gebhart/patrepeval huggingface dataset:
Profile of bictegravir/emtricitabine/tenofovir alafenamide fixed dose combination and its potential in the treatment of HIV-1 infection: evidence to date (2018)

Modern pharmacologic management of people living with HIV involves the use of fixed dose combinations of antiretrovirals that are simple to take, well tolerated, and highly effective. Specific recent pharmacologic advancements include 1) the second-generation integrase strand transfer inhibitors (dolutegravir and bictegravir) that consistently show less side effects, high tolerability, minimal drug interactions, and rapid rates of HIV viral load decline and 2) tenofovir alafenamide, a prodrug of tenofovir that concentrates in lymphoid tissue and minimizes off target effects. Bictegravir/emtricitabine/tenofovir alafenamide or B/F/TAF is a recently approved fixed dose combination that incorporates these new advancements in the management of HIV. This review focuses on the data supporting the use of B/F/TAF, reviews clinically relevant findings, and highlights the unanswered questions that may limit its clinical utility.
Methacrylate Resins (1936)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMethacrylate ResinsE. I. du Pont de NemoursCite this: Ind. Eng. Chem. 1936, 28, 10, 1160–1163Publication Date (Print):October 1, 1936Publication History Published online1 May 2002Published inissue 1 October 1936https://doi.org/10.1021/ie50322a008RIGHTS & PERMISSIONSArticle Views299Altmetric-Citations32LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (577 KB) Get e-Alerts
Sonoelasticity imaging of prostate cancer: in vitro results. (1995)

In this limited study, sonoelasticity imaging was more sensitive for tumor detection and more accurate for assessment of tumor location than was conventional US.
Wet chemical synthesis of silver nanorods and nanowires of controllable aspect ratio (2001)

Using a seed-mediated growth approach in a rodlike micellar media, silver nanorods of varied aspect ratio were prepared from nearly spherical 4 nm silver nanoparticles.
A defect in the regulation of major histocompatibility complex class II gene expression in human HLA-DR negative lymphocytes from patients with combined immunodeficiency syndrome. (1985)

Patients with an autosomal recessive combined immunodeficiency are characterized by an HLA negative phenotype of activated T and B lymphocytes. To determine the molecular basis of this syndrome we have studied the biosynthesis of class I and II antigens and the expression of relevant genes in these patients. The synthesis of the HLA A, B, and C heavy chain is markedly decreased, while beta 2 microglobulin is made in normal amounts. Biosynthesis of HLA-DR alpha-chain and beta-chain is abolished in the lymphocytes of these patients and there is a total absence of mRNA for either alpha-chains or beta-chains of HLA-DR. This indicates that the lack of class II antigen on these lymphocytes results from a block in the expression of HLA-DR genes. The Ii-chain, the invariant polypeptide associated intracellularly with HLA-DR, and its mRNA are made in normal amounts. Since the structural genes coding for class II polypeptides do not seem to be affected, the reported genetic defect in the patients concerns the regulation of the expression of HLA-DR genes.
Characterization of the family of dimers associated with Fc receptors (Fc epsilon RI and Fc gamma RIII) (1991)

The receptor for IgE (Fc epsilon RI) is a multimeric complex containing one alpha chain, one beta chain with four transmembrane domains and one homodimer of disulfide-linked gamma-chains. The Fc epsilon RI gamma-chains form additional disulfide-linked dimers with the homologous zeta- and eta-chains, as part of the TCR complex. The low affinity receptor for IgG (Fc gamma RIII)2 on NK cells is also associated with zeta-chains. Here we show that the gamma-chain is expressed in NK cells both as a group of heterogenous gamma gamma homodimers and also as a heterodimer bound to zeta. Fc gamma RIIIA is associated with three types of dimers zeta zeta, gamma zeta, and notably gamma gamma as well. In fact, gamma gamma appears to be the predominant species associating with Fc gamma RIIIA. The surface expressed Fc epsilon RI also associates with the same group of heterogenous gamma gamma homodimers. We also show that there is no C-terminal posttranslational cleavage of gamma occurring before its insertion into the plasma membrane as previously suggested. Thus, like the TCR, Fc gamma RIIIA may form a variety of receptor isoforms, though at present we do not understand the functional implications of these structures.
Nature of the Potential Energy Surfaces for the SN1 Reaction:  A Picosecond Kinetic Study of Homolysis and Heterolysis for Diphenylmethyl Chlorides (1996)

The picosecond dynamics for the photoinduced homolysis and heterolysis of (4-methylphenyl)phenylmethyl chloride and bis(4-methylphenyl)methyl chloride in acetonitrile are examined. In less than 20 ps, both the geminate radical pair and contact ion pair are formed from the first excited singlet state. The geminate radical pair decays by either diffusional separation to free radicals or electron transfer back to the ground state surface which partitions between reactant and contact ion pair. The contact ion pair decays by diffusional separation to the solvent separated ion pair or by collapse to form the carbon−chlorine bond. The kinetics for these processes are employed in the development of the potential energy surfaces for the SN1 reaction for diphenylmethyl chlorides in polar solvents.
Detection of Methane in the Atmosphere of Mars (2004)

We report a detection of methane in the martian atmosphere by the Planetary Fourier Spectrometer onboard the Mars Express spacecraft. The global average methane mixing ratio is found to be 10 +/- 5 parts per billion by volume (ppbv). However, the mixing ratio varies between 0 and 30 ppbv over the planet. The source of methane could be either biogenic or nonbiogenic, including past or present subsurface microorganisms, hydrothermal activity, or cometary impacts.
Liver Biopsy (2001)

Paul Ehrlich is credited with performing the first percutaneous liver biopsy in 1883 in Germany.1 After Menghini reported a technique for “one-second needle biopsy of the liver” in 1958, the procedure became more widely used. The average duration of the intrahepatic phase of previous liver-biopsy techniques had been 6 to 15 minutes.2 Liver biopsy is usually the most specific test to assess the nature and severity of liver diseases. In addition, it can be useful in monitoring the efficacy of various treatments. There are currently several methods available for obtaining liver tissue: percutaneous biopsy, transjugular biopsy, laparoscopic biopsy, or fine-needle . . .
Tissue-specific and differentiation-specific expression of a human K14 keratin gene in transgenic mice. (1989)

A construct containing approximately 2500 base pairs (bp) of 5' upstream and approximately 700 bp of 3' downstream sequence was used to drive the expression of an intronless human K14 gene in vitro and in vivo. To track the expression of the gene, a small sequence encoding the antigenic portion of neuropeptide substance P was inserted in frame 5' to the TGA translation stop codon of the gene. Surprisingly, this gene was expressed promiscuously in a wide variety of cultured cells transiently transfected with the construct. In contrast, when introduced into the germ line of transgenic mice, the construct was expressed in a fashion analogous to the endogenous K14 gene--namely, in the basal layer of stratified squamous epithelia. Our results suggest that some regulatory mechanism is overridden as a consequence of transient transfection but that sequences that can control proper K14 expression are present in the construct. The appropriate tissue-specific and differentiation-specific expression of K14.P in transgenic mice is an important first step in characterizing a promoter that could be employed to drive the foreign expression of drug-related genes in the epidermis of skin grafts.
Expression of Antibody Fragments in Pichia pastoris (2003)

Since the advent of hybridoma technology 25 years ago, monoclonal antibodies (Abs) have revolutionized many aspects of biological research and health care. After some initial setbacks, Abs are also beginning to make an impact as therapeutic agents in the clinic (). In the last decade, novel selection technologies, such as phage display and ribosome display, have emerged, allowing the isolation of Abs directly from diverse repertoires of V genes (). Phage display, in particular, has become a mature technology, allowing Abs with nanomolar (or even subnanomolar) affinities to be made to order against virtually any Ag, including self Ags ( see Note 1)). Furthermore, using highthroughput technologies, such as robotics and array screening, a multitude of Abs against a given Ag (or mixtures thereof) can now be isolated simultaneously, greatly increasing the options for assay or drug development (see Note 2).
Measurement of Intraoperative Brain Surface Deformation under a Craniotomy (1998)

These results suggest that intraoperative brain deformation is an important source of error that needs to be considered when using surgical navigation systems.
Autonomic Neurotransmission: 60 Years Since Sir Henry Dale (2008)

In the early twentieth century, Sir Henry Dale and others described brilliant studies of autonomic neurotransmission utilizing acetylcholine and noradrenaline. However, within the past 60 years, new discoveries have changed our understanding of the organization of the autonomic nervous system, including the structure and function of the nonsynaptic autonomic neuroeffector junction, the multiplicity of neurotransmitters, cotransmission, neuromodulation, dual control of vascular tone by perivascular nerves and endothelial cells, the molecular biology of receptors, and trophic signaling. Further, it is now recognized that an outstanding feature of autonomic neurotransmission is the inherent plasticity afforded by its structural and neurochemical organization and the interaction between expression of neural mediators and environmental factors. In this way, autonomic neurotransmission is matched to ongoing changes in demands and can sometimes be compensatory in pathophysiological situations.
Ranking Relations Using Analogies in Biological and Information Networks (2011)

Analogical reasoning depends fundamentally on the ability to learn and generalize about relations between objects. We develop an approach to rela- tional learning which, given a set of pairs of objects S = {A[super](1) : B[super](1) , A[super](2) : B[super](2),...,A[super](N) :B[super](N)}, measures how well other pairs A:B fit in with the set S. Our work addresses the following question: is the relation between objects A and B analogous to those relations found in S? Such questions are particularly relevant in information retrieval, where an investigator might want to search for analogous pairs of objects that match the query set of interest. There are many ways in which objects can be related, making the task of measuring analogies very challenging. Our approach combines a similarity measure on function spaces with Bayesian analysis to produce a ranking. It requires data containing features of the objects of interest and a link matrix specifying which relationships exist; no further attributes of such relationships are necessary. We illustrate the potential of our method on text analysis and information networks. An application on discovering functional interactions between pairs of proteins is discussed in detail, where we show that our approach can work in practice even if a small set of protein pairs is provided.
Myristoylation and Membrane Binding Regulate c-Src Stability and Kinase Activity (2010)

Myristoylation is critical for membrane association of Src kinases, but a role for myristate in regulating other aspects of Src biology has not been explored. In the c-Abl tyrosine kinase, myristate binds within a hydrophobic pocket at the base of the kinase domain and latches the protein into an autoinhibitory conformation. A similar pocket has been predicted to exist in c-Src, raising the possibility that Src might also be regulated by myristoylation. Here we show that in contrast to the case for c-Abl, myristoylation exerts a positive effect on c-Src kinase activity. We also demonstrate that myristoylation and membrane binding regulate c-Src ubiquitination and degradation. Nonmyristoylated c-Src exhibited reduced kinase activity but had enhanced stability compared to myristoylated c-Src. We then mutated critical residues in the predicted myristate binding pocket of c-Src. Mutation of L360 and/or E486 had no effect on c-Src membrane binding or localization. However, constructs containing a T456A mutation were partially released from the membrane, suggesting that mutagenesis could induce c-Src to undergo an artificial myristoyl switch. All of the pocket mutants exhibited decreased kinase activity. We concluded that myristoylation and the pocket residues regulate c-Src, but in a manner very different from that for c-Abl.
Palladium-katalysierte Kupplungsreaktionen organischer Elektrophile mit Organozinn-Verbindungen (1986)

Palladium-katalysierte Kupplungsreaktionen von Organozinn-Verbindungen mit unterschiedlichsten organischen Elektrophilen sind eine relativ neue Methode zur Knüpfung von Kohlenstoff-Kohlenstoff-Bindungen. Da sie unter milden Bedingungen abläuft und eine Vielfalt funktioneller Gruppen an jedem der beiden Reaktionspartner ermöglicht, darüber hinaus stereospezifisch, regioselektiv und in hohen Ausbeuten verläuft, eignet sie sich ideal für die Synthese komplizierter organischer Verbindungen. Wird die Kupplungsreaktion in Gegenwart von Kohlenmonoxid ausgeführt, so findet eine Verknüpfung der beiden Reaktanten unter Kohlenmonoxid-Insertion statt, so daß man Ketone erhält.
Chitinase B from Serratia marcescens BJL200 is exported to the periplasm without processing (1995)

A gene encoding a chitinase from Serratia marcescens BJL200 was cloned and expressed in Escherichia coli and S. marcescens. Nucleotide sequencing revealed an open reading frame encoding a 55.5 kDa protein of 499 amino acids without a typical signal peptide for export. The cellular localization of the chitinase was studied, using two types of cell fractionation methods of immunocytochemical techniques. These analyses showed that the chitinase is located in the cytoplasm in E. coli, whereas it is exported to the periplasm in S. marcescens. Analysis of chitinase isolated from periplasmic fractions of S. marcescens carrying the cloned gene showed that export of the enzyme is not accompanied by processing at the N-terminus. The chitinase did not show any of the characteristics that have been proposed to direct the export of other non-processed extracellular proteins such as the E. coli haemolysin and might therefore be secreted via a hitherto unknown mechanism.
Characterization of a Urinary Bufodienolide Na+,K+-ATPase Inhibitor in Patients After Acute Myocardial Infarction (1998)

Recent evidence suggests the existence of several endogenous Na+,K+-ATPase inhibitors in mammals. Previously, we have shown that the amphibian Na+,K+-ATPase inhibitor marinobufagenin (3,5-dihydroxy-14,15-epoxy bufodienolide) acts as a vasoconstrictor in isolated rat and human arteries. Mammalian plasma was shown to contain marinobufagenin-like immunoreactive material, which is responsive to saline volume expansion. The present study describes purification of a bufodienolide, which is similar to marinobufagenin, from the urine of patients after acute myocardial infarction with the use of thin-layer chromatography and reverse-phase high-performance liquid chromatography (HPLC). The purified substance cross-reacted with marinobufagenin antibody, demonstrated maximal UV absorbance at 300 nm characteristic of bufodienolides, and eluted from HPLC columns with the same retention time as marinobufagenin. Mass spectrometry of purified material revealed the presence of a substance indistinguishable from amphibian marinobufagenin and having molecular mass of 400 D. The present studies show that one of the human digitalis-like factors may have a bufodienolide structure and is likely to represent marinobufagenin or its isomer, and they suggest a role for this substance in the pathogenesis of myocardial ischemia.
Inhibition of experimental autoimmune encephalomyelitis by MHC class II binding competitor peptides depends on the relative MHC binding affinity of the disease-inducing peptide. (1994)

Blocking of the Ag presentation function of MHC molecules by competitor peptides has been proposed as a potential immunotherapy for MHC-associated autoimmune diseases. Despite the fact that successful inhibition of experimental autoimmune encephalomyelitis (EAE) by coimmunization with competitor peptides had been achieved, it remained questionable whether the in vivo activity of such peptides was solely the result of MHC blockade. In the peptide MBP72-85-induced EAE model in Lewis rats, we designed a single amino acid-substituted analogue of MBP72-85 with a superior MHC binding capacity, and with the capacity to activate encephalitogenic MBP72-85-specific T cells. Subsequently, two well-defined competitor peptides, one EAE related and one non-EAE related, were studied for their respective efficacies to inhibit the in vitro proliferation of an encephalitogenic T cell clone induced by the original MBP72-85 or the superior MHC binding analogue peptide. It appeared that the response to MBP72-85 was inhibited very efficiently by both competitor peptides, whereas the response to the superior MHC binding analogue peptide was not. Co-immunization of either the related or non-related competitor peptide together with MBP72-85 inhibited EAE induction in a concentration-dependent manner. In such protected rats, polyclonal T cell responses against MBP72-85 were dramatically decreased. However, EAE induced by the stronger MHC binding MBP72-85 analogue could not be inhibited by either of the competitor peptides. Moreover, in these rats, T cell priming for both MBP72-85 and the MBP72-85 analogue was not inhibited. These results show that competition for MHC binding in vivo could lead to inhibition of EAE induction.
Enhanced Haptic Sensitivity for Soft Tissues using Teleoperation with Shaped Impedance Reflection (2005)

status: Published
Engineering Human IgG1 Affinity to Human Neonatal Fc Receptor: Impact of Affinity Improvement on Pharmacokinetics in Primates (2009)

The pH-dependent binding of Igs to the neonatal FcR (FcRn) plays a critical role in the in vivo homeostasis of IgGs. Modulating the interaction between Fc and FcRn through protein engineering is one method for improving the pharmacokinetics of therapeutic Abs. Recent studies disputed the direct relationship between increasing FcRn affinity and improved pharmacokinetic properties. In this work, we studied the pharmacokinetics of two human IgG1 Fc variants in cynomolgus monkey to further clarify the affinity-pharmacokinetic relationship. First, we report a number of novel Fc point mutations and combination variants, including some with primate-specific FcRn-binding improvements. By studying these variants along with some previously described variants across a wide range of affinities, we discovered a direct correlation of pH 6 affinity improvements with neutral pH improvements, suggesting that all of the tested variants exhibit similar pH dependency in FcRn binding. We then evaluated the pharmacokinetics of variants N434A and N434W, which, respectively, gave approximately 4- and 80-fold improvements in pH 6-binding affinity to both human and nonhuman primate FcRn. Surprisingly, clearance of N434W was similar to that of wild type. N434W is the first variant studied in primates that exhibits significant binding to FcRn at pH 7.4, and its clearance substantiates the principle that too much affinity improvement, i.e., beyond that of N434W, does not yield improved pharmacokinetics. In contrast, N434A exhibited a approximately 2-fold decrease in clearance in cynomolgus monkey, supporting the notion that modest increases in pH 6 FcRn affinity can result in improved pharmacokinetics in primates.
Thrust Vector Control Eyed for Passenger Aircraft: A Novel Methodology to Combine Jet-Engine Tests with Sub-Scale Proof-of-Concept Flight Tests (1995)

Article Thrust Vector Control Eyed for Passenger Aircraft: A Novel Methodology to Combine Jet-Engine Tests with Sub-Scale Proof-of-Concept Flight Tests was published on December 1, 1995 in the journal International Journal of Turbo & Jet-Engines (volume 12, issue 4).
USDA MATURITY INDICES AND PALATABILITY OF BEEF RIB STEAKS1 (1988)

ABSTRACT In a population of 195 beef carcasses, as maturity increased (by whole USDA groups) from A to B, flavor, tenderness and overall palatability ratings for rib steaks decreased (P &lt; .05); further increases in maturity (B vs. E) resulted in subsequent decreases (P &lt; .05) in tenderness and overall palatability. Subdivision of whole maturity groups into thirds and subsequent data analyses supported precepts in USDA grade standards of declining palatability with advancing maturity, but the declines, when they occurred, were nearly linear through the extremes (from A − to E + ) and did not support the concept, in USDA grade standards, of a precipitous decline in eating satisfaction at or near the B + /C − maturity line. Among seven carcass maturity indices, all were similarly and singularly related (P &lt; .05) to palatability of rib steaks, with some measure of skeletal maturity (the best of these was color/shape of the rib bones) plus some measure of muscle maturity (the best of these was color of the longissimus muscle) combining (by means of multiple regression analyses) to predict tenderness (panel ratings and shear values) with maximum precision. Neither total pigment concentration (a chemical measure of muscle color), amount of ether‐extractable lipid (a chemical measure of intramuscular fatness) nor marbling score (a visual measure of intramuscular fatness) was able to explain more than about 7% of the observed variability in palatability ratings for cooked beef steaks. Data suggest that more attention should be paid to appearance of rib bones in a carcass (to better assess effects of maturity) and that less attention could be paid to differences between SLIGHT, SMALL and MODEST in marbling in the ribeyes, in attempting to predict, via USDA grading, the palatability of beef rib steaks.