gebhart/patrepeval huggingface dataset:
Hematopoietic stem cell transplantation (2010)

More than 25,000 hematopoietic stem cell transplantations (HSCTs) are performed each year for the treatment of lymphoma, leukemia, immune-deficiency illnesses, congenital metabolic defects, hemoglobinopathies, and myelodysplastic and myeloproliferative syndromes. Before transplantation, patients receive intensive myeloablative chemoradiotherapy followed by stem cell "rescue." Autologous HSCT is performed using the patient's own hematopoietic stem cells, which are harvested before transplantation and reinfused after myeloablation. Allogeneic HSCT uses human leukocyte antigen (HLA)-matched stem cells derived from a donor. Survival after allogeneic transplantation depends on donor-recipient matching, the graft-versus-host response, and the development of a graft versus leukemia effect. This article reviews the biology of stem cells, clinical efficacy of HSCT, transplantation procedures, and potential complications.
Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: Insig renders sorting signal in Scap inaccessible to COPII proteins (2007)

Two classes of sterols, cholesterol and oxysterols, block export of sterol regulatory element-binding proteins (SREBPs) from the endoplasmic reticulum (ER) to the Golgi by preventing the binding of COPII-coated proteins to a hexapeptide sorting signal (MELADL) in Scap, the SREBP-escort protein. Here, we show that anti-MELADL blocks COPII binding in vitro, and microinjection of Fab anti-MELADL blocks Scap.SREBP movement in cells. Cholesterol and oxysterols block COPII binding to MELADL by binding to different intracellular receptors, cholesterol to Scap and oxysterols to Insig. Cysteine labeling shows that both binding events produce a conformational change near the MELADL sequence, abrogating COPII binding but not anti-MELADL binding. Mutagenesis experiments raise the possibility that the distance of MELADL from the ER membrane is crucial for COPII binding, and we speculate that sterols and Insig block SREBP transport by altering the location of MELADL with respect to the membrane, rendering it inaccessible to COPII proteins.
The critical role of atypical protein kinase C in activating hepatic SREBP-1c and NFκB in obesity (2009)

Obesity is frequently associated with systemic insulin resistance, glucose intolerance, and hyperlipidemia. Impaired insulin action in muscle and paradoxical diet/insulin-dependent overproduction of hepatic lipids are important components of obesity, but their pathogenesis and inter-relationships between muscle and liver are uncertain. We studied two murine obesity models, moderate high-fat-feeding and heterozygous muscle-specific PKC-lambda knockout, in both of which insulin activation of atypical protein kinase C (aPKC) is impaired in muscle, but conserved in liver. In both models, activation of hepatic sterol receptor element binding protein-1c (SREBP-1c) and NFkappaB (nuclear factor-kappa B), major regulators of hepatic lipid synthesis and systemic insulin resistance, was chronically increased in the fed state. In support of a critical mediatory role of aPKC, in both models, inhibition of hepatic aPKC by adenovirally mediated expression of kinase-inactive aPKC markedly diminished diet/insulin-dependent activation of hepatic SREBP-1c and NFkappaB, and concomitantly improved hepatosteatosis, hypertriglyceridemia, hyperinsulinemia, and hyperglycemia. Moreover, in high-fat-fed mice, impaired insulin signaling to IRS-1-dependent phosphatidylinositol 3-kinase, PKB/Akt and aPKC in muscle and hyperinsulinemia were largely reversed. In obesity, conserved hepatic aPKC-dependent activation of SREBP-1c and NFkappaB contributes importantly to the development of hepatic lipogenesis, hyperlipidemia, and systemic insulin resistance. Accordingly, hepatic aPKC is a potential target for treating obesity-associated abnormalities.
Epitope Mapping of Human Anti-Adeno-Associated Virus Type 2 Neutralizing Antibodies: Implications for Gene Therapy and Virus Structure (2000)

Recombinant adeno-associated virus type 2 (AAV) is a common vector used in human gene therapy protocols. We characterized the humoral immune response to AAV and observed that 80% of normal human subjects have anti-AAV antibodies and that 18% have neutralizing antibodies. To analyze the effect of neutralizing antibodies on AAV readministration, we attempted to deliver recombinant AAV expressing human factor IX (AAV-hFIX) intraportally into the livers of mice which had been preexposed to AAV and shown to harbor a neutralizing antibody response. While all naive control mice expressed hFIX following administration of AAV-hFIX, none of the mice with preexisting immunity expressed hFIX, even after transient immunosuppression at the time of the second administration with anti-CD4 or anti-CD40L antibodies. This suggests that preexisting immunity to AAV, as measured by a neutralizing antibody response, may limit AAV-mediated gene delivery. Using human sera in an enzyme-linked immunosorbent assay for AAV and a capsid peptide scan library to block antibody binding, we mapped seven regions of the AAV capsid containing immunogenic epitopes. Using pools of these peptides to inhibit the binding of neutralizing antibodies, we have identified a subset of six peptides which potentially reconstitute a single neutralizing epitope. This information may allow the design of reverse genetic approaches to circumvent the preexisting immunity that can be encountered in some individuals.
Glucocorticoid treatment regimen and health outcomes in adults with congenital adrenal hyperplasia (2012)

In adults with congenital adrenal hyperplasia, dexamethasone use was associated with lower androgens but greater insulin resistance, and increasing glucocorticoid dose associated with increased blood pressure, poor disease control and mutation severity.
Conformal microwave array (CMA) applicators for hyperthermia of diffuse chest wall recurrence (2010)

The CMA applicator is an effective thermal therapy device for heating large-area superficial disease such as diffuse chest wall recurrence. It is able to cover over three times the treatment area of conventional hyperthermia devices while conforming to typical body contours.
Impact of Social Media on Lifestyle and Learning Behaviour among Adolescents (2017)

To assess the impact of social media on lifestyle and learning behavior among adolescents. A quantitative Non-experimental research approach and descriptive design was adopted. The impact of social media on learning behavior revealed that were 1(1.7%) students were mildly affected, 50 (83.3%) students were moderately affected, 09 (15%) were highly affected.
Lung monocyte chemoattractant protein-1 gene expression in bleomycin-induced pulmonary fibrosis. (1994)

Recent studies indicate that monocyte chemoattractant protein-1 (MCP-1) may play an important role in pulmonary inflammation. In vitro studies show that a number of cell types are capable of producing MCP-1. In this study, MCP-1 expression in lungs of rats with bleomycin (BLM)-induced pulmonary fibrosis is examined to evaluate its cellular origin and potential role in pathogenesis. Lung fibrosis was induced in male Fisher 344 rats by endotracheal injection on day 0. On selected days after injection, lungs were harvested for in situ and Northern hybridization analyses for MCP-1 mRNA expression, immunochemical and histochemical analyses for MCP-1 protein expression, and identification of cell type. Northern analysis revealed significant elevation in lung MCP-1 mRNA expression beginning on day 3 post-BLM treatment, increasing to a peak on day 7, and then decreasing toward control levels after day 21. In situ hybridization combined with histochemical staining with chromotrope 2R indicate that most of the cells expressing MCP-1 mRNA at these time points are primarily eosinophils. A few scattered reactive fibroblasts, some mononuclear cells, epithelial cells, and cells of certain blood vessel walls also express this mRNA. Increased MCP-1 protein expression also was found to be predominantly within and adjacent to eosinophils. The eosinophils expressing this mRNA were found predominantly within areas of active fibrosis. The kinetics of increase in the number of cells expressing significant MCP-1 mRNA in lung sections paralleled that for MCP-1 mRNA expression, as assessed by Northern analysis. These results, for the first time, demonstrate that MCP-1 is up-regulated significantly in this rat animal model, and that infiltrating eosinophils represent the major cellular source for this increased MCP-1 expression.
Chlorides and moisture assessment in concrete by GPR full waveform inversion (2010)

ABSTRACT Corrosion of rebar within reinforced concrete is a major problem for countries where salt is applied to roads for de‐icing. Concrete structures are periodically inspected in order to monitor possible damage caused by chloride‐induced corrosion of the reinforcement. However, the available drilling and visual inspections do not supply sufficient spatial information or can only be assessed in advanced stages of corrosion, respectively. Consequently, the condition of bridge decks can only be assessed with low certainty. Therefore, a spatially continuous and non‐destructive method detecting chloride in concrete structures is desirable. This paper describes a novel method to estimate material properties using the full‐waveform inversion of bistatic off‐ground ground penetrating radar data. In this way, all information present in the ground‐penetrating radar (GPR) traces is used, which enables the estimation of quantitative electromagnetic properties. A critical step for full‐waveform inversion is a proper characterization of our horn antenna GPR system by estimating the phase centre and the effective wavelet using measurements over a stainless steel plate. The inversion of GPR data measured over nine concrete specimens having different moisture and chloride contents returned a relative dielectric permittivity and a conductivity that included a frequency‐dependent component. As expected, the inversion results for almost all specimens showed for increasing chloride and humidity content specimens increasing conductivity and permittivity values, respectively. In contrast to traditional ray‐based techniques we were able to distinguish between moisture and chloride effects and to obtain quantitative values for the permittivity and conductivity. For increasing chloride content increasing frequency‐dependent conductivity values were obtained.
Natural Innate and Adaptive Immunity to Cancer (2011)

The immune system can identify and destroy nascent tumor cells in a process termed cancer immunosurveillance, which functions as an important defense against cancer. Recently, data obtained from numerous investigations in mouse models of cancer and in humans with cancer offer compelling evidence that particular innate and adaptive immune cell types, effector molecules, and pathways can sometimes collectively function as extrinsic tumor-suppressor mechanisms. However, the immune system can also promote tumor progression. Together, the dual host-protective and tumor-promoting actions of immunity are referred to as cancer immunoediting. In this review, we discuss the current experimental and human clinical data supporting a cancer immunoediting process that provide the fundamental basis for further study of immunity to cancer and for the rational design of immunotherapies against cancer.
Distinct Roles of the IκB Kinase α and β Subunits in Liberating Nuclear Factor κB (NF-κB) from IκB and in Phosphorylating the p65 Subunit of NF-κB (2002)

Phosphatidylinositol 3'-kinase (PI3K) and the serine/threonine kinase AKT have critical roles in phosphorylating and transactivating the p65 subunit of nuclear factor kappaB (NF-kappaB) in response to the pro-inflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor (TNF). Mouse embryo fibroblasts (MEFs) lacking either the alpha or beta subunit of IkappaB kinase (IKK) were deficient in NF-kappaB-dependent transcription following treatment with IL-1 or TNF. However, in contrast to IKKbeta-null MEFs, IKKalpha-null MEFs were not substantially defective in the cytokine-stimulated degradation of Ikappabetaalpha or in the nuclear translocation of NF-kappaB. The IKK complexes from IKKalpha- or IKKbeta-null MEFs were both deficient in PI3K-mediated phosphorylation of the transactivation domain of the p65 subunit of NF-kappaB in response to IL-1 and TNF, and constitutively activated forms of PI3K or AKT did not potentiate cytokine-stimulated activation of NF-kappaB in either IKKalpha- or IKKbeta-null MEFs. Collectively, these data indicate that, in contrast to IKKbeta, which is required for both NF-kappaB liberation and p65 phosphorylation, IKKalpha is required solely for the cytokine-induced phosphorylation and activation of the p65 subunit of NF-kappaB that are mediated by the PI3K/AKT pathway.
Lives of Teachers: Update on a Longitudinal Case Study (2011)

The customary folklore in teacher education is that the effects of teacher preparation programs "wash out" as soon as beginning teachers graduate and enter the real world of the classroom (Lortie, 1975; Zeichner &amp; Liston, 1987; Zeichner &amp; Tabachnik, 1981; Zeichner, Tabachnik &amp; Densmore, 1987). But is this necessarily the case? Is everything learned during a teacher preparation program lost or changed when beginning teachers face the reality of classroom life and become socialized into the profession and to school culture? How does the pedagogical understanding of teachers grow or change over time? What are some of the personal and professional influences on teachers' thinking? Studies based on longitudinal research are needed to answer these and other questions.
The effects of apparatus dead space on P(aCO2) in patients receiving lung-protective ventilation. (2006)

In patients receiving lower-V(T) ventilation, removing all the apparatus V(D) from the ventilator circuit reduces P(aCO2) and increases pH, at a lower minute ventilation. This information will help guide ventilator-circuit configuration for patients receiving lung-protective ventilation.
How C-type lectins detect pathogens (2005)

Glycosylation of proteins has proven extremely important in a variety of cellular processes, including enzyme trafficking, tissue homing and immune functions. In the past decade, increasing interest in carbohydrate-mediated mechanisms has led to the identification of novel carbohydrate-recognizing receptors expressed on cells of the immune system. These non-enzymatic lectins contain one or more carbohydrate recognition domains (CRDs) that determine their specificity. In addition to their cell adhesion functions, lectins now also appear to play a major role in pathogen recognition. Depending on their structure and mode of action, lectins are subdivided in several groups. In this review, we focus on the calcium (Ca(2+))-dependent lectin group, known as C-type lectins, with the dendritic cell-specific ICAM-3 grabbing non-integrin (DC-SIGN) as a prototype type II C-type lectin organized in microdomains, and their role as pathogen recognition receptors in sensing microbes. Moreover, the cross-talk of C-type lectins with other receptors, such as Toll-like receptors, will be discussed, highlighting the emerging model that microbial recognition is based on a complex network of interacting receptors.
Synthesis and microbiological properties of 3-amino-1-hydroxy-2-indolinone and related compounds (1973)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis and microbiological properties of 3-amino-1-hydroxy-2-indolinone and related compoundsAlvie L. Davis, David R. Smith, and Tommy J. McCordCite this: J. Med. Chem. 1973, 16, 9, 1043–1045Publication Date (Print):September 1, 1973Publication History Published online1 May 2002Published inissue 1 September 1973https://doi.org/10.1021/jm00267a020RIGHTS & PERMISSIONSArticle Views330Altmetric-Citations22LEARN 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 InReddit PDF (415 KB) Get e-Alertsclose Get e-Alerts
Modulation of the expression of human LDL-Apo B-100 epitopes by lipids and apolipoproteins. (1993)

The purpose of the present study was to determine the immunochemical properties of apolipoprotein (apo) B-100 associated with low density lipoprotein (LDL) in relation to lipid and apolipoprotein composition. LDLs were isolated by sequential ultracentrifugation (1.019 < d < 1.050 g/mL) from two healthy volunteers and 21 dyslipidemic patients to obtain heterogeneous samples of LDL. Lipid (free cholesterol, cholesteryl esters, triglycerides, and phospholipids) and apolipoprotein contents (apo B, apo C-III, apo E) were determined in each LDL sample. Immunoreactivities of apo B were tested in solid-phase competitive-binding radioimmunoassays using seven monoclonal anti-LDL antibodies that reacted with defined epitopes of apo B-100. The relation between lipid and/or protein variables and the immunoreactivity of apo B was evaluated by successive use of Spearman's rank simple correlation, partial correlation, and canonical correlation analyses. The canonical correlation analysis showed that apo B-100 immunoreactivity on LDL is highly dependent on lipid and apolipoprotein composition simultaneously. The results confirmed the influence of surface and core lipids on the expression of the apo B-100 epitopes, independent of their location on the molecule. However, the lipid requirement of LDL strongly influences the expression of epitopes mapped in the LDL receptor-recognition domain. In contrast to apo E, apo C-III does not seem to influence the expression of the apo B-100 epitopes in the LDL range studied.(ABSTRACT TRUNCATED AT 250 WORDS)
Antifungal Prophylaxis during Neutropenia or Allogeneic Bone Marrow Transplantation: What is the State of the Art? (1992)

Neutropenia induced by intensive chemotherapy and allogeneic bone marrow transplantation are increasingly commonly complicated by fungal infections; thus prophylaxis may be justified. The authors surveyed the literature and culled their experience - few randomized trials have been done and definitions have often been poor. In prophylaxis of mucosal candidosis, miconazole and clotrimazole may both be more effective than placebo. Nystatin is ineffective and ketoconazole of medicine efficacy. Fluconazole is effective at 50 mg/day and 400 mg/day. Itraconazole and amphotericin B both need further evaluation. In prevention of systemic candidosis, oral nystatin prophylaxis, up to 4 X 10(6) U/day, is usually unsuccessful, though compliance is variable. Oral amphotericin B in low doses is ineffective, but 50 mg or more 4 times daily may prevent systemic candidosis, though compliance is variable. Oral ketoconazole, 400-600 mg/day, is possibly effective prophylaxis in neutropenia but not after bone marrow transplantation; liver function (often abnormal in these patients) is a problem, as is tolerability. Oral fluconazole is well tolerated, has reliable serum concentrations and is effective following bone marrow transplantation, but the optimum dose is uncertain. In bone marrow transplantation, intravenous amphotericin B, 0.1 mg/kg/day, appears to be effective; there are no data in neutropenia. Oral itraconazole (capsules, 200 mg/day) may be active; data are scanty. In prevention of invasive aspergillosis, itraconazole, 200 mg/day, is probably active, but only if adequate serum concentrations are achieved. New oral and intravenous itraconazole formulations in cyclodextrin may achieve more reliable serum concentrations. No oral drug provides effective prophylaxis against Torulopsis, Fusarium, Trichosporon, or Pseudallescheria.
Coherent control approaches to light guidance in the nanoscale (2006)

Concepts of coherent control are extended to manipulate light in subdiffraction length scales via nanoparticle arrays. Phase and polarization control are first introduced and applied to control the pathway of electromagnetic energy through multiple branching nanoarray intersections, leading to an ultrafast optical nanoswitch below the diffraction limit. The genetic algorithm is next generalized to provide a systematic design tool, wherein both the properties of the excitation field and the structural parameters of the material system are optimized so as to make nanodevices with desired functionality. The scheme is used to gain insight into the interplay between the interactions that underlies the coherent propagation of electromagnetic energy via nanoparticle arrays. Implications to several research fields, including single molecule spectroscopy, spatially confined chemistry, optical logic, and nanoscale sensing, are envisioned.
Mutations affecting the chemosensory neurons of Caenorhabditis elegans. (1995)

We have identified and characterized 95 mutations that reduce or abolish dye filling of amphid and phasmid neurons and that have little effect on viability, fertility or movement. Twenty-seven mutations occurred spontaneously in strains with a high frequency of transposon insertion. Sixty-eight were isolated after treatment with EMS. All of the mutations result in defects in one or more chemosensory responses, such as chemotaxis to ammonium chloride or formation of dauer larvae under conditions of starvation and overcrowding. Seventy-five of the mutations are alleles of 12 previously defined genes, mutations which were previously shown to lead to defects in amphid ultrastructure. We have assigned 20 mutations to 13 new genes, called dyf-1 through dyf-13. We expect that the genes represented by dye-filing defective mutants are important for the differentiation of amphid and phasmid chemosensilla.
Intratumoral injection of dendritic cells derived in vitro in patients with metastatic cancer (2000)

This pilot study demonstrates that DCs derived in vitro can exist viably after intratumoral injection and can mediate biologic activity in situ. Tumor-derived heat shock proteins may be involved in the antitumor activity observed.