gebhart/patrepeval huggingface dataset:
MAP Kinase p38Inhibitors: Clinical Results and an Intimate Look at Their Interactions with p38α Protein (2005)

Mitogen-activated protein kinase p38 is a serine/threonine kinase originally isolated from lipopolysaccharide (LPS) stimulated monocytes. There are four isoforms p38alpha p38beta, p38gamma, and p38delta. The most thoroughly studied isoform is p38alpha, whose activation has been observed in many hematopoietic and non-hematopoietic cell types upon appropriate stimuli. Subsequently, p38alpha kinase has been shown to be involved in the biosynthesis of TNFalpha and IL-1beta at the translational and transcriptional level. MAP kinase p38alpha represents a point of convergence for multiple signaling processes that are activated in inflammation and thus a key potential target for the modulation of cytokine production. The discovery and publication of p38alpha and the pyridinyl-imidazole inhibitor initiated a huge effort by many companies to develop p38alpha inhibitors as potential treatment for inflammatory diseases. Herein we provide a brief overview of recent reported clinical results for AMG 548, BIRB 796, VX 702, SCIO 469, and SCIO 323. However, our focus will be on the binding modes of these inhibitors and other p38 inhibitors in the recent literature.
Isolation of a cDNA Encoding a Metal Response Element Binding Protein Using a Novel Expression Cloning Procedure: The One Hybrid System (1994)

A new method for isolation of cDNA clones encoding sequence-specific DNA-binding proteins is described. This method, the one-hybrid system, is based on the use of reporter genes whose transcription can be activated through synthetic cis elements recognized by the sought-after DNA-binding protein. These reporter genes are used for in vivo screening of a library of cDNAs fused to a DNA fragment encoding the GAL4 activation domain. cDNA clones expressing the appropriate fusion proteins lead to activation of these reporter genes in transformed yeast cells. We have used this approach to isolate a mammalian cDNA clone encoding a sequence-specific DNA-binding protein that recognizes the metal response elements (MREs) of the metallothionein (MT) genes. The protein encoded by this cDNA, M96, shows similarity to the trithorax proteins. Expression of a functional DNA-binding form of M96 requires Zn2+ ions. The recombinant protein binds to several different MREs but fails to recognize nonfunctional mutant MREs. M96 may be involved in the activation of MT genes in response to heavy-metal ions.
Automatic linguistic segmentation of conversational speech (2002)

As speech recognition moves toward more unconstrained domains such as conversational speech, we encounter a need to be able to segment (or resegment) waveforms and recognizer output into linguistically meaningful units such a sentences. Toward this end, we present a simple automatic segmenter of transcripts based on N-gram language modeling. We also study the relevance of several word-level features for segmentation performance. Using only word-level information, we achieve 85% recall and 70% precision on linguistic boundary detection.
Identical triplets and twins developed from isolated blastomeres of 8- and 16-cell mouse embryos supported with tetraploid blastomeres (2005)

We studied the developmental potential of single blastomeres from early cleavage mouse embryos. Eight- and sixteen-cell diploid mouse embryos were disaggregated and single blastomeres from eight-cell embryos or pairs of sister blastomeres from sixteen-cell embryos were aggregated with 4, 5 or 6 tetraploid blastomeres from 4-cell embryos. Each diploid donor embryo gave eight sister aggregates, which later were manipulated together as one group (set). The aggregates were cultured in vitro until the blastocyst stage, when they were transferred (in sets) to the oviducts of pseudopregnant recipients. Eighteen live foetuses or pups were obtained from the transfer (11.0% of transferred blastocysts) and out of those, eleven developed into fertile adults (one triplet, one pair of twins and four singletons). In all surviving adults, pups and living foetuses, only diploid cells were detected in their organs and tissues as shown by analysis of coat pigmentation and distribution of glucose phosphate isomerase isoforms. In order to explain the observed high rate of mortality of transferred blastocysts, in an accompanying experiment, the diploid and tetraploid blastomeres were labelled with different fluorochromes and then aggregated. These experiments showed the diploid cells to be present not only in the inner cell mass (ICM) but also in the trophectoderm. The low number of diploid cells and the predominance of tetraploid cells in the ICM of chimaeric blastocysts might have been responsible for high postimplantation mortality of our experimental embryos.
How much asthma is really attributable to atopy? (1999)

In recent decades it has become routine to describe asthma as an atopic disease. A theoretical paradigm has evolved in which allergen exposure produces atopic sensitisation and continued exposure leads to clinical asthma through the development of airways inflammation, bronchial hyperresponsiveness, and reversible airflow obstruction. As Martinez 1 notes, this paradigm has been used with particular insistence with regard to house dust mite allergens, 2 3 but other allergens (cat, cockroach, dog) are also believed to be important. The importance of atopy is most widely accepted for asthma in children whereas, among adults, asthma has traditionally been divided into "extrinsic" and "intrinsic" asthma, although this also has been challenged. It is acknowledged that not all cases of asthma fit this paradigm-for example, some occupational causes of asthma do not appear to involve atopy-but these are regarded as interesting minor anomalies that do not threaten the dominant paradigm.
Evaluation of rumen transfaunation after surgical correction of left-sided displacement of the abomasum in cows (2004)

Benefits of rumen transfaunation of cows after surgical correction of LDA included a lesser degree of ketonuria, greater feed intake, and higher milk yield, compared with nontransfaunated cows.
Factor XIa inhibitors: A review of the patent literature (2016)

FXIa is a promising drug target for development of effective anticoagulants with limited bleeding complications. Literature reveals a major trend in the number of patent applications over the last three years. These inhibitors exploit different approaches for target inhibition. Allosteric modulation of FXIa and biosynthetic inhibition of FXI are mechanistically unique. Despite initial results in patients undergoing knee anthroplasty as with antisense oligonucleotides, major advances should be realized, particularly with respect to pharmacokinetics, for FXI/FXIa inhibitors to enter the clinic.
All-solution based device engineering of multilayer polymeric photodiodes: Minimizing dark current (2009)

We present photodiodes fabricated with several layers of semiconducting polymers, designed to show low dark current under reverse bias operation. Dark current minimization is achieved through the presence of additional polymer layers that reduce charge carrier injection in reverse bias, when in contact with the device electrodes. All polymer layers are deposited via spin coating and are photocross-linked for allowing further polymer layer deposition, by using a bis-fluorinated phenyl-azide photocross-linking agent. Dark current density values as low as 40 pA/mm2 are achieved with a corresponding external quantum efficiency (EQE) of 20% at a reverse bias of −0.5 V when an electron-blocking layer is used. Dark current is further reduced when both an electron- and a hole-blocking layer are used but the EQE falls significantly.
New developments in monoclonal antibodies for cancer detection and therapy (1994)

Monoclonal antibodies have provided clinicians with an intriguing, target-specific approach to cancer management. Used alone or conjugated with drugs, toxins, or radionuclides, monoclonal antibodies have been shown to be useful in the detection and/or treatment of several cancers. Recent advances, such as the development of "humanized" antibodies, promise to increase their effectiveness even more. This article summarizes the status of the in vivo use of monoclonal antibodies for cancer detection and therapy.
Conotruncal myocardium arises from a secondary heart field (2001)

The primary heart tube is an endocardial tube, ensheathed by myocardial cells, that develops from bilateral primary heart fields located in the lateral plate mesoderm. Earlier mapping studies of the heart fields performed in whole embryo cultures indicate that all of the myocardium of the developed heart originates from the primary heart fields. In contrast, marking experiments in ovo suggest that the atrioventricular canal, atria and conotruncus are added secondarily to the straight heart tube during looping. The results we present resolve this issue by showing that the heart tube elongates during looping, concomitant with accretion of new myocardium. The atria are added progressively from the caudal primary heart fields bilaterally, while the myocardium of the conotruncus is elongated from a midline secondary heart field of splanchnic mesoderm beneath the floor of the foregut. Cells in the secondary heart field express Nkx2.5 and Gata-4, as do the cells of the primary heart fields. Induction of myocardium appears to be unnecessary at the inflow pole, while it occurs at the outflow pole of the heart. Accretion of myocardium at the junction of the inflow myocardium with dorsal mesocardium is completed at stage 12 and later (stage 18) from the secondary heart field just caudal to the outflow tract. Induction of myocardium appears to move in a caudal direction as the outflow tract translocates caudally relative to the pharyngeal arches. As the cells in the secondary heart field begin to move into the outflow or inflow myocardium, they express HNK-1 initially and then MF-20, a marker for myosin heavy chain. FGF-8 and BMP-2 are present in the ventral pharynx and secondary heart field/outflow myocardium, respectively, and appear to effect induction of the cells in a manner that mimics induction of the primary myocardium from the primary heart fields. Neither FGF-8 nor BMP-2 is present as inflow myocardium is added from the primary heart fields. The addition of a secondary myocardium to the primary heart tube provides a new framework for understanding several null mutations in mice that cause defective heart development.
Significance of anthraquinone formation resulting from the cloning of actinorhodin genes in heterologous streptomycetes (1992)

This review explores the underlying biochemical and genetic principles leading to the formation of hybrid anthraquinones by recombinant anthracycline-producing streptomycetes transformed with genes encoding the early steps in actinorhodin biosynthesis. Experiments indicate that simple aromatic polyketides are probably synthesized using very similar mechanisms, allowing for the interspecies cloning of polyketide synthase genes for the potential production of novel aromatic polyketide structures.
Monoclonal antibodies to murine CD40 define two distinct functional epitopes (1994)

Two rat IgG2a antibodies which define distinct epitopes on murine CD40 have been generated. These antibodies specifically bind recombinant murine CD40 expressed on L cells, and the soluble extracellular domain of murine CD40 coated onto microtiter plates. Both antibodies bind B220+ but not B220 murine spleen cells, and immunoprecipitate a 45-kDa protein from the surface of purified murine splenic B cells. These antibodies exhibit separate functional properties, consistent with the notion that they define two distinct CD40 epitopes. One of the monoclonal antibodies (designated 1C10) directly induces a specific proliferative response from mature murine B cells, up-regulates several B cell surface antigens, and rescues immature B lymphoma cells from anti-IgM-induced growth arrest. The other monoclonal antibody (designated 4F11) exhibits none of these properties, but is capable of synergizing with suboptimal amounts of either anti-IgM antibodies or the 1C10 agonistic anti-CD40 antibody to produce an optimal proliferative response of purified small dense B cells. Furthermore, 4F11 antibody synergizes with suboptimal amounts of 1C10 antibody to rescue B lymphoma cells from anti-IgM-induced growth arrest. The 1C10 and 4F11 antibodies were unable to cross-block each other's binding to recombinant CD40 expressed in L cells, providing strong support for the notion that the antibodies recognize distinct epitopes on CD40. The potential implications of two functionally distinct CD40 epitopes are discussed.
Discrimination of Major Capsular Types of Campylobacter jejuni by Multiplex PCR (2011)

The polysaccharide capsule (CPS) of Campylobacter jejuni is the major serodeterminant of the Penner serotyping scheme. There are 47 Penner serotypes of C. jejuni, 22 of which fall into complexes of related serotypes. A multiplex PCR method for determination of capsule types of Campylobacter jejuni which is simpler and more affordable than classical Penner typing was developed. Primers specific for each capsule type were designed on the basis of a database of gene sequences from the variable capsule loci of 8 strains of major serotypes sequenced in this study and 10 published sequences of other serotypes. DNA sequence analysis revealed a mosaic nature of the capsule loci, suggesting reassortment of genes by horizontal transfer, and demonstrated a high degree of conservation of genes within Penner complexes. The multiplex PCR can distinguish 17 individual serotypes in two PCRs with sensitivities and specificities ranging from 90 to 100% using 244 strains of known Penner type.
The Role of Isocitrate Dehydrogenase Mutations in Glioma Brain Tumors (2011)

Isocitrate dehydrogenases (IDHs) are enzymes long known to biologists as a component of the tricarboxylic acid (TCA) cycle that converts isocitrate to α-ketoglutarate (α-KG) with production of NADH and/or NADPH. However, it was mainly viewed as a “housekeeping” gene by cancer biologists with no previously defined role in cancer. This changed in 2008 with the discovery that IDH1 was frequently mutated in glioblastoma multiformes (GBMs) (Parsons et al., 2008). IDH mutations have now also been found in lower grade gliomas as well as in acute myelocytic leukemias. The purpose of this chapter is to review the normal functions of the IDH isoforms and their role in glioma brain tumors from initial discovery of a specific mutation in IDH1 to what is currently known about the mechanisms of action of mutant IDHs.
General synthesis procedures for FIR lossless transfer matrices, for perfect-reconstruction multirate filter bank applications (1988)

A recently reported procedure (see ibid., vol.ASSP-35, p.476-492, Apr. 1987 and Proc. IEEE Int. Conf. Acoust., Speech, Sig Processing, Apr. 1987, p.2169-2172) for the design of M-channel perfect-reconstruction quadrature mirror filter (QMF) bands uses the concept of lossless alias-component matrices. The synthesis of such QMF banks centers around the generation of a lossless M*M finite-impulse response (FIR) transfer matrix E(z). Recent results for such generation have been somewhat ad hoc, i.e. not sufficiently general. A general procedure is outlined for the generation of such transfer matrices. The procedure is based on a cascaded-lattice structure, derived from a state-space viewpoint. The structure is such that it generates only M*M lossless FIR transfer matrices (regardless of parameter values), and conversely, any M*M lossless FIR transfer matrix can be obtained by a suitable choice of parameters. These parameters turn out to be angles theta /sub k/, and the structure is such that the number of angles is minimal. A design example is presented to demonstrate the main results.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Clinical Neurophysiology Laboratory Tests to Assess the Nociceptive System in Humans (1997)

This paper presents some currently available neurophysiological tools that are helpful in the clinical setting to evaluate and document neuropathic disturbances that may be associated with pain. The specific tests described in this discussion are quantitative sensory tests (QSTs), autonomic tests (ATs), microneurography (MCNG), and laser evoked potentials (LEPs). Quantitative sensory testing of the nociceptive system includes the thermal stimulation (TST) and current perception threshold (CPT) tests. The ATs applicable to some patients with pain are sudomotor and vasomotor tests. The quantitative sudomotor axon reflex test (QSART), resting sweat output (RSO), and sympathetic skin response (SSR) are the tests for sudomotor involvement. The vasomotor system is tested by measuring skin temperature (surface thermistor or thermography) at rest and, in some cases, after provocative maneuvers. In addition, MCNG (intraneural recording of single nerve fibers or fascicles of nerves) allows examiners to look directly at muscle and skin sympathetic efferent output in normal subjects without pain or with experimental pain and in patients with neuropathic pain. This technique also provides a means of studying the physiology of primary afferent fibers in persons with neurogenic pain. Recent development of LEPs that incorporate the use of painful infrared laser-induced stimuli allow selective study of the nociceptive system, both the central and peripheral portions.
Defective B cell tolerance checkpoints in systemic lupus erythematosus (2005)

A cardinal feature of systemic lupus erythematosus (SLE) is the development of autoantibodies. The first autoantibodies described in patients with SLE were those specific for nuclei and DNA, but subsequent work has shown that individuals with this disease produce a panoply of different autoantibodies. Thus, one of the constant features of SLE is a profound breakdown in tolerance in the antibody system. The appearance of self-reactive antibodies in SLE precedes clinical disease, but where in the B cell pathway tolerance is first broken has not been defined. In healthy humans, autoantibodies are removed from the B cell repertoire in two discrete early checkpoints in B cell development. We found these checkpoints to be defective in three adolescent patients with SLE. 25-50% of the mature naive B cells in SLE patients produce self-reactive antibodies even before they participate in immune responses as compared with 5-20% in controls. We conclude that SLE is associated with abnormal early B cell tolerance.
Viscoelastic Behavior and Proppant Transport Properties of a New Associative Polymer-Based Fracturing Fluid (2014)

Abstract A new thickening system extends the temperature range of traditional viscoelastic surfactant-based fluids and provides additional downhole benefits. Based on a low-molecular-weight associative polymer, the thickener forms an associative gel with surfactants at elevated temperature. This results in a gel structure that can carry proppant. Recent laboratory work has shown that viscosity alone may not accurately assess proppant transport. Thus, the aim of this paper is to evaluate rotational and oscillatory measurements to determine the viscous and elastic properties of the fluid. In addition, dynamic and static proppant settling tests were conducted using a high pressure/ high-temperature visualization cell to confirm the effect of elastic properties on proppant settling. This combination of measurements can better predict whether the fluid can be applied successfully in the field. Thirty-three different formulae across a wide polymer and surfactant concentration range were examined at temperatures up to 250°F. Also, the effect of other fracturing fluid additives, such as friction reducers and nonemulsifying agents, were examined. Finally, proppant-settling tests were conducted with three proppant types of the same size, but different density and shape at a range of concentrations. Experimental results show that each formula had a certain operating temperature range where the elastic modulus dominates. A polymer-to-surfactant concentration ratio of 1.4 was found to give the widest working temperature range with the highest elastic characteristics; the same range also gives better proppant suspension. At temperatures less than 100°F, the viscous regime was dominant for all tested formulas. However at the same temperature, the elastic modulus increased with shear rate. This gives a good proppant-carrying capacity during dynamic conditions (mixing and injection) with a small pressure drop. The friction-reducing agent was found to have a tendency to reduce the operating temperature range. However, the non-emulsifying agent reduced the effect of the friction reducer and enhanced the performance.
Limited Efficacy of Aerosolized Recombinant Alpha Interferon against Virulent Influenza A/HK Infection in Mice (1986)

Hybrid recombinant human alpha interferon A/D (rIFN A/D) is unusual in that it has equivalent antiviral activity in in vitro assays using mouse or human tissue cells. This interferon was delivered to outbred Swiss mice in small particle aerosols before and/or after these mice were inoculated with virulent influenza A/HK/68 virus. Although rIFN A/D was effective in inhibiting influenza virus replication in vitro in primary mouse embryo cells, it had only a limited degree of effectiveness in the in vivo tests; only animals exposed to rIFN A/D for 4 hr and inoculated with influenza virus 4 hr later exhibited a significant decrease in mortality (approximately 25% reduction in deaths; P less than 0.025) compared with that of the untreated control animals. The limited effectiveness of rIFN A/D seen in these studies indicated that the use of this or similar recombinant alpha interferons alone to prevent or treat influenza virus infection in humans is not promising.
Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. (1982)

We constructed a series of recombinant genomes which directed expression of the enzyme chloramphenicol acetyltransferase (CAT) in mammalian cells. The prototype recombinant in this series, pSV2-cat, consisted of the beta-lactamase gene and origin of replication from pBR322 coupled to a simian virus 40 (SV40) early transcription region into which CAT coding sequences were inserted. Readily measured levels of CAT accumulated within 48 h after the introduction of pSV2-cat DNA into African green monkey kidney CV-1 cells. Because endogenous CAT activity is not present in CV-1 or other mammalian cells, and because rapid, sensitive assays for CAT activity are available, these recombinants provided a uniquely convenient system for monitoring the expression of foreign DNAs in tissue culture cells. To demonstrate the usefulness of this system, we constructed derivatives of pSV2-cat from which part or all of the SV40 promoter region was removed. Deletion of one copy of the 72-base-pair repeat sequence in the SV40 promoter caused no significant decrease in CAT synthesis in monkey kidney CV-1 cells; however, an additional deletion of 50 base pairs from the second copy of the repeats reduced CAT synthesis to 11% of its level in the wild type. We also constructed a recombinant, pSV0-cat, in which the entire SV40 promoter region was removed and a unique HindIII site was substituted for the insertion of other promoter sequences.
Children and Comparative Fault: Determining the Burden Small Shoulders Should Bear (1994)

Missouri has long favored a system that treats assessment of a child's contributory fault as a fact issue. Although the system, referred to as the "modem trend," has undeniable advantages and provides protection for both children and the adults who negligently injure them, the system has drawbacks when applied to very young children. The negatives of the system should lead us to question whether society is adequately protecting its youngsters or demanding far too much of them.