gebhart/patrepeval huggingface dataset:
Current therapy of pediatric Crohn’s disease (2015)

Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis, are chronic relapsing and remitting diseases of the bowel, with an unknown etiology and appear to involve interaction between genetic susceptibility, environmental factors and the immune system. Although our knowledge and understanding of the pathogenesis and causes of IBD have improved significantly, the incidence in the pediatric population is still rising. In the last decade more drugs and treatment option have become available including 5-aminosalicylate, antibiotics, corticosteroids, immunomodulators and biological agents. Before the use of anti-tumor necrosis factor (TNF)-α became available to patients with IBD, the risk for surgery within five years of diagnosis was very high, however, with anti-TNF-α treatment the risk of surgery has decreased significantly. In the pediatric population a remission in disease can be achieved by exclusive enteral nutrition. Exclusive enteral nutrition also has an important role in the improvement of nutritional status and maintained growth. In this review we summarize the current therapeutic treatments in CD. The progress in the treatment options and the development of new drugs has led to optimized tactics for achieving the primary clinical goals of therapy - induction and maintenance of remission while improving the patient's growth and overall well-being.
The Role of TNFα in Ulcerative Colitis (2007)

Standard of care for ulcerative colitis involves long-term pharmacotherapy or colectomy. Approximately 20% to 30% of patients eventually require a colectomy because patients either do not respond or cannot tolerate the currently available pharmacotherapies. Advances in our knowledge of the pathophysiology of ulcerative colitis have highlighted the importance of cytokines such as tumor necrosis factor alpha (TNFalpha) in the inflammatory process. TNFalpha is a proinflammatory mediator that plays an integral role in the pathogenesis of inflammatory bowel disease. In addition, mounting evidence indicates a genetic association between TNFalpha and ulcerative colitis. Furthermore, increased TNFalpha levels have been demonstrated in studies of patients with ulcerative colitis. TNFalpha is likely an important component in the pathophysiology of ulcerative colitis, and thus agents targeting TNFalpha in ulcerative colitis have been studied. Recent randomized controlled trials have confirmed that biologic anti-TNFalpha therapy is effective in ulcerative colitis. Soluble TNFalpha receptors or biologic agents that suppress or inhibit TNFalpha production may also show therapeutic promise.
Standardized low-resolution brain electromagnetic tomography (sLORETA): technical details. (2002)

Scalp electric potentials (electroencephalograms) and extracranial magnetic fields (magnetoencephalograms) are due to the primary (impressed) current density distribution that arises from neuronal postsynaptic processes. A solution to the inverse problem--the computation of images of electric neuronal activity based on extracranial measurements--would provide important information on the time-course and localization of brain function. In general, there is no unique solution to this problem. In particular, an instantaneous, distributed, discrete, linear solution capable of exact localization of point sources is of great interest, since the principles of linearity and superposition would guarantee its trustworthiness as a functional imaging method, given that brain activity occurs in the form of a finite number of distributed hot spots. Despite all previous efforts, linear solutions, at best, produced images with systematic nonzero localization errors. A solution reported here yields images of standardized current density with zero localization error. The purpose of this paper is to present the technical details of the method, allowing researchers to test, check, reproduce and validate the new method.
Applying time series analysis and neighbourhood voting in a decentralised approach for fault detection and classification in WSNs (2013)

Applying time series analysis and neighbourhood voting in a decentralised approach for fault detection and classification in WSNs, Applying time series analysis and neighbourhood voting in a decentralised approach for fault detection and classification in WSNs
Immunoregulatory circuits among T-cell sets. II. Physiologic role of feedback inhibition in vivo: absence in NZB mice. (1978)

We have shown that (a) purified T-helper cells induce cells of another T-cell set-, expressing the Ly123+Qa1+ surface phenotype, to exert potent suppressive activity, (b) this T-T interaction plays an important role in regulating in vivo immune responses, and (c) this interaction represents an important barrier to protocols intended to augment the immune status of individuals by adoptive (or active) immunotherapy. Our results also indicate that the Ly123+ T-cell set mediating feedback suppression in vivo is sensitive to both low doses of cyclophosphamide and removal of the thymus in adult life. The importance of this T-T interaction to normal, physiologic regulation of the immune system is emphasized by the finding that the major T-cell deficit of NZB mice (an inbred strain of mice that spontaneously develops an autoimmune disorder) is the absence or malfunction of an Ly123+ T-cell set responsible for feedback inhibition.
The selection of high-producing cell lines using flow cytometry and cell sorting (2004)

The selection of high-producing cell lines is usually time-consuming and labour-intensive. Following transfection, high-producing cells are selected using limiting dilution cloning to prevent non- and low-producing cells from outgrowing high-producing cells, a process that normally takes > 3 months. During this time, the cells have to be screened occasionally to ensure stability of the selected clone. Several new methods for selecting and screening cells using flow cytometry and cell sorting have recently been developed; these include gel microdrop technology, which encapsulates the cells in gelatine beads, and matrix-based secretion assays. This paper reviews these techniques for selecting high-producing cell lines and isolating rare cells.
Efficacy of Morpholino-modified Antisense Oligomers Directed against Tumor Necrosis Factor-α mRNA (1996)

Chemical modification of antisense oligonucleotides to increase nuclease resistance may improve their efficacy within enzyme-rich cellular targets (e.g. macrophages). We evaluated a panel of morpholino antisense oligomers (M-AS) for their ability to inhibit macrophage tumor necrosis factor-alpha (TNF-alpha) release and compared them to phosphodiester (O-AS) and phosphorothioate (S-AS) types of oligonucleotides. M-AS inhibited translation in vitro (rabbit reticulocyte lysate) of target mRNA at concentrations as low as 200 nM (e.g. percent inhibition by M-AS 2 at 0.2, 1.0, and 2.0 microM was 40.9 +/- 5.3%, 50.2 +/- 4.6%, and 57.7 +/- 3.6%, respectively, n = 4, p </= 0.002 versus control). Similarly, M-AS 2 effectively, albeit partially, inhibited TNF-alpha production by LPS-stimulated macrophages (RAW 264.7 cells). Incubation of cells with 25 microM M-AS 2 resulted in 32.6 +/- 2.6% (n = 3, p = 0.002 versus control) decrease in TNF-alpha release. In contrast, S-AS inhibited translation of the target mRNA in the rabbit reticulocyte lysate assay, but not in the cell-based assay. In fact, S-AS nonspecifically augmented TNF-alpha release. O-AS were without effect in either system. Uptake studies with fluorescent M-AS revealed that inhibitory effects were seen despite relatively low cellular uptake (intracellular concentration 30.5 +/- 6.7 nM; efficiency of uptake 0.1%). In contrast, flow cytometric and confocal analysis revealed that S-AS were avidly taken up by RAW 264. 7 cells, confirming that their lack of efficacy was not due to lack of uptake. With improved methods of delivery, M-AS may represent an important therapeutic modality.
The potential role of peroxynitrite in the vascular contractile and cellular energetic failure in endotoxic shock (1997)

1. Peroxynitrite is a toxic oxidant species produced from nitric oxide (NO) and superoxide. We have recently observed that the cell-permeable superoxide dismutase mimetic Mn(III)tetrakis(4-benzoic acid) porphyrin (MnTBAP) inhibits the suppression of mitochondrial respiration elicited by authentic peroxynitrite in vitro. Here we have investigated the relative potency of MnTBAP and a range of related compounds in terms of inhibition of peroxynitrite-induced oxidation and cytotoxicity. In addition, we tested the effects of MnTBAP on the vascular and the cellular energetic failure in rodent models of endotoxic shock. 2. We observed a dose-related inhibition of the peroxynitrite-induced oxidation of dihydrorhodamine 123 to rhodamine by MnTBAP, ZnTBAP and FeTBAP, but not by MnTMPyP [(5,10,15,20-tetrakis(N-methyl-4'-pirydyl)porphinato)-mangan ese (III)]. In addition, MnTBAP, ZnTBAP and FeTBAP, but not MnTMPyP prevented the suppression of mitochondrial respiration by authentic peroxynitrite in cultured J774 macrophages. 3. In rat cultured aortic smooth muscle cells, MnTBAP protected against the suppression of mitochondrial respiration in response to authentic peroxynitrite, immunostimulation and nitric oxide (NO) donor compounds. MnTBAP slightly reduced the amount of nitrite/nitrate produced in response to immunostimulation in these cells. 4. Administration of MnTBAP, 15 mg kg-1 i.v., before the administration of endotoxin (15 mg kg-1, i.v.) to rats ameliorated the development of vascular hyporeactivity and the development of endothelial dysfunction in the thoracic aorta ex vivo. 5. MnTBAP also prevented the endotoxin-induced decrease in mitochondrial respiration, the development of DNA single strand breaks, and the depletion of intracellular NAD+ in peritoneal macrophages ex vivo. 6. MnTBAP did not inhibit the expression by endotoxin of the inducible NO synthase in lung samples. 7. MnTBAP did not alter survival rate in mice challenged with high dose endotoxin. 8. Our findings, taken together with previous data demonstrating protective effects of NO synthase inhibitors against the endotoxin-induced contractile and energetic failure in the models of shock used in the current study, and with the known ability of peroxynitrite to cause cellular energy depletion, suggest a role for peroxynitrite in the pathogenesis of cellular energetic failure and contractile dysfunction in endotoxin shock.
Common acute lymphocytic leukemia antigen is identical to neutral endopeptidase. (1988)

We purified CALLA from human kidney and isolated a cDNA clone reactive with two oligonucleotide probes corresponding to two distinct peptides. The amino acid sequence translated from the CALLA cDNA revealed 100% identity with that of human neutral endopeptidase (NEP, enkephalinase). The distribution of CALLA antigen and NEP in normal tissues are similar.
Protective CTL-dependent immunity and enhanced immunopathology in mice immunized by particle bombardment with DNA encoding an internal virion protein. (1995)

Anti-viral CTL were induced in vitro using a particle bombardment device or "gene-gun" to deliver plasmid DNA encoding the nucleoprotein of the lymphocytic choriomeningitis virus (LCMV). Using this plasmid we were able to study T cell-mediated immunity in the absence of a neutralizing Ab response. Upon a single DNA immunization, a nearly 2 log10 reduction in splenic viral titers was observed 3 days after LCMV infection. After two or three immunizations a greater than 3 log10 inhibition of viral titers in the spleen was observed, with most animals having no detectable virus. C57BL/6 mice immunized with DNA encoding the nucleoprotein gene were also challenged with LCMV intracranially. Upon intracranial challenge, vaccinated animals displayed either protection or enhanced immunopathology leading to accelerated kinetics of death. Using limiting dilution analysis it was possible to detect LCMV-specific CTL precursors in both the spleen and lymph nodes of vaccinated animals. C57BL/6 mice inoculated with DNA demonstrated an anamnestic CTL response detectable at day 4 after LCMV challenge. Thus DNA vaccines are capable of inducing an anti-viral T cell response that can inhibit viral replication and mediate either protective immunity or immunopathology. Vaccination with DNA may therefore provide a useful alternative to current viral or subunit vaccines once the efficacy of immunization with DNA is optimized.
Challenges in the Use of Compact Disc-Based Centrifugal Microfluidics for Healthcare Diagnostics at the Extreme Point of Care (2016)

Since its inception, Compact Disc (CD)-based centrifugal microfluidic technology has drawn a great deal of interest within research communities due to its potential use in biomedical applications. The technology has been referred to by different names, including compact-disc microfluidics, lab-on-a-disk, lab-on-a-CD and bio-disk. This paper critically reviews the state-of-the-art in CD-based centrifugal microfluidics devices and attempts to identify the challenges that, if solved, would enable their use in the extreme point of care. Sample actuation, manufacturing, reagent storage and implementation, target multiplexing, bio-particle detection, required hardware and system disposal, and sustainability are the topics of focus.
Induction of adaptive immunity by flagellin does not require robust activation of innate immunity (2009)

The ability of TLR agonists to promote adaptive immune responses is attributed to their ability to robustly activate innate immunity. However, it has been observed that, for adjuvants in actual use in research and vaccination, TLR signaling is dispensable for generating humoral immunity. Here, we examined the role of TLR5 and MyD88 in promoting innate and humoral immunity to flagellin using a prime/boost immunization regimen. We observed that eliminating TLR5 greatly reduced flagellin-induced cytokine production, except for IL-18, and ablated DC maturation but did not significantly impact flagellin's ability to promote humoral immunity. Elimination of MyD88, which will ablate signaling through TLR and IL-1beta/IL-18 generated by Nod-like receptors, reduced, but did not eliminate flagellin's promotion of humoral immunity. In contrast, loss of the innate immune receptor for profilin-like protein (PLP), TLR11, greatly reduced the ability of PLP to elicit humoral immunity. Together, these results indicate that, firstly, the degree of innate immune activation induced by TLR agonists may be in great excess of that needed to promote humoral immunity and, secondly, there is considerable redundancy in mechanisms that promote the humoral immune response upon innate immune recognition of flagellin. Thus, it should be possible to design innate immune activators that are highly effective vaccine adjuvants yet avoid the adverse events associated with systemic TLR activation.
Selective CDK4/6 inhibition with tumor responses by PD0332991 in patients with mantle cell lymphoma (2012)

Mantle cell lymphoma (MCL) carries an unfavorable prognosis and requires new treatment strategies. The associated t(11:14) translocation results in enhanced cyclin D1 expression and cyclin D1-dependent kinase activity to promote cell-cycle progression. A pharmacodynamic study of the selective CDK4/6 inhibitor PD0332991 was conducted in 17 patients with relapsed disease, using 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) and 3-deoxy-3[(18)F]fluorothymidine (FLT) positron emission tomography (PET) to study tumor metabolism and proliferation, respectively, in concert with pre- and on-treatment lymph node biopsies to assess retinoblastoma protein (Rb) phosphorylation and markers of proliferation and apoptosis. Substantial reductions in the summed FLT-PET maximal standard uptake value (SUV(max)), as well as in Rb phosphorylation and Ki-67 expression, occurred after 3 weeks in most patients, with significant correlations among these end points. Five patients achieved progression-free survival time of > 1 year (range, 14.9-30.1+ months), with 1 complete and 2 partial responses (18% objective response rate; 90% confidence interval, 5%-40%). These patients demonstrated > 70%, > 90%, and ≥ 87.5% reductions in summed FLT SUV(max) and expression of phospho-Rb and Ki67, respectively, parameters necessary but not sufficient for long-term disease control. The results of the present study confirm CDK4/6 inhibition by PD0332991 at a well-tolerated dose and schedule and suggest clinical benefit in a subset of MCL patients. This study is registered at www.clinicaltrials.gov under identifier NCT00420056.
Teaching temperance ‐ lessons for today's drinking culture (2005)

Society and government policy currently demonstrate contradictory tendencies in relation to alcohol. Government policy promotes longer opening hours, but also more stringent control of public drinking through ASBOs and alcohol dispersal zones. Young people favour heavy drinking and the ‘night time economy’, while older generations oppose the extension of pub opening hours. The media debates rationing treatment for those with self‐inflicted disease, but portrays national mourning at George Best's death. In an attempt to learn from the efforts of the past, Virginia Berridge uncovers the strikingly familiar world of temperance and ponders whether we are perhaps at a ‘tipping point’ in culture in relation to alcohol?
Acyl Carrier Protein (1972)

Abstract β-Hydroxyacyl acyl carrier protein (ACP) dehydrase has been purified 2900-fold from extracts of Escherichia coli. The enzyme catalyzes the reversible dehydration of β-hydroxyacyl-ACP thioesters to yield specifically trans-2-enoyl-ACP products. It is active with trans-2-enoyl-ACP thioesters of chain lengths from 4 through 16 carbon atoms. The enzyme catalyzes the hydration of cis-5-trans-2-dodecadienoyl-ACP, an intermediate in unsaturated fatty acid synthesis, as well as the trans-2-enoyl-ACP substrates that are intermediates in saturated fatty acid synthesis. Thus this enzyme can function in the synthesis of both saturated and unsaturated fatty acids. The lowest enzyme activity was noted with trans-2-decenoyl-ACP. The relevance of this finding with respect to the activity of β-hydroxydecanoyl thioester dehydrase, which specifically catalyzes the conversion of β-hydroxydecanoyl-ACP to cis-3-decenoyl-ACP is discussed as a possible factor in control of saturated versus unsaturated fatty acid synthesis. Attempts to separate or to show distinguishing characteristics of β-hydroxyacyl-ACP dehydrase activities with short, medium, or long chain substrates were unsuccessful, and these activities are therefore attributed to a single enzyme.
Negative symptoms in the remission phase of bipolar disorder. (2007)

Objectives: Though negative symptoms (NS) are major contributors to sociooccupational dysfunction in schizophrenia, NS in remitted bipolar disorder (BPD) are little studied. We evaluated the prevalence and correlates of NS and their contribution to sociooccupational dysfunction in remitted BPD. Methods: Ninety remitted BPD patients, receiving only mood stabilizers, were evaluated with the Scale for Assessment of Negative Symptoms (SANS), Brief Psychiatric Rating Scale (BPRS) and Social and Occupational Functioning Assessment Scale. Forty-five normal controls matched for age, sex and total years of education were assessed with SANS. Results: NS were present in 26.67 % of the patients. The patients had more severe affective flattening, alogia, anhedonia-asociality and avolition-apathy. Pri-mary NS were associated with history of obstetric complications, family history of schizophrenia, earlier age of illness onset, history of mood incongruent psychotic features (MIPF), poor premorbid and current sociooccupational function-ing and a greater decline in functioning after illness onset. Factor analysis revealed three factors which explained 62.08 % of the variance- secondary negative and subaffective symptoms, primary NS, and anxiety symptoms. Conclu-sions: As NS are prevalent in remitted BPD and contribute to the patients ’ sociooccupational dysfunction, they re-quire prompt detection and management (German J Psychiatry 2007;10: 1-7).
Automatic symbolic verification of embedded systems (1996)

Presents a model-checking procedure and its implementation for the automatic verification of embedded systems. The system components are described as hybrid automata-communicating machines with finite control and real-valued variables that represent continuous environment parameters such as time, pressure and temperature. The system requirements are specified in a temporal logic with stop-watches, and verified by symbolic fixpoint computation. The verification procedure-implemented in the Cornell Hybrid Technology tool, HyTech-applies to hybrid automata whose continuous dynamics is governed by linear constraints on the variables and their derivatives. We illustrate the method and the tool by checking safety, liveness, time-bounded and duration requirements of digital controllers, schedulers and distributed algorithms.
THE EFFECT OF SOLUBLE COMPLEMENT RECEPTOR TYPE 1 ON HYPERACUTE REJECTION OF PORCINE XENOGRAFTS (1994)

The use of xenografts (Xgs) from distantly related species to relieve the increasing shortage of organs for clinical transplantation is prevented by the occurrence of hyperacute rejection (HAR). This process, in which C activation plays a central role, cannot be inhibited with currently available immunosuppressants. In two clinically relevant xenotransplantation models, this study evaluated the effect of C inhibition using recombinant soluble complement receptor type 1 (sCR1) on HAR. In an ex vivo model in which porcine cardiac Xgs were perfused with human blood, cardiac function ceased within 34 min when the perfusate blood was untreated (n = 3). When the perfusate blood was treated with sCR1 (300 micrograms/ml), cardiac Xg function was maintained for up to 4 hr (n = 3). Immunohistologic examination of these Xgs demonstrated deposition of C3b/iC3b and C3d in Xgs perfused with untreated human blood but only C3d deposition in those Xgs perfused with sCR1-treated human blood. These findings are consistent with the cofactor activity of sCR1 for factor I-mediated degradation of deposited C3b/iC3b to C3d. Treatment with sCR1 also prevented the histopathologic changes of HAR observed when untreated blood was used as the perfusate. In an in vivo pig-to-primate heterotopic cardiac xenotransplantation model, in which porcine Xgs transplanted into untreated cynomolgus monkey recipients underwent HAR in 1 hr or less (n = 3), a single intravenous bolus of sCR1 (15 mg/kg) administered to the recipient immediately before Xg reperfusion markedly inhibited total and alternative pathway serum C activity and prolonged Xg survival to between 48 and 90 hr (n = 5). These studies confirm the important role of C activation in HAR of porcine cardiac Xgs by primates and indicate that sCR1 may be a useful agent for xenotransplantation.