unstable Angina (1995)

The results of the angioscopic examination show that diabetic patients with unstable angina have a higher incidence of plaque ulceration and intracoronary thrombus formation than nondiabetic patients. This increased frequency of complex lesion morphology is consistent with the disproportionately higher risk for development of acute coronary syndromes in these patients.
Combined use of GPS and LORAN-C in Integrated Navigation Systems (2002)

In 1995, the Avionik Zentrum Braunschweig (in close co-operation with the Technical University of Braunschweig) has carried out a study to investigate the potential of a combined usage of GPS and LORAN-C in close co-operation with the German MoT, DFS and LBA. One major motive for this effort was that many states and organisation feel the need for a terrestrial back-up navigation system for the existing satellite navigation systems like GPS or GLONASS. This study has been funded by the German Ministry of Defense (MoD) and focused on an investigation in respect to user-requirements, certification and operational as well as institutional aspects. Another major emphasis was taken on a theoretical analysis of a combined GPS/LORAN-C navigation solution with respect to the special Northwest-European environment. As a result, an algorithm based on raw-data from GPS as well as LORAN-C has been developed and tested in a number of simulations. In a second phase of this project, three different pilot-projects for air, land and marine will be defined and all theoretical results carried out in this first phase will be comprehensively tested in real environments in a number of experiments.
Construction and expression of the complete Clostridium difficile toxin A gene in Escherichia coli (1991)

Cloned fragments constituting the 8.1-kb toxin A gene of Clostridium difficile were used to reconstruct the intact gene. The recombinant toxin expressed in Escherichia coli was cytotoxic, enterotoxic, and lethal. In addition, toxic lysate caused hemagglutination of rabbit erythrocytes. The toxic activities were inhibited by antibody specific for toxin A. Our findings demonstrate that the biological activities exhibited by native toxin A are functions of a single protein encoded by the 8.1-kb toxin A gene, independent of any other C. difficile gene products.
Mineralization of gold in block copolymer micelles (1997)

Abstract Ultrasmall gold particles have been prepared inside the micelles of polystyrene‐block‐poly(ethylene oxide) and polystyrene‐block‐poly(2‐vinylpyridine) in toluene. Starting point was the formation of a thermodynamically stable dispersion of HAuCl 4 or LiAuCl 4 in the inverse micelles of the block copolymer which were treated with hydrazine or pyrrole. Analysis of the effect of the reduction agent on the stability of the micelles yielded a simple model for the transformation process involving coagulation of the swelling micelles. Kinetic control of the different steps, i.e., reduction, mineralization, coagulation, film formation, allowed to prepare thin films in which highly uniform gold particles were arranged in yet unknown order. When pyrrole was employed for the reduction, the gold monocrystals got embedded in a shell of polypyrrole.
High-Modulus, High-Conductivity Nanostructured Polymer Electrolyte Membranes via Polymerization-Induced Phase Separation (2013)

The primary challenge in solid-state polymer electrolyte membranes (PEMs) is to enhance properties, such as modulus, toughness, and high temperature stability, without sacrificing ionic conductivity. We report a remarkably facile one-pot synthetic strategy based on polymerization-induced phase separation (PIPS) to generate nanostructured PEMs that exhibit an unprecedented combination of high modulus and ionic conductivity. Simple heating of a poly(ethylene oxide) macromolecular chain transfer agent dissolved in a mixture of ionic liquid, styrene and divinylbenzene, leads to a bicontinuous PEM comprising interpenetrating nanodomains of highly cross-linked polystyrene and poly(ethylene oxide)/ionic liquid. Ionic conductivities higher than the 1 mS/cm benchmark were achieved in samples with an elastic modulus approaching 1 GPa at room temperature. Crucially, these samples are robust solids above 100 °C, where the conductivity is significantly higher. This strategy holds tremendous potential to advance lithium-ion battery technology by enabling the use of lithium metal anodes or to serve as membranes in high-temperature fuel cells.
Genome Properties of the Diatom Phaeodactylum tricornutum (2002)

Diatoms are a ubiquitous class of microalgae of extreme importance for global primary productivity and for the biogeochemical cycling of minerals such as silica. However, very little is known about diatom cell biology or about their genome structure. For diatom researchers to take advantage of genomics and post-genomics technologies, it is necessary to establish a model diatom species. Phaeodactylum tricornutum is an obvious candidate because of its ease of culture and because it can be genetically transformed. Therefore, we have examined its genome composition by the generation of approximately 1,000 expressed sequence tags. Although more than 60% of the sequences could not be unequivocally identified by similarity to sequences in the databases, approximately 20% had high similarity with a range of genes defined functionally at the protein level. It is interesting that many of these sequences are more similar to animal rather than plant counterparts. Base composition at each codon position and GC content of the genome were compared with Arabidopsis, maize (Zea mays), and Chlamydomonas reinhardtii. It was found that distribution of GC within the coding sequences is as homogeneous in P. tricornutum as in Arabidopsis, but with a slightly higher GC content. Furthermore, we present evidence that the P. tricornutum genome is likely to be small (less than 20 Mb). Therefore, this combined information supports the development of this species as a model system for molecular-based studies of diatom biology. The nucleotide sequence data reported has been deposited in GenBank Nucleotide Sequence Database (dbEST section) under accession nos. BI306757 through BI307753.
Experimental Organic Chemistry: Principles and Practice (1990)

Part 1 Laboratory practice: safety in the chemical laboratory glassware and equipment in the laboratory organic reactions - from starting materials to pure organic product qualitative analysis of organic compounds spectroscopic analysis of organic compounds keeping records the laboratory notebook and the chemical literature. Part 2 Experimental procedures: introduction list of experiments experiments which can be taken in sequences experiments which illustrate particular techniques functional group interconversions carbon-carbon bond forming reactions projects. Appendices: correlating your textbook with experiments in this book.
GC/MS Characterization of Liquids Generated from Low-Temperature Pyrolysis of Wood (2003)

Conventional pyrolysis of beech wood has been carried out for heating temperatures in the range 600−900 K, reproducing conditions of interest in countercurrent fixed-bed gasification. The yields of liquids (water and tars) increase with the heating temperature from about 40 to 55% of dry wood mass, confirming results previously obtained with a laboratory-scale gasifier. Apart from qualitative identification of ∼90 species, GC/MS techniques have been applied to quantify 40−43% of tars (40 species, with major contributions from acetic acid, hydroxypropanone, hydroxyacetaldehyde, levoglucosan, formic acid, syringol, and 2-furaldehyde). Decomposition of holocellulose leads to the formation of furan derivatives and carbohydrates, with a temperature-dominated selectivity toward hydroxyacetaldehyde against levoglucosan. Syringols and guaiacols, originating from primary degradation of lignin, present a maximum for heating temperatures of about 750−800 K whereas, owing to secondary degradation, phenols continuously increase. A comparison is also provided with fast pyrolysis liquids obtained from four commercial plants.
Estimation of co-channel signals with linear complexity (2001)

To increase wireless system capacity using co-channel signals and multiple receiver antennas, we develop the partitioned Viterbi algorithm (PVA). The PVA estimation complexity increases linearly with each additional co-channel signal rather than exponentially as it does with joint maximum-likelihood sequence estimation (MLSE). The estimation problem involves multiple signals simultaneously transmitted and observed through slow-fading, frequency-selective channels. Although transmission is assumed to be in bursts according to a time-division multiple-access scheme, more than one signal can occupy the same time and frequency slot (these signals are referred to as "co-channel" signals). Separation and estimation of the symbol bursts is accomplished by exploiting channel differences, PVA estimation consists of a set of Viterbi detectors, one per signal, that operate in parallel with cross-coupling to allow approximate interference cancellation by means of tentative decisions. The forward filter of a decision feedback equalizer (DFE) is used to "prefilter" received signals prior to PVA estimation. Prefiltering delays the energy of interfering signals so that tentative decisions become reliable enough to use. Simulation results show PVA performance remains near-optimal with respect to the performance of joint MLSE.
N-Acetylcysteine potentiates inhibition of platelet aggregation by nitroglycerin. (1985)

Platelet aggregation is currently felt to play an important role in the pathogenesis of ischemic vascular disorders. The smooth muscle relaxant, nitroglycerin, has been shown to inhibit platelet aggregation in vitro, but at concentrations that were felt to be unattainable in vivo. Because the in vivo action of nitroglycerin on smooth muscle cells has been shown to depend on the presence of reduced cytosolic sulfhydryl groups, the inhibitory effect of nitroglycerin on platelet aggregation was examined in the presence of the reduced thiol, N-acetylcysteine. Millimolar concentrations of N-acetylcysteine potentiated markedly the inhibitory effect of nitroglycerin on platelet aggregation induced by ADP, epinephrine, collagen, and arachidonate, decreasing the 50% inhibitory concentration (IC50) approximately 50-fold for each of these agents. Other guanylate cyclase activators inhibited ADP-induced aggregation similarly and this inhibition was likewise potentiated by N-acetylcysteine. Platelet guanosine 3',5'-cyclic monophosphate content increased fivefold in the presence of nitroglycerin and N-acetylcysteine 2 min before maximal inhibition of ADP-induced aggregation was achieved, while simultaneously measured cyclic AMP did not change relative to base-line levels. In the absence of N-acetylcysteine, nitroglycerin induced a marked decrease in platelet-reduced glutathione content as S-nitroso-thiol adducts were produced. The synthetic S-nitroso-thiol, S-nitroso-N-acetylcysteine, markedly inhibited platelet aggregation with an IC50 of 6 nM. These data show that N-acetylcysteine markedly potentiates the inhibition of platelet aggregation by nitroglycerin and likely does so by inducing the formation of an S-nitrosothiol adduct(s), which activate guanylate cyclase.