gebhart/patrepeval huggingface dataset:
Differential Roles of Hypoxia-Inducible Factor 1α (HIF-1α) and HIF-2α in Hypoxic Gene Regulation (2003)

Transcriptional responses to hypoxia are primarily mediated by hypoxia-inducible factor (HIF), a heterodimer of HIF-alpha and the aryl hydrocarbon receptor nuclear translocator subunits. The HIF-1alpha and HIF-2alpha subunits are structurally similar in their DNA binding and dimerization domains but differ in their transactivation domains, implying they may have unique target genes. Previous studies using Hif-1alpha(-/-) embryonic stem and mouse embryonic fibroblast cells show that loss of HIF-1alpha eliminates all oxygen-regulated transcriptional responses analyzed, suggesting that HIF-2alpha is dispensable for hypoxic gene regulation. In contrast, HIF-2alpha has been shown to regulate some hypoxia-inducible genes in transient transfection assays and during embryonic development in the lung and other tissues. To address this discrepancy, and to identify specific HIF-2alpha target genes, we used DNA microarray analysis to evaluate hypoxic gene induction in cells expressing HIF-2alpha but not HIF-1alpha. In addition, we engineered HEK293 cells to express stabilized forms of HIF-1alpha or HIF-2alpha via a tetracycline-regulated promoter. In this first comparative study of HIF-1alpha and HIF-2alpha target genes, we demonstrate that HIF-2alpha does regulate a variety of broadly expressed hypoxia-inducible genes, suggesting that its function is not restricted, as initially thought, to endothelial cell-specific gene expression. Importantly, HIF-1alpha (and not HIF-2alpha) stimulates glycolytic gene expression in both types of cells, clearly showing for the first time that HIF-1alpha and HIF-2alpha have unique targets.
Endotoxin responsiveness and grain dust-induced inflammation in the lower respiratory tract (1994)

To identify the role of endotoxin responsiveness in grain dust-induced airway disease, we used two models of extotoxin hyporesponsiveness to perform inhalation exposure studies in mice. In the first model, we investigated whether genetic resistance to endotoxin would alter the inflammatory response to inhaled grain dust by comparing the inflammatory response in the lower respiratory tract of endotoxin-sensitive and -resistant male mice after inhalation of pyrogen-free saline, corn dust extract (CDE), sterile CDE (SCDE), or lipopolysaccharide (LPS). Endotoxin-sensitive and -resistant mice were exposed for 4 h to nebulized solutions of LPS, SCDE, or CDE. Another group of endotoxin-sensitive and -resistant mice was sham exposed for 4 h to nebulized sterile saline. Dose-response relationships for endotoxin were explored for LPS, SCDE, and CDE. Bronchoalveolar lavage (BAL) 5 h after the start of exposure demonstrated a higher concentration of total cells, neutrophils (PMNs), and tumor necrosis factor-alpha (TNF-alpha) in BAL fluid after inhalation of CDE, SCDE, or LPS in endotoxin-sensitive than in endotoxin-resistant mice. Whereas endotoxin-sensitive mice demonstrated a dose-response relationship between the endotoxin concentration in each of the solutions and the concentration of cells, PMNs, and TNF-alpha in BAL fluid, concentrations of TNF-alpha were significantly higher only in BAL fluid of endotoxin-resistant mice exposed to higher concentrations of SCDE or CDE. In the second model, we investigated whether acquired endotoxin tolerance would alter the inflammatory response to SCDE.(ABSTRACT TRUNCATED AT 250 WORDS)
Coherent Spontaneous Emission (1970)

Coherent spontaneous emission from a system of $N$ two-level atoms interacting with a quantized radiation field is treated for the case in which Dicke's "cooperation number" $r$ is macroscopically large. It is shown how to modify the quasiclassical approach to this problem to incorporate quantum effects that are lost in the self-consistent-field approximation. The statistics of the emitted radiation are found to vary markedly with the initial state of the system of atoms. The photon statistics tend to that typical of blackbody radiation when the initial state of the atomic system is that which would result from incoherent pumping ($m\ensuremath{\sim}r$). When, on the other hand, the atoms are initially in a superradiant state ($m\ensuremath{\ll}r$), the emitted radiation may be represented approximately by a coherent state.
Staging of chronic hyperplastic rhinosinusitis: Treatment strategies (1995)

In 1990 we reported an initial prospective study of 100 patients using a four-stage system for classification of chronic rhinosinusitis. Between January 1988 and July 1992, we used this system in staging an additional 1814 patients, on whom 2980 intranasal sphenoethmoidectomies were performed. In this staging system a protocol trial of medication was given for 2 weeks, followed by axial and coronal computed tomography. Medication consisted of a second-generation cephalosporin antibiotic, usually cefuroxime; a 4-day burst of intraoral steroids, usually prednisone; and an antihistamine decongestant if not contraindicated. The stages of chronic hyperplastic rhinosinusitis included the stages described in the 1990 report (i.e., stage I, single-focus disease; stage II, discontiguous disease throughout the ethmoid labyrinth; stage III, diffuse disease responsive to medication; and stage IV, diffuse disease unresponsive to or poorly responsive to medication). The results of this study have shown that the computed tomography staging system based on computed tomography extent of disease after medical therapy is a simple, easily remembered, and very effective modality for the classification of chronic sinusitis. This system provides a rationale for discussing and planning surgery with patients and physicians and is a convenient reference for the reporting of end results. More importantly, a linear relationship between disease stage and outcomes is demonstrated. This statistically highly significant feature of the staging system provides a firm basis for the production of outcomes after various treatment strategies, particularly ethmoidectomy and the treatment of sinusitis.
Potassium channels (2003)

The atomic structures of K+ channels have added a new dimension to our understanding of K+ channel function. I will briefly review how structures have influenced our views on ion conduction, gating of the pore, and voltage sensing.
Stille Coupling Made Easier—The Synergic Effect of Copper(I) Salts and the Fluoride Ion (2004)

Noch etwas Zauberstaub: Stille-Kupplungen von Aryl- und Vinyliodiden, -triflaten oder -bromiden mit Aryl- und Vinylstannanen verlaufen deutlich besser nach Zugabe von CsF und CuI zur Reaktionsmischung (siehe Schema, Bedingungen A: [Pd(PPh3)4]/CsF/CuI/DMF/45 °C; Bedingungen B: PdCl2/PtBu3/CsF/CuI/DMF/45 °C).
Performance of an automated Q-beta replicase amplification assay for Mycobacterium tuberculosis in a clinical trial (1997)

We present data from a clinical trial study in which an automated version (Galileo) of a previously described Q-Beta replicase-amplified probe assay (J. S. Shah et al., J. Clin. Microbiol. 33:1435-1441, 1995) was used for the direct detection of Mycobacterium tuberculosis complex in sputum. The assay was designed to target specific regions of 23S rRNA found in M. tuberculosis, Mycobacterium bovis, Mycobacterium africanum, and Mycobacterium microti and had a sensitivity ranging from approximately <10 to 300 CFU. The assay was tested for cross-hybridization by using large numbers (e.g., 10(5)to 10(10) CFU/assay) of 133 other organisms commonly found in respiratory tract samples, including non-M. tuberculosis Mycobacterium spp., other bacteria, fungi, and viruses. All of these competitors tested negative by the assay. Automated assay results for 780 respiratory tract samples (sputum or bronchoalveolar lavage specimens) collected and tested at three trial sites in the United States) were compared with the results of culture and acid-fast microscopy. Aliquots of conventionally digested and decontaminated sputum pellets were heated at 100 degrees C and mechanically disrupted prior to hybridization and background reduction, amplification, and detection in a closed disposable test pack. Pertinent elements of individual patient histories relating to tuberculosis exposure, previous active disease, antituberculosis therapy status, etc., were considered in the resolution of discrepant results for 48 (assay false-positive) samples. Seventy-one of 90 (78.9%) culture-positive samples were positive when tested in the Galileo assay, while 7% of culture-negative samples were assay positive, corresponding to a sensitivity of 79% and a specificity of 93%. Following resolution of discrepant results by chart review, the sensitivity and specificity for the Q-Beta replicase amplification assay with the Galileo analyzer were 84 and 97%, respectively. A total of 69.2% of smear-negative (culture positive) samples were detected by the assay. Ten test packs at a time were automatically processed by the Galileo analyzer without operator intervention following loading of samples. The first result was reported in approximately 3 h, and the last result was available in 6.5 h. To our knowledge, this is the first report of a clinical study with a fully automated amplification probe hybridization assay for the detection of pathogens directly from a clinical specimen.
A scalable substrate noise coupling model for design of mixed-signal IC's (2000)

This paper describes a design-oriented scalable macromodel for substrate noise coupling in heavily-doped substrates. The model requires only four parameters which can be readily extracted from a small number of device simulations or measurements. Once these parameters have been determined, the model can be used in design for any spacing between the injection and sensing contacts and for different contact geometries. The scalability of the model with separation and width provides insight into substrate coupling and optimization issues prior to and during the layout phase. The model is validated with measurements from test structures fabricated in a 0.5 /spl mu/m CMOS process. Applications of the model to circuit design are demonstrated with simulation results.
A critical role for nitric oxide in intestinal barrier function and dysfunction (1996)

There is growing evidence that endogenous nitric oxide (NO) regulates mucosal barrier integrity under physiological conditions and counters the increase in mucosal permeability associated with acute pathophysiological states. The potential mechanisms of action for the protective effects of NO are discussed. These include maintenance of blood flow, inhibition of platelet and leukocyte adhesion and/or aggregation within the vasculature, modulation of mast cell reactivity, and scavenging of reactive oxygen metabolites such as superoxide. On the basis of the data presented, we conclude that both constitutive nitric oxide synthase (cNOS)-derived endogenous NO and exogenous NO (from NO donors) appear to reduce the sequelae of acute inflammation. The second section of this review summarizes the data germane to prolonged (chronic) inflammatory conditions associated with the overproduction of NO from the inducible form of NOS (iNOS). Some emphasis is placed on the role of NO in sepsis and inflammatory bowel disease (IBD), and data to suggest that NO, or more specifically a NO-derived mediator, is involved in these disorders are summarized. These studies are compared with recent publications suggesting that inhibition of NO synthesis with nonspecific inhibitors of NOS or selective iNOS inhibitors may not protect in models of sepsis or IBD. Overall, the review highlights the potential importance of the type of NOS enzyme involved in the particular inflammatory process being studied.
Sol‐gel‐derived metal‐dispersed carbon composite amperometric biosensors (1997)

Abstract The advantages which accrue from the coupling of sol‐gel enzyme electrode preparation processes with the dispersion of electrocatalytic metal centers are described. In particular, ruthenium‐dispersed sol‐gel carbon thick‐film bioelectrodes couple the low‐temperature curing process with the elimination of contributions from easily oxidizable interfering species. The remarkable selectivity towards the glucose substrate is combined with a greatly enhanced sensitivity. Factors influencing the performance of these sol‐gel‐derived metal‐doped enzyme strips are discussed.
Regulation of Alloreactivity in Vivo by a Soluble Form of the Interleukin-1 Receptor (1990)

In vitro studies have shown that cytokines are involved in the regulation of the immune response, but their role in vivo is less well defined. Specific cytokine antagonists enable the identification of particular cytokines involved in the response and offer a means for modifying it. Systemic administration of a soluble, extracellular portion of the receptor for interleukin-1 (sIL-1R) had profound inhibitory effects on the development of in vivo alloreactivity. Survival of heterotopic heart allografts was prolonged from 12 days in controls to 17 days in mice treated with sIL-1R. Lymph node hyperplasia in response to a localized injection of allogeneic cells was completely blocked by sIL-1R treatment. The inhibition was overcome by simultaneous administration of interleukin-1 (IL-1); thus, sIL-1R acts by neutralizing IL-1. These results implicate IL-1 as a regulator of allograft rejection and demonstrate the in vivo biological efficacy of a soluble cytokine receptor.
Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial (2016)

ClinicalTrials.gov Identifier: NCT00957359.
Testing the neural sensitization and kindling hypothesis for illness from low levels of environmental chemicals. (1997)

Sensitization in the neuroscience and pharmacology literatures is defined as progressive increase in the size of a response over repeated presentations of a stimulus. Types of sensitization include stimulant drug-induced time-dependent sensitization (TDS), an animal model related to substance abuse, and limbic kindling, an animal model for temporal lobe epilepsy. Neural sensitization (primarily nonconvulsive or subconvulsive) to the adverse properties of substances has been hypothesized to underlie the initiation and subsequent elicitation of heightened sensitivity to low levels of environmental chemicals. A corollary of the sensitization model is that individuals with illness from low-level chemicals are among the more sensitizable members of the population. The Working Group on Sensitization and Kindling identified two primary goals for a research approach to this problem: to perform controlled experiments to determine whether or not sensitization to low-level chemical exposures occurs in multiple chemical sensitivity (MCS) patients; and to use animal preparations for kindling and TDS as nonhomologous models for the initiation and elicitation of MCS.
Optimization and Validation of a Multiplex, Electrochemiluminescence-Based Detection Assay for the Quantitation of Immunoglobulin G Serotype-Specific Antipneumococcal Antibodies in Human Serum (2009)

Pneumovax 23 consists of a mixture of highly purified capsular polysaccharides (Ps) from 23 of the most prevalent serotypes of Streptococcus pneumoniae. Testing of vaccine immunogenicity has been historically performed on the enzyme-linked immunosorbent assay (ELISA) platform, validated to measure immunoglobulin G (IgG) antibodies to all 23 serotypes included in Pneumovax 23. In order to significantly improve the throughput of this form of testing, we have developed and validated a direct binding electrochemiluminescence (ECL)-based multiplex assay that can measure the antibody response in human serum to eight serotypes within a single microtiter well. The pneumococcal (Pn) ECL assay is based on the Meso Scale Discovery (MSD) technology which utilizes a Sulfo-Tag-labeled anti-human IgG antibody that emits light upon electrochemical stimulation. The Pn ECL assay exhibits a wide dynamic range and provides the ability to read concentrations down to the minimum reported concentration in the Merck ELISA (0.1 microg/ml). Cross-reactivity assessment using type-specific monoclonal antibodies showed no cross talk between antigen spots within a well. By use of the WHO Pn sample reference panel, the results obtained with the Pn ECL assay were compared to the results obtained with the international Pn ELISA. The results for the Pn ECL assay satisfied the WHO-recommended acceptance criterion for concordance for all seven serotypes with published Pn ELISA values, and the overall correlation (r value) across the seven serotypes was 0.994. The MSD methodology has great potential to be extremely useful for simultaneously quantitating IgG responses to several Pn serotypes while conserving serum volumes and laboratory testing time.
First Experience of Concomitant Vaccination Against Dengue and MMR in Toddlers (2015)

The CYD-TDV has an acceptable safety and immunogenicity profile in toddlers and when coadministered with MMR.
Concise Synthesis of (−)-Hodgkinsine, (−)-Calycosidine, (−)-Hodgkinsine B, (−)-Quadrigemine C, and (−)-Psycholeine via Convergent and Directed Modular Assembly of Cyclotryptamines (2017)

The enantioselective total synthesis of (-)-hodgkinsine, (-)-calycosidine, (-)-hodgkinsine B, (-)-quadrigemine C, and (-)-psycholeine through a diazene-directed assembly of cyclotryptamine fragments is described. Our synthetic strategy enables multiple and directed assembly of intact cyclotryptamine subunits for convergent synthesis of highly complex bis- and tris-diazene intermediates. Photoextrusion of dinitrogen from these intermediates enables completely stereoselective formation of all C3a-C3a' and C3a-C7' carbon-carbon bonds and all the associated quaternary stereogenic centers. In a representative example, photoextrusion of three dinitrogen molecules from an advanced intermediate in a single-step led to completely controlled introduction of four quaternary stereogenic centers and guided the assembly of four cyclotryptamine monomers en route to (-)-quadrigemine C. The synthesis of these complex diazenes was made possible through a new methodology for synthesis of aryl-alkyl diazenes using electronically attenuated hydrazine-nucleophiles for a silver-promoted addition to C3a-bromocyclotryptamines. The application of Rh- and Ir-catalyzed C-H amination reactions in complex settings were used to gain rapid access to C3a- and C7-functionalized cyclotryptamine monomers, respectively, used for diazene synthesis. This convergent and modular assembly of intact cyclotryptamines offers the first solution to access these alkaloids through completely stereoselective union of monomers at challenging linkages and the associated quaternary stereocenters as illustrated in our synthesis of five members of the oligocyclotryptamine family of alkaloids.
Los Tiempos ¿Entre aguas por Misicuni? (2002)

En los meses de junio y mayo de 1997, los residentes de esta
ciudad seguimos y participamos del ultimo conflicto que enfrento
a instituciones y autoridades de la region contra las autoridades
nacionales por las distintas propuestas para la solucion del largo
problema que afecta a la ciudad de Cochabamba, cual es la
escasez de agua que dia a dia se agrava por el crecimiento de la
poblacion y de sus necesidades.
Comparative Evaluation of the Immune Responses and Protection Engendered by LC16m8 and Dryvax Smallpox Vaccines in a Mouse Model (2009)

The immune response elicited by LC16m8, a candidate smallpox vaccine that was developed in Japan by cold selection during serial passage of the Lister vaccine virus in primary rabbit kidney cells, was compared to Dryvax in a mouse model. LC16m8 carries a mutation resulting in the truncation of the B5 protein, an important neutralizing target of the extracellular envelope form of vaccinia virus (EV). LC16m8 elicited a broad-spectrum immunoglobulin G (IgG) response that neutralized both EV and the intracellular mature form of vaccinia virus and provoked cell-mediated immune responses, including the activation of CD4+ and CD8+ cells, similarly to Dryvax. Mice inoculated with LC16m8 had detectable but low levels of anti-B5 IgG compared to Dryvax, but both Dryvax and LC16m8 sera neutralized vaccinia virus EV in vitro. A truncated B5 protein (approximately 8 kDa) was expressed abundantly in LC16m8-infected cells, and both murine immune sera and human vaccinia virus immunoglobulin recognized the truncated recombinant B5 protein in antigen-specific enzyme-linked immunosorbent assays. At a high-dose intranasal challenge (100 or 250 50% lethal doses), LC16m8 and Dryvax conferred similar levels of protection against vaccinia virus strain WR postvaccination. Taken together, the results extend our current understanding of the protective immune responses elicited by LC16m8 and indicate that the relative efficacy in a mouse model rivals that of previously licensed smallpox vaccines.
Monocyte populations as markers of response to adalimumab plus MTX in rheumatoid arthritis (2012)

The absolute number of circulating monocytes and of their CD14⁺highCD16⁻, CD14⁺highCD16⁺ and CD14⁺lowCD16⁺ subsets at three months of adalimumab plus MTX treatment, have a predictive value (with high specificity and sensitivity) in terms of the clinical response after six months of anti-TNFα treatment in patients with RA.
Polio: No Cheap Way Out (2007)

Some experts have proposed abandoning efforts to eradicate the virus in favor of controlling it, but a new analysis says that could be more costly in the long run. (Read more.)
Analysis of BR96 Binding Sites for Antigen and Anti-Idiotype by Codon-Based Scanning Mutagenesis (1998)

We performed a scanning mutagenesis study of heavy chain complementarity-determining region (CDR) residues to identify how mutations affected binding of the anti-carcinoma mAb BR96 to Ag, Lewis Y, and to an anti-Id Ab (anti-Id). By ELISA, we demonstrated that the anti-Id bound close to the Ag binding site of BR96, but the anti-Id and Ag sites were not identical. Immunoblot analysis and screening of light and heavy chain CDR libraries with multiple mutations in each CDR suggested that the heavy chain had greater involvement in anti-Id binding. We then analyzed contributions of individual residues in the heavy chain CDRs to binding of Ag and anti-Id. In a filamentous phage vector containing BR96 V region sequences, mutations were introduced by codon-based mutagenesis at single positions within the three heavy chain CDRs. The resulting libraries of Fab fragments had all amino acids represented at a CDR position. We evaluated the expressed Fabs for binding to Ag and anti-Id by plaque lift assay. We identified the positions with mutations that had the greatest negative effect on binding to the anti-Id and to Ag and analyzed them on the basis of the BR96 x-ray structure. The residues most important for binding to the anti-Id were located in heavy chain CDR1 and CDR2 and were peripheral to the residues within the Lewis Y binding pocket.
Purified hepatocyte nuclear factor 1 interacts with a family of hepatocyte-specific promoters. (1988)

During development cell types arise through the activation or repression of classes of specific genes. One hypothesis is that this phenomenon is realized by tissue-specific factors playing a role at the transcription level. Recently we have described a liver-specific nuclear protein, hepatocyte nuclear factor 1, that appears to be involved in the transcription of the fibrinogen and alpha 1-antitrypsin genes. In this report we describe the purification of hepatocyte nuclear factor 1 and demonstrate that it interacts with essential promoter regions of many liver-specific genes, including albumin, alpha-fetoprotein, and transthyretin. This finding suggests that hepatocyte nuclear factor 1 could be one factor necessary for establishing the liver phenotype. We also show that this protein binds to the promoter of the surface-antigen gene of the hepatitis B virus, a virus characterized by a high degree of hepatotropism.