gebhart/patrepeval huggingface dataset:
Improving the Positive Predictive Value of Non-Invasive Prenatal Screening (NIPS) (2017)

We evaluated performance characteristics of a laboratory-developed, non-invasive prenatal screening (NIPS) assay for fetal aneuploidies. This assay employs massively parallel shotgun sequencing with full automation. GC sequencing bias correction and statistical smoothing were performed to enhance discrimination of affected and unaffected pregnancies. Maternal plasma samples from pregnancies with known aneuploidy status were used for assay development, verification, and validation. Assay verification studies using 2,085 known samples (1873 unaffected, 69 trisomy 21, 20 trisomy 18, 17 trisomy 13) demonstrated complete discrimination between autosomal trisomy (Z scores >8) and unaffected (Z scores <4) singleton pregnancies. A validation study using 552 known samples (21 trisomy 21, 10 trisomy 18, 1 trisomy 13) confirmed complete discrimination. Twin pregnancies showed similar results. Follow-up of abnormal results from the first 10,000 clinical samples demonstrated PPVs of 98% (41/42) for trisomy 21, 92% (23/25) for trisomy 18, and 69% (9/13) for trisomy 13. Adjustment for causes of false-positive results identified during clinical testing (eg, maternal duplications) improved PPVs to 100% for trisomy 21 and 96% for trisomy 18. This NIPS test demonstrates excellent discrimination between trisomic and unaffected pregnancies. The PPVs obtained in initial clinical testing are substantially higher than previously reported NIPS methods.
Interrupted thymidylate synthase gene of bacteriophages T2 and T6 and other potential self-splicing introns in the T-even bacteriophages (1987)

Southern hybridization analyses of procaryotic DNA from Escherichia coli, lambda bacteriophage, and T1 to T7 phages were carried out. The hybridization probes used consisted of DNA restriction fragments derived from the T4 phage intron-containing thymidylate synthase gene (td) and short synthetic oligodeoxynucleotides defining specific exon and intron regions of the gene. It was shown that intact as well as restricted DNA from the T-even phages hybridized not only to both T4 phage td intron- and exon-specific probes but also to probes defining the td 5' (exon I-intron) and 3' (intron-exon II) presplice junctions. These data strongly suggest that, analogous to the T4 phage, only the T2 and T6 phages among the procaryotes tested contain interrupted td genes. The td intervening sequence in each phage is roughly 1 kilobase pair (kb) in size and interrupts the td gene at a site analogous to that in the T4 phage. This was confirmed by data from Northern (RNA) hybridization analysis of td-specific in vitro transcripts of these phage DNAs. [alpha-32P]GTP in vitro labeling of total RNA from T4 phage-infected cells produced five species of labeled RNAs that were 1, 0.9, 0.83, 0.75, and 0.6 kb in size. Only the 1-, 0.9-, and 0.75-kb species were labeled in RNA from T2- or T6-infected cells. The commonly present 1-kb RNA is the excised td intron, which exists in both linear and circular forms in the respective T-even-phage-infected cells, while the 0.6-kb RNA unique to T4 may be the excised intron derived from the ribonucleotide reductase small subunit gene (nrdB) of the phage. The remaining labeled RNA species are likely candidates for other self-splicing introns.
Glow-to-Arc Transition (1956)

The conditions for the glow-to-arc transition at moderately high pressures (50 to 1300 mm Hg) have been studied experimentally. It is found that over the whole pressure range the transition is certain when the field at the cathode reaches a critical value. This result is shown to be consistent with a field emission mechanism for the transition. Calculations of the critical field based on this process are found to be in good agreement with the fields which are determined experimentally.
A Convenient and Regioselective Synthesis of 4,6-Diaryl-2,3,4,7-tetrahydrooxepin-2-ones1and 1,4-Diphenyl-2,3,4,7-tetrahydro-1H-azepin-2-one (1989)

Reactions of 2-vinyloxiranes and 2-vinylaziridine with dichloroketene gave the corresponding 2,3,4,7-tetrahydrooxepin-2-ones and 2,3,4,7-tetrahydroazepin-2-one derivatives, respectively.
Optimizing the Detection of Lung Cancer Patients Harboring Anaplastic Lymphoma Kinase (ALK) Gene Rearrangements Potentially Suitable for ALK Inhibitor Treatment (2010)

Abstract Purpose: Anaplastic lymphoma kinase (ALK) rearrangements, associated with sensitivity to an experimental ALK/MET inhibitor, occur in 3% to 5% of non–small cell lung cancers. Intratumoral fluorescence in situ hybridization (FISH) heterogeneity has been reported. We explored the heterogeneity basis, the requirements for accurately determining ALK FISH positivity, and the effect of enriching the tested population using clinical and molecular factors. Experimental Design: Lung cancer patients were screened by ALK and MET FISH and for EGFR and KRAS mutations. Results: Thirteen ALK-positive cases were identified from 73 screened patients. Gene copy number increases occurred together with classic rearrangements. All positive cases were adenocarcinomas, 12 were EGFR/KRAS wild-type, and 1 had a coexistent EGFR exon 20 mutation. No association with MET amplification occurred. ALK positivity was associated with &amp;lt;10–pack-year smoking status (P = 0.0004). Among adenocarcinomas, without KRAS or EGFR mutations, with &amp;lt;10–pack-year history, 44.8% of cases were ALK positive. ALK FISH positivity was heterogeneous, but mean values in tumor areas from ALK-positive patients (54% of cells; range, 22-87%) were significantly higher than in adjacent normal tissue or tumor/normal areas from ALK-negative patients (mean, 5-7%). Contiguous sliding field analyses showed diffuse heterogeneity without evidence of focal ALK rearrangements. One hundred percent sensitivity and specificity occurred when four or more fields (∼60 cells) were counted. Conclusions: Intratumoral ALK FISH heterogeneity reflects technique, not biology. The clinical activity of ALK/MET inhibitors in ALK-positive patients probably reflects ALK, but not MET, activity. Prescreening by histology, EGFR/KRAS mutations, and smoking status dramatically increases the ALK-positive hit rate compared with unselected series. Clin Cancer Res; 16(22); 5581–90. ©2010 AACR.
Cell type and cell state determine differential in vitro growth of non-neurovirulent ICP34.5-negative herpes simplex virus types 1 and 2 (1994)

The herpes simplex virus (HSV) gene RL1 encodes the protein ICP34.5, which is a specific neurovirulence factor. Null mutants in RL1 fail to replicate in the central nervous system of mice and are therefore totally non-neurovirulent. Additionally, they fail to replicate in neurons of the peripheral nervous system, although they are capable of establishing and reactivating from a latent infection. As the precise function of ICP34.5 in HSV-neuronal interactions is unknown, we have studied the role of ICP34.5 in vitro by examining in detail the phenotypes of RL1-negative viruses in two defined tissue culture systems. The first was mouse embryo fibroblast 3T6 cells, in which RL1-negative mutants are impaired and the in vivo phenotype is mimicked. This impairment is amplified when the cells are in the stationary state. The second was mouse embryo testicular carcinoma F9 cells which, in the undifferentiated state, provide a reversal of phenotype; wild-type virus fails to grow but RL1-negative virus replicates efficiently. Differentiation results in the ability to support wild-type virus growth. The stage at which the replication cycle is blocked plus the role of cellular factors is addressed in both tissue culture systems. Evidence is provided that cell type and cell state are crucial to ICP34.5-cellular interaction and hence, based on these parameters, ICP34.5 can be defined as a host-range determinant. Identification of cellular proteins that specifically interact with or are homologues of ICP34.5 may lead to the identification of neuron-specific proteins that have a similar role.
Accelerated cell-cycling of hematopoietic progenitor cells by growth factors (1995)

Recent advances in molecular biology have led to the identification of hematopoietic growth factors that support and influence the proliferation of hematopoietic progenitor cells in vitro and in vivo. Although these factors have been extensively studied, little is known of their role in the regulation of cell-cycling of hematopoietic progenitors, especially in the early stage of hematopoiesis. In the present study, we examined the effects of early acting growth factors on proliferative kinetics of hematopoietic progenitors by monitoring the number of cells in individual developing colonies, using an in vitro clonal assay. Interleukin-11 (IL-11) or steel factor (SF), alone or in combination, shortened the time for the size of IL-3-dependent colonies to double. Consecutive replating experiments provided evidence for direct action of growth factors on the growth rate of hematopoietic progenitor cells. Shortening of the time for the total cell number in the colonies to double was due to a reduction in time for each single cell within the respective colonies to become two daughter cells, and there was no alteration in the incidence of cells with a proliferative capacity. Cell-cycle analysis demonstrated that IL-11 has the potential to induce a shortened time for cell-cycle of hematopoietic progenitor cells without affecting distribution of each fraction of the cell-cycle, whereas SF has the potential to reduce cell-cycle time mainly by decreasing the time required for hematopoietic progenitor cells to go through the G1 phase. These results suggest that growth factors may modulate cell-cycling of hematopoietic progenitor cells.
The Late Endosome is Essential for mTORC1 Signaling (2010)

The multisubunit mTORC1 complex integrates signals from growth factors and nutrients to regulate protein synthesis, cell growth, and autophagy. To examine how endocytic trafficking might be involved in nutrient regulation of mTORC1, we perturbed specific endocytic trafficking pathways and measured mTORC1 activity using S6K1 as a readout. When early/late endosomal conversion was blocked by either overexpression of constitutively active Rab5 (Rab5CA) or knockdown of the Rab7 GEF hVps39, insulin- and amino acid-stimulated mTORC1/S6K1 activation were inhibited, and mTOR localized to hybrid early/late endosomes. Inhibition of other stages of endocytic trafficking had no effect on mTORC1. Overexpression of Rheb, which activates mTOR independently of mTOR localization, rescued mTORC1 signaling in cells expressing Rab5CA, whereas hyperactivation of endogenous Rheb in TSC2-/- MEFs did not. These data suggest that integrity of late endosomes is essential for amino acid- and insulin-stimulated mTORC1 signaling and that blocking the early/late endosomal conversion prevents mTOR from interacting with Rheb in the late endosomal compartment.
Postoperative Pulmonary Complications Epidural Analgesia Using Bupivacaine and Opioids Versus Parenteral Opioids (1993)

Epidural analgesia with a combination of local anesthetic and opioid improves patient comfort. However, this type of analgesia does not decrease the incidence of postoperative pulmonary complications, does not reduce the length of the hospital stay, and carries the risk of complications from episodic systemic hypotension.
Clinical diagnosis and management by laboratory methods (1979)

PART I: The Clinical Laboratory The Clinical Laboratory: Organization, Purpose and Practice Physician Office Laboratories (POLS) Principles of Instrumentation Clinical Laboratory Automation Interpreting Laboratory Results Informatics, Imaging and Interoperability Laboratory Statistics Clinical Laboratory Quality Assurance PART II: Clinical Chemistry Evaluation of Renal Function, Wather, Electrolytes, Acid-Base Balance and Blood Gases Metabolic Intermediates, Inorganic Ions and Biochemical Markers of Bone Metabolism Carbohydrates Lipids and Dyslipoproteinemia Specific Proteins Evaluation of Liver Function and Injury Clinical Enzymology Evaluation of Endocrine Function Toxicology and Therapeutic Drug Monitoring PART III: Urine and Other Body Fluids Basic Examination of Urine Cerebrospinal, Synovial, and Serious Body Fluids Andrology Laboratory and Fertility Assessment Laboratory Management of Assisted Reproductive Technology Laboratory Aspects of Gestation Management Laboratory Diagnosis of Gastrointestinal Tract and Pancreatic Disorders PART IV: Hematology, Coagulation and Transfusion Medicine Basic Examination of Blood Hematopoiesis Erythrocytic Disorders Leukocytic Disorders Blood Platelets Coagulation, Fibrinolysis and Hypercoagulation Immunohematology Transfusion Medicine Hemapheresis Tissue Banking and Progenitor Cell PART V: Immunology and Immunopathy Overview of the Immune System and Immunologic Disorders Immunoassays and Immunochemistry Laboratory Evaluation of the Cellular Immune System Laboratory Evaluation of Immunoglobin Function and Humoral Immunity Complement and Kinins: Mediators of Inflamation Cytokines and Adhesion Molecules HLA: The Major Histocompatability Complex of Man The Major Histocompatibility Complex and Disease Immunodeficiency Disorders Clinical and Laboratory Evaluation of Systemic Rheumatic Diseases Vasculitis Organ Specific Autoimmune Diseases Allergic Diseases Diagnosis and Management of Cancer Using Serologic Tumor Markers PART VI: Medical Microbiology Viral Infections Chlamydial, Rickettsial, and Mycoplasmal Infections Medical Microbiology In Vitro Testing of Antimicrobial Agents Spirochete Infections Mycobacteria Mycotic Diseases Medical Parasitology Molecular Pathology of Infectious Diseases Specimen Collection and Handling for Diagnosis of Infectious Diseases PART VII.: Molecular Pathology An Introduction to Molecular Pathology Molecular Diagnostics: Basic Principles and Techniques Polymerase Chain Reaction (PCR) and Other Amplification Technology Hybridization Array Technology Applications for Cytogenetics in Modern Pathology Establishing a Molecular Diagnostics Laboratory Oncoproteins and Early Tumor Detection Molecular Techniques in the Hematopoietic Neoplasms Molecular Diagnosis of Genetic Diseases Parentage Testing: Use of DNA Polymorphism and Other Genetic Markers Forensic Identity Testing by DNA Analysis
Design of left-handed materials with broad bandwidth and low loss using double resonant frequency structure (2004)

An element consisting of a spiral inductor loaded by a rectangular loop resonator is newly proposed to achieve double resonant frequencies. An array of such elements is then synthesized periodically to realize left-handed materials that exhibit both negative permittivity and negative permeability. With synthesis of the periodic array, the left-handed material (LHM) is characterized theoretically and numerically and is found to have a broad bandwidth and low loss. In addition, design equations used to calculate the equivalent circuit parameters are given.
A gene regulatory network in mouse embryonic stem cells (2007)

We analyze new and existing expression and transcription factor-binding data to characterize gene regulatory relations in mouse ES cells (ESC). In addition to confirming the key roles of Oct4, Sox2, and Nanog, our analysis identifies several genes, such as Esrrb, Stat3, Tcf7, Sall4, and LRH-1, as statistically significant coregulators. The regulatory interactions among 15 core regulators are used to construct a gene regulatory network in ESC. The network encapsulates extensive cross-regulations among the core regulators, highlights how they may control epigenetic processes, and reveals the surprising roles of nuclear receptors. Our analysis also provides information on the regulation of a large number of putative target genes of the network.
Schizophrenia (1994)

Insanity has afflicted humanity throughout history1. At the turn of this century, identification of the syphilitic insanities set the stage for Kraepelin to recognize the distinctive symptom patterns of the manic-depressive psychoses and dementia praecox2. In 1911, Bleuler noted that the early onset of dementia was not characteristic of Kraepelin's dementia praecox, and he coined the term “schizophrenia” to refer to the dissociation or disruption of thought processes and the split among thought, emotion, and behavior3. With recent diagnostic refinements, psychosis (that is, a break with reality usually manifested as hallucinations, delusions, or a disruption in thought . . .
The Microbead Occlusion Model: A Paradigm for Induced Ocular Hypertension in Rats and Mice (2010)

These data support a novel and flexible model of modest ocular hypertension with axon loss. The maximal duration of IOP elevation will be further characterized in future studies.
Targeting of SNAP-23 and SNAP-25 in Polarized Epithelial Cells (1998)

SNAP-23 is the ubiquitously expressed homologue of the neuronal SNAP-25, which functions in synaptic vesicle fusion. We have investigated the subcellular localization of SNAP-23 in polarized epithelial cells. In hepatocyte-derived HepG2 cells and in Madin-Darby canine kidney (MDCK) cells, the majority of SNAP-23 was present at both the basolateral and apical plasma membrane domains with little intracellular localization. This suggests that SNAP-23 does not function in intracellular fusion events but rather as a general plasma membrane t-SNARE. Canine SNAP-23 is efficiently cleaved by the botulinum neurotoxin E, suggesting that it is the toxin-sensitive factor previously found to be involved in plasma membrane fusion in MDCK cells. The localization of SNAP-25 in transfected MDCK cells was studied for comparison and was found to be identical to SNAP-23 with the exception that SNAP-25 was transported to the primary cilia protruding from the apical plasma membrane, which suggests that subtle differences in the targeting signals of both proteins exist. In contrast to its behavior in neurons, the distribution of SNAP-25 in MDCK cells remained unaltered by treatment with dibutyryl cAMP or forskolin, which, however, caused an increased growth of the primary cilia. Finally, we found that SNAP-23/25 and syntaxin 1A, when co-expressed in MDCK cells, do not stably interact with each other but are independently targeted to the plasma membrane and lysosomes, respectively.
Identification of novel FLT‐3 Asp835 mutations in adult acute myeloid leukaemia (2001)

Genomic DNA from 97 cases of adult de novo acute myeloid leukaemia (AML) was screened using polymerase chain reaction (PCR) and conformation-sensitive gel electrophoresis (CSGE) for FLT3 exon 20 mutations. Initial sequencing of four cases, representing the spectrum of CSGE abnormalities, revealed changes affecting codon Asp835 in three cases and also an intron 20 A to G change. In order to identify all possible Asp835 alterations, as well as the frequency of the intronic change nucleotide 2541 + 57 A-->G, the patient PCR products were digested with EcoRV and NlaIII respectively. Seven cases (7.2%) possessed a mutation affecting Asp835; these were identified, following DNA sequencing, as Asp835Tyr (n = 5), Asp835His (n = 1) and Asp835del (n = 1). Alterations affecting Asp835 were not found in 80 normal control DNA samples. In contrast, the nucleotide 2541 + 57 A-->G change was shown to be a polymorphism, with an allelic frequency of 0.24 for the G and 0.76 for the A allele. This study reports, for the first time, point mutations in the human FLT3 gene that, because of their homology with other class III receptor tyrosine kinase mutations, probably result in constitutive activation of the receptor.
Ionizing radiation increases adenovirus uptake and improves transgene expression in intrahepatic colon cancer xenografts (2003)

Specific targeting and transgene expression in tumors are critical in adenovirus gene therapy for intrahepatic colon carcinoma metastases. In this study, we investigated if ionizing radiation could increase adenoviral uptake by cells. Various human cell lines and rat hepatocytes were irradiated prior to exposure to a cytomegalovirus (CMV) promoter-driven green fluorescent protein (GFP) marker gene adenoviral vector. We found that gamma-radiation increased the number of GFP-positive cells in a dose- and time-dependent manner for most cells, ranging from 4.6- to 27.1-fold after a 4-Gy treatment. No induction occurred for lentiviral vector, lipofection, or naked plasmid exposure. Preincubation of cells with adenovirus failed to show an increase, suggesting that radiation might mediate adenoviral infection by inducing viral uptake into cells. We demonstrated that radiation induced internalization of a fluorescence-labeled adenovirus (Cy3-Ad) and an increase in intracellular viral DNA content. Rats bearing intrahepatic colon carcinoma xenografts were irradiated in the tumor region followed by portal venous administration of an adenoviral vector containing a CMV-beta-galactosidase (beta-gal) gene. Radiation increased beta-gal activity in tumors as much as 5.4-fold after a 25-Gy treatment. These data suggest that a combination of regional radiation treatment with adenovirus gene therapy is a rational strategy for improving adenoviral targeting and transgene expression in tumors.
An absolute and restricted requirement for IL-12 in natural killer cell IFN-γ production and antiviral defense. Studies of natural killer and T cell responses in contrasting viral infections (1996)

IL-12 is a potent induce of IFN-gamma and is associated with a wide variety of immunoregulatory activities. Using murine CMV (MCMV) and lymphocytic choriomeningitis virus (LCMV) models of acute viral infection, we show here that IL-12 is integrally involved in certain aspects of antiviral immunity. Experiments evaluating the production and function of IL-12 demonstrated the induction of biologically active factor early during Smith strain MCMV, but not Armstrong strain LCMV, infection. The MCMV-induced IL-12 was responsible for early NK cell IFN-gamma production and viral control, as in vivo IL-12 neutralization by Ab treatment blocked both of these. In contrast, NK cell IFN-gamma production could not be detected during LCMV infection, and IL-12 neutralization had no effect on early LCMV replication. In both infections, treatments neutralizing IL-12 failed to alter either early NK cell cytotoxicity or later T cell responses, including IFN-gamma production and viral clearance on days 7 and 9 after infection. These data demonstrate the induction of IL-12 production during certain viral infections and the function of IL-12 for eliciting NK cell IFN-gamma production and antiviral defense. Furthermore, they suggest the existence of IL-12-independent mechanisms for IFN-gamma induction and viral control by T cells.
Identification of a thiamin-dependent synthase in Escherichia coli required for the formation of the 1-deoxy- d -xylulose 5-phosphate precursor to isoprenoids, thiamin, and pyridoxol (1997)

In Escherichia coli , 1-deoxy- d -xylulose (or its 5-phosphate, DXP) is the biosynthetic precursor to isopentenyl diphosphate [Broers, S. T. J. (1994) Dissertation (Eidgenössische Technische Hochschule, Zürich)], thiamin, and pyridoxol [Himmeldirk, K., Kennedy, I. A., Hill, R. E., Sayer, B. G. &amp; Spenser, I. D. (1996) Chem. Commun . 1187–1188]. Here we show that an open reading frame at 9 min on the chromosomal map of E. coli encodes an enzyme ( d eoxy x ylulose-5- p hosphate synthase, DXP synthase) that catalyzes a thiamin diphosphate-dependent acyloin condensation reaction between C atoms 2 and 3 of pyruvate and glyceraldehyde 3-phosphate to yield DXP. We have cloned and overexpressed the gene ( dxs ), and the enzyme was purified 17-fold to a specific activity of 0.85 unit/mg of protein. The reaction catalyzed by DXP synthase yielded exclusively DXP, which was characterized by 1 H and 31 P NMR spectroscopy. Although DXP synthase of E. coli shows sequence similarity to both transketolases and the E1 subunit of pyruvate dehydrogenase, it is a member of a distinct protein family, and putative DXP synthase sequences appear to be widespread in bacteria and plant chloroplasts.