gebhart/patrepeval huggingface dataset:
Coassembly of Amphiphiles with Opposite Peptide Polarities into Nanofibers (2005)

The design, synthesis, and characterization of "reverse" peptide amphiphiles (PAs) with free N-termini is described. Use of an unnatural amino acid modified with a fatty acid tail allows for the synthesis of this new class of PA molecules. The mixing of these molecules with complementary ones containing a free C-terminus results in coassembled structures, as demonstrated by circular dichroism and NOE/NMR spectroscopy. These assemblies show unusual thermal stability when compared to assemblies composed of only one type of PA molecule. This class of reverse PAs has made it possible to create biologically significant assemblies with free N-terminal peptide sequences, which were previously inaccessible, including those derived from phage display methodologies.
Analysis and Ultrastructural Localization of Ehrlichia chaffeensis Proteins with Monoclonal Antibodies (1996)

Ehrlichia chaffeensis, an obligately intracellular bacterium with tropism for monocytes, is the etiologic agent of human monocytic ehrlichiosis. To determine the nature and ultrastructural location of E. chaffeensis antigens, monoclonal antibodies (MAbs) to E. chaffeensis were developed. The MAbs were used for immunofluorescence and Western immunoblotting analysis of the antigens of density gradient-purified ehrlichiae. Monoclonal antibody 6A1 recognized an epitope of a 30-kD protein. This antibody reacted with a strain-specific epitope of E. chaffeensis, Arkansas strain, and did not cross-react with any other ehrlichia tested. Monoclonal antibodies 3C7 and 7C1-B recognized Arkansas strain proteins of 30 and 29 kD and reacted with E. chaffeensis (strain 91HE17) proteins of 31 and 29 kD and an E. canis protein of 30 kD. Lack of reactivity of these two MAbs with E. sennetsu and E. risticii suggests that the epitope is group-specific. Monoclonal antibody 5D11 recognized a 58-kD protein of both strains of E. chaffeensis as well as E. canis, apparently a group-specific, conformation-independent epitope. Monoclonal antibody 7C1-C reacted with 58- and 88-kD proteins of both the Arkansas and 91HE17 strains. Trypsin treatment destroyed the reactivity of E. chaffeensis antigens with all the MAbs when tested by Western immunoblotting, indicating that these antigens are proteins with trypsin-sensitive epitopes. Immunoelectron microscopy of negatively stained intact E. chaffeensis organisms showed that the 30- and 29-kD proteins are present on the surface of the ehrlichial cell wall along with the previously localized 28-kD protein.
Oxygen Sensing, Homeostasis, and Disease (2011)

Pathways that sense a reduction in available oxygen are critical in the adaptation to lower oxygen tensions at high altitude. Alterations in this system can contribute to the pathogenesis of heart disease, cancer, stroke, chronic lung disease, and many other disorders.
Reactivity of the Human Thioltransferase (Glutaredoxin) C7S, C25S, C78S, C82S Mutant and NMR Solution Structure of Its Glutathionyl Mixed Disulfide Intermediate Reflect Catalytic Specificity, (1998)

Human thioltransferase (TTase) is a 12 kDa thiol-disulfide oxidoreductase that appears to play a critical role in maintaining the redox environment of the cell. TTase acts as a potent and specific reducing agent for protein-S-S-glutathione mixed disulfides (protein-SSG) likely formed during oxidative stress or as redox intermediates in signal transduction pathways. Accordingly, the catalytic cycle of thioltransferase itself involves a covalent glutathionyl enzyme disulfide intermediate (TTase-C22-SSG). To understand the molecular basis of TTase specificity for the glutathione moiety, we engineered a quadruple Cys to Ser mutant of human TTase (C7S, C25S, C78S, and C82S) which retains only the active site cysteine residue (C22), and we solved its high-resolution NMR solution structure in the mixed disulfide intermediate with glutathione (QM-TTase-SSG). This mutant which cannot form a C22-S-S-C25 intramolecular disulfide displays the same catalytic efficiency (Vmax/KM) and specificity for glutathionyl mixed disulfide substrates as wild-type TTase, indicating that the Cys-25-SH moiety is not required for catalysis or glutathionyl specificity. The structure of human thioltransferase is characterized by a thioredoxin-like fold which comprises a four-stranded central beta-sheet flanked on each side by alpha-helices. The disulfide-adducted glutathione in the TTase-SSG complex has an extended conformation and is localized in a cleft near the protein surface encompassing the residues from helices-alpha2,alpha3, the active site loop, and the loop connecting helix-alpha3 and strand-beta3. Numerous van der Waals and electrostatic interactions between the protein and the glutathione moiety are identified as contributing to stabilization of the complex and confering the substrate specificity. Comparison of the human thioltransferase with other thiol-disulfide oxidoreductases reveals structural and functional differences.
Immunization with a Recombinant Stage-Regulated Surface Protein from Leishmania donovani Induces Protection Against Visceral Leishmaniasis (2000)

Vaccination against visceral leishmaniasis has received limited attention compared with cutaneous leishmaniasis, although the need for an effective vaccine against visceral leishmaniasis is pressing. In this study, we demonstrate for the first time that a recombinant stage-specific hydrophilic surface protein of Leishmania donovani, recombinant hydrophilic acylated surface protein B1 (HASPB1), is able to confer protection against experimental challenge. Protection induced by rHASPB1 does not require adjuvant and, unlike soluble Leishmania Ag + IL-12, extends to the control of parasite burden in the spleen, an organ in which parasites usually persist and are refractory to a broad range of immunological and chemotherapeutic interventions. Both immunohistochemistry (for IL-12p40) and enzyme-linked immunospot assay (for IL-12p70) indicate that immunization with rHASPB1 results in IL-12 production by dendritic cells, although an analysis of Ab isotype responses to rHASPB1 suggests that this response is not sufficient in magnitude to induce a polarized Th1 response. Although both vaccinated and control-infected mice have equivalent frequencies of rHASPB1-specific CD4(+) T cells producing IFN-gamma, vaccine-induced protection correlates with the presence of rHASPB1-specific, IFN-gamma-producing CD8(+) T cells. Thus, we have identified a novel vaccine candidate Ag for visceral leishmaniasis, which appears to operate via a mechanism similar to that previously associated with DNA vaccination.
Heterologous antigen expression in Vibrio cholerae vector strains (1995)

Live attenuated vector strains of Vibrio cholerae were derived from Peru-2, a Peruvian El Tor Inaba strain deleted for the cholera toxin genetic element and attRS1 sequences, which was developed as a live, oral vaccine strain. A promoterless gene encoding the Shiga-like toxin I B subunit (slt-IB) was inserted in the V. cholerae virulence gene irgA by in vivo marker exchange, such that slt-IB was under transcriptional control of the iron-regulated irgA promoter. slt-IB was also placed under transcriptional control of the V. cholerae heat shock promoter, htpGp, and introduced into either the irgA or lacZ locus, or both loci, on the chromosome of Peru-2, generating JRB10, JRB11, or JRB12, respectively. A new technique was used to perform allelic exchange with lacZ. This method uses plasmid p6891MCS, a pBR327 derivative containing cloned V. cholerae lacZ, to insert markers of interest into the V. cholerae chromosome. Recombinants can be detected by simple color screening and antibiotic selection. In vitro measurements of Slt-IB produced by the vector strains suggested that expression of Slt-IB from the irgA and htpG promoters was synergistic and that two copies of the gene for Slt-IB increased expression over a single copy. The V. cholerae vectors colonized the gastrointestinal mucosa of rabbits after oral immunization, as demonstrated by very high serum antibody responses to V. cholerae antigens. Comparison of the serologic responses to the B subunit of cholera toxin (CtxB) following orogastric inoculation either with the wild-type C6709 or with Peru-10, a strain containing ctxB regulated by htpGp, suggested that both the cholera toxin and heat shock promoters were active in vivo, provoking comparable immunologic responses. Orogastric inoculation of rabbits with vector strains evoked serum immunoglobulin G (IgG) responses to Slt-IB in two of the four strains tested; all four strains produced biliary IgA responses. No correlation was observed between the type of promoter expressing slt-IB and the level of serum IgG or biliary IgA response, but the vector strain containing two copies of the gene for slt-IB evoked greater serum IgG responses than strains containing a single copy, consistent with the increased expression of Slt-IB from this strain observed in vitro. A comparison of the serum and biliary antibody responses to Slt-IB expressed from htpGp versus CtxB expressed from the same promoter suggested that CtxB is a more effective orally delivered immunogen.
HER2-directed therapy for metastatic breast cancer. (2013)

Human epidermal growth factor receptor 2 (HER2) overexpression drives the biology of 20% of breast cancers, and predicts a poor prognosis for patients. HER2-targeted therapies significantly improve outcomes for HER2-positive patients with both early and metastatic breast cancer. Currently three HER2-targeted agents, trastuzumab (Herceptin), lapatinib (Tykerb), and pertuzumab (Perjeta), are available for the treatment of HER2-positive metastatic breast cancer (MBC). Numerous studies have attempted to optimize their use by combining them with each other, or with endocrine and cytotoxic therapies. Most recently, the FDA approved the combination of trastuzumab, pertuzumab, and docetaxel as first-line treatment for MBC, and in late February 2013 approved a fourth HER2-targeted agent, trastuzumab emtansine (T-DM1, Kadcyla), for accelerated approval. These advances create a number of clinical dilemmas, including identification of the optimal sequence of HER2-targeted agents and the best drug combinations to use, as well as the recognition of primary and acquired drug resistance. In this article, we review clinical data informing the effective management of HER2-positive MBC.
Quantitative dealkylation of alkyl ethers via treatment with trimethylsilyl iodide. A new method for ether hydrolysis (1977)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTQuantitative dealkylation of alkyl ethers via treatment with trimethylsilyl iodide. A new method for ether hydrolysisMichael E. Jung and Mark A. LysterCite this: J. Org. Chem. 1977, 42, 23, 3761–3764Publication Date (Print):November 1, 1977Publication History Published online1 May 2002Published inissue 1 November 1977https://pubs.acs.org/doi/10.1021/jo00443a033https://doi.org/10.1021/jo00443a033research-articleACS PublicationsRequest reuse permissionsArticle Views11383Altmetric-Citations411LEARN 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 InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Dielectric film deposition by atmospheric pressure and low temperature CVD using TEOS, ozone, and new organometallic doping sources (2003)

An atmospheric-pressure CVD technology using TEOS, ozone, and new organometallic doping sources, such as tris(trimethylsilil)borate, ((CH/sub 3/)/sub 3/SiO)/sub 3/B, is described. This technology offers excellent dielectric films with respect to step coverage, film stress, moisture resistance, and thermal flow characteristics. Nondoped silicon dioxide and BSG films are deposited to cover conformably even a deeply trenched substrate. They can be used as a dielectric film between a polysilicon and an aluminum layer or between aluminum layers without any planarization process. BPSG films showed good step coverage, and could be smoothly reflowed at a low temperature.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Bryostatin and CD40‐ligand enhance apoptosis resistance and induce expression of cell survival genes in B‐cell chronic lymphocytic leukaemia (1999)

Modulating signal transduction pathways represents a promising approach for altering the biological behaviour of haemopoietic malignancies. B-cell chronic lymphocytic leukaemia (B-CLL) cells were treated in vitro with CD40-ligand (CD40L) (CD154) or the protein kinase C modulator Bryostatin-1, exploring the effects on: (a) sensitivity to apoptosis induction by chemotherapeutic drugs (fludarabine, dexamethasone) or anti-Fas antibody; (b) expression of apoptosis-regulatory proteins (Bcl-2, Bcl-X, Mcl-1, Bax, Bak, BAG-1, Flip, XIAP); (c) expression of cell surface co-stimulatory antigens (CD80 [B7.1]; CD54 [ICAM-1]; CD70); and (d) expression of immune modulatory receptors (CD27, CD40, CD95 [Fas]). CD40L and Bryostatin decreased both spontaneous and drug-induced apoptosis in most B-CLL specimens tested. Apoptosis resistance was associated with CD40L- and Bryostatin-induced elevations in the anti-apoptotic Bcl-2 family protein Mcl-1. CD40L also induced striking increases in the levels of the anti-apoptotic protein Bcl-XL in B-CLLs. CD40L stimulated increases in the surface expression of CD40, CD54, CD69, CD70, CD80 and CD95, whereas Bryostatin induced expression of CD40, CD54, CD69 and CD95 but not the co-stimulatory molecules CD70 and CD80. Despite elevations in the expression of CD95 (Fas), anti-Fas antibodies failed to induce apoptosis of CD40L- and Bryostatin-treated B-CLL cells. This Fas-resistance was associated with increased expression of the Fas-antagonist Flip in CD40L-treated, and with elevations in the caspase inhibitor XIAP in Bryostatin-treated B-CLLs. The potential anti-apoptotic properties of CD40L and Bryostatin should be taken into consideration when employing these agents in clinical trials involving patients with B-CLL.
Dental impressions using 3D digital scanners: virtual becomes reality. (2008)

The technologies that have made the use of three-dimensional (3D) digital scanners an integral part of many industries for decades have been improved and refined for application to dentistry. Since the introduction of the first dental impressioning digital scanner in the 1980s, development engineers at a number of companies have enhanced the technologies and created in-office scanners that are increasingly user-friendly and able to produce precisely fitting dental restorations. These systems are capable of capturing 3D virtual images of tooth preparations, from which restorations may be fabricated directly (ie, CAD/CAM systems) or fabricated indirectly (ie, dedicated impression scanning systems for the creation of accurate master models). The use of these products is increasing rapidly around the world and presents a paradigm shift in the way in which dental impressions are made. Several of the leading 3D dental digital scanning systems are presented and discussed in this article.
Enhancement of Growth of Primary Metastatic Fresh Human Tumors of the Nervous System by Epidermal Growth Factor in Serum-free Short Term Culture (1988)

Using the adhesive tumor cell culture system, we studied the effect of epidermal growth factor (EGF) on 16 primary and 7 metastatic fresh human tumors of the nervous system cultured in serum-free and serum-supplemented media at low cell density. In serum-free conditions, EGF significantly enhanced the growth of glial tumor cells. This positive effect was less pronounced for metastases to the brain. No significant enhancement was observed for the other tumor types (primitive neuroectodermal tumors and various tumors of neuroepithelial/mesenchymal origin). The addition of serum obscured this effect of EGF, even at the lowest cell densities. In 7 tumors, the simultaneous addition of platelet-derived growth factor did not enhance the EGF response. Subtypes of brain tumors respond to EGF in vitro under serum-free conditions.
Using Phage Display to Select Antibodies Recognizing Post-translational Modifications Independently of Sequence Context (2006)

Many cellular activities are controlled by post-translational modifications, the study of which is hampered by the lack of specific reagents due in large part to their ubiquitous and non-immunogenic nature. Although antibodies against specifically modified sequences are relatively easy to obtain, it is extremely difficult to derive reagents recognizing post-translational modifications independently of the sequence context surrounding the modification. In this study, we examined the possibility of selecting such antibodies from large phage antibody libraries using sulfotyrosine as a test case. Sulfotyrosine is a post-translational modification important in many extracellular protein-protein interactions, including human immunodeficiency virus infection. After screening almost 8000 selected clones, we were able to isolate a single specific single chain Fv using two different selection strategies, one of which included elution with tyrosine sulfate. This antibody was able to recognize sulfotyrosine independently of its sequence context in test peptides and a number of different natural proteins. Antibody reactivity was lost by antigen treatment with sulfatase or preincubation with soluble tyrosine sulfate, indicating its specificity. The isolation of this antibody signals the potential of phage antibody libraries in the derivation of reagents specific for post-translational modifications, although the extensive screening required indicates that such antibodies are extremely rare.
High-speed Phase Recovery Using Chromatic Transport of Intensity Computation in Graphics Processing Units (2010)

Quantitative phase measurements are derived from the wavelength-dependent transport of intensity equation. A dispersive optical system is used with a Bayer-filtered detector and graphics processing units to record and calculate the phase in real-time.
Childhood trauma interacted with BDNF Val66Met influence schizophrenic symptoms (2018)

The gene - environment (G × E) interaction effect is involved in severe mental disorders. However, whether the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism participates in the childhood-abuse influenced schizophrenic symptoms remains unclear. We examined the interaction between BDNF Val66Met, and childhood trauma (ChT) on psychotic symptoms in a Chinese Han population.To estimate the G × E interaction, psychiatric interviews, self-report questionnaires for ChT, and genotyping for BDNF Val66Met were carried out on 201 schizophrenic patients. G × E interactions were analyzed by generalized multifactor dimensionality reduction (GMDR).Among all patients, 11.9%, 19.4%, 23.4%, 26.4%, and 73.6% reported emotional abuses, physical abuses (PA), sexual abuses (SA), emotional neglects (EN), and physical neglects (PN), respectively. Significant negative correlations were observed between anxiety/depression factors, and ChT total scores. Patients with 3 different BDNF genotypes showed significant differences in anxiety/depression scores. Significant 2-way interactions were found for Val66Met × PN, 3-way interactions were found for Val66Met × PN × PA, and four-way interactions were found for Val66Met × PN × PA × EN with regard to the excitement scores.Our findings suggested an involvement of BDNF Val66Met polymorphism after ChT in terms of risk for schizophrenia symptoms.
Large‐scale identification of proteins expressed in mouse embryonic stem cells (2005)

A protein subset expressed in the mouse embryonic stem (ES) cell line, E14-1, was characterized by mass spectrometry-based protein identification technology and data analysis. In total, 1790 proteins including 365 potential nuclear and 260 membrane proteins were identified from tryptic digests of total cell lysates. The subset contained a variety of proteins in terms of physicochemical characteristics, subcellular localization, and biological function as defined by Gene Ontology annotation groups. In addition to many housekeeping proteins found in common with other cell types, the subset contained a group of regulatory proteins that may determine unique ES cell functions. We identified 39 transcription factors including Oct-3/4, Sox-2, and undifferentiated embryonic cell transcription factor I, which are characteristic of ES cells, 88 plasma membrane proteins including cell surface markers such as CD9 and CD81, 44 potential proteinaceous ligands for cell surface receptors including growth factors, cytokines, and hormones, and 100 cell signaling molecules. The subset also contained the products of 60 ES-specific and 41 stemness genes defined previously by the DNA microarray analysis of Ramalho-Santos et al. (Ramalho-Santos et al., Science 2002, 298, 597-600), as well as a number of components characteristic of differentiated cell types such as hematopoietic and neural cells. We also identified potential post-translational modifications in a number of ES cell proteins including five Lys acetylation sites and a single phosphorylation site. To our knowledge, this study provides the largest proteomic dataset characterized to date for a single mammalian cell species, and serves as a basic catalogue of a major proteomic subset that is expressed in mouse ES cells.
Point mutant mice with hypersensitive α4 nicotinic receptors show dopaminergic deficits and increased anxiety (2001)

Knock-in mice were generated that harbored a leucine-to-serine mutation in the alpha4 nicotinic receptor near the gate in the channel pore. Mice with intact expression of this hypersensitive receptor display dominant neonatal lethality. These mice have a severe deficit of dopaminergic neurons in the substantia nigra, possibly because the hypersensitive receptors are continuously activated by normal extracellular choline concentrations. A strain that retains the neo selection cassette in an intron has reduced expression of the hypersensitive receptor and is viable and fertile. The viable mice display increased anxiety, poor motor learning, excessive ambulation that is eliminated by very low levels of nicotine, and a reduction of nigrostriatal dopaminergic function upon aging. These knock-in mice provide useful insights into the pathophysiology of sustained nicotinic receptor activation and may provide a model for Parkinson's disease.
Pancreatic Carcinoma Cell Killing Via Adenoviral Mediated Delivery of the Herpes Simplex Virus Thymidine Kinase Gene (1997)

Pancreatic carcinoma cells are highly susceptible to transduction with recombinant adenoviral vector and elicit a potent bystander effect on neighboring tumor cells. Additionally, in vivo treatment of tumor-bearing animals results in dramatic reduction of overall tumor burden, thus providing the rationale for molecular chemotherapy of pancreatic carcinoma.