gebhart/patrepeval huggingface dataset:
Pathogenesis of hepatitis B virus infection (2007)

Infection with hepatitis B virus (HBV) leads to a wide spectrum of clinical presentations ranging from an asymptomatic carrier state to self-limited acute or fulminant hepatitis to chronic hepatitis with progression to cirrhosis and hepatocellular carcinoma. Infection with HBV is one of the most common viral diseases affecting man. Both viral factors as well as the host immune response have been implicated in the pathogenesis and clinical outcome of HBV infection. In this review, we will discuss the impact of virus-host interactions for the pathogenesis of HBV infection and liver disease. These interactions include the relevance of naturally occurring viral variants for clinical disease, the role of virus-induced apoptosis for HBV-induced liver cell injury and the impact of antiviral immune responses for outcome of infection.
Multiple welding of long fiber epoxy vitrimer composites (2016)

Vitrimers appear as a new class of polymers that exhibit mechanical strength and are insoluble even at high temperatures, like thermosets, and yet, like thermoplastics, they are heat processable, recyclable and weldable. The question arises whether this welding property is maintained in composite materials made of more than 50 vol% of reinforcing fibers. In this paper, we quantitatively analyze the bond strength of epoxy vitrimer-based composite plates made by resin transfer molding and compare them to their non-vitrimer counterparts made of a standard thermoset epoxy. It is demonstrated that only epoxy vitrimer samples show substantial bond strength and the ability to be repeatedly welded thanks to the exchange reactions, which promote improved surface conformity and chemical bonding between the adherands at the joint interface. This opens the way towards joining composite parts without adhesives nor mechanical fasteners.
NEW HERITABLE FRAGILE SITE ON CHROMOSOME 8 INDUCED BY DISTAMYCIN A (1988)

A possible new heritable fragile site at band 8q24.1, which is known to be a breakpoint in various cancers and contains the c-myc locus, was found in the lymphocytes from a woman with mastopathy. This fragile site was induced by distamycin A treatment, and expressed as gaps and breaks in 18% of the metaphases examined. The lymphocytes from one of her two sons examined also revealed gaps or breaks at the same site of chromosome 8 in 34% of the metaphases. This fragile 8q24.1 band is considered to be a new heritable fragile site induced by distamycin A.
Recent advances in the treatment of infections due to resistant Staphylococcus aureus (2004)

The promising data that have emerged in the last year indicate that we may have six available drugs to treat resistant S. aureus infections within the next few years. The next goal is to determine the appropriate indications and cost-effectiveness of each of these drugs in our treatment strategy against S. aureus and other Gram-positive pathogens.
Evolution of Bacteriophage in Continuous Culture: a Model System To Test Antiviral Gene Therapies for the Emergence of Phage Escape Mutants (2002)

The emergence of viral escape mutants is usually a highly undesirable phenomenon. This phenomenon is frequently observed in antiviral drug applications for the treatment of viral infections and can undermine long-term therapeutic success. Here, we propose a strategy for evaluating a given antiviral approach in terms of its potential to provoke the appearance of resistant virus mutants. By use of Q beta RNA phage as a model system, the effect of an antiviral gene therapy, i.e., a virus-specific repressor protein expressed by a recombinant Escherichia coli host, was studied over the course of more than 100 generations. In 13 experiments carried out in parallel, 12 phage populations became resistant and 1 became extinct. Sequence analysis revealed that only two distinct phage mutants emerged in the 12 surviving phage populations. For both escape mutants, sequence variations located in the repressor binding site of the viral genomic RNA, which decrease affinity for the repressor protein, conferred resistance to translational repression. The results clearly suggest the feasibility of the proposed strategy for the evaluation of antiviral approaches in terms of their potential to allow resistant mutants to appear. In addition, the strategy proved to be a valuable tool for observing virus-specific molecular targets under the impact of antiviral drugs.
Establishing a Mechanistic Basis for the Large Kinetic Steps of the NS3 Helicase (2008)

The NS3 helicase from hepatitis C virus is a prototypical DEx(H/D) RNA helicase. NS3 has been shown to unwind RNA in a discontinuous manner, pausing after long apparent steps of unwinding. We systematically examined the effects of duplex stability and ionic conditions on the periodicity of the NS3 unwinding cycle. The kinetic step size for NS3 unwinding was examined on diverse substrate sequences. The kinetic step size (16 bp/step) was found to be independent of RNA duplex stability and composition, but it exhibited strong dependence on monovalent salt concentration, decreasing to approximately 11 bp/step at low [NaCl]. We addressed this behavior by analyzing the oligomeric state of NS3 at various salt concentrations. Whereas only NS3 oligomers are capable of processive unwinding, we found that monomeric NS3 is an active helicase that unwinds with low processivity. We demonstrate that low salt conditions enhance unwinding by monomeric NS3, which is likely to account for the reduction in apparent step size under low salt conditions. Based on results reported here, as well as available structural and single molecule data, we present an unwinding mechanism that addresses the apparent periodicity of NS3 unwinding, the magnitude of the step size, and that integrates the various stepwise motions observed for NS3. We propose that the large kinetic step size of NS3 unwinding reflects a delayed, periodic release of the separated RNA product strand from a secondary binding site that is located in the NTPase domain (Domain II) of NS3. These findings suggest that the mechanism of product release represents an important and unexplored feature of helicase mechanism.
Deconstructing Amazon EC2 Spot Instance Pricing (2013)

Cloud providers possessing large quantities of spare capacity must either incentivize clients to purchase it or suffer losses. Amazon is the first cloud provider to address this challenge, by allowing clients to bid on spare capacity and by granting resources to bidders while their bids exceed a periodically changing spot price. Amazon publicizes the spot price but does not disclose how it is determined. By analyzing the spot price histories of Amazon’s EC2 cloud, we reverse engineer how prices are set and construct a model that generates prices consistent with existing price traces. Our findings suggest that usually prices are not market-driven, as sometimes previously assumed. Rather, they are likely to be generated most of the time at random from within a tight price range via a dynamic hidden reserve price mechanism. Our model could help clients make informed bids, cloud providers design profitable systems, and researchers design pricing algorithms.
Membrane-Proximal Epitope Facilitates Efficient T Cell Synapse Formation by Anti-FcRH5/CD3 and Is a Requirement for Myeloma Cell Killing (2017)

The anti-FcRH5/CD3 T cell-dependent bispecific antibody (TDB) targets the B cell lineage marker FcRH5 expressed in multiple myeloma (MM) tumor cells. We demonstrate that TDBs trigger T cell receptor activation by inducing target clustering and exclusion of CD45 phosphatase from the synapse. The dimensions of the target molecule play a key role in the efficiency of the synapse formation. The anti-FcRH5/CD3 TDB kills human plasma cells and patient-derived myeloma cells at picomolar concentrations and results in complete depletion of B cells and bone marrow plasma cells in cynomolgus monkeys. These data demonstrate the potential for the anti-FcRH5/CD3 TDB, alone or in combination with inhibition of PD-1/PD-L1 signaling, in the treatment of MM and other B cell malignancies.
Two‐step elution of human serum proteins from different glass‐modified bioactive surfaces: A comparative proteomic analysis of adsorption patterns (2004)

Plasma protein adsorption patterns on surfaces may give vital information to evaluate biocompatibility of biomaterials designed for direct blood-contacting applications or tissue integration. Adsorption of human serum proteins on four different types of biomaterials (glass, aminosilanized glass, hyaluronan and sulfated hyaluronan) was analyzed by two-dimensional electrophoresis. Desorption of proteins from the surfaces was first classically achieved by sodium dodecyl sulfate (SDS) elution. We introduced a second elution step (by use of isoelectric focusing (IEF) sample buffer consisting of urea, 3-[(3-cholamidopropyl)dimethylammonio]-1-propansulfonate, and dithioerythritol) which allows more stringent elution conditions and is a tool to evaluate the protein adsorption strength to biomaterials. Moreover, the two-step elution may discriminate between irreversible and reversible adsorption of plasma proteins for biomaterials, thus helping to elucidate the structure of protein multilayers which form a complex system at the surfaces. The IEF sample buffer proved not to alter the biomaterial structure and integrity. Hydrophobic bonds resulted to be the main strength driving protein adsorption onto our biomaterials. Apolipoproteins were the most important proteins interacting with the surfaces suggesting that high-density lipoprotein (HDL) particles could play a role in biocompatibility due to their beneficial effects on endothelial cells.
McCarthy’s 4Ps: Timeworn or Time-Tested? (1995)

This paper evaluates Jerome McCarthy’s 4Ps paradigm from an historical and philosophical perspective. Since its introduction in 1960, McCarthy’s paradigm has been widely used as a pedagogical tool by academics and practitioners, but it has also been a frequent target of academic critics. The authors review criticisms of the 4Ps paradigm and conclude that it has proven to be sufficiently robust for contemporary marketing applications. That is, the 4Ps paradigm is time-tested! It is as valuable for 1990s’ professors, students and managers as it was in 1960.
DAB389 Interleukin-2 Receptor Binding Domain Mutations (1996)

Site-directed mutagenesis was used to generate point mutations in the diphtheria toxin-related fusion protein, DAB389 interleukin-2 (IL-2). Thr-439, in the IL-2 receptor binding domain of the fusion toxin, was changed to a Pro residue. The resultant fusion toxin, DAB389 IL-2(T439P), was 300-fold less cytotoxic than wild type DAB389 IL-2, partially as the result of a 100-fold decrease in binding affinity for the high affinity form of the IL-2 receptor. However, DAB389 IL-2(T439P) stimulated DNA synthesis to a greater extent than expected. Studies of intoxication kinetics indicated that the increased stimulation might result from an increased contact time between the mutated IL-2 receptor binding domain and the receptor, perhaps due to a decreased internalization rate. Another mutant, DAB389 IL-2(Q514D), in which a Gln residue at position 514 was changed to an Asp, was 2000-fold less cytotoxic than wild type DAB389 IL-2. This mutant had a 50-fold decrease in binding affinity, did not stimulate DNA synthesis and also had a reduced rate of intoxication. Gln-514 appears to play a role in receptor binding and activation, whereas Thr-439 appears to be involved with receptor binding and signaling internalization of the fusion toxin-receptor complex.
RERUPTURE AND DEEP INFECTION FOLLOWING TREATMENT OF TOTAL ACHILLES TENDON RUPTURE (2002)

The incidence of Achilles tendon reruptures and deep infections has increased. The outcome is satisfactory after a simple rerupture without infection, but the results after a deep infection are often devastating.
Design and preliminary characterization of a miniature pulsed RF APGD torch with downstream injection of the source of reactive species (2005)

The design of a miniature low-power atmospheric pressure glow discharge torch (APGD-t) and the results of its preliminary electrical and spectroscopic characterization are presented. A capacitively-coupled pulsed RF (13.56 MHz) helium plasma jet is formed in a converging confinement tube and O2 is injected downstream in the plasma afterglow region through a capillary electrode. With 1 SLM He, the APGD-t produced a non-thermal plasma jet of 500 µm-diameter and ≈2.5 mm-long at power levels ranging from 1 to 5 W. At ≈1 W, the gas temperature and He excitation temperature near the nozzle exit were ≈50°C and slightly below 2000 K, respectively. The breakdown voltage in 1 SLM He is approximately 220 Vpk−to−0. Careful electric probe measurements and circuit analysis revealed the strong effect of the voltage probe on the total load impedance. The injection of 10 SCCM O2 through the capillary electrode led to the transport of atomic O further downstream in the plasma jet and to a slight increase of the He excitation temperature without significant effects on the electrical properties and jet length. Alternatively, the addition of an equivalent amount of O2 (1 v/v%) to the plasma-forming gas affected the electrical properties slightly, but led to a drastic contraction of the plasma jet. The atomic oxygen production and transport conditions provided by the APGD-t are promising for precise bio-applications such as the treatment of skin tissues and cells.
Diacyl acid dihydrazides (1990)

Abstract N,N ′‐Diacyl acid dihydrazides were prepaed by the reaction of acid dihydazides with two equivalents of acyl chlorides. The structures of these compounds were elucidated by 1 H and 13 C NMR spectroscopy.
The novel CXCR4 antagonist, PRX177561, reduces tumor cell proliferation and accelerates cancer stem cell differentiation in glioblastoma preclinical models (2017)

Glioblastoma is the most frequent and the most lethal primary brain tumor among adults. Standard of care is the association of radiotherapy with concomitant or adjuvant temozolomide. However, to date, recurrence is inevitable. The CXCL12/CXCR4 pathway is upregulated in the glioblastoma tumor microenvironment regulating tumor cell proliferation, local invasion, angiogenesis, and the efficacy of radio-chemotherapy. In this study, we evaluated the effects of the novel CXCR4 antagonist, PRX177561, in preclinical models of glioblastoma. CXCR4 expression and PRX177561 effects were assessed on a panel of 12 human glioblastoma cells lines and 5 patient-derived glioblastoma stem cell cultures. Next, the effect of PRX177561 was tested in vivo, using subcutaneous injection of U87MG, U251, and T98G cells as well as orthotopic intrabrain inoculation of luciferase-transfected U87MG cells. Here we found that PRX177561 impairs the proliferation of human glioblastoma cell lines, increases apoptosis, and reduces CXCR4 expression and cell migration in response to stromal cell-derived factor 1alpha in vitro. PRX177561 reduced the expression of stem cell markers and increased that of E-cadherin and glial fibrillary acidic protein in U87MG cells consistent with a reduction in cancer stem cells. In vivo, PRX177561 reduced the weight and increased the time to progression of glioblastoma subcutaneous tumors while increasing disease-free survival and overall survival of mice bearing orthotopic tumors. Our findings suggest that targeting stromal cell-derived factor 1 alpha/CXCR4 axis by PRX177561 might represent a novel therapeutic approach against glioblastoma and support further investigation of this compound in more complex preclinical settings in order to determine its therapeutic potential.
Genetic Engineering of Mammalian Embryos3 (1986)

A gene consisting of the mouse metallothionein I promoter/regulator (MT) fused to the human growth hormone (hGH) structural gene (MThGH) was microinjected into rabbit, sheep and pig eggs. Visualization of nuclear structures was accomplished by interference-contrast (I-C) microscopy for rabbit and sheep eggs and by centrifugation and I-C microscopy for pig eggs. The gene integrated into the chromosomes of each species with an efficiency of 13% in rabbits, 1% in sheep and 10% in pigs. Human GH mRNA was detected in the liver of transgenic rabbits as well as tail and ear samples of pigs. Immunoreactive hGH was present in the serum of a transgenic rabbit and plasma of most transgenic pigs. In several pigs hGH levels increased between birth and 90 d of age. The presence of substantial quantities of hGH in plasma of pigs did not increase postnatal somatic growth rates. Founder animals will be bred and their transgenic and control progeny used to assess the effects of hGH on feed efficiency and carcass composition. These experiments demonstrate the feasibility of introducing foreign genes into the genome of several animal species by microinjection of eggs.
Hook effect in immunometric assays for prostate-specific antigen (1995)

Journal Article Hook effect in immunometric assays for prostate-specific antigen Get access A Charrié, A Charrié Search for other works by this author on: Oxford Academic Google Scholar G Charriére, G Charriére Search for other works by this author on: Oxford Academic Google Scholar A Guerrier A Guerrier Search for other works by this author on: Oxford Academic Google Scholar Clinical Chemistry, Volume 41, Issue 3, 1 March 1995, Pages 480–481, https://doi.org/10.1093/clinchem/41.3.480 Published: 01 March 1995
IL-20: a new target for the treatment of inflammatory skin disease (2003)

The discovery of dramatic pro-inflammatory effects of IL-20 on skin highlighted a novel regulatory pathway in cutaneous inflammation. Specific receptor complexes for IL-20 are induced on keratinocytes and transmit potent signals via the signal transducer and activator of transcription-3. In response to IL-20, keratinocytes proliferate and express pro-inflammatory genes including TNF-alpha, which leads to activation of NF-kappaB. Recently, two related cytokines, IL-19 and IL-24, have been shown to trigger the IL-20 receptor, and a second receptor complex has also been found to respond to IL-20 and IL-24. IL-20 signalling appears to be a prominent component of cutaneous inflammation, but the extent to which inflammatory processes rely upon it is unknown. Nonetheless, the prevalence of diseases involving pathological cutaneous inflammation makes the identification of safe and effective anti-inflammatory therapies for the skin a priority. Detailed understanding of the signal transduction pathways by which the skin responds to IL-20 and related factors may make it possible to develop new pharmaceutical agents to selectively suppress cutaneous inflammation.
Protein Nanostructures Produce Self-Adjusting Hyperpolarized Magnetic Resonance Imaging Contrast through Physical Gas Partitioning (2018)

Signal amplification strategies are critical for overcoming the intrinsically poor sensitivity of nuclear magnetic resonance (NMR) reporters in noninvasive molecular detection. A mechanism widely used for signal enhancement is chemical exchange saturation transfer (CEST) of nuclei between a dilute sensing pool and an abundant detection pool. However, the dependence of CEST amplification on the relative size of these spin pools confounds quantitative molecular detection with a larger detection pool typically making saturation transfer less efficient. Here we show that a recently discovered class of genetically encoded nanoscale reporters for <sup>129</sup>Xe magnetic resonance overcomes this fundamental limitation through an elastic binding capacity for NMR-active nuclei. This approach pairs high signal amplification from hyperpolarized spins with ideal, self-adjusting saturation transfer behavior as the overall spin ensemble changes in size. These reporters are based on gas vesicles, i.e., microbe-derived, gas-filled protein nanostructures. We show that the xenon fraction that partitions into gas vesicles follows the ideal gas law, allowing the signal transfer under hyperpolarized xenon chemical exchange saturation transfer (Hyper-CEST) imaging to scale linearly with the total xenon ensemble. This conceptually distinct elastic response allows the production of quantitative signal contrast that is robust to variability in the concentration of xenon, enabling virtually unlimited improvement in absolute contrast with increased xenon delivery, and establishing a unique principle of operation for contrast agent development in emerging biochemical and in vivo applications of hyperpolarized NMR and magnetic resonance imaging.
IgM myeloma: Case report with immunophenotypic profile (1998)

Immunoglobulin (Ig)M myeloma is a distinct subtype of multiple myeloma (MM) displaying clinical and pathologic features of both MM and Waldenström's macroglobulinemia (WM). Although the immunophenotypic characteristics of classic MM and WM have been reported, the surface antigen expression of IgM myeloma has not been reported. We report a case of IgM myeloma and describe its immunophenotypic profile using flow cytometry. The cells showed a hybrid MM-WM phenotype, strongly expressing CD38 but lacking CD45 and DR, typical for plasma cells; however, pan-B cell antigens CD20 and FMC7 as well as weak monoclonal surface Ig also were positive, resembling B-cell lymphoproliferative malignancies. Discordant B-cell antigen expression was present, in that pan-B antigens CD19 and CD22 were absent. In addition, B-cell activation antigen CD23, early B-precursor antigen CD10, and pan-T antigen CD5 were not expressed. Although CD20 and weak surface Ig expression have been reported in MM, FMC7 positivity has not been seen. The data therefore suggest that IgM myeloma may have a unique phenotype with characteristics of both MM and WM.
Soy protein ingredients prepared by new processes—Aqueous processing and industrial membrane isolation (1981)

Abstract The production of food ingredients from undefatted soybeans by aqueous processing and isolation of protein from soy flour by ultrafiltration membranes has been demonstrated adequately during the past decade. These relatively new techniques offer significant advantages over conventional soy processing methods. Aqueous processing requires no petroleum‐based solvent and consequently provides increased safety and flexibility of operation (because start‐up and shutdown are safe and easy). It also provides opportunities for removal or deactivation of undesirable constituents of raw materials with appropriate water‐soluble chemicals. It is, however, less efficient in oil extraction, and demulsification is required to recover clear oil when emulsions form. Ultrafiltration processes recover protein directly from soy flour extracts and thereby avoid generation of the whey which results from the conventional isoelectric precipitation. These processes have the advantages of increased isolate yield (as whey proteins are recovered in the isolate), and produce products having enhanced functionality and nitrogen solubility. The two processing techniques have subsequently been combined to obtain a single procedure with the advantages of each. Extracts from undefatted soybeans have been membrane processed with and without separating the oil to produce a variety of new soy protein ingredients.