gebhart/patrepeval huggingface dataset:
A natural variant of the cysteine protease virulence factor of group A Streptococcus with an arginine-glycine-aspartic acid (RGD) motif preferentially binds human integrins α v β 3 and α IIb β 3 (1999)

The human pathogenic bacterium group A Streptococcus produces an extracellular cysteine protease [streptococcal pyrogenic exotoxin B (SpeB)] that is a critical virulence factor for invasive disease episodes. Sequence analysis of the speB gene from 200 group A Streptococcus isolates collected worldwide identified three main mature SpeB (mSpeB) variants. One of these variants (mSpeB2) contains an Arg-Gly-Asp (RGD) sequence, a tripeptide motif that is commonly recognized by integrin receptors. mSpeB2 is made by all isolates of the unusually virulent serotype M1 and several other geographically widespread clones that frequently cause invasive infections. Only the mSpeB2 variant bound to transfected cells expressing integrin alphavbeta3 (also known as the vitronectin receptor) or alphaIIbbeta3 (platelet glycoprotein IIb-IIIa), and binding was blocked by a mAb that recognizes the streptococcal protease RGD motif region. In addition, mSpeB2 bound purified platelet integrin alphaIIbbeta3. Defined beta3 mutants that are altered for fibrinogen binding were defective for SpeB binding. Synthetic peptides with the mSpeB2 RGD motif, but not the RSD sequence present in other mSpeB variants, blocked binding of mSpeB2 to transfected cells expressing alphavbeta3 and caused detachment of cultured human umbilical vein endothelial cells. The results (i) identify a Gram-positive virulence factor that directly binds integrins, (ii) identify naturally occurring variants of a documented Gram-positive virulence factor with biomedically relevant differences in their interactions with host cells, and (iii) add to the theme that subtle natural variation in microbial virulence factor structure alters the character of host-pathogen interactions.
Second scatter contribution to dose in a cobalt‐60 beam (1981)

Semi-analytic and direct numerical integration approaches have been used to study the contribution of doubly scattered photons to dose at a point P in a homogeneous water medium irradiated by a cobalt-60 point source. The semi-analytic analysis was used for an infinite field radius to calculate the variation of second scatter dose with depth, the angular dependence of the second scatter dose, and the spectra. Direct numerical integration was used to calculate the second scatter dose at a depth of 10 cm for various finite field radii ranging from 0 to 25 cm. Maps were made of the locations of scattering sites that were important to the second scatter dose. These calculations show that the second scatter contribution is generally less than the first scatter dose with the exception of a few sites remote from the point of interest. In many ways, the pattern of dose deposition by second scatter is similar to first scatter with less pronounced features. In other respects, the second scatter appears more isotropic. The implications of these calculations for approximate radiotherapy dose calculations are discussed.
Differential effects of spinal (R)-ketoprofen and (S)-ketoprofen against signs of neuropathic pain and tonic nociception: evidence for a novel mechanism of action of (R)-ketoprofen against tactile allodynia (2000)

The spinal activity of racemic ketoprofen and its enantiomers in models of neuropathic and tonic pain was explored in rats. Tactile allodynia and thermal hyperalgesia were induced by tight ligation of the L(5)/L(6) spinal nerves. Tonic pain was modeled by the formalin-induced flinch response. The spinal injection of (S)-ketoprofen alone or of morphine alone did not produce antiallodynic activity. A 1:1 combination of these drugs produced a robust dose-dependent antiallodynic action, consistent with previous observations where (S)-ketorolac combined with morphine also produced antiallodynia. (R)-ketoprofen given alone spinally produced a dose-dependent antiallodynia, but its activity was not augmented by spinal morphine. Conversely, (S)-ketoprofen, but not (R)-ketoprofen, blocked the second phase of the formalin-induced flinch response; neither enantiomer significantly blocked phase one of the formalin response. Again, (S)-, but not (R)-ketoprofen, interacted synergistically with spinal morphine in suppressing the phase II formalin response. These results are consistent with a spinal COX inhibitory action of (S)-ketoprofen. These results also point to a novel, as yet undefined, mechanism of action of (R)-ketoprofen against signs of neuropathic pain that does not appear to involve COX inhibition. The ability to modulate tactile allodynia is of special interest as this represents an aspect of clinical neuropathic pain that is very difficult to treat adequately.
The clinical use of bone stimulators. (2003)

Delay or failure of healing in long bone fracture is a common clinical problem confronting the orthopaedic surgeon, and can have significant impact on the quality of life for patients who have it. One treatment option for this problem is the use of electrical or ultrasonic bone stimulation. Electrical signals can be delivered with an implantable direct current stimulator, or noninvasively using inductive or capacitive coupling to induce currents in the tissues. Low-intensity ultrasound can speed the healing of fresh fractures. Although regarded with skepticism by many physicians, there is abundant evidence from clinical studies of the effectiveness of these treatments. In addition to dozens of retrospective reports, randomized, prospective, double-blind controlled trials have shown the efficacy of electrical stimulation for nonunion and ultrasound for speeding healing. Patients with unacceptable deformity, synovial pseudarthrosis, or large gaps are generally not good candidates for this treatment modality. This article is a review of the clinical literature regarding treatment of long bone nonunion with bone stimulators.
Gene transfer into normal human hematopoietic cells using in vitro and in vivo assays (1991)

The ability to transfer new genetic material into human hematopoietic cells provides the foundation for characterizing the organization and developmental program of human hematopoietic stem cells. It also provides a valuable model in which to test gene transfer and long-term expression in human hematopoietic cells as a prelude to human gene therapy. At the present time such studies are limited by the absence of in vivo assays for human stem cells, although recent descriptions of the engraftment of human hematopoietic cells in immune-deficient mice may provide the basis for such an assay. This study focuses on the establishment of conditions required for high efficiency retrovirus-mediated gene transfer into human hematopoietic progenitors that can be assayed in vitro in short-term colony assays and in vivo in immune-deficient mice. Here we report that a 24-hour preincubation of human bone marrow in 5637-conditioned medium, before infection, increases gene transfer efficiency into in vitro colony-forming cells by sixfold; interleukin-6 (IL-6) and leukemia inhibitory factor (LIF) provide the same magnitude increase as 5637-conditioned medium. In contrast, incubation in recombinant growth factors IL-1, IL-3, and granulocyte-macrophage colony-stimulating factor increases gene transfer efficiency by 1.5- to 3-fold. Furthermore, preselection in high concentrations of G418 results in a population of cells significantly enriched for G418-resistant progenitors (up to 100%). These results, obtained using detailed survival curves based on colony formation in G418, have been substantiated by directly detecting the neo gene in individual colonies using the polymerase chain reaction. Using these optimized protocols, human bone marrow cells were genetically manipulated with a neo retrovirus vector and transplanted into immune-deficient bg/nu/xid mice. At 1 month and 4 months after the transplant, the hematopoietic tissues of these animals remained engrafted with genetically manipulated human cells. More importantly, G418-resistant progenitors that contained the neo gene were recovered from the bone marrow and spleen of engrafted animals after 4 months. These experiments establish the feasibility of characterizing human stem cells using the unique retrovirus integration site as a clonal marker, similar to techniques developed to elucidate the murine stem cell hierarchy.
T Lymphocytes Are Required for Protection of the Vaginal Mucosae and Sensory Ganglia of Immune Mice Against Reinfection with Herpes Simplex Virus Type 2 (1998)

Intravaginal inoculation of mice with an attenuated strain of herpes simplex virus type 2 (HSV-2) resulted in vigorous HSV-specific immune responses that protected against subsequent challenge with fully virulent HSV-2 strains. Even in the presence of high titers of HSV-specific Ab, T cell-dependent mechanisms were required for protection of the vaginal mucosae of HSV-immune mice and could be detected by 24 h after intravaginal reinoculation. Depletion of specific T cell subsets from HSV-immune mice before HSV-2 reinoculation demonstrated that CD4+ T cells were primarily responsible for this protection. Similarly, optimal protection of the sensory ganglia against reinfection with HSV-2 was dependent on the presence of T cells. Infectious HSV-2 was not detected in the sensory ganglia or spinal cord of HSV-immune mice depleted of only CD4+ or CD8+ T cells, suggesting that the T cell-mediated protection could be provided by either subset. Similarly, neutralization of IFN-gamma during challenge of HSV-immune mice resulted in diminished protection of the vaginal mucosa, but not of the sensory ganglia. These results suggest that the ability to induce vigorous HSV-specific T cell responses is an important consideration in the design of vaccines to protect both the vaginal mucosa and sensory ganglia against HSV-2.
Dioxychlorane (1981)

Dioxychlorane is a five-membered cyclic halogenated diether which has been reported to be anesthetic at an inspired concentration of 0.3% atm and to have an oil/gas partition coefficient of 260 to 275. These values suggested that dioxychlorane might represent a significant deviation from the correlation of anesthetic potency with lipid solubility. However, the results of this study did not confirm the above data: MAC in four dogs was 0.11 ± 0.02 (SE) % atm, and the oil/gas partition coefficient was 1,286 ± 44. Dioxychlorane appears not to be an exception to the correlation of anesthetic potency with lipid solubility.
Microbubble-Size Dependence of Focused Ultrasound-Induced Blood–Brain Barrier Opening in MiceIn Vivo (2009)

The therapeutic efficacy of neurological agents is severely limited, because large compounds do not cross the blood-brain barrier (BBB). Focused ultrasound (FUS) sonication in the presence of microbubbles has been shown to temporarily open the BBB, allowing systemically administered agents into the brain. Until now, polydispersed microbubbles (1-10 microm in diameter) were used, and, therefore, the bubble sizes better suited for inducing the opening remain unknown. Here, the FUS-induced BBB opening dependence on microbubble size is investigated. Bubbles at 1-2 and 4-5 microm in diameter were separately size-isolated using differential centrifugation before being systemically administered in mice (n = 28). The BBB opening pressure threshold was identified by varying the peak-rarefactional pressure amplitude. BBB opening was determined by fluorescence enhancement due to systemically administered, fluorescent-tagged, 3-kDa dextran. The identified threshold fell between 0.30 and 0.46 MPa in the case of 1-2 microm bubbles and between 0.15 and 0.30 MPa in the 4-5 microm case. At every pressure studied, the fluorescence was greater with the 4-5 mum than with the 1-2 microm bubbles. At 0.61 MPa, in the 1-2 microm bubble case, the fluorescence amount and area were greater in the thalamus than in the hippocampus. In conclusion, it was determined that the FUS-induced BBB opening was dependent on both the size distribution in the injected microbubble volume and the brain region targeted.
Preparation of New Electron-Accepting π-Conjugated Polyquinoxalines. Chemical and Electrochemical Reduction, Electrically Conducting Properties, and Use in Light-Emitting Diodes (1996)

Dehalogenation polycondensation of 5,8-dibromoquinoxaline derivatives and 2,6-dibromoquinoxaline with zerovalent nickel complex affords a series of π-conjugated polyquinoxalines with a molecular weight of 6 × 103 to 260 × 103. The polymers are electrochemically reduced (or n-doped) with an E° value of −1.75 to −2.35 V vs Ag/Ag+ and converted into electrically conducting materials with a conductivity of 1 × 10-4 to 7 × 10-3 S cm-1 by chemical reduction. Poly(quinoxaline-5,8-diyl)s with aromatic substituents give strong fluorescence with emission peaks at 450−520 nm in solutions as well as in cast films. A light-emitting diode (LED), ITO/polymer/Mg(Ag) (polymer = poly(2,3-diphenylquinoxaline-5,8-diyl)), emits blue-green light (λmax at about 500 nm). Introduction of hole-transporting layers such as vacuum-deposited or spin-coated thin layers of poly(thiophene-2,5-diyl), poly(p-phenylene), and poly(N-vinylcarbazole) between ITO and the light-emitting layer enhances electroluminescence efficiency by about 2 orders of magnitude. Polyquinoxalines have an ionization potential of 5.83 ± 0.11 eV and a band gap of 2.56 ± 0.26 eV.
Liver Cancer Stem Cells (2008)

In an effort to review the evidence that liver cancer stem cells exist, two fundamental questions must be addressed. First, do hepatocellular carcinomas (HCC) arise from liver stem cells? Second, do HCCs contain cells that possess properties of cancer stem cells? For many years the finding of preneoplastic nodules in the liver during experimental induction of HCCs by chemicals was interpreted to support the hypothesis that HCC arose by dedifferentiation of mature liver cells. More recently, recognition of the role of small oval cells in the carcinogenic process led to a new hypothesis that HCC arises by maturation arrest of liver stem cells. Analysis of the cells in HCC supports the presence of cells with stem-cell properties (ie, immortality, transplantability, and resistance to therapy). However, definitive markers for these putative cancer stem cells have not yet been found and a liver cancer stem cell has not been isolated.
Mechanism of Charge Recombination in Dye-Sensitized Nanocrystalline Semiconductors:  Random Flight Model (2002)

The trap-filling effect on the kinetics of charge recombination in dye-sensitized TiO2 nanoparticles is discussed on the basis of the random flight model. The model assumes that electrons move between trap sites on the surface of a nanoparticle by diffusion in the conduction band. After an electron is thermally detrapped into the conduction band, it can subsequently be captured by any empty trap or recombine with a cation within the same nanoparticle. This is an alternative to the nearest-neighbor random walk. A reasonable agreement with recent experimental data is observed. It is concluded, in accord with the previous studies, that the reaction is governed by the energy redistribution of trapped electrons rather than by spatial diffusion.
Structural basis for UCN-01 (7-hydroxystaurosporine) specificity and PDK1 (3-phosphoinositide-dependent protein kinase-1) inhibition (2003)

PDK1 (3-phosphoinositide-dependent protein kinase-1) is a member of the AGC (cAMP-dependent, cGMP-dependent, protein kinase C) family of protein kinases, and has a key role in insulin and growth-factor signalling through phosphorylation and subsequent activation of a number of other AGC kinase family members, such as protein kinase B. The staurosporine derivative UCN-01 (7-hydroxystaurosporine) has been reported to be a potent inhibitor for PDK1, and is currently undergoing clinical trials for the treatment of cancer. Here, we report the crystal structures of staurosporine and UCN-01 in complex with the kinase domain of PDK1. We show that, although staurosporine and UCN-01 interact with the PDK1 active site in an overall similar manner, the UCN-01 7-hydroxy group, which is not present in staurosporine, generates direct and water-mediated hydrogen bonds with active-site residues. Inhibition data from UCN-01 tested against a panel of 29 different kinases show a different pattern of inhibition compared with staurosporine. We discuss how these differences in inhibition could be attributed to specific interactions with the additional 7-hydroxy group, as well as the size of the 7-hydroxy-group-binding pocket. This information could lead to opportunities for structure-based optimization of PDK1 inhibitors.
Improved survival at low lung function in cystic fibrosis: cohort study from 1990 to 2007 (2011)

A marked improvement has occurred in the survival of patients with cystic fibrosis with an FEV(1) less than 30% predicted. Secondary analyses suggest that some of this improvement may be due to use of recombinant human DNase.
Resistance to Paclitaxel Is Proportional to Cellular Total Antioxidant Capacity (2005)

Paclitaxel, one of the most commonly prescribed chemotherapeutic agents, is active against a wide spectrum of human cancer. The mechanism of its cytotoxicity, however, remains controversial. Our results indicate that paclitaxel treatment increases levels of superoxide, hydrogen peroxide, nitric oxide (NO), oxidative DNA adducts, G2-M arrest, and cells with fragmented nuclei. Antioxidants pyruvate and selenium, the NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester, and the NO scavenger manganese (III) 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide all decreased paclitaxel-mediated DNA damage and sub-G1 cells. In contrast, the glutamylcysteine synthase inhibitor buthionine sulfoximine (BSO) and the superoxide dismutase (SOD) inhibitor 2-methoxyestradiol (2-ME) increased the sub-G1 fraction in paclitaxel-treated cells. These results suggest that reactive oxygen and nitrogen species are involved in paclitaxel cytotoxicity. This notion is further supported with the observation that concentrations of paclitaxel required to inhibit cell growth by 50% correlate with total antioxidant capacity. Moreover, agents such as arsenic trioxide (As2O3), BSO, 2-ME, PD98059, U0126 [mitogen-activated protein/extracellular signal-regulated kinase inhibitors], and LY294002 (phosphatidylinositol 3-kinase/Akt inhibitor), all of which decrease clonogenic survival, also decrease the total antioxidant capacity of paclitaxel-treated cells, regardless whether they are paclitaxel sensitive or paclitaxel resistant. These results suggest that paclitaxel chemosensitivity may be predicted by taking total antioxidant capacity measurements from clinical tumor samples. This, in turn, may then improve treatment outcomes by selecting out potentially responsive patients.
A Pool of Extramitochondrial Frataxin That Promotes Cell Survival (2006)

Frataxin is a mitochondrial protein involved in iron metabolism. Defective expression of frataxin causes Friedreich ataxia (FA), an inherited degenerative syndrome characterized by ataxia, cardiomyopathy, and high incidence of diabetes. Here we report that frataxin-deficient cells are more prone to undergo stress-induced mitochondrial damage and apoptosis, while the overexpression of frataxin confers protection to a variety of cell types. Moreover, we reveal the existence of an extramitochondrial pool of frataxin, which can efficiently prevent mitochondrial damage and apoptosis in different cellular systems. Remarkably, extramitochondrial frataxin can fully replace mitochondrial frataxin in promoting survival of FA cells.
Coping with Volume and Variety in Temporal Event Sequences: Strategies for Sharpening Analytic Focus (2016)

The growing volume and variety of data presents both opportunities and challenges for visual analytics. Addressing these challenges is needed for big data to provide valuable insights and novel solutions for business, security, social media, and healthcare. In the case of temporal event sequence analytics it is the number of events in the data and variety of temporal sequence patterns that challenges users of visual analytic tools. This paper describes 15 strategies for sharpening analytic focus that analysts can use to reduce the data volume and pattern variety. Four groups of strategies are proposed: (1) extraction strategies, (2) temporal folding, (3) pattern simplification strategies, and (4) iterative strategies. For each strategy, we provide examples of the use and impact of this strategy on volume and/or variety. Examples are selected from 20 case studies gathered from either our own work, the literature, or based on email interviews with individuals who conducted the analyses and developers who observed analysts using the tools. Finally, we discuss how these strategies might be combined and report on the feedback from 10 senior event sequence analysts.
Efficacy of Inhaled Budesonide and Oral Theophylline in Asthmatic Subjects (2001)

The aim of present study was to evaluate clinical, functional, and anti-inflammatory effects of inhaled budesonide and oral theophylline treatments in patients with mild to moderate asthma. The study included 38 patients. After a 10-day run-in period, the patients were randomly assigned into two groups. Group 1 received inhaled budesonide (Pulmicort Turbuhaler) 800 microg/day for 4 weeks. Group 2 received oral theophylline (Talotren tablets, 200 mg twice daily) for 4 weeks. Inhaled budesonide therapy was accompanied by a significant decrease in serum interleukin (IL)-5 levels (p < 0.0005) and blood, sputum, and nasal eosinophil counts (p < 0.005). It produced a significant reduction in daytime (p < 0.01) and nighttime (p < 0.005) symptom scores and an increase in morning (p < 0.005) and evening (p < 0.05) peak expiratory flow (PEF) and forced expiratory volume in I sec (FEV1) values (p < 0.01). Theophylline therapy was associated with a significant decrease in blood (p < 0.02) and nasal (p < 0.01) eosinophil counts and serum IL-5 levels (p < 0.01). It resulted in significant improvements in daytime and nighttime symptom scores (p < 0.05), and morning PEF and FEV1 values (p < 0.05). These changes were more significant in group I than in group 2. There was no statistically significant difference between the two groups with respect to post-treatment values. Our results confirm the role of inhaled corticosteroids in the treatment of asthma and are consistent with the recommendation that theophylline exerts an anti-inflammatory effect. Further studies should be conducted to determine long-term benefits of theophylline.
Redundancy strategies for a high splitting optically amplified passive optical network (2001)

High splitting, optically amplified, passive optical networks (SuperPONs) are investigated in terms of redundancy provision and protection mechanisms. Options for redundancy, including the important special case of dual homing, are detailed, and it is determined as to which of these options (duplication of the feeder and first distribution section, and N+1 protection of the optical amplifiers in the amplified splitter) would be required to be provided to all attached users to facilitate appropriate availability of the basic telephony service. The distributed amplified splitter dual homing solution is found to outperform the single amplified splitter solution in terms of its survivability. The protection mechanisms necessary to automatically switch to the redundant provision are discussed and it is seen that with the aid of suitable regular precautionary procedures protection switching can generally be provided rapidly (<50 ms). Finally, an availability, and cost versus availability, study confirms the aforementioned redundancy assessment for fiber-to-the-home (FTTH) implementations, but shows fiber-to-the-curb (FTTC) as needing additional redundancy.
2000年:新闻与大众传播教育的使命与目标———一份来自美国新闻教育机构的报告 (1998)

２０００年：新闻与大众传播教育的使命与目标———一份来自美国新闻教育机构的报告［美］威廉·Ｇ·克莱斯特泰瑞·汉尼斯张咏编译新闻与大众传播教育的使命和目标是什么？９０年代初，由于美国经济衰退，很多不同学科被纳入所谓“传播”的建系中。这一院系建制的改变，...