gebhart/patrepeval huggingface dataset:
ChemInform Abstract: Suzuki Cross‐Coupling of Carbohydrates: Synthesis of β‐Arylmethyl‐C‐glycosides and Aryl‐Scaffolded Trisaccharide Mimics. (1998)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
The Future of Immunotherapy: A 20-Year Perspective (2017)

Immunotherapy is the field of immunology that aims to identify treatments for diseases through induction, enhancement or suppression of an immune response. Immunotherapies designed to instigate or enhance an immune response are considered "activating immunotherapies" while those designed to repress an immune response are "suppressive immunotherapies." This perspective will focus on two areas of immunotherapy, activating immunotherapies for cancer and suppressive immunotherapies for autoimmunity both of which have seen a resurgence in interest in recent years and are likely to transform the treatment of many human diseases in the next 20 years. Effective immunotherapies for cancer, where the aim is to activate tumor-specific immune responses, will be totally different from those designed to suppress the immune response to self-antigens in autoimmune disease. Furthermore, the reader will appreciate that the degree to which side effects of immunotherapies are acceptable will differ drastically between life-threatening cancers and chronic, debilitating but not necessarily life-threatening autoimmune conditions.
Presentation of native epitopes in the V1/V2 and V3 regions of human immunodeficiency virus type 1 gp120 by fusion glycoproteins containing isolated gp120 domains (1994)

The immune response to viral glycoproteins is often directed against conformation- and/or glycosylation-dependent structures; synthetic peptides and bacterially expressed proteins are inadequate probes for the mapping of such epitopes. This report describes a retroviral vector system that presents such native epitopes on chimeric glycoproteins in which protein fragments of interest are fused to the C terminus of the N-terminal domain of the murine leukemia virus surface protein, gp70. The system was used to express two disulfide-bonded domains from gp120, the surface protein of human immunodeficiency virus type 1 (HIV-1), that include potent neutralization epitopes. The resulting fusion glycoproteins were synthesized at high levels and were efficiently transported and secreted. A fusion protein containing the HXB2 V1/V2 domain was recognized by an HIVIIIB-infected patient serum as well as by 17 of 36 HIV-1 seropositive hemophiliac, homosexual male and intravenous drug user patient sera. Many of these HIV+ human sera reacted with V1/V2 domains from several HIV-1 clones expressed in fusion glycoproteins, indicating the presence of cross-reactive antibodies against epitopes in the V1/V2 domain. Recognition of gp(1-263):V1/V2HXB2 by the HIVIIIB-infected human patient serum was largely blocked by synthetic peptides matching V1 but not V2 sequences, while recognition of this construct by a broadly cross-reactive hemophiliac patient serum was not blocked by individual V1 or V2 peptides or by mixtures of these peptides. A construct containing the V3 domain of the IIIB strain of HIV-1, gp(1-263):V3HXB2, was recognized by sera from a human and a chimpanzee that had been infected by HIVIIIB but not by sera from hemophiliac patients who had been infected with HIV-1 of MN-like V3 serotype. The reactive sera had significantly higher titers when assayed against gp(1-263):V3HXB2 than when assayed against matching V3 peptides. Immunoprecipitation of this fusion glycoprotein by the human serum was only partially blocked by V3 peptide, indicating that this infected individual produced antibodies against epitopes in V3 that were expressed on the fusion glycoprotein but not by synthetic peptides. These data demonstrated that the chimeric glycoproteins described here effectively present native epitopes present in the V1/V2 and V3 domains of gp120 and provide efficient methods for detection of antibodies directed against native epitopes in these regions and for characterization of such epitopes.
The carboxy-terminal domain initiates trimerization of bacteriophage T4 fibritin. (1999)

Bacteriophage T4 fibritin is a triple-stranded, parallel, segmented alpha-helical coiled-coil protein. Earlier we showed that the C-terminal globular domain (foldon) of fibritin is essential for correct trimerization and folding of the protein. We constructed the chimerical fusion protein W31 in which the fibritin foldon sequence is followed by the small globular non-alpha-helical protein gp31 of the T4 phage. We showed that the foldon is capable of trimerization in the absence of the coiled-coil part of fibritin. A deletion mutant of fibritin (NB1) with completely deleted foldon is unable to fold and trimerize correctly. An excess of this mutant protein did not influence the refolding of fibritin in vitro, and the chimerical protein inhibited this process efficiently. Our conclusion is that the trimerization of the foldon is the initial step of fibritin refolding and is followed by the formation of the coiled-coil structure.
Long‐term efficacy of ustekinumab in patients with moderate‐to‐severe psoriasis treated for up to 5 years in the PHOENIX 1 study (2012)

Through 5 years of continuous treatment, ustekinumab demonstrated stable clinical response and a safety profile consistent with previous reports.
Improved Corneal Wound Healing through Modulation of Gap Junction Communication Using Connexin43-Specific Antisense Oligodeoxynucleotides (2012)

Application of Cx43 AsODN to the cornea reduces stromal edema and inflammation, promoting faster wound closure and a more uniform repair of the epithelial basal lamina after laser ablation.
Adhesion molecules in implantation (1997)

At implantation, trophectoderm attaches to the apical uterine luminal epithelial cell surface. Molecular anatomy studies in humans and mice, and data from experimental models have identified several adhesion molecules that could take part in this process: integrins of the alpha v family, trophinin, CD44, cad-11, the H type I and Lewis y oligosaccharides and heparan sulfate. The endometrial cell surface mucin MUC1 may play a role in both steric inhibition of attachment and selective glycan display. After attachment, interstitial trophoblast invasion occurs requiring a new repertoire of adhesive interactions with maternal extracellular matrix as well as stromal and vascular cell populations. Human anchorage sites contain columns of cytotrophoblasts in which self-attachment gives way progressively to adhesion to extracellular matrix and then interstitial migration. The beta 1 integrins are important during these later stages of implantation and placentation.
Identification of Mycobacterium species by using amplified ribosomal DNA restriction analysis (1993)

A rapid procedure for the identification of cultured Mycobacterium isolates, based on the combination of enzymatic amplification and restriction analysis, is described. The 16S rRNA genes (rDNA) of 99 strains belonging to 18 different species of the genus Mycobacterium were enzymatically amplified. Amplified rDNA restriction analysis with the enzymes CfoI, MboI, and RsaI was carried out. The combination of the amplified rDNA restriction analysis patterns obtained after restriction with CfoI and MboI enabled differentiation between Mycobacterium asiaticum (number of strains = 4), M. avium (n = 22), M. chelonae (n = 5), M. flavescens (n = 1), M. fortuitum (n = 6), M. gordonae (n = 6), M. intracellulare (n = 13), M. marinum (n = 7), M. nonchromogenicum (n = 1), M. simiae (n = 5), M. terrae (n = 5), the M. tuberculosis complex (n = 11), and 2 of 4 strains of M. xenopi. Further restriction with RsaI was necessary to differentiate between the species M. kansasii (n = 5), M. scrofulaceum (n = 4), and the 2 other M. xenopi strains. The M. avium-M. intracellulare complex was characterized by a specific MboI pattern, and M. avium and M. intracellulare strains could further be differentiated by restriction with CfoI. The whole procedure, including sample preparation prior to the polymerase chain reaction, can be carried out within 8 h, starting from a pure culture.
Exploring Strategies for Training Deep Neural Networks (2009)

Deep multi-layer neural networks have many levels of non-linearities allowing them to compactly represent highly non-linear and highly-varying functions. However, until recently it was not clear how to train such deep networks, since gradient-based optimization starting from random initialization often appears to get stuck in poor solutions. Hinton et al. recently proposed a greedy layer-wise unsupervised learning procedure relying on the training algorithm of restricted Boltzmann machines (RBM) to initialize the parameters of a deep belief network (DBN), a generative model with many layers of hidden causal variables. This was followed by the proposal of another greedy layer-wise procedure, relying on the usage of autoassociator networks. In the context of the above optimization problem, we study these algorithms empirically to better understand their success. Our experiments confirm the hypothesis that the greedy layer-wise unsupervised training strategy helps the optimization by initializing weights in a region near a good local minimum, but also implicitly acts as a sort of regularization that brings better generalization and encourages internal distributed representations that are high-level abstractions of the input. We also present a series of experiments aimed at evaluating the link between the performance of deep neural networks and practical aspects of their topology, for example, demonstrating cases where the addition of more depth helps. Finally, we empirically explore simple variants of these training algorithms, such as the use of different RBM input unit distributions, a simple way of combining gradient estimators to improve performance, as well as on-line versions of those algorithms.
Electrical, contractile and structural remodeling during atrial fibrillation (2002)

The natural history of atrial fibrillation (AF) is characterized by a gradual worsening with time. The recent finding that AF itself produces changes in atrial function and structure has provided a possible explanation for the progressive nature of this arrhythmia. Electrical remodeling (shortening of atrial refractoriness) develops within the first days of AF and contributes to an increase in stability of AF. However, 'domestication of AF' must also depend on a 'second factor' since the persistence of AF continues to increase after electrical remodeling has been completed. Atrial contractile remodeling (loss of contractility) leads to a reduced atrial transport function after cardioversion of AF. An important clinical consequence is that during several days after restoration of sinus rhythm, the risk of atrial thrombus formation is still high. In addition, the reduction of atrial contractility during AF may enhance atrial dilatation which may add to the persistence of AF. Tachycardia-induced structural remodeling takes place in a different time domain (weeks to months). Myolysis probably contributes to the loss of atrial contractile force. Although it might explain the loss of efficacy of pharmacological cardioversion and the development of permanent AF, the role of structural remodeling in the progression of AF is still unclear. Atrial structural remodeling also occurs as a result of heart failure and other underlying cardiovascular diseases. The associated atrial fibrosis might explain intra-atrial conduction disturbances and the susceptibility for AF. Thus, both AF itself and the underlying heart disease are responsible for the development of the arrhythmogenic substrate. New strategies for prevention and termination of AF should be build on our knowledge of the mechanisms and time course of AF-induced atrial remodeling.
Effect of Frequent Nocturnal Hemodialysis vs Conventional Hemodialysis on Left Ventricular Mass and Quality of Life (2007)

isrctn.org Identifier: ISRCTN25858715.
Acute Liver Failure (1996)

Acute liver failure (ALF), or fulminant hepatic failure, is a distinct clinical syndrome which crosses medical disciplines. A relatively rare condition, ALF remains a major focus of clinical and research attention and with the advent of transplantation, the importance of understanding management of ALF has taken on a new urgency. In this 1997 volume, the editors bring together a distinguished team of contributors to describe the aetiology, pathology and treatment of this important syndrome. Also covered are consensus techniques in liver transplantation for ALF patients, as well as descriptions of artificial and bioartificial liver assist devices. A section on future treatments includes hepatocyte transplantation, auxiliary grafts and other temporary liver support. Notable for the high level of authors' expertise, this comprehensive volume should prove invaluable to internists, gastroenterologists, surgeons, and intensive care providers.
Stem Cells — Scientific, Medical, and Political Issues (2002)

It is rare that a scientific subject causes controversy not only among scientists but also among politicians and the public. Stem-cell biology is such a subject. The media reports new claims as soon as (or before) they appear in the scientific literature or are presented at scientific meetings. Talk-show hosts present their views, and both Congress and the executive branch follow with policy initiatives. But in its present state, there is little certitude in the science of stem cells, and the hard facts are emerging slowly. It is important for the public and policy makers to understand the fundamentals of . . .
Quantitative structural temporal constraints on repeating events (2002)

Presents a model of the temporal structure of repeating events. This model allows for the specification of constraints dealing with the part-whole structure of these events. The temporal structure of repeating events is viewed as being composed of six aspects: sub-interval number, gap number, sub-interval duration, gap duration, period and extent. A set of constraints involving these aspects collectively specifies the conditions under which repeating events can be assigned times, and thus partially formalizes a solution to the scheduling problem for repeating events. The consistency and tightness of a set of such constraints can be tested by identifying determinacy relationships among the different aspects. These relationships can also be used to infer constraints about one structural aspect from others. This paper also introduces a new category of quantitative temporal constraints involving repeating events which specifies that the duration or period of events be distributed randomly over a set of values.
The sea pansy Renilla reniformis luciferase serves as a sensitive bioluminescent reporter for differential gene expression in Candida albicans (1996)

The infectious yeast Candida albicans progresses through two developmental programs which involve differential gene expression, the bud-hypha transition and high-frequency phenotypic switching. To understand how differentially expressed genes are regulated in this organism, the promoters of phase-specific genes must be functionally characterized, and a bioluminescent reporter system would facilitate such characterization. However, C. albicans has adopted a nontraditional codon strategy that involves a tRNA with a CAG anticodon to decode the codon CUG as serine rather than leucine. Since the luciferase gene of the sea pansy Renilla reinformis contains no CUGs, we have used it to develop a highly sensitive bioluminescent reporter system for C. albicans. When fused to the galactose-inducible promoter of GAL1, luciferase activity is inducible; when fused to the constitutive EF1 alpha 2 promoter, luciferase activity is constitutive; and when fused to the promoter of the white-phase-specific gene WH11 or the opaque-phase-specific gene OP4, luciferase activity is phase specific. The Renilla luciferase system can, therefore, be used as a bioluminescent reporter to analyze the strength and developmental regulation of C. albicans promoters.
Diagnostic value of anti-Saccharomyces cerevisiae and antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease (2001)

Correct diagnosis of inflammatory bowel disease (IBD), especially the differentiation between Crohn's disease (CD) and ulcerative colitis (UC), is highly important toward treatment and prognosis. Serological markers are noninvasive diagnostic tools that could be of value in differentiating CD from UC, in cases of indeterminate colitis, and in the identification of subgroups in IBD. The aim of this study was to evaluate the diagnostic accuracy of perinuclear antineutrophil cytoplasmic (pANCA) and anti-Saccharomyces cerevisiae antibodies (ASCA) for IBD.ASCA and pANCA were studied in a large cohort of consecutive IBD patients (n = 582: 407 CD, 147 UC, and 28 indeterminate colitis), patients with non-IBD diarrheal illnesses (n = 74), and healthy controls (n = 157). An indirect immunofluorescence technique and a standardized ELISA were performed for detection of pANCA and ASCA, respectively.Prevalence of ASCA and pANCA was high in CD patients (59.7%) and UC (49.7%) patients, respectively. Positivity for both markers was significantly lower in healthy and non-IBD controls. Accuracy data (sensitivity, specificity, PPV, and NPV, respectively) for differentiating IBD from controls are as follows: ASCA+: 60% (243/407), 91% (345/378), 88% (243/276), and 68% (345/509); pANCA+: 50% (73/147), 95% (605/638), 69% (73/106), and 89% (605/679); ASCA+/pANCA-: 56% (229/407), 94% (355/378), 91% (229/252), and 67% (355/533); and pANCA+/ASCA-: 44% (65/147), 97% (620/638), 78% (65/83), and 88% (620/702).Specificity of serological markers for IBD is high, but low sensitivity makes them less useful as diagnostic tests. The combination of tests is probably more powerful, although, clinical subgroups still need to be defined. The usefulness of these markers in indeterminate colitis needs to be studied prospectively.
Molecular Characterization of a Fully Human Chimeric T-Cell Antigen Receptor for Tumor-Associated Antigen EpCAM (2012)

The transduction of T cells to express chimeric T-cell antigen receptor (CAR) is an attractive strategy for adaptive immunotherapy for cancer, because the CAR can redirect the recognition specificity of T cells to tumor-associated antigens (TAAs) on the surface of target cells, thereby avoiding the limitations of HLA restriction. However, there are considerable problems with the clinical application of CAR, mostly due to its xenogeneic components, which could be immunogenic in humans. Moreover, while extensive studies on the CARs have been performed, the detailed molecular mechanisms underlying the activation of CAR-grafted T cells remain unclear. In order to eliminate potential immunogenicity and investigate the molecular basis of the CAR-mediated T-cell activation, we constructed a novel CAR (CAR57-28ζ) specific for one of the most important TAAs, epithelial cell adhesion molecule (EpCAM), using only human-derived genes. We revealed that in Jurkat T cells, lentivirally expressed CAR57-28ζ can transmit the T-cell-activating signals sufficient to induce IL-2 production upon EpCAM stimulation. An immunofluorescent analysis clearly showed that the CAR57-28ζ induces the formation of signaling clusters containing endogenous CD3ζ at the CAR/EpCAM interaction interface. These results suggest that this CAR gene may be safely and effectively applied for adaptive T-cell immunotherapy.
Advanced Materials for Co‐Delivery of Drugs and Genes in Cancer Therapy (2012)

With cancer being the major cause of mortality worldwide, the continued development of safe and efficacious treatments is warranted. A better understanding of the molecular mechanism and genetic basis of tumor initiation and progression, coupled with advances in chemistry, molecular biology and engineering have led to discovery of a wide range of therapeutic agents for cancer therapy. However, multidrug-resistance, which is mainly caused by malfunction of genes, has become a major problem in chemotherapy. To overcome this problem, the simultaneous delivery of genes to cancer cells has been proposed to correct the malfunctioned genes to sensitize the cells to chemotherapeutics. This progress report summarizes key advances in drug and gene delivery with focus on the development of polymers, peptides, liposomes and inorganic materials as nanocarriers for co-delivery of small molecular drugs and macromolecular genes or proteins. In addition, challenges and future perspectives in the design of nanocarriers for the co-delivery of therapeutic drugs and genes are discussed.
Aminomodified Probes for Atomic Force Microscopy (2002)

Abstract A procedure for direct functionalization of silicon nitride atomic force microscope (AFM) probes with 3-aminopropyltriethoxy silane (APTES) was developed. The probes were modified in vapors of APTES at ambient conditions (AP-tips). The functionalization of tips was monitored by fluorescent microscopy and the force measurements with AFM. AP-tips were derivatized with a non-fluorescent quinoline analog (FQ) which reacts with primary amines to form a strongly fluorescent isoindole. AP-tip fluorescence was significantly higher than control probes. Amino modified tips manifest a strong adhesion to freshly cleaved mica and this behavior is qualitatively similar to the interaction of unmodified silicone nitride probes with AP-mica. The adhesion of AP-tips to mica or AP-mica to unmodified tips decreases as ionic strength increases indicating a dominant electrostatic component of the adhesion effect. This interpretation is supported by the experiments at different pH and the reaction of AP-tips with glutaraldehyde. The adhesion effect is very small at basic pH due to the deprotonation of amino groups. The reaction of immobilized amines by the treatment of the tips with glutaraldehyde decreases the tip-surface interaction dramatically. Like AP-mica, AP-trips are stable during storage and thus can be used for additional derivation steps. Keywords: Atomic Force Microscopy (AFM)ProbesFunctionalizationAdhesive ForcesAminosilanes
c‐erbB‐2 and ras expression levels in breast cancer are correlated and show a co‐operative association with unfavorable clinical outcome (1991)

c-erbB-2 and ras expression was measured on tumor extracts from 132 human primary breast carcinomas, by immunoblotting analysis. Expression of the c-erbB-2-encoded p185 protein was observed in 39% of the samples and found to correlate with c-erbB-2 gene amplification, detected by Southern analysis in 19 of the 77 available tumor DNAs. p185 expression was linked to the absence of progesterone receptors, but it was not related to lymph-node status or to other clinico-pathological parameters. Levels of the ras-encoded p21 proteins higher than in normal breast tissues were found in 71% of the samples. No significant correlation was seen between p21 level and the available clinical parameters. Conversely, there was a strong positive correlation between p21 and p185 levels. Analysis of follow-up data revealed that p185 expression was associated with a shorter time to relapse and death. Most notably, the contemporaneous expression of p185 and of high p21 levels was more effective than p185 expression alone in identifying cases with poor prognosis. The prognostic value of p185/p21 co-expression was particularly significant in progesterone-receptor-positive tumors. Our data suggest that c-erbB-2 and ras may act synergistically to endow breast-tumor cells with a highly aggressive phenotype.