gebhart/patrepeval huggingface dataset:
Inactivated whole-virus vaccine derived from a proviral DNA clone of simian immunodeficiency virus induces high levels of neutralizing antibodies and confers protection against heterologous challenge. (1992)

We tested the ability of macaques vaccinated with inactivated whole simian immunodeficiency virus (SIV) to resist challenge with either homologous or heterologous cell-free uncloned SIV administered by the intravenous route. The vaccine virus was derived from a proviral DNA clone and thus was considered genetically homogeneous. Sixteen macaques received either hepatitis B surface antigen (n = 6) or the inactivated whole-SIV vaccine (n = 10) at weeks 0, 4, and 49 of the study. All SIV vaccine recipients developed high levels of homologous and heterologous neutralizing antibodies in response to vaccination. At the time of challenge (week 53), vaccinees were further stratified to receive either homologous (n = 10) or heterologous (n = 6) uncloned live SIV. The envelope glycoproteins of the homologous and heterologous challenge viruses were 94% and 81% identical to the vaccine virus, respectively. Regardless of challenge inoculum, all vaccinees in the control group (hepatitis B surface antigen) became infected, whereas all SIV vaccinees were protected against detectable infection. These data support the concept that an efficacious vaccine for HIV might be possible, and suggest that genetic variation of HIV might not be an insurmountable obstacle for vaccine development.
Ripening of the human cervix and induction of labor with intracervical purified porcine relaxin. (1986)

In a randomized double-blind placebo-controlled trial involving 71 patients, a viscous gel containing distilled water or 1 or 2 mg pure porcine relaxin was instilled in the cervical canal on the evening before the surgical induction of labor. Eleven of 48 patients receiving relaxin labored overnight, whereas only one of 23 patients went into labor. Only the 2-mg dose significantly improved the mean cervical score compared with the placebo treatment; the effect was greatest in primigravid patients with unripe cervixes. Intracervical application appeared to confer no benefit over vaginal application in effecting cervical ripening or inducing labor. Systemic absorption of the porcine relaxin after its intracervical application was confirmed by the measurement of immunoreactive relaxin in a homologous porcine relaxin radioimmunoassay. Thus, the cervical ripening effect of exogenous relaxin may be mediated either systemically or by direct action at the site of local application. This trial confirms the responsiveness of the human term cervix to exogenous relaxin and supports the suggestion that endogenous relaxin may play a similar role at term in facilitating cervical ripening and parturition.
Quantum flux parametron: a single quantum flux device for Josephson supercomputer (1991)

A quantum flux parametron (QFP), a single quantum flux superconductive device that has a potential of up to 100-GHz switching with nW-order power dissipation, is considered. The potential of the QFP and key technologies when QFPs are applied to a Josephson supercomputer are described. Switching speed, stability, and power dissipation of a QFP are discussed. QFP gates, circuits, and systems are next described. Then, ultra-fast clock distribution using a standing wave is explained. High-speed operation at more than 10 GHz and 10/sup 14/ error-free operations per QFP have been demonstrated. Finally described is a high-density packaging scheme by three-dimensional integration, which is very important for ultra-high speed circuits because the propagation delay becomes dominant in such circuits.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Potential Usefulness of Basic Fibroblast Growth Factor as a Treatment for Stroke (1999)

Within the past few years, a growing body of evidence has accumulated indicating that exogenously administered neurotrophic growth factors may limit the extent of acute ischemic neural injury and enhance functional neurorecovery following stroke. One of the most widely studied growth factor in this regard is basic fibroblast growth factor (bFGF). In preclinical studies, bFGF administered intravenously within hours after the onset of ischemia reduces infarct size, presumably due to direct protection of cells at the borders (penumbra) of cerebral infarction. On the other hand, if bFGF is administered intracisternally starting at one day after ischemia, infarct size is not reduced, but recovery of sensorimotor function of the impaired limbs is increased, presumably due to enhancement of new neuronal sprouting and synapse formation in the intact uninjured brain. Clinical trials of the intravenous administration of bFGF as a cytoprotective agent in acute stroke are in progress. Trials of the delayed administration of bFGF as a recovery-promoting agent in subacute stroke are anticipated.
Disulfide Cross-Linked Hyaluronan Hydrogels (2002)

A new disulfide cross-linking strategy was developed to prepare hyaluronic acid (HA) hydrogel from thiol-modified HA. First, dithiobis(propanoic dihydrazide) (DTP) and dithiobis(butyric dihydrazide) (DTB) were synthesized and then coupled to HA with carbodiimide chemistry. Next, disulfide bonds of the initially formed gel were reduced using dithiothreitol (DTT) to give, after exhaustive dialysis, the corresponding thiol-modified macromolecular derivatives HA-DTPH and HA-DTBH. The degree of substitution of HA-DTPH and HA-DTBH could be controlled from 20% to 70% of available glucuronate carboxylic acid groups. The pK(a) values of the HA-thiol derivatives were determined spectrophotometrically to be pK(a) = 8.87 (HA-DTPH) and pK(a) = 9.01 (HA-DTBH). The thiol groups could be oxidized in air to reform disulfide linkages, which resulted in HA-DTPH and HA-DTBH hydrogel films. Further oxidation of these hydrogels with dilute H(2)O(2) created additional cross-links and afforded poorly swellable films. The disulfide cross-linking was reversible, and films could be again reduced to sols with DTT. Release of blue dextran from cross-linked films was used as a model for drug release. The rapid gelation of the HA-DTPH solution under physiological conditions was also achieved, which demonstrated the capacity for in situ cell encapsulation. Thus, L-929 murine fibroblasts were encapsulated in HA-DTPH hydrogel; these cells remained viable and proliferated during 3 days of culture in vitro.
Akt Phosphorylates Tal1 Oncoprotein and Inhibits Its Repressor Activity (2005)

The helix-loop-helix transcription factor Tal1 is required for blood cell development and its activation is a frequent event in T-cell acute lymphoblastic leukemia. The Akt (protein kinase B) kinase is a key player in transduction of antiapoptotic and proliferative signals in T cells. Because Tal1 has a putative Akt phosphorylation site at Thr90, we investigated whether Akt regulates Tal1. Our results show that Akt specifically phosphorylates Thr90 of the Tal1 protein within its transactivation domain in vitro and in vivo. Coimmunoprecipitation experiments showed the presence of Tal1 in Akt immune complexes, suggesting that Tal1 and Akt physically interact. We further showed that phosphorylation of Tal1 by Akt causes redistribution of Tal1 within the nucleus. Using luciferase assay, we showed that phosphorylation of Tal1 by Akt decreased repressor activity of Tal1 on EpB42 (P4.2) promoter. Thus, these data indicate that Akt interacts with Tal1 and regulates Tal1 by phosphorylation at Thr90 in a phosphatidylinositol 3-kinase-dependent manner.
KLOTSKI: Reprioritizing Web Content to Improve User Experience on Mobile Devices (2018)

Despite web access on mobile devices becoming commonplace, users continue to experience poor web performance on these devices. Traditional approaches for improving web performance (e.g., compression, SPDY, faster browsers) face an uphill battle due to the fundamentally conflicting trends in user expectations of lower load times and richer web content. Embracing the reality that page load times will continue to be higher than user tolerance limits for the foreseeable future, we ask: How can we deliver the best possible user experience? To this end, we present KLOTSKI, a system that <em>prioritizes</em> the content most relevant to a user’s preferences. In designing KLOTSKI, we address several challenges in: (1) accounting for inter-resource dependencies on a page; (2) enabling fast selection and load time estimation for the subset of resources to be prioritized; and (3) developing a practical implementation that requires no changes to websites. Across a range of user preference criteria, KLOTSKI can significantly improve the user experience relative to native websites.
A saturable reactor‐assisted soft switching PWM DC‐DC converter (1993)

Abstract Owing to the demand to increase the power density of switched‐mode power converters, resonant topologies have attracted much attention because of their low switching losses and low EMI. However, they require relatively large resonant components and necessitate high current or voltage ratings at semiconductor devices. This paper describes a new soft‐switching PWM full‐bridge DC‐DC converter which can overcome these drawbacks by utilizing a small saturable reactor. The principles of operation and the steady‐state characteristics are illustrated and the role of the saturable reactor is discussed. Moreover, the voltage and current stresses for active and passive components are also presented. To verify the results, experiments were performed with a 350 W, 500 kHz prototype converter. They demonstrated that the converter achieves soft switching in a wide load range with no substantial increase in voltage and current stresses on active and passive components.
Regeneration of Amputated Avian Bone by a Coral Skeletal Implant (1999)

Bone fractures are common in both wild and captive birds (1, 2). Avian bones are thin and brittle and tend to break into fragments or shatter upon a variety of natural events (midair collisions, fights with other animals; ref. 2) or anthropogenic experiences (wounding by gunfire, collisions with cars or fences, encounters with traps, attacks by dogs or cats, etc.; ref. 1). The prospect of full recovery following repair of avian bone fracture is often poor, and the complication rate is high (3). For wild birds, anything less than complete normal function cannot be regarded as successful, and slight malunion or a change in a few degrees of rotation can produce a severe loss of flight function (4). Furthermore, in nomadic species, time is critical because long periods of rehabilitation may prevent the birds from reuniting with their flocks. In experiments with implantation of fragments of skeleton from the coral Stylophora pistillata, we found the implants to be avian osteo-conductive biomaterial, acting as a scaffold for a direct osteoblastic deposition. In the case study presented here, the bird regained complete flight activity within 2 weeks after surgery, with full regeneration of the amputated ulna.
Overexpression of toll‐like receptors 3 and 4 in synovial tissue from patients with early rheumatoid arthritis: Toll‐like receptor expression in early and longstanding arthritis (2008)

Our findings of high expression of TLRs, particularly TLRs 3 and 4, at an early stage of RA and the reactivity of synovial fibroblasts in vitro to TLR ligands suggest that TLR signaling pathways resulting in persistent inflammation and joint destruction are activated early in the disease process.
Requirement for Phosphatidylinositol-3 Kinase in the Prevention of Apoptosis by Nerve Growth Factor (1995)

Nerve growth factor (NGF) induces both differentiation and survival of neurons by binding to the Trk receptor protein tyrosine kinase. Although Ras is required for differentiation, it was not required for NGF-mediated survival of rat pheochromocytoma PC-12 cells in serum-free medium. However, the ability of NGF to prevent apoptosis (programmed cell death) was inhibited by wortmannin or LY294002, two specific inhibitors of phosphatidylinositol (Pl)-3 kinase. Moreover, platelet-derived growth factor (PDGF) prevented apoptosis of PC-12 cells expressing the wild-type PDGF receptor, but not of cells expressing a mutant receptor that failed to activate Pl-3 kinase. Cell survival thus appears to be mediated by a Pl-3 kinase signaling pathway distinct from the pathway that mediates differentiation.
Substrate Binding and Turnover by the Highly Specific I-PpoI Endonuclease (1996)

Intron-encoded endonucleases are distinguished by their ability to catalyze the cleavage of double-stranded DNA with high specificity. I-PpoI endonuclease, an intron-encoded endonuclease from the slime mold Physarum polycephalum, is a small enzyme (2 x 20 kDa) that catalyzes the cleavage of a large asymmetric DNA sequence (15 base pairs). Here, the interactions of I-PpoI with its substrate were examined during both binding (in the absence of Mg2+) and catalysis (in the presence of Mg2+). Using circular permutation assays, I-PpoI was shown to bend its substrate by 38 +/- 4 degrees upon binding. Two independent methods, gel mobility shift assays and fluorescence polarization assays, revealed that I-PpoI binds tightly to its substrate. Values of Kd range from 3.3 to 112 nM, increasing with increasing NaCl concentration. Similar salt effects on the values of Km were observed during steady-state catalysis. At low salt concentrations, the value of kcat/Km for the cleavage of an oligonucleotide duplex approaches 10(8) M-1 s-1. Although other divalent cations can replace Mg2+, catalysis by I-PpoI is most efficient in the presence of an oxophilic metal ion that prefers an octahedral geometry: Mg2+ > Mn2+ > Ca2+ = Co2+ > Ni2+ > Zn2+. Together, these results provide the first chemical insight into substrate binding and turnover by an intron-encoded endonuclease.
The Art of Computer Programming, Volumes 1-3 Boxed Set (1998)

PROSPERO CRD42020141212; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=141212.
P2Y receptors in dendritic cells: from inflammation to tolerance (2012)

Abstract Extracellular nucleotides released in the context of immune and inflammatory responses regulate all components of dendritic cell (DC) function: chemotaxis, antigen uptake, expression of costimulatory molecules, and cytokine secretion. Furthermore, mainly using gene expression profiling, we identified a large number of ATP target genes in human DCs that could play a role in tolerance and tumor development. We have now integrated these findings and related publications in a nonexhaustive review of the wide action of ATP on DCs. ATP, which was previously considered as a danger signal, is also a potent regulator of immunosuppressive and tolerogenic proteins such as thrombospondin‐1 and indoleamine 2′,3′‐dioxygenase. ATP induces a semimaturation state of DCs that can be associated with immune tolerance by regulating costimulatory molecules and cytokine/chemokine expression profiles. Immune tolerance could thus be initiated at the level of DCs. These actions are mediated by the P2Y11 receptor and P2Y11 agonists could thus be used to generate tolerogenic DCs and as useful tools for DC‐based immunotherapies. ATP released from tumor cells can have a tumorigenic action through the generation of semimature tolerogenic DCs and the secretion of angiogenic factors such as vascular endothelial growth factor (VEGF) and amphiregulin from DCs. Antagonists of ATP receptors expressed on DCs and antibodies blocking ATP target genes could have a therapeutic potential by acting as antitumor agents. WIREs Membr Transp Signal 2013, 2:37–42. doi: 10.1002/wmts.75 For further resources related to this article, please visit the WIREs website .
Coregistration of diffuse optical spectroscopy and magnetic resonance imaging in a rat tumor model (2003)

We report coregistration of near-infrared diffuse optical spectroscopy (DOS) and magnetic resonance imaging (MRI) for the study of animal model tumors. A combined broadband steady-state and frequency-domain apparatus was used to determine tissue oxyhemoglobin, deoxyhemoglobin, and water concentration locally in tumors. Simultaneous MRI coregistration provided structural (T2-weighted) and contrast-enhanced images of the tumor that were correlated with the optical measurements. By use of Monte Carlo simulations, the optically sampled volume was superimposed on the MR images, showing precisely which tissue structure was probed optically. DOS and MRI coregistration measurements were performed on seven rats over 20 days and were separated into three tumor tissue classifications: viable, edematous, and necrotic. A ratio of water concentration to total hemoglobin concentration, as measured optically, was performed for each tissue type and showed values for edematous tissue to be greater than viable tissue (1.2 +/- 0.49 M/microM versus 0.48 +/- 0.15 M/microM). Tissue hemoglobin oxygen saturation (StO2) also showed a large variation between tissue types: viable tissue had an optically measured StO2 value of 61 +/- 5%, whereas StO2 determined for necrotic tissue was 43 +/- 6%.
Recombinant Chimeric Borrelia Proteins for Diagnosis of Lyme Disease (2000)

Current serologic Lyme disease tests use whole borrelia cells as the source of antigen. These assays are difficult to standardize and to optimize for sensitivity and specificity. To help solve these problems, we constructed a library of recombinant chimeric proteins composed of portions of key antigens of Borrelia burgdorferi. These proteins were then used to develop an enzyme-linked immunosorbent assay. We compared our assay with the most sensitive of three whole-cell borrelia assays. We found that the recombinant assay could detect antibodies significantly better from early Lyme disease sera (P<0.05), and had the same sensitivity for late Lyme disease sera, as the most sensitive whole-cell borrelia assay. On potentially cross-reactive sera, the recombinant assay was more specific, but not significantly so, than the best whole-cell borrelia assay. Optimization of the recombinant assay offers the potential for a significant improvement in both sensitivity and specificity.
Analysis of Expressed Sequence Tags of Porphyra yezoensis (2000)

Single direct partial sequencing of anonymous cDNA clones was performed to obtain genetic information on red algae Porphyra yezoensis of which genetic information is not available. This expressed sequence tags (EST) analysis revealed 81 clones (42%) had significant homologies to known genes in GenBank. Of these clones, eight are related to known algal genes, whereas above 90% of the EST clones were newly identified in algae. Putative functional categories of these clones showed that the most abundant genes were involved in stress and defense mechanisms and that the next abundant genes were associated with protein synthetic pathways.
A meta-analysis on verbal working memory in children and adolescents with ADHD (2019)

<b>Objective:</b> Previous meta-analyses have demonstrated verbal working memory (WM) dysfunction in children and adolescents with attention deficit/hyperactivity disorder (ADHD); however, the findings are inconsistent. The main objective of this meta-analysis was to investigate the performance of children and adolescents with ADHD in the Digit Span Backwards (DSB) subtest from the Wechsler Intelligence Scale for Children or Wechsler Adult Intelligence Scale. We also sought to provide an updated meta-analysis on WM in children and adolescents with ADHD.<b>Method:</b> PubMed, PsyINFO, Scopus, and Web of Science were searched to locate studies published between 1990 and 2016 that report DSB scores both of children and adolescents with ADHD and matched controls. Potential moderator variables were also analyzed.<b>Results:</b> Forty-nine studies comparing children and adolescents with ADHD (<i>n</i> = 4956) against healthy controls (<i>n</i> = 3249) generated a medium-sized effect (Hedges' <i>g</i>) of 0.56 (95% CI [0.49, 0.64]), indicating poorer verbal WM performance in those with ADHD. A subgroup meta-analysis of studies with participants aged 8-16 years only demonstrated low heterogeneity (<i>I</i><sup>2</sup> = 17.06, cf. 55.50 for the main analysis). Moreover, the meta-regression showed a negative association (<i>β</i> = -.05, <i>p</i> = .02) between DSB performance differences and increasing age, indicating that for every one year increase in age the effect size decreased by .05.<b>Conclusion:</b> These results, which emanated from the largest meta-analysis concerning verbal WM in ADHD reported to date, reinforce WM as a key domain of cognitive dysfunction in ADHD, and point to age as the main variable influencing DSB performance difficulties.
Halcón, Fátima; Herrera, Francisco y Recio, Álvaro; prólogo, Pleguezuelo Alfonso. El retablo sevillano. Desde sus orígenes a la actualidad. Sevilla: Fundación Real Maestranza de Caballería de Sevilla, Obra Social de Cajasol y Diputación de Sevilla, 2009 (2011)

Es resena de: El retablo sevillano: desde sus origenes a la actualidad. Francisco Herrera; Alvaro Recio, Fatima Halcon; Alfonso Pleguezuelo Hernandez Sevilla: Fundacion Real Maestranza de Caballeria de Sevilla, Obra Social de Cajasol y Diputacion de Sevilla, 2009. ISBN 978-84-7798-280-7
The GPU enters computing's mainstream (2003)

The Siggraph/Eurographics Graphics Hardware 2003 workshop, held in San Diego, will likely be remembered as a turning point in modern computing. In one of those rare moments when a new paradigm visibly begins changing general-purpose computing's course, what has traditionally been a graphics-centric workshop shifted its attention to the nongraphics applications of the graphics processing unit. GPUs, made by Nvidia (www.nvidia.com) and ATI (www.ati.com), function as components in graphics subsystems that power everything from Microsoft's Xbox to high-end visualization systems from Hewlett-Packard and SGI. The GPUs act as coprocessors to CPUs such as Intel's Pentium, using a fast bus such as Intel's Advanced Graphics Port. AGP8x has a peak bandwidth of 2.1 gigabytes per second - speed it needs to avoid inflicting bus starvation on data-hungry GPU coprocessors.
Cochlear Gene Therapy for Sensorineural Hearing Loss: Current Status and Major Remaining Hurdles for Translational Success (2018)

Sensorineural hearing loss (SNHL) affects millions of people. Genetic mutations play a large and direct role in both congenital and late-onset cases of SNHL (e.g., age-dependent hearing loss, ADHL). Although hearing aids can help moderate to severe hearing loss the only effective treatment for deaf patients is the cochlear implant (CI). Gene- and cell-based therapies potentially may preserve or restore hearing with more natural sound perception, since their theoretical frequency resolution power is much higher than that of cochlear implants. These biologically-based interventions also carry the potential to re-establish hearing without the need for implanting any prosthetic device; the convenience and lower financial burden afforded by such biologically-based interventions could potentially benefit far more SNHL patients. Recently major progress has been achieved in preclinical studies of cochlear gene therapy. This review critically evaluates recent advances in the preclinical trials of gene therapies for SNHL and the major remaining challenges for the development and eventual clinical translation of this novel therapy. The cochlea bears many similarities to the eye for translational studies of gene therapies. Experience gained in ocular gene therapy trials, many of which have advanced to clinical phase III, may provide valuable guidance in improving the chance of success for cochlear gene therapy in human trials. A discussion on potential implications of translational knowledge gleaned from large numbers of advanced clinical trials of ocular gene therapy is therefore included.