gebhart/patrepeval huggingface dataset:
Use of vertically-aligned carbon nanotube array to enhance the performance of electrochemical capacitors (2011)

In the domain of energy storage, electrochemical capacitors have numerous applications ranging from hybrid vehicles to consumer electronics, with very high power density at the cost of relatively low energy storage. Here, we report an approach that uses vertically aligned carbon nanotube arrays as electrodes in electrochemical capacitors. Different electrolytes were used and multiple parameters of carbon nanotube array were compared: carbon nanotube arrays were shown to be two to three times better than graphite in term of specific capacitance, while the surface functionalization was demonstrated to be a critical factor in both aqueous and nonaqueous solutions to increase the specific capacitance. We found that a maximum energy density of 21 Wh/kg at a power density of 1.1 kW/kg for a hydrophilic electrode, could be easily achieved by using tetraethylammonium tetrafluoroborate in propylene carbonate. These are encouraging results in the path of energy-storage devices with both high energy density and power density, using only carbon-based materials for the electrodes with a very long lifetime, of tens of thousands of cycles.
Effect of Hookworm Infection on Wheat Challenge in Celiac Disease – A Randomised Double-Blinded Placebo Controlled Trial (2011)

ClinicalTrials.gov NCT00671138.
Haloanilino Derivatives of Pyrimidines, Purines, and Purine Nucleoside Analogs: Synthesis and Activity against Human Cytomegalovirus (1995)

2-Anilinopurines and 6-anilinopyrimidines bearing 3,4- or 3,5-dichloro substituents in the anilino ring inhibited virus-specific DNA synthesis by human cytomegalovirus (HCMV)-infected human embryonic lung (HEL) cells in culture. In general, active compounds had moderate to low selectivity for viral vs host cell DNA synthesis. Nucleoside and acyclonucleoside analogs of 2-(3,5-dichloroanilino)purines inhibited both HCMV and cellular DNA synthesis at similar concentrations. 2-Amino-4-chloro-6-(3,5-dichloroanilino)pyrimidine and several related compounds inhibited HCMV growth in yield reduction assays at concentrations that were nontoxic to HEL cells.
Enhanced exon skipping and prolonged dystrophin restoration achieved by TfR1-targeted delivery of antisense oligonucleotide using FORCE conjugation in mdx mice (2022)

Current therapies for Duchenne muscular dystrophy (DMD) use phosphorodiamidate morpholino oligomers (PMO) to induce exon skipping in the dystrophin pre-mRNA, enabling the translation of a shortened but functional dystrophin protein. This strategy has been hampered by insufficient delivery of PMO to cardiac and skeletal muscle. To overcome these limitations, we developed the FORCETM platform consisting of an antigen-binding fragment, which binds the transferrin receptor 1, conjugated to an oligonucleotide. We demonstrate that a single dose of the mouse-specific FORCE-M23D conjugate enhances muscle delivery of exon skipping PMO (M23D) in mdx mice, achieving dose-dependent and robust exon skipping and durable dystrophin restoration. FORCE-M23D-induced dystrophin expression reached peaks of 51%, 72%, 62%, 90% and 77%, of wild-type levels in quadriceps, tibialis anterior, gastrocnemius, diaphragm, and heart, respectively, with a single 30 mg/kg PMO-equivalent dose. The shortened dystrophin localized to the sarcolemma, indicating expression of a functional protein. Conversely, a single 30 mg/kg dose of unconjugated M23D displayed poor muscle delivery resulting in marginal levels of exon skipping and dystrophin expression. Importantly, FORCE-M23D treatment resulted in improved functional outcomes compared with administration of unconjugated M23D. Our results suggest that FORCE conjugates are a potentially effective approach for the treatment of DMD.
IL-12, independently of IFN-gamma, plays a crucial role in the pathogenesis of a murine psoriasis-like skin disorder. (1999)

The onset of acute psoriasis and the exacerbation of chronic psoriasis are often associated with a history of bacterial infection. We demonstrate that while only few scid/scid mice develop disease when CD4+CD45Rbhigh T cells are transferred alone, coadministration of LPS plus IL-12 or staphylococcal enterotoxin B into scid/scid mice 1 day after CD4+CD45Rbhigh T cell transfer greatly enhances disease penetrance and severity. Most importantly, the skin lesions induced by this method exhibit many of the histologic hallmarks observed in human psoriasis. Skin infiltrating CD4+ T cells were predominantly memory/effector cells (CD45Rblow) and exhibited a highly polarized Th1 phenotype. To test whether the development of pathogenic T cells was dependent on their production of IFN-gamma, we transferred IFN-gamma-/- CD4+CD45Rbhigh T cells into scid/scid or into T, B and NK cell-deficient scid/beige mice. Surprisingly, the incidence of psoriasis was similar to scid/scid animals that received IFN-gamma+/+ T cells, although acanthosis of the skin was attenuated. In contrast, the development of psoriasis was abolished if anti-IL-12 mAb was administered on day 7 and 35 after T cell transfer. Skin-derived IFN-gamma-/- inflammatory cells, but not cells from anti-IL-12-treated animals, secreted substantial amounts of TNF-alpha, suggesting that the inflammatory effect of IFN-gamma-/- T cells may be partly exerted by TNF-alpha and that the therapeutic effect of anti-IL-12 may depend on its ability to down-regulate both TNF-alpha and IFN-gamma. Overall, these results suggest that IL-12, independently of IFN-gamma, is able to induce pathogenic, inflammatory T cells that are able to induce psoriasiform lesions in mice.
Polypeptides coded for by the region pre-S and gene S of hepatitis B virus DNA with the receptor for polymerized human serum albumin: expression on hepatitis B particles produced in the HBeAg or anti-HBe phase of hepatitis B virus infection. (1986)

There are four polypeptides coded for by the region Pre-S and gene S on DNA of hepatitis B virus that carry the receptor for polymerized human serum albumin (poly-HSA), i.e., P31 and P39, as well as their glycosylated counterparts P35 and P43. With the use of monoclonal antibodies directed to Pre-S(1) sequence and Pre-S(2) sequence (bearing the receptor for poly-HSA), the content of these polypeptides, as well as their expression on the surface, was determined for hepatitis B particles of various categories. P39 and P43, carrying both Pre-S(1) and Pre-S(2) sequences, were contained abundantly in Dane and tubular particles, and to a much lesser extent in small spherical particles, all of which were purified from plasma containing hepatitis B e antigen (HBeAg). P31 and P35, carrying Pre-S(2) but not Pre-S(1) sequence, were contained comparably in these three categories of hepatitis B particles. In remarkable contrast, small spherical particles derived from plasma containing antibody to HBeAg were very low in the content of any Pre-S polypeptides. P31 and P39 showed higher activities for poly-HSA receptor than their glycosylated versions. When Dane particles were digested with trypsin, the poly-HSA receptor was deprived in parallel with the loss of antigenicity for Pre-S(2) sequence. The antigenicity for Pre-S(1) sequence was much less affected, and that for the product of gene S was virtually unchanged by the digestion.
Gadolinium‐induced oxidative stress triggers endoplasmic reticulum stress in rat cortical neurons (2010)

Introduction of Gadolinium (Gd) to the nervous system is linked to the development of neurotoxicity involving both oxidative and endoplasmic reticulum (ER) stress. Gd levels (0.2-20 μm) in the form of gadolinium trichloride (GdCl(3)) cause neurotoxicity in vitro. We investigated the signaling pathways in primary cultured rat cortical neurons and tested whether GdCl(3) induced oxidative and ER stress. Results showed that Gd-induced neural cell death followed a rapid accumulation of intracellular reactive oxygen species. In addition, Gd exposure resulted in spliced X-box binding protein 1 mRNA and increased expression of binding immunoglobulin protein, thus activating transcription factor 4 (ATF4), ATF6, and C/EBP homologous protein mRNA. Up-regulated expression of binding immunoglobulin protein is a hallmark of ER stress and C/EBP homologous protein is an ER stress-related pro-apoptotic transcription factor. Activation of ER stress downstream substrates, inositol-requiring kinase 1 and ATF6, was also observed in Gd-treated cells. The neurotoxic effects of Gd were blocked by the antioxidant N-acetylcysteine. Results demonstrated that Gd-induced cytotoxicity in neurons occurs via oxidative injury and ER stress-related signal transduction, thus offering new insight into the neurotoxicology of gadolinium.
A suicide‐substrate mechanism for hydrolysis of β‐lactams by an anti‐idiotypic catalytic antibody (2001)

The catalytic mechanism of an anti-idiotypic antibody, 9G4H9, displaying a beta-lactamase activity was investigated. Kinetics experiments suggest that some penicillinic derivatives behave both as substrates and inactivators. Biochemical and immunological experiments strongly indicate that ampicillin may be regarded as a suicide substrate for hydrolysis by 9G4H9. The anti-idiotypic network appears as a way to create enzyme mimics with modified catalytic activities.
Detection of RASSF1A promoter hypermethylation in serum from gastric and colorectal adenocarcinoma patients (2008)

Aberrant CpG island methylation within the promoter region of RASSF1A is a promising biomarker for gastric and colorectal cancer.
Vascular Endothelial Growth Factor (VEGF) Acts Via Auto- and Paracrine Mechanisms as a Critical Microenvironmental Factor for the Survival of Chronic Lymphocytic Leukemia (CLL) Cells. (2009)

Abstract Abstract 4376 The major pathophysiological characteristic of chronic lymphocytic leukemia (CLL) is the accumulation of malignant, immuno-incomptetent B-cells, which is commonly known as the apoptotic block. Recently, it was speculated that vascular endothelial growth factor (VEGF) might be involved in this process. Whereas most of the available studies are solely descriptive, functional data are largely missing. The aim of this study was therefore to describe the effect and functional background of VEGF on CLL cells for the identification of potential strategies for a targeted CLL therapy. We identified an autocrine VEGF feedback loop in CLL cells, but not healthy B-cells. Recombinant human (rh) VEGF stimulation lead to increased expression of the anti-apoptotic proteins Mcl1 and XIAP, but was not sufficient to prolong survival. When CLL cells were cocultured with the bone marrow derived stromal cell line HS5, survival was significantly enhanced 28.5 ± 6.5% after 72h relative to monoculture, whereas healthy B-cells did not profit from coculture (-0.5 ± 4.7%). HS5 cells produce and secrete high amounts of VEGF themselves. When cocultured with HS5 CLL cells also showed an increased VEGF expression, indicating the existence of a paracrine VEGF feedback loop. The actual relevance of VEGF in the coculture mediated survival support was proofed by siRNA experiments. When VEGF expression and secretion was downregulated in HS5 cell by siRNA, the survival advantage CLL cells obtained from the coculture was reduced down to that in monoculture. Also the addition of a VEGF-neutralizing monoclonal antibody largely reversed the survival supporting effect of the coculture, clearly indicating the critical role of VEGF in bone marrow stromal cell-mediated CLL cell survival. We further found rhVEGF to induce upregulation and activation of STAT3 via Tyr705-phosphorylation and a subsequent expression of STAT3 targets such as Cyclin D1 and BclXL. VEGF-stimulation further induced downregulation of the tumor suppressor RB1 and E2F1, which act as proapoptotic factors. Vice versa inhibition of VEGF by using selective VEGF-R inhibitors reduced both, Tyr705 phosphorylation and expression of STAT3 target genes. We therefore, propose a dual mechanism of VEGF-mediated CLL cell survival support via upregulation of the potent oncogene STAT3 and downregulation of the tumor suppressor RB1/E2F1. Hence, VEGF might function as a potential new therapeutic target to overcome the apoptotic block in CLL cells. Disclosures: Hallek: BayerScheringAG: Honoraria, Research Funding.
Neuroimaging and genetics of borderline personality disorder: a review (2007)

Borderline personality disorder (BPD) is a highly prevalent psychiatric disorder that carries a severe risk factor for adolescent and young adult suicide. Relatively little research has examined its biological etiology. Differences in the volume and activity in brain structures related to emotion and impulsivity have been observed between individuals who have BPD and those who do not. The present study seeks to assess current research on the neuroanatomical differences observed between individuals with and without BPD and the genes that may play a role in the development of this disorder.
Changes in chemical composition of homogenized leaf-cured and air-cured burley tobacco stored in controlled environments (1982)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChanges in chemical composition of homogenized leaf-cured and air-cured burley tobacco stored in controlled environmentsRoger A. Andersen, Michael J. Kasperbauer, Harold R. Burton, James L. Hamilton, and Elmon E. YoderCite this: J. Agric. Food Chem. 1982, 30, 4, 663–668Publication Date (Print):July 1, 1982Publication History Published online1 May 2002Published inissue 1 July 1982https://pubs.acs.org/doi/10.1021/jf00112a010https://doi.org/10.1021/jf00112a010research-articleACS PublicationsRequest reuse permissionsArticle Views177Altmetric-Citations13LEARN 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
Authenticity Control of Oils and Fats via Large Capacity Sorptive Extraction (2011)

Advanced tools for the rapid identity check and authenticity control for complex flavor raw materials as well as the analysis of contaminants is of increasing importance for food and flavor companies. The mega trend for natural ingredients requires an optimized combination of effective sample clean-up and target analysis for key compounds. In this context modern adsorption technologies are providing selectivity adjusted analytical work procedures for direct analysis of difficult matrices such as dairy products and other fat and oil containing raw materials as well as complex juice derived materials. For this purpose the polymer adsorption based Large Capacity Sorptive Extraction (LCSE) technology offers a rapid access to a broad spectrum of flavor and taste active materials. The combination of LCSE technology with other analytical methodologies such as LC-MS provides a comprehensive picture of the identity and authenticity of raw materials with a parallel insight into the sensorial performance in the final application. This approach is of particular interest for the analysis of oils and lipids, which are often showing difficulties in flavor analysis because of the limited recovery rate for specific aroma active substances and corresponding matrix effects.
Targeting Fibroblast Activation Protein in Tumor Stroma with Chimeric Antigen Receptor T Cells Can Inhibit Tumor Growth and Augment Host Immunity without Severe Toxicity (2013)

The majority of chimeric antigen receptor (CAR) T-cell research has focused on attacking cancer cells. Here, we show that targeting the tumor-promoting, nontransformed stromal cells using CAR T cells may offer several advantages. We developed a retroviral CAR construct specific for the mouse fibroblast activation protein (FAP), comprising a single-chain Fv FAP [monoclonal antibody (mAb) 73.3] with the CD8α hinge and transmembrane regions, and the human CD3ζ and 4-1BB activation domains. The transduced muFAP-CAR mouse T cells secreted IFN-γ and killed FAP-expressing 3T3 target cells specifically. Adoptively transferred 73.3-FAP-CAR mouse T cells selectively reduced FAP(hi) stromal cells and inhibited the growth of multiple types of subcutaneously transplanted tumors in wild-type, but not FAP-null immune-competent syngeneic mice. The antitumor effects could be augmented by multiple injections of the CAR T cells, by using CAR T cells with a deficiency in diacylglycerol kinase, or by combination with a vaccine. A major mechanism of action of the muFAP-CAR T cells was the augmentation of the endogenous CD8(+) T-cell antitumor responses. Off-tumor toxicity in our models was minimal following muFAP-CAR T-cell therapy. In summary, inhibiting tumor growth by targeting tumor stroma with adoptively transferred CAR T cells directed to FAP can be safe and effective, suggesting that further clinical development of anti-human FAP-CAR is warranted.
Molecular basis for the thiol sensitivity of insulin-degrading enzyme (2008)

Insulin-degrading enzyme (IDE) is a ubiquitous zinc-metalloprotease that hydrolyzes several pathophysiologically relevant peptides, including insulin and the amyloid beta-protein (Abeta). IDE is inhibited irreversibly by compounds that covalently modify cysteine residues, a mechanism that could be operative in the etiology of type 2 diabetes mellitus (DM2) or Alzheimer's disease (AD). However, despite prior investigation, the molecular basis underlying the sensitivity of IDE to thiol-alkylating agents has not been elucidated. To address this topic, we conducted a comprehensive mutational analysis of the 13 cysteine residues within IDE. Our analysis implicates C178, C812, and C819 as the principal residues conferring thiol sensitivity. The involvement of C812 and C819, residues quite distant from the catalytic zinc atom, provides functional evidence that the active site of IDE comprises two separate domains that are operational only in close apposition. Structural analysis and other evidence predict that alkylation of C812 and C819 disrupts substrate binding, whereas alkylation of C178 interferes with the apposition of active-site domains and subtly repositions zinc-binding residues. Unexpectedly, alkylation of C590 was found to activate hydrolysis of Abeta significantly, while having no effect on insulin, demonstrating that chemical modulation of IDE can be both bidirectional and highly substrate selective. Our findings resolve a long-standing riddle about the basic enzymology of IDE with important implications for the etiology of DM2 and AD. Moreover, this work uncovers key details about the mechanistic basis of the unusual substrate selectivity of IDE that may aid the development of pharmacological agents or IDE mutants with therapeutic value.
Structure and Dynamics of a β-Helical Antifreeze Protein, (2002)

Antifreeze proteins (AFPs) protect many types of organisms from damage caused by freezing. They do this by binding to the ice surface, which causes inhibition of ice crystal growth. However, the molecular mechanism of ice binding leading to growth inhibition is not well understood. In this paper, we present the solution structure and backbone NMR relaxation data of the antifreeze protein from the yellow mealworm beetle Tenebrio molitor (TmAFP) to study the dynamics in the context of structure. The full (15)N relaxation analysis was completed at two magnetic field strengths, 500 and 600 MHz, as well as at two temperatures, 30 and 5 degrees C, to measure the dynamic changes that occur in the protein backbone at different temperatures. TmAFP is a small, highly disulfide-bonded, right-handed parallel beta-helix consisting of seven tandemly repeated 12-amino acid loops. The backbone relaxation data displays a periodic pattern, which reflects both the 12-amino acid structural repeat and the highly anisotropic nature of the protein. Analysis of the (15)N relaxation parameters shows that TmAFP is a well-defined, rigid structure, and the extracted parameters show that there is similar restricted internal mobility throughout the protein backbone at both temperatures studied. We conclude that the hydrophobic, rigid binding site may reduce the entropic penalty for the binding of the protein to ice. The beta-helical fold of the protein provides this rigidity, as it does not appear to be a consequence of cooling toward a physiologically relevant temperature.
Draft Crystal Structure of the Vault Shell at 9-Å Resolution (2007)

Vaults are the largest known cytoplasmic ribonucleoprotein structures and may function in innate immunity. The vault shell self-assembles from 96 copies of major vault protein and encapsulates two other proteins and a small RNA. We crystallized rat liver vaults and several recombinant vaults, all among the largest non-icosahedral particles to have been crystallized. The best crystals thus far were formed from empty vaults built from a cysteine-tag construct of major vault protein (termed cpMVP vaults), diffracting to about 9-A resolution. The asymmetric unit contains a half vault of molecular mass 4.65 MDa. X-ray phasing was initiated by molecular replacement, using density from cryo-electron microscopy (cryo-EM). Phases were improved by density modification, including concentric 24- and 48-fold rotational symmetry averaging. From this, the continuous cryo-EM electron density separated into domain-like blocks. A draft atomic model of cpMVP was fit to this improved density from 15 domain models. Three domains were adapted from a nuclear magnetic resonance substructure. Nine domain models originated in ab initio tertiary structure prediction. Three C-terminal domains were built by fitting poly-alanine to the electron density. Locations of loops in this model provide sites to test vault functions and to exploit vaults as nanocapsules.
Direct Activation of Bax by p53 Mediates Mitochondrial Membrane Permeabilization and Apoptosis (2004)

The tumor suppressor p53 exerts its anti-neoplastic activity primarily through the induction of apoptosis. We found that cytosolic localization of endogenous wild-type or trans-activation-deficient p53 was necessary and sufficient for apoptosis. p53 directly activated the proapoptotic Bcl-2 protein Bax in the absence of other proteins to permeabilize mitochondria and engage the apoptotic program. p53 also released both proapoptotic multidomain proteins and BH3-only proteins [Proapoptotic Bcl-2 family proteins that share only the third Bcl-2 homology domain (BH3)] that were sequestered by Bcl-xL. The transcription-independent activation of Bax by p53 occurred with similar kinetics and concentrations to those produced by activated Bid. We propose that when p53 accumulates in the cytosol, it can function analogously to the BH3-only subset of proapoptotic Bcl-2 proteins to activate Bax and trigger apoptosis.