gebhart/patrepeval huggingface dataset:
LOC387715/HTRA1 gene polymorphisms and susceptibility to age-related macular degeneration: A HuGE review and meta-analysis. (2010)

HTRA1 rs11200638 G→A polymorphism and LOC387715/ARMS2 rs10490924 G→T polymorphism play important roles in AMD. Gene-gene and gene-environmental interactions, as well as precise mechanisms underlying common variants in the HTRA1 gene and LOC387715/ ARMS2 gene, potentially increase the risk of AMD and need further exploration.
High expression of Nectin-4 is associated with unfavorable prognosis in gastric cancer (2018)

Nectins are Ca<sup>2+</sup>-independent immunoglobulin-like cell adhesion molecules that belong to a family of four members that function in a number of biological cellular activities. Nectin-4 is overexpressed in several types of human cancer; however, the functional and prognostic significance of Nectin-4 in gastric cancer (GC) remains unclear. In the present study, the reverse transcription-quantitative polymerase chain reaction and tissue microarray immunohistochemical analysis were used to investigate the expression of Nectin-4 in GC as well as its function in the prognosis of patients with GC. The results indicated that mRNA and protein expression of Nectin-4 were increased in tumor tissues compared with the matched non-tumor tissues. Expression of Nectin-4 was closely associated with differentiation (P=0.004), primary tumor (P=0.001), lymph node metastasis (P<0.001) and tumor-node-metastasis (TNM) stage (P<0.001). Positive Nectin-4 expression (P=0.001) and advanced TNM stage (P<0.001) were demonstrated to be associated with overall survival time in multivariate analyses. These results suggest that Nectin-4 may serve a significant function in GC and may serve as a novel clinic pathological biomarker and therapeutic target in GC.
Acetaminophen Overdose: Incidence, Diagnosis, and Management in 416 Patients (1978)

Acetaminophen overdose was studied in 416 patients as part of a nationwide multiclinic open study. Twenty-seven percent of the patients were toxic by plasma acetaminophen level. The 12- to 21-year-old age group had the highest incidence of toxic blood levels (47%). Children under age 5 had the mildest toxicity of any age group; only two of 16 patients had toxic blood levels. No relationship to subsequent Reye's syndrome could be demonstrated. Acetylcysteine is a safe, effective treatment if administered within the first ten hours; it has some efficacy with no toxicity if used after ten hours. Acetylcysteine has advantages over both cysteamine and methionine. All patients in this study recovered with no sequelae.
Systemic acquired resistance signal transduction (1996)

Abstract Systemic acquired resistance (SAR) is an inducible plant defense response in which a prior foliar pathogen infection activates resistance in noninfected foliar tissues. Salicylic acid (SA) accumulation is essential for the establishment of SAR. While SA is probably not the long‐distance systemic signal instrumental for SAR activation, it is required for transduction of the signal in noninfected tissues. Although SAR was first described as a response to necrogenic pathogen infection, synthetic chemicals have been identified that effectively activate SAR. Elucidation of SAR signal transduction has been facilitated by the identification and characterization of Arabidopsis mutants. Disease lesion mimic mutants exhibit constitutive SAR as well as spontaneous lesion formation similar to pathogen‐associated hypersensitive cell death. Some disease lesion mimic mutants do not exhibit a lesioned phenotype when SA accumulation is prevented, thereby providing evidence for a feedback loop in SAR signal transduction. Moreover, characterization of mutants compromised for SAR activation has provided additional evidence for common signaling components between SAR and gene‐for‐gene resistance.
High-Performance Air-Stable n-Type Carbon Nanotube Transistors with Erbium Contacts (2013)

So far, realization of reproducible n-type carbon nanotube (CNT) transistors suitable for integrated digital applications has been a difficult task. In this work, hundreds of n-type CNT transistors from three different low work function metals-erbium, lanthanum, and yttrium-are studied and benchmarked against p-type devices with palladium contacts. The crucial role of metal type and deposition conditions is elucidated with respect to overall yield and performance of the n-type devices. It is found that high oxidation rates and sensitivity to deposition conditions are the major causes for the lower yield and large variation in performance of n-type CNT devices with low work function metal contacts. Considerable improvement in device yield is attained using erbium contacts evaporated at high deposition rates. Furthermore, the air-stability of our n-type transistors is studied in light of the extreme sensitivity of these metals to oxidation.
Structure of Nerve Growth Factor Complexed with the Shared Neurotrophin Receptor p75 (2004)

Neurotrophins are secreted growth factors critical for the development and maintenance of the vertebrate nervous system. Neurotrophins activate two types of cell surface receptors, the Trk receptor tyrosine kinases and the shared p75 neurotrophin receptor. We have determined the 2.4 A crystal structure of the prototypic neurotrophin, nerve growth factor (NGF), complexed with the extracellular domain of p75. Surprisingly, the complex is composed of an NGF homodimer asymmetrically bound to a single p75. p75 binds along the homodimeric interface of NGF, which disables NGF's symmetry-related second p75 binding site through an allosteric conformational change. Thus, neurotrophin signaling through p75 may occur by disassembly of p75 dimers and assembly of asymmetric 2:1 neurotrophin/p75 complexes, which could potentially engage a Trk receptor to form a trimolecular signaling complex.
Identification of Diacylglycerol Pyrophosphate as a Novel Metabolic Product of Phosphatidic Acid during G-protein Activation in Plants (1996)

We provide evidence that phosphatidic acid (PtdOH) formed during signaling in plants is metabolized by a novel pathway. In much of this study, 32Pi-labeled Chlamydomonas cells were used, and signaling was activated by adding the G-protein activator mastoparan. Within seconds of activation, large amounts of [32P]PtdOH were formed, with peak production at about 4 min, when the level was 5-25-fold higher than the control. As the level of [32P]PtdOH subsequently decreased, an unknown phospholipid (PLX) increased in radiolabeling; before activation it was barely detectable. The chromatographic properties of PLX resembled those of lyso-PtdOH and CMP.PtdOH but on close inspection were found to be different. PLX was shown to be diacylglycerol pyrophosphate (DGPP), the product of a newly discovered enzyme, phosphatidate kinase, whose in vitro activity was described recently (Wissing, J. B., and Behrbohm, H. (1993) Plant Physiol. 102, 1243-1249). The identity of DGPP was established by co-chromatrography with a standard and by degradation analysis as follows: [32P]DGPP was deacylated, and the product (glycerolpyrophosphate, GroPP) was hydrolyzed by mild acid treatment or pyrophosphatase to produce GroP and Pi as the only radioactive products. Since DGPP is the pyrophosphate derivative of PtdOH and is formed as the concentration of PtdOH decreases, we assumed that PtdOH was converted in vivo to DGPP. This was confirmed by showing that during a short labeling protocol while the specific radioactivity of DGPP was increasing, the specific radioactivity of the 32Pi derived from DGPP as above was higher than that of [32P]GroP. DGPP was also formed in suspension cultures of tomato and potato cells, and its synthesis was activated by mastoparan. Moreover, it was also found in intact tissues of a number of higher plants, for example, carnation flower petals, vetch roots, leaves of fig-leaved goosefoot, and common persicaria and microspores of rape seed. Our results suggest that DGPP is a common but minor plant lipid that increases in concentration when signaling is activated. Possible functions of DGPP in phospholpase C and D signaling cascades are discussed.
The molecular medicine of viral hepatitis (1997)

Partial table of contents: Viral Hepatitis: A Brief Introduction (A. Zuckerman). The Molecular Basis of Attenuation of Hepatitis A Virus (S. Lemon, et al.). Development of Vaccines Against Hepatitis E Virus Infection (S. Panda & S. Nanda). Immunisation Against Hepatitis B (T. Harrison). The Molecular Role of Hepatitis B Virus in the Development of Hepatocellular Carcinoma (R. Koshy). Replication of Hepatitis D Virus (J. Taylor). Quantification of Hepatitis C Viraemia (J. Wilber, et al.). Genotypes and Genetic Variation of Hepatitis C Virus (G. Maertens & L. Stuyver). Index.
Fabrication of Luminescent Nanostructures and Polymer Nanowires Using Dip-Pen Nanolithography (2001)

We used a combination of dip-pen nanolithography and scanning optical confocal microscopy to fabricate and visualize luminescent nanoscale patterns of various materials on glass substrates. We show that this method can be used successfully to push the limits of dip-pen nanolithography down to controlled deposition of single molecules. We also demonstrate that this method is able to create and visualize protein patterns on surfaces. Finally, we show that our method can be used to fabricate polymer nanowires of controlled size using conductive polymers. We also discuss the factors that influence the size of these nanowires.
Safety and immunogenicity of a DNA vaccine encoding carcinoembryonic antigen and hepatitis B surface antigen in colorectal carcinoma patients. (2002)

Despite an abundance of preclinical data, relatively little is known regarding the efficacy of DNA vaccination in humans. Here, we present results from a dose-escalation clinical trial of a dual expression plasmid encoding carcinoembryonic antigen (CEA) and hepatitis B surface antigen (HBsAg) in 17 patients with metastatic colorectal carcinoma. CEA was selected as a prototypic tumor-associated self-antigen, and the HBsAg cDNA was included as a positive control for immune response to the DNA vaccine without relying upon breaking tolerance to a self-antigen. Groups of 3 patients received escalating single i.m. doses of the DNA vaccine at 0.1, 0.3, and 1.0 mg. Subsequent groups of 3 patients received three repetitive 0.3- or 1.0-mg doses at 3-week intervals. A final group of 2 patients received three repetitive 2.0 mg doses at 3-week intervals. Toxicity was limited to transient grade 1 injection site tenderness, fatigue, and creatine kinase elevations, each affecting a minority of patients in a non-dose-related manner. Repetitive dosing of the DNA vaccine induced HBsAg antibodies in 6 of 8 patients, with protective antibody levels achieved in four of these patients. CEA-specific antibody responses were not observed, but 4 of 17 patients developed lymphoproliferative responses to CEA after vaccination. No objective clinical responses to the DNA vaccine were observed among this population of patients with widely metastatic colorectal carcinoma. Nevertheless, this pilot trial has provided encouraging human immune response data in support of this vaccine technology.
Nucleotide sequence of the gene for heat-stable enterotoxin II of Escherichia coli (1983)

Previously, the gene for heat-stable enterotoxin II (STII) has been mapped by transposon Tn5 insertion mutagenesis in the chimeric R-Ent plasmid pCG86 (Mazaitis, A. J., R. Maas, and W. K. Maas, J. Bacteriol. 145:97-105, 1981). DNA segments containing this gene were cloned from the wild-type and STII-insertion-mutant plasmid. The position of the Tn5 insertion was determined, and a 530-base-pair-long segment of the wild-type plasmid corresponding to the Tn5 insertion site was sequenced. An open reading frame for the STII gene was identified and is characterized by typical promoter and ribosome binding site sequences. The deduced STII structural gene codes for a protein 71 amino acids long, including a typical signal peptide of 23 amino acids and a mature protein of 48 amino acids. The size and overall structure of STII are similar to those of STI, but the amino acid compositions of the two heat-stable enterotoxins are completely different.
Correlation between the serum level of hepatitis C virus RNA and disease activities in acute and chronic hepatitis C (1992)

Abstract The influence of viremia on hepatic injury in patients infected with hepatitis C virus was examined by analysis of the relationship between alanine aminotransferase activity and the amount of hepatitis C virus RNA in sequential serum samples from 1 untreated patient with acute hepatitis C and 3 untreated patients with chronic hepatitis C. Semiquantitative analysis by the competitive‐reverse‐transcription/polymerase‐chain‐reaction method indicated that the quantity of hepatitis C virus RNA in the serum affected the disease activities of acute and chronic hepatitis C through their natural clinical courses in all these patients. The nucleotide sequence encoding the putative envelope region of the viral genome in the patient with acute hepatitis C was examined. Blood samples taken serially at 2 times of exacerbation of the hepatitis revealed 2 nucleotide mutations, resulting in changes of predicted amino acid residues. This finding suggests that nucleotide mutations in the envelope region of the viral genome may be responsible for the recurrent hepatic injury attributed to recurrence of viremia in patients with hepatitis C. From these aspects, the serial divergence of the virus genome in infected individuals, especially in the region encoding the viral envelope protein, may possibly play an important role in developing chronic infection of hepatitis C virus. © 1992 Wiley‐Liss, Inc.
ASSAY OF THE FOLLICLE STIMULATING HORMONE BASED ON THE AUGMENTATION WITH HUMAN CHORIONIC GONADOTROPIN (1953)

INTRODUCTION There have been in the past numerous attempts to quantitatively assay the follicle stimulating hormone (FSH) of the anterior pituitary. Fevold et al. (1937, 1940) and many others have used the increase in ovarian weight in immature female rats. Evans et al. (1939) have employed an histological assay based upon the production of healthy (nonatretic) follicles with small antra in the ovaries of hypophysectomized female rats. Many other workers use uterine weight as a criterion for the estimation of FSH activity. In hypophysectomized male rats Greep et al. (1940, 1942) have employed the increase in testicular weight, in the absence of hypertrophy of the prostate and seminal vesicles, as a means of determination of FSH. It has been known for some time that human chorionic gonadotropin (HCG) will augment the action of FSH in the ovary. Bates and Schooley (1942) in their excellent article on this subject indicated that it might be possible to use it as an assay method.
A simulation study of methods for selecting subgroup‐specific doses in phase 1 trials (2017)

Patient heterogeneity may complicate dose-finding in phase 1 clinical trials if the dose-toxicity curves differ between subgroups. Conducting separate trials within subgroups may lead to infeasibly small sample sizes in subgroups having low prevalence. Alternatively,it is not obvious how to conduct a single trial while accounting for heterogeneity. To address this problem,we consider a generalization of the continual reassessment method on the basis of a hierarchical Bayesian dose-toxicity model that borrows strength between subgroups under the assumption that the subgroups are exchangeable. We evaluate a design using this model that includes subgroup-specific dose selection and safety rules. A simulation study is presented that includes comparison of this method to 3 alternative approaches,on the basis of nonhierarchical models,that make different types of assumptions about within-subgroup dose-toxicity curves. The simulations show that the hierarchical model-based method is recommended in settings where the dose-toxicity curves are exchangeable between subgroups. We present practical guidelines for application and provide computer programs for trial simulation and conduct.
Extracellular matrix proteins characterize human tumor cell lines (1981)

Extracellular matrix proteins synthesized and secreted by adherent human tumor cell lines were analyzed using metabolic labelling with glycine and proline in the presence of ascorbate, polypeptide analysis and polyacrylamide gel electrophoresis, affinity chromatography, collagenase digestion, and immunofluorescence staining. The results showed a characteristic pattern of matrix proteins for each tumor cell type. Tumor cell lines of mesenchymal origin produced mostly interstitial types (I and II) of collagen and fibronectin. Carcinoma cell lines secreted only basement membrane proteins, type IV collagen, laminin and fibronectin, but not interstitial collagen. A melanoma and a rhabdomyosarcoma cell line produced type V of procollagen that has not previously been described in cell culture. Neuroblastoma cells were shown to be phenotypically heterogeneous also with respect to matrix protein production. We propose that the analysis of extracellular matrix proteins may serve as an adjunct in the classification of human tumors.
An Instrument to Measure Functional Status Outcomes for Disorders of Excessive Sleepiness (1997)

This article reports the development of the functional outcomes of sleep questionnaire (FOSQ). This is the first self-report measure designed to assess the impact of disorders of excessive sleepiness (DOES) on multiple activities of everyday living. Three samples were used in the development and psychometric analyses of the FOSQ: Sample 1 (n = 153) consisted of individuals seeking medical attention for a sleep problem and persons of similar age and gender having no sleep disorder; samples 2 (n = 24) and 3 (n = 51) were composed of patients from two medical centers diagnosed with obstructive sleep apnea (OSA). Factor analysis of the FOSQ yielded five factors: activity level, vigilance, intimacy and sexual relationships, general productivity, and social outcome. Internal reliability was excellent for both the subscales (alpha = 0.86 to alpha = 0.91) and the total scale (alpha = 0.95). Test-retest reliability of the FOSQ yielded coefficients ranging from r = 0.81 to r = 0.90 for the five subscales and r = 0.90 for the total measure. The FOSQ successfully discriminated between normal subjects and those seeking medical attention for a sleep problem (T157 = -5.88, p = 0.0001). This psychometric evaluation of the FOSQ demonstrated parameters acceptable for its application in research and in clinical practice to measure functional status outcomes for persons with DOES. Thus, the FOSQ can be used to determine how disorders of excessive sleepiness affect patients' abilities to conduct normal activities and the extent to which these abilities are improved by effective treatment of DOES.
BRCT Repeats As Phosphopeptide-Binding Modules Involved in Protein Targeting (2003)

We used a proteomic approach to identify phosphopeptide-binding modules mediating signal transduction events in the DNA damage response pathway. Using a library of partially degenerate phosphopeptides, we identified tandem BRCT (BRCA1 carboxyl-terminal) domains in PTIP (Pax transactivation domain-interacting protein) and in BRCA1 as phosphoserine- or phosphothreonine-specific binding modules that recognize substrates phosphorylated by the kinases ATM (ataxia telangiectasia-mutated) and ATR (ataxia telangiectasia- and RAD3-related) in response to gamma-irradiation. PTIP tandem BRCT domains are responsible for phosphorylation-dependent protein localization into 53BP1- and phospho-H2AX (gamma-H2AX)-containing nuclear foci, a marker of DNA damage. These findings provide a molecular basis for BRCT domain function in the DNA damage response and may help to explain why the BRCA1 BRCT domain mutation Met1775 --> Arg, which fails to bind phosphopeptides, predisposes women to breast and ovarian cancer.
Estimating neural sources from each time-frequency component of magnetoencephalographic data (2000)

We have developed a method that incorporates the time-frequency characteristics of neural sources into magnetoencephalographic (MEG) source estimation. This method, referred to as the time-frequency multiple-signal-classification algorithm, allows the locations of neural sources to be estimated from any time-frequency region of interest. In this paper, we formulate the method based on the most general form of the quadratic time-frequency representations. We then apply it to two kinds of nonstationary MEG data: gamma-band (frequency range between 30-100 Hz) auditory activity data and spontaneous MEG data. Our method successfully detected the gamma-band source slightly medial to the N1m source location. The method was able to selectively localize sources for alpha-rhythm bursts at different locations. It also detected the mu-rhythm source from the alpha-rhythm-dominant MEG data that was measured with the subject's eyes closed. The results of these applications validate the effectiveness of the time-frequency MUSIC algorithm for selectively localizing sources having different time-frequency signatures.
Digital radiology using amorphous selenium and active-matrix flat-panel readout: photoconductive gain and gain fluctuations (1998)

New radiological imaging techniques have to be capable of high image quality, high acquisition speed, compactness, and versatility in operation. We have been investigating a flat panel imager based on the direct conversion of x-ray energy to an electric charge signal in a layer of amorphous selenium (a- Se) and an active matrix real-time self scanning read out, that is expected to achieve these goals. Although prototype imagers have demonstrated both real-time acquisition and the quality necessary for radiography, systematic investigations of the photoconductive properties of a-Se were undertaken to understand and extend the photoconductor range of operation and facilitate the designs for specialized radiological applications, such as fluoroscopy. The method of pulse height spectroscopy was adapted to accurately measure the reciprocal photoconductive gain W<SUB>+/- </SUB> (eV/e<SUP>-</SUP>h<SUP>+</SUP>) as a function of the incident photon energy (epsilon) and the applied field E. Improvements were taken until spectral peaks could be well resolved. The accuracy of the measurements was increased by calibration with a Si-PIN diode with a known W<SUB>+/- </SUB>. The measured values of W<SUB>+/- </SUB> showed that gain increases of a factor of 2.6 could be realized at the highest fields. The spectral widths were corrected to give the gain fluctuations and then used to calculate the contribution to imaging noise, i.e. the Swank factor. The imaging noise contribution was shown to be negligible, in agreement with previous calculations. The data suggests a new model of charge recombination in low mobility semiconductors which can be used to calculate W<SUB>+/- </SUB> at different fields and x-ray spectra for the full range of radiological applications.