gebhart/patrepeval huggingface dataset:
Generation of high-energy pulses using a large-mode-area erbium-doped fiber amplifier (1996)

Summary form only given. In conclusion, we have developed a large-mode-area Er-doped fiber amplifier and demonstrated a substantial improvement in reducing fiber nonlinearities and ASE-induced suppression of gain to increase the extracted pulse energies from a fiber-based CPA system. Using this technique we have produced pulses with energies >20 /spl mu/J.
Regional cerebral blood flow and glucose metabolism following transient forebrain ischemia (1982)

Progressive brain damage after transient cerebral ischemia may be related to changes in postischemic cerebral blood flow and metabolism. Regional cerebral blood flow (rCBF) and cerebral glucose utilization (rCGU) were measured in adult rats prior to, during (only rCBF), and serially after transient forebrain ischemia. Animals were subjected to 30 minutes of forebrain ischemia by occluding both common carotid arteries 24 hours after cauterizing the vertebral arteries. Regional CBF was measured by the indicator-fractionation technique using 4-iodo-[14C]-antipyrine. Regional CGU was measured by the 2-[14C]deoxyglucose method. The results were correlated with the distribution and progression of ischemic neuronal damage in animals subjected to an identical ischemic insult. Cerebral blood flow to forebrain after 30 minutes of moderate to severe ischemia (less than 10% control CBF) was characterized by 5 to 15 minutes of hyperemia; rCBF then fell below normal and remained low for as long as 24 hours. Post-ischemic glucose utilization in the forebrain, except in the hippocampus, was depressed below control values at 1 hour and either remained low (neocortex, striatum) or gradually rose to normal (white matter) by 48 hours. In the hippocampus, glucose utilization equaled the control value at 1 hour and fell below control between 24 and 48 hours. The appearance of moderate to severe morphological damage in striatum and hippocampus coincided with a late rise of rCBF above normal and with a fall of rCGU; the late depression of rCGU was usually preceded by a period during which metabolism was increased relative to adjacent tissue. Further refinement of these studies may help identify salvageable brain after ischemia and define ways to manipulate CBF and metabolism in the treatment of stroke.
Meta-analysis of association of ACE2 G8790A polymorphism with Chinese Han essential hypertension (2009)

The meta-analysis suggests that ACE2 G8790A polymorphism may not be a genetic risk factor for essential hypertension in a Chinese Han population.
Fed‐batch fermentor synthesis of 3‐dehydroshikimic acid using recombinant Escherichia coli (1999)

3-Dehydroshikimic acid (DHS), in addition to being a potent antioxidant, is the key hydroaromatic intermediate in the biocatalytic conversion of glucose into aromatic bioproducts and a variety of industrial chemicals. Microbial synthesis of DHS, like other intermediates in the common pathway of aromatic amino acid biosynthesis, has previously been examined only under shake flask conditions. In this account, synthesis of DHS using recombinant Escherichia coli constructs is examined in a fed-batch fermentor where glucose availability, oxygenation levels, and solution pH are controlled. DHS yields and titers are also determined by the activity of 3-deoxy-D-arabino-heptulosonic acid 7-phosphate (DAHP) synthase. This enzyme's expression levels, sensitivity to feedback inhibition, and the availability of its substrates, phosphoenolpyruvate (PEP) and D-erythrose 4-phosphate (E4P), dictate its in vivo activity. By combining fed-batch fermentor control with amplified expression of a feedback-insensitive isozyme of DAHP synthase and amplified expression of transketolase, DHS titers of 69 g/L were synthesized in 30% yield (mol/mol) from D-glucose. Significant concentrations of 3-dehydroquinic acid (6.8 g/L) and gallic acid (6.6 g/L) were synthesized in addition to DHS. The pronounced impact of transketolase overexpression, which increases E4P availability, on DHS titers and yields indicates that PEP availability is not a limiting factor under the fed-batch fermentor conditions employed. © 1999 John Wiley & Sons, Inc. Biotechnol Bioeng 64: 61–73, 1999.
Modulation of Airway Inflammation by Passive Transfer of Allergen-Specific Th1 and Th2 Cells in a Mouse Model of Asthma (1999)

Although evidence is strong that Th cells play a major role in mediating the airway inflammation observed in asthma, the relative contributions of the Th cell subsets, Th1 and Th2, are unclear. It has been suggested that asthma is driven by Th2 predominant responses in the lung, but other data suggest a role for Th1 cells as well. Here we show by intracellular cytokine staining and flow cytometric analysis that in the murine model of OVA-induced airway inflammation, both Th1 and Th2 cells are recruited to the airways. Th1 cells predominate early in the response and Th2 cells predominate late. We further show that increasing the number of Th1 cells by passive transfer of OVA-specific Th1 cells results in increased inflammation. This effect is observed regardless of whether the T cells are transferred before sensitization or after airway inflammation is already in progress. Transfer of Th1 cells also results in increased recruitment of host T cells of both Th1 and Th2 phenotypes. Passive transfer of Th2 cells results in little change in the inflammatory response. These results demonstrate that Ag-specific Th1 cells are not protective in this model of asthma, but rather may potentiate the inflammatory response.
Role of Conserved Disulfide Bridges and Aromatic Residues in Extracellular Loop 2 of Chemokine Receptor CCR8 for Chemokine and Small Molecule Binding (2016)

Chemokine receptors play important roles in the immune system and are linked to several human diseases. The initial contact of chemokines with their receptors depends on highly specified extracellular receptor features. Here we investigate the importance of conserved extracellular disulfide bridges and aromatic residues in extracellular loop 2 (ECL-2) for ligand binding and activation in the chemokine receptor CCR8. We used inositol 1,4,5-trisphosphate accumulation and radioligand binding experiments to determine the impact of receptor mutagenesis on both chemokine and small molecule agonist and antagonist binding and action in CCR8. We find that the seven-transmembrane (TM) receptor conserved disulfide bridge (7TM bridge) linking transmembrane helix III (TMIII) and ECL-2 is crucial for chemokine and small molecule action, whereas the chemokine receptor conserved disulfide bridge between the N terminus and TMVII is needed only for chemokines. Furthermore, we find that two distinct aromatic residues in ECL-2, Tyr(184) (Cys + 1) and Tyr(187) (Cys + 4), are crucial for binding of the CC chemokines CCL1 (agonist) and MC148 (antagonist), respectively, but not for small molecule binding. Finally, using in silico modeling, we predict an aromatic cluster of interaction partners for Tyr(187) in TMIV (Phe(171)) and TMV (Trp(194)). We show in vitro that these residues are crucial for the binding and action of MC148, thus supporting their participation in an aromatic cluster with Tyr(187) This aromatic cluster appears to be present in a large number of CC chemokine receptors and thereby could play a more general role to be exploited in future drug development targeting these receptors.
Cell Death in Chondrocytes, Osteoblasts, and Osteocytes (2016)

Cell death in skeletal component cells, including chondrocytes, osteoblasts, and osteocytes, plays roles in skeletal development, maintenance, and repair as well as in the pathogenesis of osteoarthritis and osteoporosis. Chondrocyte proliferation, differentiation, and apoptosis are important steps for endochondral ossification. Although the inactivation of <i>P53</i> and <i>RB</i> is involved in the pathogenesis of osteosarcomas, the deletion of <i>p53</i> and inactivation of Rb are insufficient to enhance chondrocyte proliferation, indicating the presence of multiple inhibitory mechanisms against sarcomagenesis in chondrocytes. The inflammatory processes induced by mechanical injury and chondrocyte death through the release of danger-associated molecular patterns (DAMPs) are involved in the pathogenesis of posttraumatic osteoarthritis. The overexpression of <i>BCLXL</i> increases bone volume with a normal structure and maintains bone during aging by inhibiting osteoblast apoptosis. p53 inhibits osteoblast proliferation and enhances osteoblast apoptosis, thereby reducing bone formation, but also exerts positive effects on osteoblast differentiation through the Akt-FoxOs pathway. Apoptotic osteocytes release ATP, which induces the receptor activator of nuclear factor κ-B ligand (Rankl) expression and osteoclastogenesis, from pannexin 1 channels. Osteocyte death ultimately results in necrosis; DAMPs are released to the bone surface and promote the production of proinflammatory cytokines, which induce Rankl expression, and osteoclastogenesis is further enhanced.
Heat Assisted Magnetic Recording (2008)

Heat-assisted magnetic recording is a promising approach for enabling large increases in the storage density of hard disk drives. A laser is used to momentarily heat the recording area of the medium to reduce its coercivity below that of the applied magnetic field from the recording head. In such a system, the recording materials have a very high magnetic anisotropy, which is essential for the thermal stability of the magnetization of the extremely small grains in the medium. This technology involves new recording physics, new approaches to near field optics, a recording head that integrates optics and magnetics, new recording materials, lubricants that can withstand extremely high temperatures, and new approaches to the recording channel design. This paper surveys the challenges for this technology and the progress that has been made in addressing them.
Oncolytic Herpes Simplex Virus Vector G47Δ in Combination with Androgen Ablation for the Treatment of Human Prostate Adenocarcinoma (2005)

These results suggest that oncolytic virus therapy with G47Delta can be usefully combined with androgen ablation therapy for the treatment of prostate cancer.
Stress Urinary Incontinence (2004)

Stress urinary incontinence, the complaint of involuntary leakage during effort or exertion, occurs at least weekly in one third of adult women. The basic evaluation of women with stress urinary incontinence includes a history, physical examination, cough stress test, voiding diary, postvoid residual urine volume, and urinalysis. Formal urodynamics testing may help guide clinical care, but whether urodynamics improves or predicts the outcome of incontinence treatment is not yet clear. The distinction between urodynamic stress incontinence associated with hypermobility and urodynamic stress incontinence associated with intrinsic sphincter deficiency should be viewed as a continuum, rather than a dichotomy, of urethral function. Initial treatment should include behavioral changes and pelvic floor muscle training. Estrogen is not indicated to treat stress urinary incontinence. Bladder training, vaginal devices, and urethral inserts also may reduce stress incontinence. Bulking agents reduce leakage, but effectiveness generally decreases after 1-2 years. Surgical procedures are more likely to cure stress urinary incontinence than nonsurgical procedures but are associated with more adverse events. Based on available evidence at this time, colposuspension (such as Burch) and pubovaginal sling (including the newer midurethral synthetic slings) are the most effective surgical treatments.
Protection of Cotton Rats against Human Respiratory Syncytial Virus by Vaccination with a Novel Chimeric FG Glycoprotein (1989)

The cotton rat model of experimental human respiratory syncytial virus (RSV) infection was used to study the efficacy of FG, a novel chimeric glycoprotein which was expressed in insect cells using a baculovirus vector. FG contained the extracellular regions of the F (fusion) and G (attachment) glycoproteins of RSV. Vaccination with FG resulted in induction of neutralizing antibody and was correlated with protection of lung tissue from RSV challenge against both serogroup A and B virus strains. Both crude FG taken from supernatants of insect cells and affinity-purified FG were immunogenic and active against RSV. FG vaccination was effective by three routes of administration, following a single dose, and when administered with different adjuvants.
The puzzling multiple lives of PML and its role in the genesis of cancer (2000)

PML, the gene associated with acute promyelocytic leukemia (APL); PML, the target of numerous viral agents; PML, the growth suppressor; PML, the mediator of multiple apoptotic pathways; PML, the tumor suppressor; PML, the protein which epitomizes a novel nuclear structure, the nuclear body; PML, the transcription co-factor. Despite the recent flurry of reports attributing multiple biological roles to the PML protein, PML still lacks a definitive biochemical function. This is probably the reason why PML is so attractive to many investigators. Here, we will summarize the facts and speculations on this puzzling protein. BioEssays 22:827–835, 2000. © 2000 John Wiley & Sons, Inc.
Imaging metal atoms in air and water using the atomic force microscope (1990)

Gold atoms in an epitaxial film on mica are clearly visible in images obtained with an atomic force microscope (AFM). The measured lattice spacing of 3.0± 0.3 Å is consistent with previous scanning tunneling microscope images obtained in air and vacuum. Atoms are visible even if the sample surface, tip, and cantilever are submerged in water in a closed cell. Electrochemical studies of metal electrodes at atomic resolution may now be possible with the AFM.
Long-term genome stability and minimal genotypic and phenotypic alterations in HPV16 E7-, but not E6-, immortalized human uroepithelial cells. (1994)

Parameters of genome instability and morphological alterations associated with cell transformation were studied in an isogeneic set of clonal human uroepithelial cell (HUC) lines immortalized by the human papilloma virus 16 (HPV16) E6 and/or E7 gene(s). HPV16 E6 binds p53, leading to rapid degradation of p53, whereas E7 binds and alters pRb and other proteins. We report that two independent E7-immortalized HUC lines showed minimal phenotypic or genotypic alterations, except that both lines contained amplification of 20q DNA sequences and a greater polyploidization at an early passage. The E7-immortalized HUC line resembled normal HUC lines, except that they failed to senesce. In contrast, the E6-immortalized HUC lines were morphologically altered, contained numerous random chromosome aberrations, and showed unstable evolving karyotypes with passage in culture. No amplified DNA sequences were detected in E6-immortalized HUC lines. Instead, clonal losses of chromosome regions (i.e., -3p, -6q, -9p), putatively containing tumor suppressor or senescence genes, accompanied the E6-HUC immortalization event. E6-immortalized HUC lines showed transformed phenotypes similar to E6/E7-HUC lines. The difference in genome stability between E6- and E7-immortalized HUC was highly significant statistically (p-value < 10(-6). Thus, the HPV16 E7 gene led to HUC immortalization by a pathway that blocked cellular senescence, but did not disrupt genome stability. These results implicate p53 loss, but not pRb alteration, in genome destabilization.
Pharmacodynamic effects of inhaled dry powder formulations of fenoterol and colforsin in asthma (1993)

The airway and tremor response and cardiovascular and hypokalemic effects of single doses of inhalative fenoterol dry powder capsules (0.4 mg) were compared with the fenoterol metered dose inhaler (0.4 mg) and colforsin (forskolin) dry powder capsules (10.0 mg), a direct activator of the adenylate cyclase system, in 16 patients with asthma. Subjects (FEV1 < or = 60% predicted) were investigated in a randomized, double-masked, placebo-controlled, four-period, crossover trial for a 120 minute period. All active drugs caused a significant increase in specific airway conductance (p < 0.05); the order of potency (mean +/- SEM maximum increase from baseline) was fenoterol metered dose inhaler (0.51 +/- 0.06 sec-1 x kPa-1), fenoterol dry powder capsules (0.49 +/- 0.07), and colforsin dry powder capsules (0.30 +/- 0.03). A marked increase in finger tremor amplitude resulted after fenoterol metered dose inhaler only (62.93% +/- 10.21%; p < 0.05) in contrast to fenoterol dry powder capsules (15.84% +/- 4.35%; p < 0.05) and colforsin dry powder capsules (12.87% +/- 10.44%; p > 0.05). A decrease in plasma potassium was found after fenoterol (metered dose inhaler > dry powder capsules; p < 0.05). In conclusion, fenoterol dry powder capsules caused less tremor response and hypokalemic effects than the metered dose inhaler, although the bronchodilator capacity was similar. Colforsin dry powder capsules resulted in a measurable bronchodilatation in patients with asthma.
In vitro infection of adult normal human hepatocytes in primary culture by hepatitis C virus. (1998)

In vitro infection of adult normal human hepatocytes in primary culture has been performed for investigating the replication cycle of hepatitis C virus (HCV) in differentiated cells. Hepatocytes were prepared from liver tissue resected from donors who tested negative for HCV, and inoculation was performed 3 days after plating with 33 HCV serum samples of different virus load and genotype. The presence of intracellular HCV RNA, detected by a strand-specific rTth RT-PCR assay, was used as evidence of infection. A kinetics analysis of HCV replication revealed that intracellular negative-strand RNA appeared at day 1 post-infection with a maximum level at days 3 and 5, followed by a decrease until day 14. At day 5, we estimated that the copy level of viral RNA was amplified at least 15-fold in infected cells. The level of intracellular HCV RNA in response to different serum samples was reproducible from one hepatocyte culture to another, suggesting that there is no inter-individual variability in the susceptibility of hepatocytes to HCV infection. These findings indicate that adult human hepatocytes in primary culture retain their susceptibility to in vitro HCV infection and support HCV RNA replication. This model should represent a valuable tool for the study of initial steps of the HCV replication cycle and for the evaluation of antiviral molecules.
Correction: Effects of Precipitation Increase on Soil Respiration: A Three-Year Field Experiment in Subtropical Forests in China (2012)

The aim of this study was to determine response patterns and mechanisms of soil respiration to precipitation increases in subtropical regions.
Faster methods for random sampling (1984)

Several new methods are presented for selecting n records at random without replacement from a file containing N records. Each algorithm selects the records for the sample in a sequential manner—in the same order the records appear in the file. The algorithms are online in that the records for the sample are selected iteratively with no preprocessing. The algorithms require a constant amount of space and are short and easy to implement. The main result of this paper is the design and analysis of Algorithm D, which does the sampling in O ( n ) time, on the average; roughly n uniform random variates are generated, and approximately n exponentiation operations (of the form a b , for real numbers a and b) are performed during the sampling. This solves an open problem in the literature. CPU timings on a large mainframe computer indicate that Algorithm D is significantly faster than the sampling algorithms in use today.
Quantitative CT Imaging of the Spatial and Temporal Distribution of Liposomes in a Rabbit Tumor Model (2009)

Successful employment of noninvasive imaging techniques to quantitatively assess the in vivo pharmacokinetics and biodistribution of nanoparticle drug delivery systems will facilitate the rational design of novel targeted drug carriers. This study reports on the bulk organ/tissue (liver, kidneys, spleen, tumor and blood) and intratumoral distribution of liposomes containing iohexol and gadoteridol over a 14-day period in VX2 sarcoma-bearing New Zealand White rabbits using computed tomography (CT). The vascular half-life of the liposomes was found to be 63.6 +/- 5.8 h and the maximum tumor-to-muscle iodine concentration ratio of 11.9 +/- 6.0 was measured 7 days postinjection with 1.13 +/- 0.29% ID of liposomes accumulating at the tumor site. The liposomes achieved their highest intratumoral distribution volume ratio at 48 h postadministration, occupying 72 +/- 5% of the total tumor volume. This investigation demonstrated the feasibility of using CT to perform quantitative, volumetric and longitudinal assessment of the pharmacokinetics and biodistribution of iodinated liposomes with sensitivities in the range of microg/cm3 while maintaining the ability to identify boundaries of anatomical structures at submillimeter resolution and with imaging time of less than one minute per scan. If successfully approved for clinical adoption, the use of CT imaging to monitor nanoparticulate drug delivery will provide an opportunity for online adjustment of therapeutic regimens and implementation of personalized medicine.
Alignment-free sequence comparison—a review (2003)

Most of the alignment-free algorithms reviewed were implemented in MATLAB code and are available at http://bioinformatics.musc.edu/resources.html
Crystal Structure of a Class I Ubiquitin Conjugating Enzyme (Ubc7) from Saccharomyces cerevisiae at 2.9 Å Resolution, (1997)

Ubiquitin-conjugating enzymes are a family of related proteins that participate in the ubiquitination of proteins. Previous studies on the crystal structures of Saccharomyces cerevisiae Ubc4 and Arabidopsis thaliana Ubc1 indicated that the smallest enzymes (class I), which consist entirely of the conserved core domain, share a common tertiary fold. Here we report the three-dimensional structure of the S. cerevisiae class I enzyme encoded by the UBC7 gene. The crystal structure has been solved using molecular replacement techniques and refined by simulated annealing to an R-factor of 0.183 at 2.93 A resolution. Bond lengths and angles in the molecule have root-mean-square deviations from ideal values of 0.016 A and 2.3 degrees, respectively. Ubc7 is an alpha/beta protein with four alpha-helices and a four-stranded antiparallel beta-sheet. With the exception of two regions where extra residues are present, the tertiary folding of Ubc7 is similar to those of the other two enzymes. The ubiquitin-accepting cysteine is located in a cleft between two loops. One of these loops is nonconserved, as this region of the Ubc7 molecule differs from the other two enzymes by having 13 extra residues. There is also a second single amino acid insertion that alters the orientation of the turn between the first two beta-strands. Analysis of the 13 ubiquitin-conjugating enzyme sequences in S. cerevisiae indicates that there may be two other regions where extra residues could be inserted into the common tertiary fold. Both of these other regions exhibit significant deviations in the superposition of the three structures and, like the two insertion regions in Ubc7, may represent hypervariable regions within a common tertiary fold. As ubiquitin-conjugating enzymes interact with different substrates or other accessory proteins in the ubiquitination pathway, these variable surface regions may confer distinct specificity to individual enzymes.