gebhart/patrepeval huggingface dataset:
Identification of Two Serine Residues Essential for Agonist-Induced 5-HT2AReceptor Desensitization (2003)

5-HT(2A) serotonin receptors represent the principal molecular targets for LSD-like hallucinogens and atypical antipsychotic drugs. It has been proposed that a dysregulation of 5-HT(2A) receptor-mediated signaling may contribute to the pathogenesis of schizophrenia and related diseases. A major mechanism for the attenuation of GPCR signaling following agonist activation typically involves the phosphorylation of serine and/or threonine residues by various kinases. Ser/Thr phosphorylation leads to the binding of accessory proteins and the uncoupling of the G proteins, thereby preventing further signaling. The molecular mechanisms by which 5-HT(2A) receptors are desensitized are unknown, and to date, no residues essential for agonist-mediated desensitization have been identified. Thus, we mutated, individually or in groups, all of the 37 serines and threonines in the cytoplasmic domains of the 5-HT(2A) receptor and assessed the effects of these mutations on agonist-mediated desensitization. We discovered that mutation of two residues, S421 in the C-terminal tail and S188 in the second intracellular loop, to alanine resulted in a significant block of agonist-induced desensitization. Intriguingly, a single-nucleotide polymorphism, of unreported frequency, at the S421 locus has been reported (S421F); the S421F mutation, like the S421A mutation, significantly attenuated agonist-mediated desensitization. Taken together, these findings indicate that the process of agonist-mediated desensitization of 5-HT(2A) receptors requires the presence of two nonconserved serine residues located in distinct intracellular loops.
Antiviral drug resistance in human cytomegalovirus (1999)

Drug-resistant cytomegalovirus (CMV) should be considered when viral shedding persists after several weeks of therapy. The problem is most likely to arise in the setting of a severely immunosuppressed host with continuing or relapsing disease. Not all treatment failure can be attributed to drug resistance. The testing of CMV isolates for drug resistance in cell culture is time-consuming and labor-intensive, but recent advances in understanding of the genetics of resistance have resulted in rapid genotypic assays for specific mutations in the viral UL97 phosphotransferase or UL54 DNA polymerase genes that can predict resistance and cross-resistance to specific drugs. This information may help in the selection of alternative therapy.
Role of structural defects on the half-metallic character ofCo2MnGeandCo2MnSiHeusler alloys (2004)

Heusler alloys, such as ${\mathrm{Co}}_{2}\mathrm{MnSi}$ and ${\mathrm{Co}}_{2}\mathrm{MnGe},$ have been predicted from first--principles to be half metallic and potential candidates for spintronic applications. However, spin polarizations of only 50--60 % were experimentally obtained for these compounds---a decrease attributed to defects in the Mn and Co sublattices. Accurate ab initio full-potential linearized augmented plane wave calculations are performed in order to determine the effects of several types of defects (such as antisites and atomic swaps) on the electronic and magnetic properties of the bulk Heusler compounds. Our findings, in general agreement with experiments, show that Mn antisites have the lowest formation energy and retain the half-metallic character. On the other hand, Co antisites have a slightly higher formation energy and a dramatic effect on the electronic properties: the defect states that locally destroy half metallicity are energetically localized and are screened out in a couple of atomic shells. In this case, the spin polarization at the Fermi level is strongly reduced, and the spin polarization due to the s electrons, responsible for the tunneling current, is in excellent agreement with experiment. Finally, both Mn-Si and Mn-Co atomic swaps have very high formation energies, keeping however the half-metallic character.
Immunohistological analysis of immune cell infiltration of a human colon tumor xenograft after treatment with Stealth® liposome-encapsulated tumor necrosis factor-α and radiation (2002)

The toxicity associated with tumor necrosis factor-alpha (TNF-alpha) has limited its usefulness as an anticancer agent. However, encapsulation of TNF-alpha in Stealth (SL) liposomes can minimize risk for toxicity and thus increase its potential as an adjuvant treatment. Our recent studies have shown that SL-TNF-alpha plus radiation is more effective at inhibiting LS174T colon tumor growth than either radiation alone or free TNF-alpha plus radiation. This increase in efficacy was coincident with a modulation of immune parameters in blood and spleen. The aim of this study was to determine if infiltration of natural killer (NK) cells, macrophages, and neutrophils into LS174T tumors was altered by SL-TNF-alpha treatment and whether any observed changes could potentially contribute to the enhanced antitumor efficacy seen with SL-TNF-alpha plus radiation treatment. Sections of excised tumors were examined histologically and quantitative analysis was performed using laser scanning cytometry. The data showed that the group receiving multiple treatments with SL-TNF-alpha plus radiation had the smallest tumors, but yet the level of necrosis was similar to that found in groups with much larger tumors. Furthermore, the necrotic areas in the SL-TNF-alpha plus radiation group had signs of recent and/or continuing cell death and the highest levels of NK cell and macrophage infiltrates. In time course experiments, a single injection of SL-TNF-alpha (but not free TNF-alpha) induced fluctuations in leukocyte infiltration into tumors that correlated inversely with our previous findings in blood and spleen. Overall, the data indicate that the mechanisms underlying the increased efficacy of SL-TNF-alpha compared to free TNF-alpha include a rapid and relatively sustained recruitment of NK cells, macrophages, and neutrophils.
Emergence of zidovudine and multidrug-resistance mutations in the HIV-1 reverse transcriptase gene in therapy-naive patients receiving stavudine plus didanosine combination therapy (1999)

Stavudine/didanosine combination therapy is associated with emergence of zidovudine-related resistance or MDR mutations in naive patients. These findings should be considered when optimizing salvage therapy for patients who have received a treatment including stavudine/didanosine combination.
Cellular and Genetic Aspects of Antigenic Variation in Trypanosomes (1990)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Emission Spectra of LSO and LYSO Crystals Excited by UV Light, X-Ray and $\gamma$-ray (2008)

Because of their high stopping power (X <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">o</sub> = 1.14 cm, R <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Moliere</sub> = 2.07 cm) and fast (~ 40 ns) bright (4 times of BGO) scintillation, cerium doped lutetium oxyorthosilicate (LSO) and cerium doped lutetium-yttrium oxyorthosilicate (LYSO) crystals have attracted a broad interest in the high energy physics community. This paper presents a comparative study on emission spectra measured for large size BGO, lead tungstate (PbWO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sub> ), LSO and LYSO samples excited by UV light (photo-luminescence) with and without internal absorption, X-ray (X-luminescence) and gamma-ray (radio-luminescence). A red shift was observed between the emission spectra with internal absorption as compared to that without. An additional red shift and a significant red component were observed in the radio-luminescence spectra measured for LSO samples but not LYSO samples, which were disappeared after a gamma-ray irradiation with an accumulated dose of 5 x 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> rad. This is the only significant difference observed between the large size LSO and LYSO samples. The origin of these red shifts and the consequence to their light output and applications in the high energy and nuclear physics experiments are discussed.
Discovery of Novel Benzoxaborole-Based Potent Antitrypanosomal Agents (2010)

We report the discovery of benzoxaborole antitrypanosomal agents and their structure-activity relationships on central linkage groups and different substitution patterns in the sulfur-linked series. The compounds showed in vitro growth inhibition IC50 values as low as 0.02 μg/mL and in vivo efficacy in acute murine infection models against Tryapnosoma brucei.
Dereverberation for reverberation-robust microphone arrays (2013)

This paper discusses using dereverberation technologies to improve the robustness of beamforming microphone arrays against reverberation. It is known that, while conventional adaptive beamformers are able to effectively cancel the interference from spatially separate noise sources in the absence of reverberation, their efficacy deteriorates in reverberant rooms. To provide a widely applicable solution to this problem, we propose an adaptive multiple point blind equalizer that can shorten all the room impulse responses between the sound sources and microphones. This algorithm reduces the impact of reverberation on the interference cancellation performance when it is used to pre-process the microphone signals prior to beamforming. Experimental results using real conversation data show that a system combining the proposed equalizer and the adaptive beamformer improves noise reduction performance without degrading the speech quality.
The NOX toolbox: validating the role of NADPH oxidases in physiology and disease (2012)

Reactive oxygen species (ROS) are cellular signals but also disease triggers; their relative excess (oxidative stress) or shortage (reductive stress) compared to reducing equivalents are potentially deleterious. This may explain why antioxidants fail to combat diseases that correlate with oxidative stress. Instead, targeting of disease-relevant enzymatic ROS sources that leaves physiological ROS signaling unaffected may be more beneficial. NADPH oxidases are the only known enzyme family with the sole function to produce ROS. Of the catalytic NADPH oxidase subunits (NOX), NOX4 is the most widely distributed isoform. We provide here a critical review of the currently available experimental tools to assess the role of NOX and especially NOX4, i.e. knock-out mice, siRNAs, antibodies, and pharmacological inhibitors. We then focus on the characterization of the small molecule NADPH oxidase inhibitor, VAS2870, in vitro and in vivo, its specificity, selectivity, and possible mechanism of action. Finally, we discuss the validation of NOX4 as a potential therapeutic target for indications including stroke, heart failure, and fibrosis.
edición crítica de "Adán Buenosayres" (1995)

These findings show that the effect of PDGF-BB on MAP kinase activation is independent of calcium level. [Ca2+]i might be implicated in the PDGF-BB-induced mitogenic process only in conjugation with other signalling components.
Clinical pharmacogenetics implementation consortium guidelines for CYP2C9 and HLA-B genotypes and phenytoin dosing. (2014)

Phenytoin is a widely used antiepileptic drug with a narrow therapeutic index and large interpatient variability, partly due to genetic variations in the gene encoding cytochrome P450 (CYP)2C9 (CYP2C9). Furthermore, the variant allele HLA-B*15:02, encoding human leukocyte antigen, is associated with an increased risk of Stevens-Johnson syndrome and toxic epidermal necrolysis in response to phenytoin treatment. We summarize evidence from the published literature supporting these associations and provide recommendations for the use of phenytoin based on CYP2C9 and/or HLA-B genotype (also available on PharmGKB: http://www.pharmgkb.org). The purpose of this guideline is to provide information for the interpretation of HLA-B and/or CYP2C9 genotype tests so that the results can guide dosing and/or use of phenytoin. Detailed guidelines for the use of phenytoin as well as analyses of cost-effectiveness are out of scope. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines are periodically updated at http://www.pharmgkb.org.
The Grand Challenges to Cellular and Molecular Oncology (2011)

SPECIALTY GRAND CHALLENGE article Front. Oncol., 29 March 2011Sec. Molecular and Cellular Oncology Volume 1 - 2011 | https://doi.org/10.3389/fonc.2011.00002
Theory and measurement of backscattering from RFID tags (2006)

This paper presents a method for measuring signal backscattering from RFID tags, and for calculating a tag's radar cross section (RCS). We derive a theoretical formula for the RCS of an RFID tag with a minimum-scattering antenna. We describe an experimental measurement technique, which involves using a network analyzer connected to an anechoic chamber with and without the tag. The return loss measured in this way allows us to calculate the backscattered power and to find the tag's RCS. Measurements were performed using an RFID tag operating in the UHF band. To determine whether the tag was turned on, we used an RFID tag tester. The tag's RCS was also calculated theoretically, using electromagnetic simulation software. The theoretical results were found to be in good agreement with experimental data.
I ntrabody‐based strategies for inhibition of vascular endothelial growth factor receptor‐2: effects on apoptosis, cell growth, and angiogenesis (2003)

VEGF, an endothelial-specific mitogen, is an important tumor angiogenesis growth factor. The major receptor for VEGF on endothelial cells is KDR. We hypothesized that an intrabody could bind newly synthesized KDR and block receptor transport to the cell surface, thereby inhibiting important VEGF effects. We expressed a single chain antibody (p3S5) to KDR with or without the endoplasmic reticulum (ER) retention signal (KDEL), using either a plasmid (p3S5-HAK) or a tet-off adenoviral system (Ad-HAK). Plasmid-mediated expression of the tethered intrabody significantly reduced KDR expression (from 82.5+/-12.5% to 27.9+/-13.6% of cells; P<0.01) and thymidine incorporation in successfully transfected cells. Ad-HAK infection resulted in intrabody expression in >90% of human umbilical vein endothelial cells (HUVECs), producing marked (80%) apoptosis at 48 h postinfection. The intrabody was essential for these effects, as confirmed by inhibiting its expression with doxycycline or by expressing irrelevant genes (lacZ, GFP). Cell death was dependent on KDR, because Ad-HAK infection of cell lines with minimal or no KDR had little effect on cell viability. Infected HUVECs were unable to form tubes on Engelbreth Holm-Swarm (EHS) tumor gel matrix. These results demonstrate the potential for development of an intrabody-based strategy to block angiogenesis and prevent tumor growth.
Minimizing Chlorite Ion and Chlorate Ion in Water Treated With Chlorine Dioxide (1990)

Minimizing the inorganic by‐products chlorite ion and chlorate ion in drinking water treated with chlorine dioxide is important if Cl0 2 is to remain a viable alternative in potable water treatment. The use of sulfur dioxide‐sulfite ion chemistry to quantitatively remove chlorite ion to below the 0.1‐mg/L level is described, along with the use of free chlorine to remove the sulfur dioxide‐sulfite ion. The stoichiometry and the rate law are described for pH values of 5.5 to 8.5 so that the chemistry can be applied directly in existing drinking water treatment facilities.
Mixl1is required for axial mesendoderm morphogenesis and patterning in the murine embryo (2002)

In Xenopus, the Mix/Bix family of homeobox genes has been implicated in mesendoderm development. Mixl1 is the only known murine member of this family. To examine the role of Mixl1 in murine embryogenesis, we used gene targeting to create mice bearing a null mutation of Mixl1. Homozygous Mixl1 mutant embryos can be distinguished from their littermates by a marked thickening of the primitive streak. By the early somite stage, embryonic development is arrested, with the formation of abnormal head folds, foreshortened body axis, absence of heart tube and gut, deficient paraxial mesoderm, and an enlarged midline tissue mass that replaces the notochord. Development of extra-embryonic structures is generally normal except that the allantois is often disproportionately large for the size of the mutant embryo. In chimeras, Mixl1(-/-) mutant cells can contribute to all embryonic structures, with the exception of the hindgut, suggesting that Mixl1 activity is most crucial for endodermal differentiation. Mixl1 is therefore required for the morphogenesis of axial mesoderm, the heart and the gut during embryogenesis.
Effect of Osmolality and Phosphate, 'Tris', 'Tes', 'Mes', and 'Hepes' Hydrogen Ion Buffers on the Motility of Bull Spermatozoa Stored At 37 Or 5°C (1972)

Bull spermatozoa survived incubation, in unstoppered tubes at 5 and 37°C, better in solutions of 250 m-05molesJkg than in solutions of higher or lower osmolali-ties regardless of the concentrations of sodium chloride or citrate in the solutions relative to the concentrations of phosphate, Tris, TES, MES, or HEPES. When buffer solutions contributed 120 m-osmolesJkg to a total diluent strength of 250 m-osmolesJkg, the ranking from best to worst on the basis of survival of spermatozoa was: MES, HEPES, TES, Tris, and phosphate. Comparisons when 50 mM con-centrations of the buffers were used showed the same ranking except that HEPES was as good as.MES.
Isolation of multiple normal and functionally defective forms of uridine diphosphate-glucuronosyltransferase from inbred Gunn rats. (1987)

Gunn rats are a mutant strain of Wistar rats that have unconjugated hyperbilirubinemia due to absence of hepatic uridine diphosphate-glucuronosyltransferase (UDPGT; EC. 2.4.1.17) activity toward bilirubin. We isolated five UDPGT isoforms from solubilized microsomal fractions from liver of inbred Wistar (RHA) rats and congeneic Gunn rats. UDPGT isoform V (elution pH 7.5) from Wistar (RHA) rats is active toward bilirubin and 4'-hydroxydimethylaminoazobenzene. The corresponding isoform from Gunn rat liver was enzymically inactive but exhibited normal elution pH and mobility on NaDodSO4/polyacrylamide gel electrophoresis (Mr 53,000), and was recognized by a UDPGT-specific antiserum. UDPGT isoform I (elution pH 8.7) from Wistar (RHA) and Gunn rats was active toward 4-nitrophenol. The isoform from Gunn rat liver had only 10% of normal UDPGT activity, however UDPGT activity increased to normal upon addition of 15 mM diethylnitrosamine in vitro. Isoforms II (elution pH 8.4), III (elution pH 8.0), and IV (elution pH 7.8) from Gunn rats had normal UDPGT activities, except that Isoform IV was inactive toward bilirubin.
Stoichiometry of Antibody Neutralization of Human Immunodeficiency Virus Type 1 (2005)

The human immunodeficiency virus envelope glycoproteins function as trimers on the viral surface, where they are targeted by neutralizing antibodies. Different monoclonal antibodies neutralize human immunodeficiency virus type 1 (HIV-1) infectivity by binding to structurally and functionally distinct moieties on the envelope glycoprotein trimer. By measuring antibody neutralization of viruses with mixtures of neutralization-sensitive and neutralization-resistant envelope glycoproteins, we demonstrate that the HIV-1 envelope glycoprotein trimer is inactivated by the binding of a single antibody molecule. Virus neutralization requires essentially all of the functional trimers to be occupied by at least one antibody. This model applies to antibodies differing in neutralizing potency and to virus isolates with various neutralization sensitivities. Understanding these requirements for HIV-1 neutralization by antibodies will assist in establishing goals for an effective AIDS vaccine.
Improved Hematopoietic Differentiation Efficiency of Gene-Corrected Beta-Thalassemia Induced Pluripotent Stem Cells by CRISPR/Cas9 System (2014)

The generation of beta-thalassemia (β-Thal) patient-specific induced pluripotent stem cells (iPSCs), subsequent homologous recombination-based gene correction of disease-causing mutations/deletions in the β-globin gene (HBB), and their derived hematopoietic stem cell (HSC) transplantation offers an ideal therapeutic solution for treating this disease. However, the hematopoietic differentiation efficiency of gene-corrected β-Thal iPSCs has not been well evaluated in the previous studies. In this study, we used the latest gene-editing tool, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9), to correct β-Thal iPSCs; gene-corrected cells exhibit normal karyotypes and full pluripotency as human embryonic stem cells (hESCs) showed no off-targeting effects. Then, we evaluated the differentiation efficiency of the gene-corrected β-Thal iPSCs. We found that during hematopoietic differentiation, gene-corrected β-Thal iPSCs showed an increased embryoid body ratio and various hematopoietic progenitor cell percentages. More importantly, the gene-corrected β-Thal iPSC lines restored HBB expression and reduced reactive oxygen species production compared with the uncorrected group. Our study suggested that hematopoietic differentiation efficiency of β-Thal iPSCs was greatly improved once corrected by the CRISPR/Cas9 system, and the information gained from our study would greatly promote the clinical application of β-Thal iPSC-derived HSCs in transplantation.
Phylogenetic Relationships of Butyrate-Producing Bacteria from the Human Gut (2000)

Butyrate is a preferred energy source for colonic epithelial cells and is thought to play an important role in maintaining colonic health in humans. In order to investigate the diversity and stability of butyrate-producing organisms of the colonic flora, anaerobic butyrate-producing bacteria were isolated from freshly voided human fecal samples from three healthy individuals: an infant, an adult omnivore, and an adult vegetarian. A second isolation was performed on the same three individuals 1 year later. Of a total of 313 bacterial isolates, 74 produced more than 2 mM butyrate in vitro. Butyrate-producing isolates were grouped by 16S ribosomal DNA (rDNA) PCR-restriction fragment length polymorphism analysis. The results indicate very little overlap between the predominant ribotypes of the three subjects; furthermore, the flora of each individual changed significantly between the two isolations. Complete sequences of 16S rDNAs were determined for 24 representative strains and subjected to phylogenetic analysis. Eighty percent of the butyrate-producing isolates fell within the XIVa cluster of gram-positive bacteria as defined by M. D. Collins et al. (Int. J. Syst. Bacteriol. 44:812-826, 1994) and A. Willems et al. (Int. J. Syst. Bacteriol. 46:195-199, 1996), with the most abundant group (10 of 24 or 42%) clustering with Eubacterium rectale, Eubacterium ramulus, and Roseburia cecicola. Fifty percent of the butyrate-producing isolates were net acetate consumers during growth, suggesting that they employ the butyryl coenzyme A-acetyl coenzyme A transferase pathway for butyrate production. In contrast, only 1% of the 239 non-butyrate-producing isolates consumed acetate.
Local observability matrix and its application to observability analyses (2002)

A local observability matrix for a linear time-varying system is introduced. The matrix is useful for observability analysis; it is much easier to use than the usual observability grammian for linear time-varying systems. The matrix is applied to a terrain-aided inertial navigation system to reveal the observability of the system in terms of the nature of the terrain. Results of a simulated covariance analysis are presented and discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>