gebhart/patrepeval huggingface dataset:
In Vitro and In Vivo Evidence That Ex Vivo Cytokine Priming of Donor Marrow Cells May Ameliorate Posttransplant Thrombocytopenia (1998)

Thrombocytopenia is typically observed in patients undergoing hematopoietic stem cell transplantation. We hypothesized that delayed platelet count recovery might be ameliorated by increasing the number of megakaryocyte colony- forming units (CFU-Meg) in the hematopoietic cell graft. To test this hypothesis, we evaluated cytokine combinations and culture medium potentially useful for expanding CFU-Meg in vitro. We then examined the ability of expanded cells to accelerate platelet recovery in an animal transplant model. Depending on the cytokine combination used, we found that culturing marrow CD34+cells for 7 to 10 days in serum-free cultures was able to expand CFU-Meg ∼40 to 80 times over input number. Shorter incubation periods were also found to be effective and when CD34+ cells were exposed to thrombopoietin (TPO), kit ligand (KL), interleukin-1α (IL-1α), and IL-3 in serum-free cultures for as few as 48 hours, the number of assayable CFU-Meg was still increased ∼threefold over input number. Of interest, cytokine primed marrow cells were also found to form colonies in vitro more quickly than unprimed cells. The potential clinical utility of this short-term expansion strategy was subsequently tested in an in vivo animal model. Lethally irradiated Balb-C mice were transplanted with previously frozen syngeneic marrow mononuclear cells (106/mouse), one tenth of which (105) had been primed with [TPO, KL, IL-1a, and IL-3] under serum-free conditions for 36 hours before cryopreservation. Mice receiving the primed frozen marrow cells recovered their platelet and neutrophil counts 3 to 5 days earlier than mice transplanted with unprimed cells. Mice which received marrow cells that had been primed after thawing but before transplantation had similar recovery kinetics. We conclude that pretransplant priming of hematopoietic cells leads to faster recovery of all hematopoietic lineages. Equally important, donor cell priming before transplant may represent a highly cost-effective alternative to constant administration of cytokines during the posttransplant recovery period.
Site-Specific Immunomodulator: A Novel Treatment for Crohn’s Disease (2015)

We investigated the mechanism of action, safety, and efficacy of the Site-Specific Immunomodulator (SSI) QBECO, a novel immunotherapy for Crohn's disease (CD). Using human monocytic THP-1 cells, we demonstrate that SSI QBECO (derived from the common colon bacteria E. coli) activates macrophages to an M1 phenotype (associated with enhanced capacity to eliminate bacteria and activate innate immune responses). We assessed SSI QBECO in a compassionate use protocol of ten adult patients with active CD. Patients with moderate to severe clinical symptoms receiving conventional CD treatments and/or complementary therapies were included, except patients receiving anti-TNF medications. SSI QBECO was self-administered subcutaneously every second day, for a minimum of 2.5 months and a maximum of 11 months. All 10 patients reported improvement of symptoms while on the SSI QBECO treatment. Seven patients reported full resolution of clinical symptoms during a course of SSI QBECO of at least three months. Three patients have experienced ongoing sustained clinical remission after discontinuing all medications, including SSI treatment. The longest case of clinical remission is still ongoing (>4 years). No serious severe adverse clinical events were reported. Collectively, we conclude that treatment with the immunoactive SSI QBECO was well tolerated and effective for treatment of Crohn's disease in this case series.
Probiotics: current evidences and new perspectives (2014)

Probiotics are viable microorganisms that can exert potential benefits to human health. Use of probiotics in different human diseases and clinical conditions has gained much attention in the last decades. Several data exist about the potential benefits of probiotics in pediatric age for the management of some clinical conditions, with different and sometimes contrasting results. Currently, strong evidences support the use of probiotics for treatment of acute infectious diarrhoea and prevention of antibiotic-associated diarrhoea: bacteria belonging to the genus of lactobacilli and Saccharomyces boulardii showed the stronger evidences of benefits in different clinical trials and meta-analysis [1,2]. For other pediatric diseases and clinical conditions, evidences of the benefits of a probiotic supplementation are still not so strong. The recommendation to administer a probiotics supplementation in preterm, very low birth weight neonates at risk of developing necrotizing enterocolitis has recently been criticized by a critical review of the literature that conclude that well-designed clinical trials are still needed for suggesting its routinely use in these neonates [3]. Discussion is still ongoing about the benefits of probiotics in prevention or treatment of other pediatric diseases such as respiratory tract infections, urinary tract infections, Helicobacter pylori infection or allergic diseases. Clinical trials and meta-analysis about the use of probiotics in these pediatric clinical conditions have been published and still continued to be published; however, study designs are not always comparable and sometimes inadequate, species of probiotics used in the studies are different and the benefits demonstrated for one microorganism are not generalizable to other bacteria, results of the studies are still often not unequivocal or contrasting so that strong recommendations are still lacking. The use of probiotics has been suggested to be potentially beneficial for the management of gastrointestinal functional disorders, such as irritable bowel syndrome, again, with different results. These clinical conditions are supposed to be the result of a perturbation of the microbiota balance that leads to dysbiosis, responsible for the appearance of the characteristic symptoms. However, pathogenesis of gastrointestinal functional disorders appear to be much more complex and involve the nervous system and its bidirectional interactions with the intestine. Moreover, it has been hypothesized that intestinal microbial composition may itself influence end-points related to mood state, brain function, and mental outlook. A new fascinating perspective in studies about microbiota and probiotics is the characterization of the alterations of intestinal microbiome and their correlation with abnormalities in the bidirectional gut-brain interactions.
간호대상자로서의 지역사회 개념 및 지역사회간호사정에 관한 문헌분석 (2000)

The purpose of this study was to compare the concept of community and community health, community health assessment tool, and community health nursing diagnosis based on the concept of 'Community as Client'. The method for this purpose was to search the articles and textbooks related to community as...
Cache Me If You Can (2019)

DNS depends on extensive caching for good performance, and every DNS zone owner must set Time-to-Live (TTL) values to control their DNS caching. Today there is relatively little guidance backed by research about how to set TTLs, and operators must balance conflicting demands of caching against agility of configuration. Exactly how TTL value choices affect operational networks is quite challenging to understand due to interactions across the distributed DNS service, where resolvers receive TTLs in different ways (answers and hints), TTLs are specified in multiple places (zones and their parent's glue), and while DNS resolution must be security-aware. This paper provides the first careful evaluation of how these multiple, interacting factors affect the effective cache lifetimes of DNS records, and provides recommendations for how to configure DNS TTLs based on our findings. We provide recommendations in TTL choice for different situations, and for where they must be configured. We show that longer TTLs have significant promise in reducing latency, reducing it from 183 ms to 28.7 ms for one country-code TLD.
Design and performance of an electrostatically focused 5-kw X-band traveling-wave tube (1964)

A new type of high-power traveling-wave tube employing electrostatic beam focusing was developed and tested. An electrode system permitting the electrostatic focusing of a high-perveance electron beam was evolved and the incorporation of the focusing electrodes in the slow-wave circuit was accomplished without significant deterioration of the original RF characteristic. Feasibility was proven on a narrow-band <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">X</tex> -band amplifier operated in a continuously pumped vacuum chamber which produced up to 10 kw of peak power. A sealed-off wide-band tube, subsequently, gave 2.5 kw over a 26 per cent bandwidth.
Proteolytic digestion of reovirus in the intestinal lumens of neonatal mice (1989)

Two approaches were used to demonstrate proteolysis of reovirus in the intestine of the neonatal mouse. The first approach utilized peroral inoculation of radiolabeled virus into neonatal mice; the intestinal washings were harvested at 0 to 30 min postinoculation. The virus recovered from the intestinal washings was electrophoresed in polyacrylamide to determine whether proteolytic digestion of viral proteins had occurred. Complete loss of sigma 3 and generation of the mu 1c cleavage product delta demonstrated that digestion occurred within 10 to 30 min after the inoculation, resulting in the rapid generation of intermediate subviral particles (ISVPs). The products formed resembled those seen when the virus is digested in vitro with chymotrypsin. The second approach took advantage of the fact that ISVPs grow in cells treated with NH4Cl, whereas intact virus does not grow under these conditions (L. J. Sturzenbecker, M. Nibert, D. Furlong, and B. N. Fields, J. Virol. 61:2351-2361, 1987). Thus, assaying virus for its ability to grow in NH4Cl-treated cells represents a means of ascertaining whether the samples contain ISVPs. Using this approach, we demonstrated that up to 8 h postinoculation ISVPs predominate in the intestinal tissue and in the intestinal lumen. Between 8 and 15 h postinoculation, there is a loss in the proportion of ISVPs in the tissue so that by 15 h postinoculation ISVPs are no longer detectable in intestinal tissue washed of lumen contents and virus. In contrast, the lumen of the intestine contains some ISVPs at all times postinoculation. Thus, after peroral inoculation, the mammalian reoviruses are converted to proteolytically cleaved virus, suggesting that proteolysis plays an important role in initiation of infection in the gastrointestinal tract.
ADP‐induced bladder contractility is mediated by P2Y <sub>12</sub> receptor and temporally regulated by ectonucleotidases and adenosine signaling (2014)

Purinergic signaling comprises one key pathway in modulating bladder smooth muscle (BSM) contractility, disorders of which become highly prevalent with aging. ADP was first observed to modulate BSM contractility >40 yr ago, yet the underlying molecular mechanism still remains unclear. Here, we demonstrate, using myography, that ADP and ADPβS dose-dependently induce mouse BSM contraction, and ADP-induced BSM contraction is blocked by a selective P2Y12 receptor (P2Y12R) antagonist, PSB 0739 (25 μM), but is unaffected by P2Y1 and P2Y13 receptor antagonists. P2Y12R in BSM exhibits distinct pharmacological properties that are different from P2Y12R in platelets. After an immediate contraction, prolonged exposure to ADP causes BSM to become refractory to further ADP-mediated contraction. However, in mice lacking ectonucleotidases Entpd1 (ATP→ADP→AMP) or Nt5e (AMP→adenosine), or by inhibiting adenosine signaling, the refractory response was altered, resulting in repeated BSM contractions in response to repeated ADP (0.1-1 mM) stimulation. Our data indicate that P2Y12R undergoes slow desensitization; ADP-P2Y12 signaling is tightly regulated by Entpd1/Nt5e activity and adenosine receptors; and ADP-adenosine signaling play an important role in modulating P2X-mediated BSM contraction. The identification of P2Y12R in BSM, and the current clinical availability of P2Y12R inhibitors, such as clopidogrel, offers potentially novel treatment strategies for bladder contractility disorders.
Flux free flip chip attach technology for BGA/CSP packages (2003)

The solder flip chip attach without flux using plasma treatment has been developed in order to eliminate the flux residue cleaning process for manufacturing the BGA/CSP packages. The plasma treatment is composed of roughening the solder surface and improving the solder wettability. Argon gas added hydrogen (Ar+H/sub 2/) plasma has been very superior to argon plasma for etching/roughening the solder surface, therefore, a mixed gas plasma composed of carbon tetrafluoride and argon or oxygen(CF/sub 4//Ar or CF/sub 4//O/sub 2/) has modified the solder surface for good solderability without damage to the Si chip, the passivation film and the organic substrate because of the active solder surface. After the Si chip was mounted on the organic substrate with the solder bumps treated with plasma, the solder bumps were renewed at 230/spl deg/C and underfilled. Package reliability has been demonstrated by the temperature cycle test (TCT) and temperature humidity bias test (THB) and this flux free flip chip attach technology with plasma treatment has been sufficiently verified such that it can be applied to packaging processes.
Early intervention in cancer using monoclonal antibodies and other biological ligands: micropharmacology and the "binding site barrier". (1992)

Monoclonal antibodies and other biological ligands tend to distribute nonuniformly in bulky tumors after systemic administration. In part, that observation reflects intrinsic heterogeneity of the tumor; in part, it represents poor percolation through tumor substance. Theoretical considerations led us several years ago to formulate the "binding site barrier" hypothesis, the idea that macromolecular ligands could be prevented from penetrating tumors by the very fact of their successful binding to the target receptor. All else being equal, the higher the density of target moieties (e.g., antigens) and the higher the affinity, the greater the barrier. Experimental evidence for this hypothesis remained circumstantial until we recently obtained direct experimental verification in an animal tumor system. As shown by calculations in the present study, metabolism of ligand in free form or once it has bound to the target can also limit dramatically the extent of penetration. The PERC program package, developed to examine these issues in the case of monoclonal antibodies, has now been applied to other types of ligands as well. We speculate that the same microscopic factors have influenced the evolution of biological ligands, such as the autocrine-paracrine and chemotactic factors. Micropharmacological issues (binding sites, molecular size, and charge) should be taken into account as we design the next generation of biological ligands for systemic administration. The same issues are, perhaps, even more important with respect to molecular design of biological factors to be secreted by genetically modified cells in the treatment of cancer and in cancer vaccines. Since the PERC calculations and experiments relate to aggregates of tumor cells no more than a few hundred micron across, the ideas appear relevant to the problems of early detection and intervention. However, barriers associated with organized epithelial cell layers and basement membrane in the case of early carcinomas and carcinomatous change remain to be understood.
Effects of basic fibroblast growth factor on human microvessel endothelial cell migration on collagen I correlates inversely with adhesion and is cell density dependent (1996)

Angiogenesis, new vessel growth from existing vessels, is critical to tissue development and healing. Much is known about the molecular and cellular elements of angiogenesis, such as the effects of growth factors and matrix molecules on proliferation and migration. However, it is not clear how these elements are coordinated to produce specific microvascular beds. To address this, the effects of basic fibroblast growth factor (bFGF) on beta 1 integrin-mediated adhesion relative to migration in human microvessel endothelial cells (HMVEC) was examined. Using two assays of migration that differ in the density of cells being examined, bFGF stimulated single cell migration and reduced cell migration from a confluent monolayer on collagen I. Adhesion to collagen I of HMVEC treated at low density (2-4 x 10(4) cells/cm2) with bFGF for 22 h was reduced, while bFGF increased cell adhesion of HMVEC treated at high density (6-8 x 10(4) cells/cm2). Adhesion of both bFGF-treated and untreated HMVEC was mediated by the beta 1 integrin matrix receptor. Basic FGF treatment did not significantly alter surface expression of the beta 1 integrin subunit. Reduction in bFGF-mediated adhesion correlated with delayed cell spreading and altered organization of beta 1 integrin into substrate contacts. Thus, integrin-mediated cell adhesion in microvessel endothelial cells is sensitive to regulation by a growth factor. Furthermore, the nature of the response to this signal depends on another cell regulator, cell density. In addition, modulation of cell adhesion by a growth factor may be a central regulatory feature in controlling endothelial cell migration.
Intelligent Tutoring Goes To School in the Big City (2018)

This paper reports on a large-scale experiment introducing and evaluating intelligent tutoring in an urban High School setting. Critical to the success of this project has been a client-centered design approach that has matched our client's expertise in curricular objectives and classroom teaching with our expertise in artificial intelligence and cognitive psychology. The Pittsburgh Urban Mathematics Project (PUMP) has produced an algebra curriculum that is centrally focused on mathematical analysis of real world situations and the use of computational tools. We have built an intelligent tutor, called PAT, that supports this curriculum and has been made a regular part of 9th grade Algebra in 3 Pittsburgh schools. In the 1993-94 school year, we evaluated the effect of the PUMP curriculum and PAT tutor use. On average the 470 students in experimental classes outperformed students in comparison classes by 15% on standardized tests and 100% on tests targeting the PUMP objectives. This study provides further evidence that laboratory tutoring systems can be scaled up and made to work, both technically and pedagogically, in real and unforgiving settings like urban high schools.
Defining Identification: A Theoretical Look at the Identification of Audiences With Media Characters (2001)

Abstract In this article I argue that although the notion of identification with media characters is widely discussed in media research, it has not been carefully conceptualized or rigorously tested in empirical audience studies. This study presents a theoretical discussion of identification, including a definition of identification and a discussion of the consequences of identification with media characters for the development of identity and socialization processes. It is suggested that a useful distinction can be made between identification and other types of reactions that media audiences have to media characters. A critical look at media research involving identification exposes the inherent conceptual problems in this research and leads to hypotheses regarding the antecedents and consequences of identification with media characters. The importance of a theory of identification to media research and communication research, more broadly, is presented.
Symmetries within chaos: A route to effective mixing (1989)

Experimental studies show that simple two-dimensional time-periodic flows can produce chaotic mixing. However, the mixing is not always complete; depending on the choice of the period, there can exist large dynamic structures, called islands, that stretch and compress in a time-periodic manner but remain segregated even after long times. Obviously, a flow that contains very few islands is desired. Unfortunately, in most real systems, an analytic expression for the velocity field (or the motion) does not usually exist, making theoretical prediction of the location and size of islands virtually impossible. However, using only minimal knowledge of the gross properties of the velocity field, the flow can be analyzed in terms of its symmetries. Symmetries can be detected without reference to precise mathematical equations. Large islands are located on lines of symmetry, or in pairs on opposite sides of the line. With this knowledge, it is possible to manipulate symmetries in a systematic way so as to move an island into a region of good mixing. Applying this idea repeatedly results in a recursively generated flow history that is neither periodic nor random, but is self-similar. Mixing in these flows is efficient over the entire flow domain. In addition, the idea of recursively generated flow histories might have implications for understanding the mechanisms of turbulent flow.
A phase III comparative study of nivolumab (anti-PD-1; BMS-936558; ONO-4538) versus everolimus in patients (pts) with advanced or metastatic renal cell carcinoma (mRCC) previously treated with antiangiogenic therapy. (2013)

TPS4592 Background: Standard approved treatments for pts with mRCC include interleukin-2 as well as therapies that target the vascular endothelial growth factor (eg, sunitinib, pazopanib) or mammalian target of rapamycin (eg, temsirolimus, everolimus) pathways. However, most pts may develop resistance, and overall survival (OS) improvement has only been shown in one phase 3 trial in poor-risk pts. Everolimus demonstrated a 3-month improvement in median progression-free survival (PFS) vs placebo, with no OS improvement (Motzer RJ, et al. Lancet. 2008;372:449-56). A phase 1 study of the fully human programmed death-1 (PD-1) receptor blocking monoclonal antibody nivolumab showed encouraging antitumor activity with previously treated mRCC (objective response rate [ORR], 29% (10/34); stable disease at ≥24 weeks [wks], 27% [9/34]). PD-1 is an immune checkpoint receptor that negatively regulates T-cell activation and PD-1 overexpression by tumor infiltrating lymphocytes has been associated with poor prognosis in multiple tumor types. Therefore, an ongoing, randomized, open-label, global phase 3 trial was developed to evaluate the clinical benefit of nivolumab in mRCC pts previously treated with anti-angiogenic therapy. Methods: Approximately 822 pts with advanced or metastatic clear-cell mRCC who have received ≤2 prior anti-angiogenic therapies and ≤3 total prior systemic regimens will be randomized 1:1 to receive nivolumab 3 mg/kg IV every 2 wks (Arm A) or everolimus 10 mg PO daily (Arm B). Pts will be stratified by region, MSKCC risk group, and number of prior anti-angiogenic therapy regimens. Tumor response will be assessed using RECIST 1.1 every 8 wks following randomization for the first year and then every 12 wks until disease progression or treatment discontinuation, whichever occurs later. The primary endpoint is OS. Secondary endpoints include PFS, ORR, OR duration, adverse events, OS in PD ligand 1 (PD-L1) positive or negative subgroups, and patient-reported outcomes. The trial is open and enrolling pts. Clinical trial information: NCT01668784.
Solvothermal Synthesis of [C6H17N3]Sb10S16: A New Thioantimonate(III) with an in situ Formed Organic Amine Cation. (2005)

For Abstract see ChemInform Abstract in Full Text.