gebhart/patrepeval huggingface dataset:
Chronic hyperglycemia is associated with impaired glucose influence on insulin secretion. A study in normal rats using chronic in vivo glucose infusions. (1986)

We have proposed that chronic hyperglycemia alters the ability of glucose to modulate insulin secretion, and have now examined the effects of different levels of hyperglycemia on B cell function in normal rats using chronic glucose infusions. Rats weighing 220-300 g were infused with 0.45% NaCl or 20, 30, 35, or 50% glucose at 2 ml/h for 48 h, which raised the plasma glucose by 18 mg/dl in the 30% rats, 37 mg/dl in the 35% rats, and 224 mg/dl in the 50% group. Insulin secretion was then examined using the in vitro isolated perfused pancreas. Glucose-induced insulin secretion remained intact in the normoglycemic 20% glucose rats and it was potentiated in the mildly hyperglycemic 30% glucose rats. However, with even greater hyperglycemia in the 35% glucose group the insulin response to a high glucose perfusate was severely blunted, and it was totally lost in the most hyperglycemic 50% glucose rats. In a second protocol that examined glucose potentiation of arginine-stimulated insulin release, a similar impairment in the ability of glucose to modulate the insulin response to arginine was found with increasing levels of chronic hyperglycemia. On the other hand, the ability of a high glucose concentration to inhibit arginine-stimulated glucagon release was preserved in all glucose-infused rats, but the glucagon levels attained in response to the arginine at 2.8 mM glucose were much less in the 50% glucose rats than in all the other groups. These data clearly show that after 48 h of marked hyperglycemia, glucose influence upon insulin secretion in the rat is severely impaired. This model provides a relatively easy and reproducible method to study the effects of long-term hyperglycemia on B cell function.
Superiority of trimodality therapy to surgery alone in esophageal cancer: Results of CALGB 9781 (2006)

4012 Background: CALGB 9781 was a prospective randomized Intergroup trial of trimodality therapy versus surgery alone for the treatment of stages 1–3 esophageal cancer. Methods: Five-hundred patients were targeted for enrollment with three years of follow-up planned. The primary endpoint was overall survival. All patents had EGD with biopsy, barium esophagogram and CT. Additional staging by EUS and/or thoracoscopy/laparoscopy was recommended. Patients were randomized to treatment with either surgery alone or cisplatin (100mg/m 2 ) and 5FU (1000 mg/m 2 /d × 4d) weeks 1 and 5 concurrent with radiation therapy (50.4 Gy- 1.8 Gy/fx over 5.6 weeks) followed by esophagectomy with lymph node dissection. Results: A total of 56 patients were entered on study between October 1997 and March 2000 when the trial was closed due to poor accrual. Thirty patients were randomized to trimodality therapy and 26 to surgery alone. Patient characteristics were similar between groups. Surgical staging was conducted in just over 50% of patients in both groups. The primary toxicities of Gr 3 or greater with preoperative therapy were hematopoietic (54%), and esophagitis/dysphagia (40%). There were 14 and 17 patients with surgical complications on the trimodality and surgery alone arms, respectively, with 2 post-surgical deaths (within 30 days), both on the surgery alone arm. Postoperative hospital stays were 11.5 and 10 days, respectively. Median follow-up is 6 years. An intent- to- treat analysis showed a median survival of 4.5 yrs vs 1.8 yrs in favor of trimodality therapy (log-rank p=0.02). A log rank test with stratifications by N stage, staging approach and histology demonstrated a p-value of 0.005. 5-year survival was 39% (95% CI [21%, 57%]) vs 16% (95% CI [5%, 33%]) in favor of trimodality therapy. Analysis of progression-free survival is underway. Conclusions: This randomized study demonstrates a long-term survival advantage with the use of chemoradiation therapy followed by surgery in the treatment of esophageal cancer. Although accrual was well below that planned, the observed survival difference is statistically significant and suggests that trimodality therapy is an appropriate standard of care for patients with this disease. No significant financial relationships to disclose.
Fidelity of nucleic acid amplification with avian myeloblastosis virus reverse transcriptase and T7 RNA polymerase. (1994)

The Nucleic Acid Sequence-Based Amplification (NASBA) process involves alternate steps of DNA synthesis from an RNA template and RNA synthesis from a DNA template, using avian myeloblastosis virus (AMV) reverse transcriptase and T7 RNA polymerase, respectively. The overall fidelity of the amplification process was determined by sequence analysis of cloned DNA products of NASBA reactions. An error frequency of less than 0.3% was observed in cloned DNA products from two different segments of the HIV-1 gag gene. Partial substitution of GTP with ITP in the NASBA reaction did not significantly change the fidelity of the process. An error rate of 2 x 10(-4) was calculated for the combined effects of both polymerases.
Test-Treatment Strategies for Patients Suspected of Having Lyme Disease: A Cost-Effectiveness Analysis (1998)

Neither testing nor antibiotic treatment is cost-effective if the pretest probability of Lyme disease is low. Empirical antibiotic therapy is recommended if the pretest probability is high, and two-step testing is recommended if the pretest probability is intermediate.
ChemInform Abstract: THE ORTHO‐DISUBSTITUTED F‐BENZENES. IV. THE FORMATION OF 2‐ACYL‐F‐PHENYL CARBOXYLATES FROM (F‐BENZO)FURANS BY THE OXIDATIVE CLEAVAGE OF THE FURAN RING (1982)

Abstract Bei der Oxidation der Phenylfurane (I) erfolgt Spaltung des Furanringes zu den Carboxylaten (II).
All Your Base: a fast and accurate probabilistic approach to base calling (2012)

The accuracy of base calls produced by Illumina sequencers is adversely affected by several processes, with laser cross-talk and cluster phasing being prominent. We introduce an explicit statistical model of the sequencing process that generalizes current models of phasing and cross-talk and forms the basis of a base calling method which improves on the best existing base callers, especially when comparing the number of error-free reads. The novel algorithms implemented in All Your Base (AYB) are comparable in speed to other competitive base-calling methods, do not require training data and are designed to be robust to gross errors, producing sensible results where other techniques struggle. AYB is available at http://www.ebi.ac.uk/goldman-srv/AYB/.
Signatures of the hydrogen bonding in the infrared bands of water (2005)

Infrared spectroscopy measurements have been completed over a wide range of frequencies allowing to measure the evolution of both intramolecular and intermolecular vibrational modes in water as a function of temperature. Emphasis is made on the high frequency OH stretching band and the so-called connectivity band that lies in the far infrared region. The substructures of the two infrared bands are analyzed in terms of different levels of connectivity of the water molecules, along the statements of the percolation model. Both band profiles appear to be related to the different degrees of connectivity of water molecules. Comparison of the data with the predictions of the percolation model shows good agreement as for the temperature evolution of liquid water. This work provides additional support to the interpretation of water bands substructures as signatures of its very specific connectivity pattern.
T-cell receptor gene transfer exclusively to human CD8+ cells enhances tumor cell killing (2012)

Transfer of tumor-specific T-cell receptor (TCR) genes into patient T cells is a promising strategy in cancer immunotherapy. We describe here a novel vector (CD8-LV) derived from lentivirus, which delivers genes exclusively and specifically to CD8(+) cells. CD8-LV mediated stable in vitro and in vivo reporter gene transfer as well as efficient transfer of genes encoding TCRs recognizing the melanoma antigen tyrosinase. Strikingly, T cells genetically modified with CD8-LV killed melanoma cells reproducibly more efficiently than CD8(+) cells transduced with a conventional lentiviral vector. Neither TCR expression levels, nor the rate of activation-induced death of transduced cells differed between both vector types. Instead, CD8-LV transduced cells showed increased granzyme B and perforin levels as well as an up-regulation of CD8 surface expression in a small subpopulation of cells. Thus, a possible mechanism for CD8-LV enhanced tumor cell killing may be based on activation of the effector functions of CD8(+) T cells by the vector particle displaying OKT8-derived CD8-scFv and an increase of the surface density of CD8, which functions as coreceptor for tumor-cell recognition. CD8-LV represents a powerful novel vector for TCR gene therapy and other applications in immunotherapy and basic research requiring CD8(+) cell-specific gene delivery.
Counting stream registers: An efficient and effective snoop filter architecture (2012)

We introduce a counting stream register snoop filter, which improves the performance of existing snoop filters based on stream registers. Over time, this class of snoop filters loses the ability to filter memory addresses that have been loaded, and then evicted, from the caches that are filtered; they include cache wrap detection logic, which resets the filter whenever the contents of the cache have been completely replaced. The counting stream register snoop filter introduced here replaces the cache wrap detection logic with a direct-mapped update unit and augments each stream register with a counter, which acts as a validity checker; loading new data into the cache increments the counter, while replacements, snoopy invalidations, and evictions decrement it. A cache wrap is detected whenever the counter reaches zero. Our experimental evaluation shows that the counting stream register snoop filter architecture improves the accuracy compared to traditional stream register snoop filters for representative embedded workloads.
The race to an orally active Factor Xa inhibitor: recent advances. (2004)

Factor Xa (fXa) is a key enzyme in the coagulation cascade and an essential component of the prothrombinase complex, which activates prothrombin to thrombin, leading to fibrin clot formation. In the search for a more effective and safer orally active anticoagulant, fXa has emerged as a major target for potential therapeutic applications in the treatment and prevention of thrombosis. This review focuses on recent advances in the chemistry of drug design and lead optimization of orally bioavailable fXa inhibitors. Many of these orally active fXa inhibitors are currently in clinical trials and are anticipated to change the landscape of thrombosis therapy.
Differential Accumulation of Proteoglycans and Hyaluronan in Culprit Lesions (2002)

Specific accumulation of versican, hyaluronan, and CD44 at the sites of plaque erosion implicates an involvement of these molecules in events associated with acute coronary thrombosis.
Modeling and Analysis of a Dual-Channel Plasma Torch in Pulsed Mode Operation for Industrial, Space, and Launch Applications (2015)

Dual-channel thermal plasma torch can operate with air, argon, or combustible gases to produce high-temperature plasma flow. This plasma torch can be used in various important applications such as metal industry recycling, surface coating and hardening, space operations using controlled thrust, and macroparticle acceleration based on the electrothermal nature of thermal torches and electrical-to-thermal energy conversion. Power for this torch is supplied from the electric mains and the voltage is stepped up to 6 kV. However, the torch can also operate on dc or pulsed mode. The electrical operation is characterized by the voltampere relationship to determine the power rating of the torch as well as diagnosing the dynamic behavior of the plasma. Experiments on the torch using air and argon have shown plasma temperatures in the range of 0.4-0.6 eV with plasma number density in the range of 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">24</sup> -10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">25</sup> /m <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> , indicating a dense plasma regime with the plasma tends to be weakly nonideal. Plasma kinetic temperature and electron number density were obtained from optical emission spectroscopy using the relative line method as the plasma is near local thermodynamic equilibrium condition. Plasma temperature has its peak for low flow rates and decreases for increased flow rates. The torch modeling was conducted using an electrothermal plasma code to simulate and predict the parameters for pulsed mode operation. Simulation was conducted on a single channel as the dual torch is symmetric. Code results for extended pulselength show a plasma temperature between 0.6 and 0.8 eV for nitrogen, oxygen, and helium; which are in good correlation with plasma temperatures obtained from optical emission spectra and measured plasma resistivity. A set of computational experiments using short pulses at higher discharge currents has shown temperature in the range of 2.0-2.5 eV for nitrogen and helium.
3‘–>5‘ exonuclease active site of phi 29 DNA polymerase. Evidence favoring a metal ion-assisted reaction mechanism. (1994)

The residues forming the 3'-->5' exonuclease active site of phi 29 DNA polymerase, located at the N-terminal conserved motifs Exo I, Exo II and Exo III, have been defined by site-directed mutagenesis (Bernad, A., Blanco, L., Lázaro, J. M., Martin, G., and Salas, M. (1989) Cell 59, 219-228; Soengas, M. S., Esteban, J. A., Lázaro, J. M., Bernad, A., Blasco, M. A., Salas, M., and Blanco, L. (1992) EMBO J. 11, 4227-4237). To understand their catalytic role, the residual exonuclease activity of mutants at these active site residues has been kinetically studied. The critical function of residues Asp12, Glu14, Asp66, and Asp169 is supported by a 10(5)-fold reduction in the exonuclease catalytic rate upon single mutation. Residue Tyr165 seems to play a secondary role in the exonuclease reaction based on the 10(2)-10(3)-fold reduced catalytic rate of mutants Y165F and Y165C. Most of the mutants were specially active in the presence of Mn2+ ions, which could be indicative of a direct involvement of these residues in a metal ion-assisted exonucleolytic reaction. The data obtained strongly suggest that the 3'-->5' exonuclease active site of phi 29 DNA polymerase is structurally and functionally similar to that of the Escherichia coli DNA polymerase I. In addition, these residues were also very important for the strand displacement ability of phi 29 DNA polymerase, suggesting a structural overlapping of this activity with the 3'-->5' exonuclease.
An Asynchronous Router for Multiple Service Levels Networks on Chip (2005)

Networks on chip that can guarantee quality of service (QNoC) are based on special routers that can support multiple service levels. GALS SoCs call for asynchronous NoC implementations, to eliminate the need for synchronization when crossing clock domains. An asynchronous multi-service level QNoC router is investigated. It comprises multiple interconnected input and output ports, and arbitration mechanisms that resolve any output port and service level conflicts. Buffering and credit based transport are enabled, enhancing throughput. A synchronous and an asynchronous router have been designed, and their performance is compared. The asynchronous router requires less area and enables a higher data rate.
Unstable Richtmyer–Meshkov growth of solid and liquid metals in vacuum (2012)

Abstract We present experimental results supporting physics-based ejecta model development, where our main assumption is that ejecta form as a special limiting case of a Richtmyer–Meshkov (RM) instability at a metal–vacuum interface. From this assumption, we test established theory of unstable spike and bubble growth rates, rates that link to the wavelength and amplitudes of surface perturbations. We evaluate the rate theory through novel application of modern laser Doppler velocimetry (LDV) techniques, where we coincidentally measure bubble and spike velocities from explosively shocked solid and liquid metals with a single LDV probe. We also explore the relationship of ejecta formation from a solid material to the plastic flow stress it experiences at high-strain rates ( $1{0}^{7} ~{\mathrm{s} }^{\ensuremath{-} 1} $ ) and high strains (700 %) as the fundamental link to the onset of ejecta formation. Our experimental observations allow us to approximate the strength of Cu at high strains and strain rates, revealing a unique diagnostic method for use at these extreme conditions.
Clinical experience of treatment of metastatic melanoma and solid tumours adopting a derivative of diphtheria toxin: cross-reacting material 197. (2013)

CRM197, injected subcutaneously at 5 mg, elicited a generic inflammatory response causing toxicity, and did not exert a significant degree of antitumor activity in patients with advanced melanoma and solid tumour.
Nitric oxide and malondialdehyde levels in plasma and tissue of psoriasis patients (2011)

NO and MDA levels are elevated in psoriasis patients, which may indicate that oxidative stress plays an important role in the aetiopathogenesis of psoriasis.
Autophagy in Protein and Organelle Turnover (2011)

Macroautophagy is an evolutionarily conserved degradation system in the cell. In autophagy, intracellular components are sequestered by autophagosomes and subsequently degraded upon fusion with lysosomes. Genetic analysis of autophagy in mammals has revealed that autophagy is important for various physiological processes, such as adaptive responses to starvation, embryogenesis, quality control of intracellular proteins and organelles, tumor suppression, degradation of intracellular pathogens, and anti-aging. In this review I describe the various roles of autophagy, with a particular focus on the turnover of cytoplasmic proteins and organelles.
The Central Role of Chemokines (Chemotactic Cytokines) in the Immunopathogenesis of Ulcerative Colitis and Crohnʼs Disease (1998)

The final composition of leukocytes present in a site of inflammation in response to chemokine stimulation and activation may depend on both the nature of the secreted chemokines as well as the relative expression of the multitude of specific chemokine cell surface receptors on many different cell types. Because related receptors with different affinities and cross-reactive binding capabilities are present on each type of leukocyte, relative differences in receptor distribution and receptor affinity for specific chemokines may significantly influence which cells are ultimately attracted to and activated by each individual chemokine. Production of IL-8, MCP-1, and ENA-78 by endothelial cells, LPMNC, and epithelial cells in IBD could establish a chemotactic gradient capable of influencing the increased migration of monocytes/macrophages, granulocytes, and lymphocytes from the blood stream through the endothelium into both the mucosa and submucosa during chronic IBD. The ability of chemokines to induce chemotaxis, leukocyte activation, granule exocytosis, increased production of metalloenzymes, and up-regulation of respiratory burst activity indicates that there may be a variety of different mechanisms by which chemokines could markedly increase chronic inflammation and chronic intestinal tissue destruction in IBD.
A Critical Role of a Cellular Membrane Traffic Protein in Poliovirus RNA Replication (2008)

Replication of many RNA viruses is accompanied by extensive remodeling of intracellular membranes. In poliovirus-infected cells, ER and Golgi stacks disappear, while new clusters of vesicle-like structures form sites for viral RNA synthesis. Virus replication is inhibited by brefeldin A (BFA), implicating some components(s) of the cellular secretory pathway in virus growth. Formation of characteristic vesicles induced by expression of viral proteins was not inhibited by BFA, but they were functionally deficient. GBF1, a guanine nucleotide exchange factor for the small cellular GTPases, Arf, is responsible for the sensitivity of virus infection to BFA, and is required for virus replication. Knockdown of GBF1 expression inhibited virus replication, which was rescued by catalytically active protein with an intact N-terminal sequence. We identified a mutation in GBF1 that allows growth of poliovirus in the presence of BFA. Interaction between GBF1 and viral protein 3A determined the outcome of infection in the presence of BFA.
Site-directed point mutations in embryonic stem cells: a gene-targeting tag-and-exchange strategy. (1993)

Sequential gene targeting was used to introduce point mutations into one alpha 2 isoform Na,K-ATPase homolog in mouse embryonic stem (ES) cells. In the first round of targeted replacement, the gene was tagged with selectable markers by insertion of a Neor/HSV-tk gene cassette, and this event was selected for by gain of neomycin (G418) resistance. In the second targeted replacement event, the tagged genomic sequence was exchanged with a vector consisting of homologous genomic sequences carrying five site-directed nucleotide substitutions. Embryonic stem cell clones modified by exchange with the mutation vector were selected for loss of the HSV-tk gene by resistance to ganciclovir. Candidate clones were further screened and identified by polymerase chain reaction and Southern blot analysis. By this strategy, the endogenous alpha 2 isoform Na,K-ATPase gene was altered to encode two other amino acids so that the enzyme is resistant to inhibition by cardiac glycosides while maintaining its transmembrane ion-pumping function. Since the initial tagging event and the subsequent mutation-exchange event are independent of one another, a tagged cell line can be used to generate a variety of mutant lines by exchange with various mutation vectors at the tagged locus. This method should be useful for testing specific mutations introduced into the genomes of tissue culture cells and animals and for developing animal models encompassing the mutational variability of known genetic disorders.
Considerations in the Evaluation of the Biological Effects of Exposure to Microwave Radiation (1970)

The increasing use of microwave (SHF) and ultra-high-frequency (UHF) radiation in industry and in the home suggests the need for a re-evaluation of the available information concerning the biological effects of such exposures. A review of the thermal (> 10mW/cm2) and nonthermal effects of microwave and UHF exposure on organisms, organs, cells, bacteria, and biological molecules is presented, as well as the exposure limits that have been based on such data. It is suggested that the area of greatest uncertainty is the effects of nonthermal exposure on the central nervous system. Suggestions are made for additional research on the effects of nonthermal exposures at various levels of biological systems.
Somatostatin-Receptor Imaging in the Localization of Endocrine Tumors (1990)

The 123I-labeled Tyr3-octreotide scanning technique is a rapid and safe procedure for the visualization of some tumors with somatostatin receptors. A positive scan may predict the ability of octreotide therapy to control symptoms of hormonal hypersecretion.