gebhart/patrepeval huggingface dataset:
Discovery of Benzotriazolo[4,3-d][1,4]diazepines as Orally Active Inhibitors of BET Bromodomains (2015)

Inhibition of the bromodomains of the BET family, of which BRD4 is a member, has been shown to decrease myc and interleukin (IL) 6 in vivo, markers that are of therapeutic relevance to cancer and inflammatory disease, respectively. Herein we report substituted benzo[b]isoxazolo[4,5-d]azepines and benzotriazolo[4,3-d][1,4]diazepines as fragment-derived novel inhibitors of the bromodomain of BRD4. Compounds from these series were potent and selective in cells, and subsequent optimization of microsomal stability yielded representatives that demonstrated dose- and time-dependent reduction of plasma IL-6 in mice.
Insulin response of a hybrid amylase/CAT gene in transgenic mice. (1988)

Expression of an amylase/CAT hybrid gene was analyzed in transgenic mice. The amylase promoter was derived from a pancreatic amylase gene whose expression is repressed in diabetic animals. Pancreas-specific expression of the amylase/chloramphenicol acetyl-transferase (CAT) construct was observed in two independent transgenic lines. Correct initiation of transcription was demonstrated by protection of an anti-sense riboprobe. To evaluate the insulin dependence of the hybrid gene, diabetes was induced by treatment with streptozotocin. As a result of this treatment, pancreatic CAT activity was reduced to undetectable levels. Subsequent administration of insulin restored CAT activity to normal levels. The abundance of CAT transcripts was also greatly reduced in diabetic pancreas. These studies localize the determinants of pancreas specificity and insulin dependence to the region between -208 and +19 of the mouse pancreatic Amy-2.2 gene. The results are consistent with an effect of insulin on amylase transcription, rather than post-transcriptional regulation of mRNA processing or stability.
RNase III cleavage is obligate for maturation but not for function of Escherichia coli pre-23S rRNA. (1984)

RNase III makes the initial cleavages that excise Escherichia coli precursor 16S and 23S rRNA from a single large primary transcript. In mutants deficient in RNase III, no species cleaved by RNase III are detected and the processing of 23S rRNA precursors to form mature 23S rRNA fails entirely. Instead, 50S ribosomes are formed with rRNAs up to several hundred nucleotides longer than mature 23S rRNA. Unexpectedly, these aberrant subunits function well enough to participate in protein synthesis and permit cell growth. Consistent with the inference that RNase III cleavages are absolutely required for 23S rRNA maturation, when 50S ribosomes from a strain deficient in RNase III were incubated with a ribosome-free extract from a RNase III+ strain, rRNA species processed by RNase III and species with normal mature 23S rRNA termini were produced.
Rethinking Nutritional Support for Persons with Cancer Cachexia (2003)

Cancer cachexia is a poorly understood syndrome of anorexia, weight loss, and muscle wasting that negatively impacts quality of life and survival in cancer patients. Research has clearly implicated pro-inflammatory cytokines in the biology of cancer cachexia. More recent research implicates products of arachidonic acid and suggests that cachexia may be a chronic inflammatory condition rather than a nutritional aberration. To date, nutritional support to slow weight loss has focused primarily on increasing calorie intake. Alternatively, many foods contain factors that can modulate the synthesis or activity of pro-inflammatory mediators, especially the synthesis of prostaglandin E2 from arachidonic acid. These factors and foods are sometimes called nutraceuticals, and research is needed to evaluate their efficacy in combating cancer cachexia.
H-Type Dimer Formation of Fluorophores: A Mechanism for Activatable, in Vivo Optical Molecular Imaging (2009)

In vivo molecular imaging with target-specific activatable "smart" probes, which yield fluorescence only at the intended target, enables sensitive and specific cancer detection. Dimerization and fluorescence quenching has been shown to occur in concentrated aqueous solutions of various fluorophores. Here, we hypothesized that fluorophore dimerization and quenching after conjugation to targeting proteins can occur at low concentration. This dimerization can be exploited as a mechanism for fluorescence activation. Rhodamine derivatives were conjugated to avidin and trastuzumab, which target D-galactose receptor and HER2/neu antigen, respectively. After conjugation, a large proportion of R6G and TAMRA formed H-type dimers, even at low concentrations, but could be fully dequenched upon dissociation of the dimers to monomers. To demonstrate the fluorescence activation effect during in vivo fluorescence endoscopic molecular imaging, a highly quenched probe, avidin-TAMRA, or a minimally quenched probe, avidin-Alexa488, was administered into mice with ovarian metastases to the peritoneum. The tumors were clearly visualized with avidin-TAMRA, with low background fluorescence; in contrast, the background fluorescence was high for avidin-Alexa488. Thus, H-dimer formation as a mechanism of fluorescence quenching could be used to develop fluorescence activatable probes for in vivo molecular imaging.
Distributed vs. centralized power systems frequency control (2013)

This paper considers a distributed control algorithm for frequency control of electrical power systems. We propose a distributed controller which retains the reference frequency of the buses under unknown load changes, while asymptotically minimizing a quadratic cost of power generation. For comparison, we also propose a centralized controller which also retains the reference frequency while minimizing the same cost of power generation. We derive sufficient stability criteria for the parameters of both controllers. The controllers are evaluated by simulation on the IEEE 30 bus test network, where their performance is compared.
A Phase II trial of suramin monthly × 3 for hormone‐refractory prostate carcinoma (2003)

Monthly bolus suramin was well tolerated, reduced PSA levels, and induced objective responses, even in patients who previously had received chemotherapy.
Photonic Boson Sampling in a Tunable Circuit (2012)

Quantum computers are unnecessary for exponentially efficient computation or simulation if the Extended Church-Turing thesis is correct. The thesis would be strongly contradicted by physical devices that efficiently perform tasks believed to be intractable for classical computers. Such a task is boson sampling: sampling the output distributions of n bosons scattered by some passive, linear unitary process. We tested the central premise of boson sampling, experimentally verifying that three-photon scattering amplitudes are given by the permanents of submatrices generated from a unitary describing a six-mode integrated optical circuit. We find the protocol to be robust, working even with the unavoidable effects of photon loss, non-ideal sources, and imperfect detection. Scaling this to large numbers of photons should be a much simpler task than building a universal quantum computer.
B Cell Activating Factor (BAFF) and T Cells Cooperate to Breach B Cell Tolerance in Lupus-Prone New Zealand Black (NZB) Mice (2010)

The presence of autoantibodies in New Zealand Black (NZB) mice suggests a B cell tolerance defect however the nature of this defect is unknown. To determine whether defects in B cell anergy contribute to the autoimmune phenotype in NZB mice, soluble hen egg lysozyme (sHEL) and anti-HEL Ig transgenes were bred onto the NZB background to generate double transgenic (dTg) mice. NZB dTg mice had elevated levels of anti-HEL antibodies, despite apparently normal B cell functional anergy in-vitro. NZB dTg B cells also demonstrated increased survival and abnormal entry into the follicular compartment following transfer into sHEL mice. Since this process is dependent on BAFF, BAFF serum and mRNA levels were assessed and were found to be significantly elevated in NZB dTg mice. Treatment of NZB sHEL recipient mice with TACI-Ig reduced NZB dTg B cell survival following adoptive transfer, confirming the role of BAFF in this process. Although NZB mice had modestly elevated BAFF, the enhanced NZB B cell survival response appeared to result from an altered response to BAFF. In contrast, T cell blockade had a minimal effect on B cell survival, but inhibited anti-HEL antibody production. The findings suggest that the modest BAFF elevations in NZB mice are sufficient to perturb B cell tolerance, particularly when acting in concert with B cell functional abnormalities and T cell help.
Chemical Studies on Amino Acid Acceptor Ribonucleic Acids. IV. Position of the Amino Acid Residue in Aminoacyl S-RNA: Chemical Approach* (1965)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChemical Studies on Amino Acid Acceptor Ribonucleic Acids. IV. Position of the Amino Acid Residue in Aminoacyl S-RNA: Chemical Approach*Calvin S. McLaughlin and Vernon M. IngramCite this: Biochemistry 1965, 4, 7, 1442–1447Publication Date (Print):July 1, 1965Publication History Published online1 May 2002Published inissue 1 July 1965https://doi.org/10.1021/bi00883a032RIGHTS & PERMISSIONSArticle Views32Altmetric-Citations34LEARN 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 (603 KB) Get e-Alertsclose Get e-Alerts
Identification of a lysin associated with a bacteriophage (A25) virulent for group A streptococci (1981)

A phage-associated lysin was found in culture lysates resulting from the propagation of virulent bacteriophage A25 on the group A streptococcal strain designated K56. In contrast to the previously described group C streptococcal phage-associated lysins, A25 phage-associated lysin was more active on chloroform-treated cells, was not phage bound, and was active on some group G and H strains, as well as on group A and C strains. A25 phage-associated lysin had an optimum pH of 6.7 and was inactivated by 10(-3) M p-hydroxymercuribenzoate. Group A cells exposed to penicillin were more susceptible to A25 phage-associated lysin, whereas chloramphenicol-treated cells became resistant to lysis. Release of lipoteichoic acid appeared to precede lysis, and cardiolipin treatment of cells reversed the effects of chloroform and penicillin treatments. These results suggest the possibility that A25 phage-associated lysin may have a mechanism similar to the mechanism of an autolysin or that cell lysis may be due to the activation of an autolysin.
Characterization of the cell surface receptor for granulocyte-macrophage colony-stimulating factor. (1986)

125I-labeled recombinant murine granulocyte-macrophage colony-stimulating factor (GM-CSF) was used to characterize receptors specific for this lymphokine on the surface of cells of both myelomonocytic and T-cell origin. GM-CSF binding to these cells was specific and saturable. Equilibrium binding studies revealed that on all cell types examined, GM-CSF bound to a single class of high affinity receptor (1000-5000 receptors/cell) with a Ka of 10(8)-10(9) M-1. More extensive characterization with P388D1 cells showed that binding of GM-CSF was rapid at 37 degrees C with a slow subsequent dissociation rate. Among a panel of lymphokines and growth hormones, only unlabeled natural or recombinant GM-CSF were able to compete for the binding of 125I-GM-CSF to these cells. Affinity cross-linking experiments with the homobifunctional cross-linking reagents disuccinimidyl suberate, disuccinimidyl tartrate, and dithiobis(succinimidyl propionate) resulted in the identification of a receptor protein with a Mr of 130,000 on five out of the seven cell types examined. This protein was extremely sensitive to proteolysis and in the absence of protease inhibitors was degraded to a form with an approximate Mr of 70,000. A receptor protein of Mr 180,000, in addition to the Mr 70,000 protein, was found on bone marrow cells and on P815 cells. The potential tissue-specific molecular heterogeneity associated with the GM-CSF receptor may help to explain some of the diverse biological effects associated with this growth and differentiation factor.
Isolation and structural elucidation of the degradation products of pregnanediol disulfate obtained by hot acid hydrolysis (Clinical analysis on steroids. XXI). (1982)

Besides the main products, 17α-ethyl-17β-methyl-18-nor-5β-androst-13-en-3α-ol (7a), 17α-methyl-D-homo-5β-androstane-3α, 17aβ-diol (8), and 17α-methyl-17aβ-chloro-D-homo-5β-androstan-3α-ol (9), other minor degradation products of pregnanediol 3, 20-disulfate (2) were obtained under reflux in 3 N hydrochloric acid, and were structurally identified by comparison with synthetic specimens. The steroidal mono olefins isolated were 5β-pregn-3-en-20α-ol (10a), 5β-pregn-2-en-20α-ol (11a), 5β-pregn-20-en-3α-ol (12a), and 5β-pregn-17 (20)-en-3α-ol (13a). The Z-isomer of 13a, 5β-pregn-17 (20)-en-3α-ol (14a), was detected by gas chromatography and identified by gas chromatography-mass spectrometric comparison with synthetic compound. Steroidal dienes were obtained as a mixture of Δ2-and Δ3-compounds having partial D-ring structures corresponding to 7a, 12a, and 13a. Although it was a minor product, 5β-pregnane-3α, 20β-diol (16) was also obtained, and its isolation suggests the formation of a C20-carbonium ion in the course of the hydrolysis. The yield of intact steroid, pregnanediol (1), was only 18.4% of the total products obtained.
Affinity chromatography of thyroid hormone receptors. Biospecific elution from support matrices, characterization of the partially purified receptor. (1981)

In the preceding paper we reported the synthesis of affinity matrices containing 3,5,3'-triiodo-~-thyonine (T3) Linked via its amino group and the diactivated ester of glutaric acid to the free amino groups of diaminohexane-Sepharose.This report describes the optimization of this system for the purification of the intranuclear thyroid hormone receptor.The thyroid hormone receptors (Kd for T3 -50 to 200 PM) were solubilized from nuclei obtained from rat, sheep, or steer liver.These receptors were partially purified by Sephadex G-100 chromatography and then bound to the affinity gel.After the receptor-containing gel was washed, the receptors were eluted with free TI.An exchange assay was developed for measuring the binding capacity of the eluted receptor; after most of the unlabeled T3 in the affinity-gel eluate had been removed by chromatography on Sephadex G-26, the small amount of nonradioactive Ta remaining was displaced from the receptor by incubation with ["'1]T3.The recovery of the receptors from the affinity gel was stimulated approximately 5-fold by the addition of purified core histones (HzA, HZB, H3, and H4, themselves devoid of T3-binding activity) to the wash, elution, and assay buffers, but was not enhanced by the addition of several other acidic or basic proteins.In the presence of 25 to 50 pg/ml of core histones, recovery of receptor from the gel was 10 to 35%, with a purification of more than 500-fold.Scatchard analysis of hormone binding by the affinity-purified material showed an apparent Kd of 50 p~ for Ta and 1 n M for thyroxine (3,5,3',5'-tetraiodo-~-thyronine).The relative binding affinities of the affinitypurified receptor €or various hormones and analogs
LoRa Backscatter: Enabling The Vision of Ubiquitous Connectivity (2017)

The vision of embedding connectivity into billions of everyday objects runs into the reality of existing communication technologies --- there is no existing wireless technology that can provide reliable and long-range communication at tens of microwatts of power as well as cost less than a dime. While backscatter is low-power and low-cost, it is known to be limited to short ranges. This paper overturns this conventional wisdom about backscatter and presents the first wide-area backscatter system. Our design can successfully backscatter from any location between an RF source and receiver, separated by 475 m, while being compatible with commodity LoRa hardware. Further, when our backscatter device is co-located with the RF source, the receiver can be as far as 2.8 km away. We deploy our system in a 4,800 $ft^{2}$ (446 $m^{2}$) house spread across three floors, a 13,024 $ft^{2}$ (1210 $m^{2}$) office area covering 41 rooms, as well as a one-acre (4046 $m^{2}$) vegetable farm and show that we can achieve reliable coverage, using only a single RF source and receiver. We also build a contact lens prototype as well as a flexible epidermal patch device attached to the human skin. We show that these devices can reliably backscatter data across a 3,328 $ft^{2}$ (309 $m^{2}$) room. Finally, we present a design sketch of a LoRa backscatter IC that shows that it costs less than a dime at scale and consumes only 9.25 $μ$W of power, which is more than 1000x lower power than LoRa radio chipsets.
Antigen-Specific Antitumor Responses Induced by OX40 Agonist Are Enhanced by the IDO Inhibitor Indoximod (2018)

Although an immune response to tumors may be generated using vaccines, so far, this approach has only shown minimal clinical success. This is attributed to the tendency of cancer to escape immune surveillance via multiple immune suppressive mechanisms. Successful cancer immunotherapy requires targeting these inhibitory mechanisms along with enhancement of antigen-specific immune responses to promote sustained tumor-specific immunity. Here, we evaluated the effect of indoximod, an inhibitor of the immunosuppressive indoleamine-(2,3)-dioxygenase (IDO) pathway, on antitumor efficacy of anti-OX40 agonist in the context of vaccine in the IDO<sup>-</sup> TC-1 tumor model. We demonstrate that although the addition of anti-OX40 to the vaccine moderately enhances therapeutic efficacy, incorporation of indoximod into this treatment leads to enhanced tumor regression and cure of established tumors in 60% of treated mice. We show that the mechanisms by which the IDO inhibitor leads to this therapeutic potency include (i) an increment of vaccine-induced tumor-infiltrating effector T cells that is facilitated by anti-OX40 and (ii) a decrease of IDO enzyme activity produced by nontumor cells within the tumor microenvironment that results in enhancement of the specificity and the functionality of vaccine-induced effector T cells. Our findings suggest a translatable strategy to enhance the overall efficacy of cancer immunotherapy. <i>Cancer Immunol Res; 6(2); 201-8. ©2018 AACR</i>.
Effects of commonly used cooking practices on total mercury concentration in fish and their impact on exposure assessments. (1997)

The effects of cooking practices commonly used by Native Americans on total mercury concentrations in fish were investigated. A preparation factor relating mercury concentrations in fish as prepared for consumption to mercury concentration data as measured in typical environmental monitoring programs was calculated. Preparation factors are needed to provide risk assessors with a more accurate estimate of the actual amount of mercury ingested through consumption of contaminated fish. Data on fish preparation and consumption practices of two communities of Chippewa residing on the shores of Lake Superior in northern Wisconsin were used to select practices for study. The most commonly consumed species, walleye and lake trout, were selected. Whitefish livers were also selected for study. Commonly used cooking techniques including panfrying, deep-frying, baking, boiling, and smoking were duplicated in the laboratory. Total mercury concentrations were determined in fish portions before and after cooking and in a portion representative of that analyzed in programs to assess water quality (skin-on fillets). Total mercury was determined by microwave digestion-cold vapor atomic absorption spectroscopy. Mercury concentrations (wet weight basis) in panfried, baked, and boiled walleye fillets and deep-fried and baked whitefish livers ranged from 1.1 to 1.5 times higher than in corresponding raw portions. In lake trout, mercury concentrations were 1.5 to 2.0 times higher in cooked portions than in the raw portion. However, total mercury levels were constant before and after cooking, indicating the concentration effect is caused by weight (moisture and fat) loss. The addition of lemon juice to potentially release mercury from its bound state and promote volatilization did not exert any measurable influence on mercury concentrations in cooked walleye. In some cases mercury concentrations were increased with increased cooking times due to further loss of moisture and fat. Preparation factors (defined as the ratio of mercury concentration in cooked fish to the mercury concentration in the environmental portion) ranged from 1.3 to 2.0. Results suggest that consideration be given to the use of preparation factors in risk assessments, exposure assessments, or issuance of fish advisories where mercury concentration in raw fish tissue are used in conjunction with cooked fish meal sizes.
Monitoring Duchenne Muscular Dystrophy Gene Therapy with Epitope-Specific Monoclonal Antibodies (2010)

Several molecular approaches to Duchenne muscular dystrophy (DMD) therapy are at or near the point of clinical trial and usually involve attempts to replace the missing dystrophin protein. Although improved muscle function is the ultimate measure of success, assessment of dystrophin levels after therapy is essential to determine whether any improved function is a direct consequence of the treatment or, in the absence of improved function, to determine whether new dystrophin is present, though ineffective. The choice of a monoclonal antibody (mAb) to distinguish successful therapy from naturally occurring "revertant" fibres depends on which dystrophin exons are deleted in the DMD patient. Over the past 20 years, we have produced over 150 "exon-specific" mAbs, mapped them to different regions of dystrophin and made them available through the MDA Monoclonal Antibody Resource for research and for clinical trials tailored to individual patients. In this protocol, we describe the use of these mAb to monitor DMD gene therapy.