gebhart/patrepeval huggingface dataset:
High-power amplification of femtosecond optical pulses in a diode-pumped fiber system (1994)

We report a compact all-diode-laser-pumped erbium-doped fiber system consisting of an environmentally stable Kerr-type mode-locked fiber oscillator and a fiber amplifier. High-repetition-rate (38 MHz) 200-fs-duration pulses were amplified to as much as 3 nJ of energy and 150 mW of average power. Amplification of unstretched and stretched pulses was studied. Using chirped-pulse amplification, we obtained clean pedestal-free 420-fs pulses. Amplification of unstretched pulses produced 84-fs pulses with a broad pedestal.
DNA-based vaccines for malaria: a heterologous prime-boost immunisation strategy. (2000)

A generic approach to inducing high level CD8+ T cell responses would be of value for prophylactic and therapeutic immunisation against several infectious diseases. However, it has been very difficult to achieve such immune responses using available vaccination strategies. Malaria is one of several diseases against which a new generation of better CD8+ T cell-inducing vaccines might be useful and is unusual in that it allows assessment of vaccine efficacy in small numbers of volunteers in carefully controlled challenge studies. Here we review the identification of a heterologous prime-boost regime using DNA priming and recombinant modified vaccinia Ankara (MVA) boosting that induces high level T cell responses in both mice and non-human primates. Clinical trials to determine whether this prime-boost approach is immunogenic in humans are in progress.
Approximation algorithms for combinatorial problems (1973)

Simple, polynomial-time, heuristic algorithms for finding approximate solutions to various polynomial complete optimization problems are analyzed with respect to their worst case behavior, measured by the ratio of the worst solution value that can be chosen by the algorithm to the optimal value. For certain problems, such as a simple form of the knapsack problem and an optimization problem based on satisfiability testing, there are algorithms for which this ratio is bounded by a constant, independent of the problem size. For a number of set covering problems, simple algorithms yield worst case ratios which can grow with the log of the problem size. And for the problem of finding the maximum clique in a graph, no algorithm has been found for which the ratio does not grow at least as fast as 0(nε), where n is the problem size and ε> 0 depends on the algorithm.
Bacterial Biocatalysts: Molecular Biology, Three-Dimensional Structures, and Biotechnological Applications of Lipases (1999)

Bacteria produce and secrete lipases, which can catalyze both the hydrolysis and the synthesis of long-chain acylglycerols. These reactions usually proceed with high regioselectivity and enantioselectivity, and, therefore, lipases have become very important stereoselective biocatalysts used in organic chemistry. High-level production of these biocatalysts requires the understanding of the mechanisms underlying gene expression, folding, and secretion. Transcription of lipase genes may be regulated by quorum sensing and two-component systems; secretion can proceed either via the Sec-dependent general secretory pathway or via ABC transporters. In addition, some lipases need folding catalysts such as the lipase-specific foldases and disulfide-bond-forming proteins to achieve a secretion-competent conformation. Three-dimensional structures of bacterial lipases were solved to understand the catalytic mechanism of lipase reactions. Structural characteristics include an alpha/beta hydrolase fold, a catalytic triad consisting of a nucleophilic serine located in a highly conserved Gly-X-Ser-X-Gly pentapeptide, and an aspartate or glutamate residue that is hydrogen bonded to a histidine. Four substrate binding pockets were identified for triglycerides: an oxyanion hole and three pockets accommodating the fatty acids bound at position sn-1, sn-2, and sn-3. The differences in size and the hydrophilicity/hydrophobicity of these pockets determine the enantiopreference of a lipase. The understanding of structure-function relationships will enable researchers to tailor new lipases for biotechnological applications. At the same time, directed evolution in combination with appropriate screening systems will be used extensively as a novel approach to develop lipases with high stability and enantioselectivity.
Pharmaceutical “Gold” from Neurostabilizing Agents: Topiramate and Successor Molecules (2009)

ADVERTISEMENT RETURN TO ISSUEPerspectiveNEXTPharmaceutical "Gold" from Neurostabilizing Agents: Topiramate and Successor MoleculesBruce E. Maryanoff†View Author Information Johnson & Johnson Pharmaceutical Research & Development, Spring House, Pennsylvania 19477-0776† Contact information. Phone: 215-628-5530. Fax: 215-540-4612. E-mail: [email protected]Cite this: J. Med. Chem. 2009, 52, 11, 3431–3440Publication Date (Web):April 22, 2009Publication History Received3 February 2009Published online22 April 2009Published inissue 11 June 2009https://pubs.acs.org/doi/10.1021/jm900141jhttps://doi.org/10.1021/jm900141jreview-articleACS PublicationsCopyright © 2009 American Chemical SocietyRequest reuse permissionsArticle Views3192Altmetric-Citations29LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Drug discovery,Molecules,Pharmaceuticals,Rodent models,Therapeutics Get e-Alerts
First-in-human use of the OneShot™ renal denervation system from Covidien (2013)

Percutaneous transcatheter renal sympathetic denervation (RDN) is a promising treatment for refractory hypertension (HT). RDN was found in one series of clinical studies to reduce systolic blood pressure (SBP) by as much as a mean of 30 mmHg with 85% of subjects experiencing sustained reductions of 10 mm or more out to two years after RDN. This degree of blood pressure reduction may reduce stroke and myocardial infarction rates and is anticipated to translate into improved life expectancy. The lowering of blood pressure by RDN has been shown to improve glycaemic control and reverse left ventricular hypertrophy. Beneficial effects on renal function, sleep apnoea and heart failure are suggested as well. This report describes the first patient treated using the OneShot™ Renal Denervation System (formerly Maya Medical now Covidien, Campbell, CA, USA).
Clinical Question: Can Exercise Training Reduce the Restenosis Rate in a Man with Coronary Artery Disease after Percutaneous Transluminal Coronary Angioplasty with Stent? (2006)

The purpose of ”Evidence in Practice” is to illustrate how evidence is gathered and used to guide clinical decision making. Plenty of evidence suggested that exercise training on a regular basis or cardiac rehabilitation program is beneficial for the functional capacity and quality of life in patients with cardiac diseases, but little attention was focused on the restenosis rate after percutaneous transluminal coronary angioplasty (PTCA). Restenosis is a common problem that has great impact on patient's outcome. For answering this clinical question, we decided to search the literature to see if there was evidence to demonstrate that an exercise training program could reduce the restenosis rate in the patient with coronary artery disease after PTCA. Only one randomized controlled trial was found from the search, it appears there is no evidence to support the beneficial effects on outcome of restenosis rate after exercise training. Future studies are needed on this issue to provide more evidence.
Insertion mutants of herpes simplex virus have a duplication of the glycoprotein D gene and express two different forms of glycoprotein D (1983)

We produced insertion mutants of herpes simplex virus (HSV) that contain two functional copies of genes encoding different forms of glycoprotein D (gD). These viruses have the gene for HSV type 2 (HSV-2) gD at the normal locus and the gene for HSV-1 gD inserted into the thymidine kinase locus. Results of immunoprecipitation experiments done with monoclonal antibodies revealed that both gD genes were expressed by these viruses, regardless of orientation of the inserted HSV-1 gD gene, and that maximal synthesis of both glycoproteins depended on viral DNA replication. This apparently normal expression of the inserted HSV-1 gD gene was from a DNA fragment (SacI fragment, 0.906 to 0.924 map units) containing nucleotide sequences extending from approximately 400 base pairs upstream of the 5' end of the gD mRNA to about 200 base pairs upstream of the 3' end. The glycoproteins expressed from both genes were incorporated into the surfaces of infected cells. Electrophoretic analyses of purified virions and neutralization studies suggest that both glycoproteins were also incorporated into virions. This nonpreferential utilization of both gene products makes these viruses ideal strains for the generation and characterization of a variety of mutations.
Interesterification of Triglyceride and Fatty Acid in a Microaqueous Reaction System Using Lipase–Surfactant Complex (1995)

Lipase-surfactant complex (LSC) was prepared by mixing an aqueous solution of lipase (EC 3.1.1.3) derived from Pseudomonas sp. and an ethanol solution of sorbitan mono-stearate. The LSC was used to catalyze the interesterification of triglyceride and fatty acid in a solvent system with hexane or in a solvent-free system. The optimum reaction temperature for the LSC was found to be 50°C. The LSC also had catalytic activity in a solvent-free system at 80–100°C. The optimum added water content at which the enzyme had maximum activity was found to be 100mmol H2O/(g-LSC) for various substrates and enzyme concentrations. This shows that the amount of water required depends on the amount of enzyme. Ethanol and diethylene glycol could be used as water substitutes, and the optimum hydroxyl group content was 100 mmol [OH]/(g-LSC).
Neurorestoration induced by the HDAC inhibitor sodium valproate in the lactacystin model of Parkinson's is associated with histone acetylation and up‐regulation of neurotrophic factors (2015)

The histone acetylation and up-regulation of neurotrophic/neuroprotective factors associated with valproate treatment culminate in a neuroprotective and neurorestorative phenotype in this animal model of PD. As valproate induced structural re-modelling of the brain, further research is required to determine whether valproate represents a viable candidate for disease treatment; however, the results suggest that HDACIs could hold potential as disease-modifying agents in PD.
Enantiopure Chiral Concave 1,10‐Phenanthrolines (2016)

Abstract Chiral information has been introduced into concave 1,10‐phenanthrolines of different ring sizes by using a 2,7‐disubstituted naphthalene bridgehead, which causes axial chirality. A tetraphenolic 2‐(dihydroxynaphthyl)‐9‐(dihydroxyphenyl)‐1,10‐phenanthroline was synthesized as a key intermediate. Two strategies were followed to obtain the bimacrocyclic chiral concave 1,10‐phenanthrolines: quadruple Williamson ether synthesis or alkenylation of the OH groups and subsequent ring‐closing metathesis followed by hydrogenation. The overall yields of bimacrocyles 19 were 10 to 17 % starting from the respective Suzuki coupling of the substituted arenes 11 and 13 to 2,9‐dichloro‐1,10‐phenanthroline ( 5 ). Racemic mixtures of the three concave 1,10‐phenanthrolines 19 were separated by using chiral high‐performance liquid chromatography (HPLC) techniques, and their absolute stereochemistry was assigned by comparison of simulated and experimental circular dichroism (CD) spectra. The enantiopure concave 1,10‐phenanthrolines were used as ligands in a copper‐catalysed cyclopropanation, and their selectivity was determined by chiral gas chromatography (GC).
Hybrid III–V-on-Si MOS microring resonator (2016)

The high power consumption and limited bandwidth of conventional metal interconnects has become the main obstacle to the extension of Moore's Law. Optics is the perfect solution because of its broad bandwidth, low latency, low power consumption, and low crosstalk. The hybrid III-V-on-Si platform has been developed extensively recently as a promising integrated platform to build robust Si-based light sources and seamlessly integrate with other high-performance Si photonic circuits in a low-cost, high-volume process. In standard hybrid chips Silicon is used for optical waveguides and mechanically supporting the III-V layer. For the first time, we experimentally demonstrate a hybrid metal-oxide-semiconductor (MOS) capacitor by sandwiching a layer of dielectric between Si and III-V during wafer bonding step to utilize the electrical property of the Si in this hybrid platform. We fabricated a tunable microring resonator based on this hybrid MOS capacitor. Compared to a traditional microring resonator which relies on heat to tune the resonant wavelength, this MOS microring resonator is tuned by changing the MOS bias voltage, which changes the refractive index and thus the resonance wavelength due to plasma dispersion effect. A power reduction by a factor of over a billion has been achieved. A picture of a 20 μm MOS ring is shown in the inset of Fig. 1(a). The silicon bus waveguide next to the ring and the grating couplers at ends are used to couple light in and out of the ring. A schematic of the cross section of the MOS ring is shown in Fig. 1(b). It consists of 150nm thick InP based III-V epi on top of 250nm thick Si, with 15nm thick Al <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> O <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> sandwiched in between. The air trench shown in Fig. 1(b) is etched prior to wafer bonding in order to optimize the overlap between the capacitor and the fundamental optical mode (Fig. 1(b)) as well as eliminating the higher order transverse modes in the cavity. Under forward bias between terminals P and N, holes in Si and electrons in InP accumulate at the semiconductor/oxide interface. The simulated interface carrier density in Si and III-V are shown in Fig. 1(a). The measured resonance wavelength shift is shown in Fig. 1(c). Consistent with simulation results (not shown here), blue shift is observed as the bias voltage is increased, indicating a true plasma dispersion effect rather than heating. Over 8 dB extinction ratio is achieved at 4V bias, and the wavelength tuning power efficiency is 4 fW/GHz due to fA-level leakage current. This result represents a 9 orders of magnitude improvement over conventional thermal tuning.
Anomalous proximity effect in d-wave superconductors (1998)

The anomalous proximity effect between a d-wave superconductor and a thin disordered normal layer is studied theoretically in the framework of Eilenberger equations. It is shown that disorder of the quasiparticle reflection from this thin layer leads to the formation of an s-wave component localized near the boundary. The angular and spatial structure of the pair potential near the interface is studied.
Induction of leukemia inhibitory factor in human synovial fibroblasts by IL-1 and tumor necrosis factor-alpha (1993)

The cytokines, IL-1 alpha and TNF-alpha, induced a dose-dependent production of leukemia inhibitory factor (LIF) in cultured human synovial fibroblast-like cells, as measured by a radioreceptor competition assay. Significant levels of LIF were first detected in cell supernatants between 2 and 4 h after cytokine addition. Increases were also observed in LIF mRNA steady-state expression. Evidence is presented for down-regulation of the IL-1-induced LIF activity by an endogenous cyclo-oxygenase product(s); the glucocorticoid, dexamethasone, lowered the IL-1-induced LIF activity and mRNA expression. A synergistic effect was noted between the actions of IL-1 alpha and TNF-alpha, and between IL-1 and transforming growth factor-beta. IFN-gamma could not induce LIF formation in the synovial cells but inhibited the stimulatory effect of IL-1. These results suggest that cytokine-stimulated synovial fibroblasts may be a major source of intraarticular LIF production in the joints of patients with inflammatory arthritis. Synoviocyte-derived LIF may activate monocyte/macrophages in the lesions and may contribute to the bone changes and certain systemic manifestations in patients with inflammatory joint disease.
RO 농축수내 고농도 염분이 생물학적 폐수처리공정내 미생물 순응/배양에 미치는 영향평가 (2012)

There are a lot of parameters affecting microbial acclimation/cultivation characteristics such as dynamic conditions, F/M ratio and substrate affinity. From the process control point of view, the effect of high salinity on the removal efficiencies of BOD and SS have been documented by few researchers. In this research, lab-scale CAS(Conventional Activated Sludge) process and modified A2O(Anaerobic/Anoxic/Oxic) process were operated and monitored to evaluate the characteristics of microbial acclimation and cultivation under high salinity wastewater during the period of three weeks. As a result of acute microbial activity test(6hr) at various Clconcentration, the appropriate Cl- concentration for microbial growth and acclimation ranged under 3,100 mg/l. As a result of acclimation/cultivation test, the trend of COD removal efficiency reduced gradually as time elapsed. It is considered that NH4-N removal phenomenon of the conventional pollutants removal mechanisms gave little effect to the microbial acclimation/cultivation under high salinity wastewater.
Mechanism of abnormal bleeding in patients undergoing cardiopulmonary bypass: acquired transient platelet dysfunction associated with selective alpha-granule release. (1980)

The hemostatic alterations underlying the occasional bleeding diathesis associated with cardiopulmonary bypass surgery have been defined in 31 selected patients by simultaneously measuring the serial changes in concentration, function and kinetics of platelets, coagulation factors, and fibrinolytic components. The effects of uncomplicated bypass surgery were evaluated in 21 elective patients. Immediately upon bypass, the circulating levels of platelets, coagulation factors, and plasminogen regularly fell about 50% due to dilution with nonblood prime in the oxygenator apparatus. However, none of these components was reduced below established hemostatic levels at any time during or following the procedure. Furthermore, the functional transformation of fibrinogen to fibrin was not measurably impaired. Heparin effectively blocked both fibrinolysis and fibrinogen consumption during bypass and was consistently neutralized with protamine without rebound at the end of bypass. Circulating platelets were uniformly activated in elective patients during bypass through a process that involved release and partial depletion of α-granules, but not release of dense granule constituents. Platelet activation was associated with transient marked impairment of function as evidenced by striking prolongation of the bleeding time and defective aggregation in vitro. In uncomplicated patients, platelet function largely normalized within 1 hr after bypass. Controlled studies in baboons demonstrated that platelet dysfunction was produced by either cardiopulmonary bypass under normothermic conditions or by hypothermia alone without bypass. In the baboon model, defective platelet function was also transient and characterized by selective depletion of platelet a-granule contents without release of dense granule contents. By contrast, in all of 10 patients in whom bypass surgery was complicated by substantial abnormal bleeding, there was persistent bleeding time prolongation to greater than 25 min that persisted for hours after bypass despite platelet counts above 100,000/µl. With platelet transfusions, the bleeding time shortened rapidly, followed by cessation of bleeding. From these studies we conclude that cardiopulmonary bypass patients demonstrate abnormal clinical bleeding when there is a persistence of platelet dysfunction manifested as a bleeding time of greater than 20 min after protamine administration. Such bleeding patients with a prolonged bleeding time should receive platelet transfusions even when the platelet count is greater than 100,000/µl.
Flt-3L Expansion of Recipient CD8α+ Dendritic Cells Deletes Alloreactive Donor T Cells and Represents an Alternative to Posttransplant Cyclophosphamide for the Prevention of GVHD (2018)

<b>Purpose:</b> Allogeneic bone marrow transplantation (BMT) provides curative therapy for leukemia via immunologic graft-versus-leukemia (GVL) effects. In practice, this must be balanced against life threatening pathology induced by graft-versus-host disease (GVHD). Recipient dendritic cells (DC) are thought to be important in the induction of GVL and GVHD.<b>Experimental Design:</b> We have utilized preclinical models of allogeneic BMT to dissect the role and modulation of recipient DCs in controlling donor T-cell-mediated GVHD and GVL.<b>Results:</b> We demonstrate that recipient CD8α<sup>+</sup> DCs promote activation-induced clonal deletion of allospecific donor T cells after BMT. We compared pretransplant fms-like tyrosine kinase-3 ligand (Flt-3L) treatment to the current clinical strategy of posttransplant cyclophosphamide (PT-Cy) therapy. Our results demonstrate superior protection from GVHD with the immunomodulatory Flt-3L approach, and similar attenuation of GVL responses with both strategies. Strikingly, Flt-3L treatment permitted maintenance of the donor polyclonal T-cell pool, where PT-Cy did not.<b>Conclusions:</b> These data highlight pre-transplant Flt-3L therapy as a potent new therapeutic strategy to delete alloreactive T cells and prevent GVHD, which appears particularly well suited to haploidentical BMT where the control of infection and the prevention of GVHD are paramount. <i>Clin Cancer Res; 24(7); 1604-16. ©2018 AACR</i>.
Detection and differentiation of cellulase components using low molecular mass fluorogenic substrates (1985)

The 4‐methylumbelliferyl β‐D‐glycosides of glucose, cellobiose, cellotriose and lactose are used to differentiate several exo‐cellobiohydrolase, endocellulase and β‐glucosidase activities in crude cellulase from Trichoderma reesei . Spectrophotometric or fluorimetric assays allow simple detection and quantitative measurements of eluate activities from ion‐exchange chromatography and after analytical gel electrofocusing. Using the fluorophoric glucoside several β‐glucosidases can be visualised after isoelectric focusing on polyacrylamide gels. The use of the lactoside and of the same substrate supplemented with cellobiose as inhibitor allows a clearcut distinction to be made between endocellulase II and exo‐cellobiohydrolase I. Both enzymes are present as ‘iso‐enzyme’ mixtures. With the cellotrioside only one fraction is detectable (endocellulase III). The same methods could be used in culture growth experiments.