gebhart/patrepeval huggingface dataset:
The structural basis of allergenicity: recombinant DNA‐based strategies for the study of allergens (1989)

The use of recombinant DNA techniques for the study of allergenicity of proteins is a viable, and in many ways a preferred, alternative to the traditional procedures of protein purification, digestion and analysis of peptides for both allergenicity and amino acid sequence. The process of protein purification can be difficult and in many instances workers are forced to use only partially pure fractions that make the identification of the allergenic proteins uncertain. Furthermore, the purification and sequencing of peptides and their testing for retention of allergenic properties, represents a substantial and time-consuming work load. The synthesis of families of synthetic peptides to characterize the amino acids important for allergenic properties is also expensive and time-consuming. On the other hand, the preparation of a cDNA library from an allergen source is today a relatively easy and inexpensive task. The isolation and purification of cDNA clones is comparatively trivial compared to protein purification. Using the techniques described in this text, it can be seen that the molecular biological approach, although in some respects similar in principle to those of the protein chemist to study allergens, provides the capability to study several clones at the same time, and to compare clones for the presence of conserved regions corresponding to allergenic determinants. In addition, the techniques for generating mutant sequences provides perhaps the most powerful and simple set of procedures available for defining the amino acid structures essential for proteins or peptides to behave as allergens.
The many faces of p38 mitogen-activated protein kinase in progenitor/stem cell differentiation (2012)

Regulation of stem cells is essential for development and adult tissue homoeostasis. The proper control of stem cell self-renewal and differentiation maintains organ physiology, and disruption of such a balance results in disease. There are many mechanisms that have been established as stem cell regulators, such as Wnt or Notch signals. However, the intracellular mechanisms that mediate and integrate these signals are not well understood. A new intracellular pathway that has been reported to be involved in the regulation of many stem cell types is that of p38 MAPK (mitogen-activated protein kinase). In particular, p38α is essential for the proper differentiation of many haematopoietic, mesenchymal and epithelial stem/progenitor cells. Many reports have shown that disruption of this kinase pathway has pathological consequences in many organs. Understanding the extracellular cues and downstream targets of p38α in stem cell regulation may help to tackle some of the pathologies associated with improper differentiation and regulation of stem cell function. In the present review we present a vision of the current knowledge on the roles of the p38α signal as a regulator of stem/progenitor cells in different tissues in physiology and disease.
A universal retroviral vector for efficient constitutive expression of exogenous genes (1987)

Journal Article A universal retroviral vector for efficient constitutive expression of exogenous genes Get access Catherine A. Boulter, Catherine A. Boulter European Molecular Biology LaboratoryPostfach 10.2209, 6900 Heidelberg, FRG Search for other works by this author on: Oxford Academic PubMed Google Scholar Erwin F. Wagner Erwin F. Wagner European Molecular Biology LaboratoryPostfach 10.2209, 6900 Heidelberg, FRG Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 15, Issue 17, 11 September 1987, Page 7194, https://doi.org/10.1093/nar/15.17.7194 Published: 11 September 1987 Article history Received: 28 July 1987 Published: 11 September 1987
Mutating the CX3C Motif in the G Protein Should Make a Live Respiratory Syncytial Virus Vaccine Safer and More Effective (2017)

Respiratory syncytial virus (RSV) belongs to the family <i>Paramyxoviridae</i> and is the single most important cause of serious lower respiratory tract infections in young children, yet no highly effective treatment or vaccine is available. Through a CX3C chemokine motif (<sup>182</sup>CWAIC<sup>186</sup>) in the G protein, RSV binds to the corresponding chemokine receptor, CX3CR1. Since RSV binding to CX3CR1 contributes to disease pathogenesis, we investigated whether a mutation in the CX3C motif by insertion of an alanine, A<sup>186</sup>, within the CX3C motif, mutating it to CX4C (<sup>182</sup>CWAIAC<sup>187</sup>), which is known to block binding to CX3CR1, might decrease disease. We studied the effect of the CX4C mutation in two strains of RSV (A2 and r19F) in a mouse challenge model. We included RSV r19F because it induces mucus production and airway resistance, two manifestations of RSV infection in humans, in mice. Compared to wild-type (wt) virus, mice infected with CX4C had a 0.7 to 1.2 log<sub>10</sub>-fold lower virus titer in the lung at 5 days postinfection (p.i.) and had markedly reduced weight loss, pulmonary inflammatory cell infiltration, mucus production, and airway resistance after challenge. This decrease in disease was not dependent on decrease in virus replication but did correspond to a decrease in pulmonary Th2 and inflammatory cytokines. Mice infected with CX4C viruses also had higher antibody titers and a Th1-biased T cell memory response at 75 days p.i. These results suggest that the CX4C mutation in the G protein could improve the safety and efficacy of a live attenuated RSV vaccine.<b>IMPORTANCE</b> RSV binds to the corresponding chemokine receptor, CX3CR1, through a CX3C chemokine motif (<sup>182</sup>CWAIC<sup>186</sup>) in the G protein. RSV binding to CX3CR1 contributes to disease pathogenesis; therefore, we investigated whether a mutation in the CX3C motif by insertion of an alanine, A<sup>186</sup>, within the CX3C motif, mutating it to CX4C (<sup>182</sup>CWAIAC<sup>187</sup>), known to block binding to CX3CR1, might decrease disease. The effect of this mutation and treatment with the F(ab')<sub>2</sub> form of the anti-RSV G 131-2G monoclonal antibody (MAb) show that mutating the CX3C motif to CX4C blocks much of the disease and immune modulation associated with the G protein and should improve the safety and efficacy of a live attenuated RSV vaccine.
Disruption of overlapping transcripts in the ROSA βgeo 26 gene trap strain leads to widespread expression of β-galactosidase in mouse embryos and hematopoietic cells (1997)

The ROSA beta geo26 (ROSA26) mouse strain was produced by random retroviral gene trapping in embryonic stem cells. Staining of ROSA26 tissues and fluorescence-activated cell sorter-Gal analysis of hematopoietic cells demonstrates ubiquitous expression of the proviral beta geo reporter gene, and bone marrow transfer experiments illustrate the general utility of this strain for chimera and transplantation studies. The gene trap vector has integrated into a region that produces three transcripts. Two transcripts, lost in ROSA26 homozygous animals, originate from a common promoter and share identical 5' ends, but neither contains a significant ORF. The third transcript, originating from the reverse strand, shares antisense sequences with one of the noncoding transcripts. This third transcript potentially encodes a novel protein of at least 505 amino acids that is conserved in humans and in Caenorhabditis elegans.
Self-Assembly and Tribological Property of a Novel 3-Layer Organic Film on Silicon Wafer with Polydopamine Coating as the Interlayer (2009)

A novel 3-layer organic film was fabricated on silicon wafer with a polydopamine coating (coded as PDAc) as the interlayer by a multistep self-assembly process. The formation and structure of the films were analyzed by means of ellipsometric thickness measurement, water contact angle measurement, and attenuated total reflection-Fourier transform infrared spectrometry (ATR-FTIR). Meanwhile, an atomic force microscope (AFM) characterization was performed to evaluate the adhesive and microtribological behaviors of the 3-layer film, and a ball-on-plate tribometer was used to test macrotribological performance. As results show, the as-prepared 3-layer film possessed the excellent tribological properties characterized by lower friction and higher antiwear ability, which was ascribed to the special chemical structure of the film, i.e., the strong adhesion of the film to the silicon wafer, the chemical bonding between the adjacent layers, the cross-linked structure of the PDAc interlayer, and the hydrophobicity, high flexibility, and high elasticity of the stearoyl chloride (STC) outer layer. Hopefully, the present work provides a feasible route to construct a multilayer film with excellent structural stability and tribological behavior. The titled multilayer film might find potential applications in boundary lubrication and many other areas.
Structural and functional characterization of full-length heparin-binding growth associated molecule. (1992)

Heparin-binding growth-associated molecule (HB-GAM) was purified from adult bovine brain and chicken heart. The yield of HB-GAM is increased by 5- to 10-fold when 250 mM NaCl is added to the homogenization buffer, indicating that HB-GAM may exist as a complex with an insoluble component of the tissue. The complete amino acid sequence of the brain-derived HB-GAM was established by automated Edman degradation of the intact protein and chemically or enzymatically derived fragments. The mass of bovine HB-GAM as determined by plasma desorption time-of-flight mass spectrometry is 15,291 mass units, which compares favorably with the calculated mass of 15,289 based on the amino acid sequence. Therefore, HB-GAM has not undergone any major post-translational modifications other than cleavage of the signal peptide. These results indicate that previous amino acid sequence analysis of this protein was carried out using truncated HB-GAM. Full-length HB-GAM is not a mitogen for Balb/3T3 clone A31, Balb MK, NRK, or human umbilical vein endothelial cells. HB-GAM does, however, have adhesive properties and neurite extension activity for chick embryo cerebral cortical derived neurons when presented to these cells as a substrate. HB-GAM had little neurite extension activity when presented as a soluble factor.
Simple and Scalable Response Prediction for Display Advertising (2014)

Clickthrough and conversation rates estimation are two core predictions tasks in display advertising. We present in this article a machine learning framework based on logistic regression that is specifically designed to tackle the specifics of display advertising. The resulting system has the following characteristics: It is easy to implement and deploy, it is highly scalable (we have trained it on terabytes of data), and it provides models with state-of-the-art accuracy.
Transfer of proteins to membranes facilitates both cyanogen bromide cleavage and two-dimensional proteolytic mapping. (1990)

We have found that the transfer of gel-fractionated proteins to membranes facilitates phosphopeptide mapping. Nitrocellulose proves to be an excellent matrix for both cyanogen bromide cleavage and proteolytic digestion. Digestion of p56lck bound to a nitrocellulose membrane with cyanogen bromide or trypsin generated patterns of phosphopeptides indistinguishable from those produced by digestion of p56lck eluted from a gel. Immobilon-P and nylon membranes can also be used for proteolytic mapping, but not for cyanogen bromide cleavage. Since the use of membrane-bound protein eliminates the need for elution and precipitation of the protein, analysis is rapid. In addition, the recovery of the peptides from proteins digested on membranes is better and more consistent than it is from eluted and precipitated proteins.
Antigenic variation among strains of Chlamydia pneumoniae (1991)

The antigenic profiles of six strains of Chlamydia pneumoniae were analyzed by the microimmunofluorescence test (MIF) and immunoblotting with human serum and murine monoclonal antibody. MIF-derived antibody titers in serum samples from culture-positive patients were four- to eightfold higher against autologous isolate antigen than they were against the prototype antigen strain TW-183. Sera of patients with respiratory illness that were culture negative and complement fixation positive for Chlamydia spp. produced higher titers by MIF against a strain of C. pneumoniae isolated in the area than they did against TW-183. For two of five cases, the criteria for establishing the diagnosis of acute infection were met only with use of the antigen from the local strain; TW-183 was inadequate for this purpose. Immunoblot profiles revealed antigenic differences between strains that varied with the human serologic response; i.e., unique antigens were recognized by the sera of some individuals and not by the sera of others. Using the reactivity of a genus-specific monoclonal antibody against a major outer membrane protein, we found that strain CWL-011, isolated in Atlanta, Ga., may possess a major outer membrane protein with a molecular mass between those of C. trachomatis L2 and other C. pneumoniae strains. These data provide evidence of several new and unique serotypes of C. pneumoniae and suggest that the serologic diagnosis of C. pneumoniae infection may require the use of antigens from more than one strain of this species.
Prevention of gastroduodenal damage with omeprazole in patients receiving continuous NSAIDs treatment. A double blind placebo controlled study. (1998)

Omeprazole, 20 mg once daily, provides effective prophylactic therapy in patients at risk of developing NSAID-associated gastric and duodenal ulcer.
New Synthetic Technology for the Stereocontrolled Construction of 1,1‘-Disaccharides and 1,1‘:1‘‘,2-Trisaccharides. Synthesis of the FG Ring System of Everninomicin 13,384-1 (1997)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTNew Synthetic Technology for the Stereocontrolled Construction of 1,1'-Disaccharides and 1,1':1'',2-Trisaccharides. Synthesis of the FG Ring System of Everninomicin 13,384-1K. C. Nicolaou, F. L. van Delft, S. R. Conley, H. J. Mitchell, Z. Jin, and R. M. RodríguezView Author Information Department of Chemistry and The Skaggs Institute for Chemical Biology The Scripps Research Institute 10550 North Torrey Pines Road La Jolla, California 92037 Department of Chemistry and Biochemistry University of California, San Diego 9500 Gilman Drive, La Jolla, California 92093 Cite this: J. Am. Chem. Soc. 1997, 119, 38, 9057–9058Publication Date (Web):September 24, 1997Publication History Received15 May 1997Published online24 September 1997Published inissue 1 September 1997https://doi.org/10.1021/ja971574fCopyright © 1997 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views809Altmetric-Citations41LEARN 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 Read OnlinePDF (147 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Anions,Carbohydrates,Chemical synthesis,Group 14 compounds,Molecular structure Get e-Alerts
Quantification of myocardial blood flow using non–ECG‐triggered MR imaging (2014)

We have developed a non-ECG-triggered perfusion imaging method with T1 based measurement of the AIF in a single slice. In this preliminary study, our results demonstrate that MBF measured using the proposed method is comparable to the conventional ECG-triggered method.
Physicochemical comparison between microcrystalline cellulose and silicified microcrystalline cellulose (1998)

Silicified microcrystalline cellulose (SMCC) has been compared with a standard grade of microcrystalline cellulose (MCC) using several physicochemical techniques in order to elucidate any chemical or polymorphic changes in the material that could be attributed to the silicification process. Samples of SMCC, MCC and dry and wet mixes of MCC and silicon dioxide were analysed using FT-IR, 13C NMR, powder X-ray diffraction, mercury porosimetry, helium pycnometry and scanning electron microscopy together with particle size analysis and deaggregation studies. Analysis of the data obtained from these methods suggested that there were no discernible chemical or polymorphic differences between the samples, indicating that the `silicification' process produces a material which is chemically and physically very similar to standard MCC.
Latent transforming growth factor-beta 1 associates to fibroblast extracellular matrix via latent TGF-beta binding protein (1994)

The role of latent transforming growth factor-beta (TGF-beta) binding protein (LTBP) in the association of TGF-beta 1 to the extracellular matrix of cultured fibroblasts and HT-1080 fibrosarcoma cells was studied by immunochemical methods. The matrices were isolated from the cells, and the levels of LTBP and TGF-beta 1 were estimated by immunoblotting and immunoprecipitation. LTBP, TGF-beta 1, and its propeptide (latency-associated peptide, LAP) were found to associate to the extracellular matrix. Immunoblotting analysis indicated that treatment of the cells with plasmin resulted in a concomitant time and dose dependent release of both LTBP and TGF-beta 1 from the extracellular matrix to the supernatant. Comparison of molecular weights suggested that plasmin treatment resulted in the cleavage of LTBP from the high molecular weight fibroblast form to a form resembling the low molecular weight LTBP found in platelets. Pulse-chase and immunoprecipitation analysis indicated that both the free form of LTBP and LTBP complexed to latent TGF-beta were efficiently incorporated in the extracellular matrix, from where both complexes were slowly released to the culture medium. Addition of plasmin to the chase solution resulted, however, in a rapid release of LTBP from the matrix. Fibroblast derived LTBP was found to associate to the matrix of HT-1080 cells in a plasmin sensitive manner as shown by immunoprecipitation analysis. These results suggest that the latent form of TGF-beta 1 associates with the extracellular matrix via LTBP, and that the release of latent TGF-beta 1 from the matrix is a consequence of proteolytic cleavage(s) of LTBP.
Modeling cerebellar granular layer excitability and combinatorial computation with spikes (2010)

The cerebellum input stage has been known to perform combinatorial operations [1] [3] on input signals. In this paper, we developed a model to study information transmission and signal recoding in the cerebellar granular layer and to test observations like center-surround organization and time-window hypothesis [1] [2]. We also developed simple neuron models for abstracting timing phenomena in large networks. Detailed biophysical models were used to study synaptic plasticity and its effect in generation and modulation of spikes in the granular layer network. Our results indicated that spatio-temporal information transfer through the granular network is controlled by synaptic inhibition [1]. Spike amplitude and number of spikes were modulated by L TP and LTD. Both in vitro and in vivo simulations indicated that inhibitory input via Golgi cells acts as a modulator and regulates the post synaptic excitability.
A measure of the information gain attributable to cueing (1991)

The high false alarm rate of automatic target recognition systems used in conjunction with imaging systems has precluded their use as completely autonomous devices for the targeting and launching of weapons in military systems and has prompted their use primarily as an aid to final target recognition by a trained observer. Automatic target recognition systems used in this manner are termed cuers and are assumed by many to improve the probability of detection and recognition of a target by an observer searching an image. The efficacy of these cuers and methods of evaluating their performance are under investigation since no quantifiable measure exists. The author addresses the automated part of the problem and presents a proposed objective measure of cuer effectiveness based on an information measure. The usefulness of this measure is in discriminating among competing cuer designs. Cuers are classified according to the type of information that they extract from the image and a measure of information for each type of cuer is proposed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
DNA vaccines: prime time is now (2020)

Recently newer synthetic DNA vaccines have been rapidly advanced to clinical study and have demonstrated an impressive degree of immune potency and tolerability. Improvements in DNA delivery over prior needle and syringe approaches include jet delivery, gene gun delivery, among others. Among the most effective of these new delivery methods, advanced electroporation (EP), combined with other advances, induces robust humoral and cellular immunity in both preventative as well as therapeutic studies. Advancements in the design of the DNA inserts include leader sequence changes, RNA and codon optimizations, improved insert designs, increased concentrations of DNA, and skin delivery, appear to complement newer delivery strategies. These advances also provide a framework for the in vivo production of synthetic DNA biologics. In this review, we focus on recent studies of synthetic DNA vaccines in the clinic for the prevention or treatment of infectious diseases with a focus on adaptive electroporation for delivery, and briefly summarize novel preclinical data advancing the in vivo delivery of DNA-encoded antibody-like biologics.
Ratios of activated matrix metalloproteinase‐9 to tissue inhibitor of matrix metalloproteinase‐1 in wound fluids are inversely correlated with healing of pressure ulcers (2002)

Previous analyses of fluids collected from chronic, nonhealing wounds found elevated levels of inflammatory cytokines, elevated levels of proteinases, and low levels of growth factor activity compared with fluids collected from acute, healing wounds. This led to the general hypothesis that chronic inflammation in acute wounds produces elevated levels of proteinases that destroy essential growth factors, receptors, and extracellular matrix proteins, which ultimately prevent wounds from healing. To test this hypothesis further, pro- and activated matrix metalloproteinases (MMP-2 and MMP-9), tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2), and the ratios of MMPs/TIMPs were assayed in fluids and biopsies collected from 56 patients with chronic pressure ulcers. Specimens included ulcers treated for 0, 10, and 36 days with conventional therapy or with exogenous cytokine therapies. Quantitative assay data were correlated with the amount of healing. The average MMP-9/TIMP-1 ratio in fluids from 56 ulcers decreased significantly as the chronic pressure ulcers healed. Furthermore, the average MMP-9/TIMP-1 ratio was significantly lower for fluids collected on day 0 from wounds that ultimately healed well (> or =85% reduction in initial wound volume) compared with wounds that healed poorly (< 50% wound volume reduction). These data show that the ratio of MMP-9/TIMP-1 levels is a predictor of healing in pressure ulcers and they provide additional support for the hypothesis that high levels of MMP activity and low levels of MMP inhibitor impair wound healing in chronic pressure ulcers.