gebhart/patrepeval huggingface dataset:
CD25 Blockade Depletes and Selectively Reprograms Regulatory T Cells in Concert with Immunotherapy in Cancer Patients (2012)

Regulatory T cells (T(regs)) are key mediators of immune tolerance and feature prominently in cancer. Depletion of CD25(+) FoxP3(+) T(regs) in vivo may promote T cell cancer immunosurveillance, but no strategy to do so in humans while preserving immunity and preventing autoimmunity has been validated. We evaluated the Food and Drug Administration-approved CD25-blocking monoclonal antibody daclizumab with regard to human T(reg) survival and function. In vitro, daclizumab did not mediate antibody-dependent or complement-mediated cytotoxicity but rather resulted in the down-regulation of FoxP3 selectively among CD25(high) CD45RA(neg) T(regs). Moreover, daclizumab-treated CD45RA(neg) T(regs) lost suppressive function and regained the ability to produce interferon-γ, consistent with reprogramming. To understand the impact of daclizumab on T(regs) in vivo, we performed a clinical trial of daclizumab in combination with an experimental cancer vaccine in patients with metastatic breast cancer. Daclizumab administration led to a marked and prolonged decrease in T(regs) in patients. Robust CD8 and CD4 T cell priming and boosting to all vaccine antigens were observed in the absence of autoimmunity. We conclude that CD25 blockade depletes and selectively reprograms T(regs) in concert with active immune therapy in cancer patients. These results suggest a mechanism to target cancer-associated T(regs) while avoiding autoimmunity.
Crystal structure of the MurG:UDP-GlcNAc complex reveals common structural principles of a superfamily of glycosyltransferases (2003)

MurG is an essential glycosyltransferase that forms the glycosidic linkage between N-acetyl muramyl pentapeptide and N-acetyl glucosamine in the biosynthesis of the bacterial cell wall. This enzyme is a member of a major superfamily of NDP-glycosyltransferases for which no x-ray structures containing intact substrates have been reported. Here we present the 2.5-A crystal structure of Escherichia coli MurG in complex with its donor substrate, UDP-GlcNAc. Combined with genomic analysis of other superfamily members and site-specific mutagenesis of E. coli MurG, this structure sheds light on the molecular basis for both donor and acceptor selectivity for the superfamily. This structural analysis suggests that it will be possible to evolve new glycosyltransferases from prototypical superfamily members by varying two key loops while maintaining the overall architecture of the family and preserving key residues.
A Variable-Bit-Rate Buried-Data Channel for Compact Disc (1995)

Recently an elegant method was published to add buried data to a CD signal in a compatible way. This method is based on subtractively dithered noise-shaped quantization and provides a fixed-rate buried-data channel. An adaptive extension to this method, resulting in a variable rate of higher average value, is described
New therapies for the treatment of systemic lupus erythematosus (2007)

Systemic lupus erythematosus (SLE) is an autoimmune disease that, although uncommon, affects millions of patients worldwide. The foundation of therapy with antimalarials, corticosteroids and immunosuppressants, such as azathioprine or cyclophosphamide, has remained unchanged for a number of years. However, these drugs can be associated with significant side effects. Limitations of existing agents have driven interest in developing new therapies for SLE.
Biochemical and biophysical characterization of human recombinant IgE-binding protein, an S-type animal lectin. (1992)

IgE-binding protein (epsilon BP) was originally identified by virtue of its affinity for IgE. It is now known to be a beta-galactoside-binding lectin with the characteristic of an S-type carbohydrate recognition domain. The protein is composed of two domains: the amino-terminal domain consisting of tandem repeats and the carboxyl-terminal domain containing sequences shared by other S-type carbohydrate recognition domains. The amino-terminal domain also contains a number of potential recognition sites for collagenase cleavage. In this study, human epsilon BP was first expressed in Escherichia coli, and the carboxyl-terminal domain (epsilon BP-C) was then generated by collagenase digestion of epsilon BP. By equilibrium dialysis, the association constants of epsilon BP and epsilon BP-C for lactose were found to be similar (6.0 +/- 0.70) x 10(4) M-1 and (4.7 +/- 0.27) x 10(4) M-1, respectively. Both polypeptides contain only one lactose-binding site/molecule. By an assay involving binding of 125I-labeled epsilon BP or epsilon BP-C to solid phase IgE, and inhibition of this binding by saccharides, it was determined that epsilon BP-C retains the saccharide specificity of epsilon BP. Importantly, although unlabeled epsilon BP-C inhibited the binding of the radiolabeled epsilon BP to IgE, unlabeled epsilon BP caused increased binding to IgE, suggesting self-association among epsilon BP molecules. Oligomeric structures resulting from self-association of epsilon BP were confirmed by chemical cross-linking studies. Furthermore, epsilon BP possesses hemagglutination activity on rabbit erythrocytes, whereas epsilon BP-C lacks such activity. Based on these results, we propose a structural model for multivalency of epsilon BP: dimerization or oligomerization of epsilon BP occurs through intermolecular interaction involving the amino-terminal domain.
Capsaicin sensitivity and voltage-gated sodium currents in colon sensory neurons from rat dorsal root ganglia (1999)

DiI-labeled colon sensory neurons were acutely dissociated from S1 rat dorsal root ganglia (DRG) and studied using perforated whole cell patch-clamp techniques. Forty-six percent (54/116) of labeled sensory neurons responded to capsaicin (10(-8)- 10(-5) M) with an increase in inward current, which was a nonspecific cation conductance. Responses to capsaicin applied by puffer ejection were dependent on dose, with a half-maximal response at 4.9 x 10(-7) M; bath application was characterized by marked desensitization. Voltage-gated Na(+) currents in 23 of 30 DRG cells exhibited both TTX-sensitive and TTX-resistant components. In these cells, capsaicin induced an inward current in 11 of 17 cells tested. Of the cells containing only a TTX-sensitive component, none of six cells tested was sensitive to capsaicin. In all cells that responded to capsaicin with an increase in inward current, capsaicin abolished voltage-gated Na(+) currents (n = 21). Capsazepine (10(-6) M) significantly attenuated both the increase in inward current and the reduction in Na(+) currents. Na(+) currents were not significantly altered by adenosine, bradykinin, histamine, PGE(2), or serotonin at 10(-6) M and 10(-5) M. These findings may have important implications for understanding both the irritant and analgesic properties of capsaicin.
Complement in paroxysmal nocturnal hemoglobinuria: exploiting our current knowledge to improve the treatment landscape (2014)

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematological disorder associated with an acquired deficiency in glycophosphatidylinositol-anchor biosynthesis that renders erythrocytes susceptible to complement attack. Intravascular hemolysis via the membrane attack complex is a clinical hallmark of the disease, and C5 blockade is currently the only approved treatment for PNH. However, residual anemia is an emerging observation for many PNH patients receiving anti-C5 treatment. A range of complement-targeted therapeutic approaches, encompassing surface-directed inhibition of C3 convertases, blockade of membrane attack complex assembly or C3 interception using peptidic inhibitors, has yielded promising results and offers leverage for even more effective treatment of PNH. This article discusses recent advances in this rapidly evolving field, integrating critical perspectives from preclinical PNH models and diverse complement modulation strategies with genetic insights and therapy response profiles. It also evaluates the relative efficacy, limitations and benefits afforded by C3 or C5 inhibition in the context of PNH therapeutics.
Schizophrenia After Prenatal Famine (1996)

Prenatal nutritional deficiency may play a role in the origin of some cases of schizophrenia.
Nuclear Receptors in Lipid Metabolism: Targeting the Heart of Dyslipidemia (2006)

Dyslipidemia is the sine qua non of atherosclerosis, but it is also strongly associated with the metabolic syndrome, obesity, diabetes, and fatty liver disease. The molecular basis for future therapies requires understanding the pivotal role of nuclear hormone receptors in lipid and inflammatory homeostasis. This review summarizes evidence that the liver X receptor (LXR) and peroxisome proliferator-activated receptor (PPAR) are key transcriptional regulators in lipid metabolism. Additionally, their effects on glucose homeostasis and inflammation make LXR and PPAR signaling networks attractive molecular targets for managing lipid-related diseases.
Generation 3D: Living in Virtual Worlds (2007)

Videogames have provided the killer application for 3D virtual worlds over the past decade. SIMNET was not a persistent world - it offered no central server to maintain the simulation's global state. Wolfenstein 3D and other first-person shooter games followed the same model. In a departure from more traditional videogames, some developers have begun creating large-scale virtual worlds such as Second Life (http://secondlife.com) for social networking. Educators have recognized the power of collaborative presence for students in the virtual world. More than 200 universities - including Harvard and Princeton - now experiment with MMORPGs as learning environments.
Resting B cells as Inducers of Antigen-Specific T Regulatory Cells (83.22) (2010)

Abstract We have previously shown that resting B cells are able to expand T regulatory cells through TGF-beta3 whereas activated B cells induce increased apoptosis of T regulatory cells. Thus, we hypothesize that resting B cells can be used to induce antigen-specific T regulatory cells. To test our hypothesis, we isolate resting B cells from mice and load the cells with Ova, and then adoptively transfer the B cells to Ova-specific TCR transgenic mice. We determine numbers of OVA-specific T effector cells and T regulatory cells in the adoptively transferred mice and in control mice that receive untreated resting B cells alone by flow cytometry (Foxp3). We further determine if these T regulatory cells mediate immunosuppressive activities by using proliferation assay in vitro and by in vivo prevention of immune response against challenge with OVA + adjuvant. This study will provide basis to develop approaches to induce antigen-specific T regulatory cells to treat inflammatory diseases such as allergy and autoimmune diseases.
Function and structure of RNA polymerase from vesicular stomatitis virus. (1976)

The RNA-dependent RNA polymerase associated with vesicular stomatitis virus was isolated to apparent homogeneity by a newly developed procedure, which includes stepwise removal of proteins from virions by successive treatment with high concentrations of cesium sulfate and cesium chloride, followed by glycerol gradient centrifugation or chromatography on phosphocellulose or DEAE-Sephadex column. The polymerase thus purified contained L (large protein) and NS proteins as the intrinsic subunits and multiple species of enzyme were found which differ in the molar ratio of L to NS. Since the enzyme with the highest activity was composed of equimolar amounts of the two subunits and exhibited the sedimentation coefficient of approximately 11 S in a buffer containing 0.2 M NaCl, the structure of active protomer was suggested to be (L)1(NS)1. In accordance with this conclusion, enzyme preparations deficient in the content of NS protein, were activated by the addition of preparations deficient in the content of NS protein. The purified RNA polymerase catalyzed the synthesis of poly(A), which was covalently attached to the 3' termini of RNA products, and RNA, only in the presence of all 4 substrates. The present finding might be the first which indicates that the transcriptase itself catalyzes post-transcriptional modification of mRNA by adding poly(A) sequences to the 3'-OH termini. The molecular mechanism of the switch from transcription to poly(A) synthesis, however, remains to be investigated.
An Active Low-Frequency Ripple Control Method Based on the Virtual Capacitor Concept for BIPV Systems (2013)

This paper proposes an active low-frequency ripple control device (ALFRCD) based on virtual capacitor concept for building-integrated photovoltaic (BIPV) systems. With this method, the power quality of the BIPV system can be enhanced, and the lifetime and reliability are superior by reducing electrolytic capacitors. The low-frequency ripple current caused by the single-phase inverter can be compensated promptly by introducing a current integrator instead of unit feedback in the control strategy of the ALFRCD. With this current integrator, the device is unable to output dc current, which is similar to the function of a capacitor. Compared with the conventional method with high-pass filter, the presented method can achieve better compensation efficiency at most of the low frequencies and the response speed is superior as well. In addition, only one more integrator is needed in the control loop, which indicates the conciseness of the method. The performance is analyzed and the design algorithm is introduced in detail. Simulations and experimental results verified the proposed method's reliability and superiority in comparison with the method with high-pass filter and a proportional-integral controller.
Interleukin-1 beta mRNA expression in ischemic rat cortex. (1993)

Brain interleukin-1 beta mRNA is elevated acutely after permanent focal ischemia and especially in hypertensive rats. These data suggest that this potent proinflammatory and procoagulant cytokine might have a role in brain damage following ischemia.
Topical retinoids in the treatment of photoaging (2005)

A large number of different substances comprise the family of retinoids, which are traditionally described as vitamin A derivatives. By exerting their action through nuclear and cytoplasmic receptors they may improve photoaging. Tretinoin is the best studied retinoid in the treatment of photoaging. Others such as isotretinoin, retinaldehyde, and tazarotene, although less well studied, have given promising results.
Protein C anticoagulant activity in relation to anti-inflammatory and anti-apoptotic activities (2006)

The anticoagulant protein C system is a dual function cofactor-dependent system. On one hand, it is designed to regulate coagulation, maintain the fluidity of the vasculature and prevent thrombosis. On the other hand, the protein C pathway provides anti-inflammatory and cytoprotective activities. Protein C, a vitamin K-dependent serine protease zymogen that circulates in plasma, is converted by limited proteolysis to activated protein C (APC) by the thrombin-thrombomodulin-endothelial protein C receptor complex on endothelial surfaces. APC and the cofactors of the protein C pathway exert two major distinct types of activities, namely a well-studied anticoagulant activity and a more recently revealed cytoprotective activity due to direct effects on cells. Because of these pleiotropic properties, APC and the protein C pathway components have important roles in the body's host-defense system and provide opportunities for therapeutic treatment of complex and challenging medical disorders, including thrombosis, severe sepsis and stroke.
Invasive pneumococcal disease: epidemiology in children and adults prior to implementation of the conjugate vaccine in the Oxfordshire region, England (2008)

A 10-year invasive pneumococcal disease (IPD) enhanced surveillance project in the Oxfordshire region of the UK between 1996 and 2005 identified a total of 2691 Streptococcus pneumoniae isolates from all ages that provided a comprehensive description of pneumococcal epidemiology. All isolates were serotyped and those from children under 5 years of age were genotyped and a matched case-control study using adults hospitalized between 1995 and 2000 was performed to estimate the effectiveness of the pneumococcal polysaccharide vaccine in the local population. Fifty-one serotypes were isolated, with different age distributions. The overall incidence of IPD was 9.2 cases per 100 000 population per annum [95 % confidence interval (CI), 8.6-9.9] and that of meningitis was 0.7 per 100 000 population per annum (95 % CI 0.5-0.9). After adjusting for age, serotype 1 was found to be less likely to be associated with meningitis versus other IPD, compared with the most common serotype 14, whereas serotype 12F was more likely to cause meningitis than other IPD. There were significant temporal changes in IPD incidence of four serotypes, with decreases in serotypes 1, 12F and 14 and increases in serotype 8. A possible novel variant (from serotype 6A to 6B) was found using multilocus sequence typing analysis. From the matched case-control study of adults, the pneumococcal polysaccharide vaccine effectiveness was estimated to be 43 % (2-68 %), which did not change significantly after adjustment for pre-existing co-morbidities. The data provide a baseline against which the impact of the pneumococcal conjugate vaccine introduced in the UK in 2006 could be measured.
Abstract 830: ISU104, a fully human antibody targeting a specific epitope on the ErbB3, displays potent inhibition of tumor growth in multiple xenograft tumor models (2018)

Abstract Members of the epidermal growth factor receptor family (ErbB family) are known as potent mediators in the development and progression of cancer. Activated ErbBs recruit various adaptors and signaling molecules through the phosphorylated cytoplasmic domain, which further leads to activation of downstream oncogenic signaling pathways. There are approved therapeutics for ErbB1 (EGFR) and ErbB2 (HER2) in the treatment of human cancers, while monoclonal antibodies targeting ErbB3 are just undergoing clinical trials. ISU104 is a fully human anti-ErbB3 antibody isolated from phage display antibody library. We performed the hydrogen/deuterium exchange mass spectrometry (HDX-MS) analysis with ErbB3 extracellular domain and ISU104, and that indicated that ISU104 mainly binds with domain 3 and weakly interacts with domain 1 of ErbB3. The binding property of ISU104 induced dose-dependent inhibition of ligand (heregulin, HRG) binding, blocking of dimerization of ErbB3 with other ErbBs and subsequently inactivated the downstream signaling of ErbB3. Also, ISU104 occasioned internalization of ErbB3 from plasma membrane, and downregulated the expression level of ErbB3. We demonstrated the biologic effect of ISU104 in several ErbB3-expressing cancer cell lines, including head and neck squamous cell carcinoma (HNSCC) and breast cancers. ISU104 completely suppressed the HRG-induced ErbB3/AKT phosphorylation, reduced cell proliferation and survival. Next, we evaluated efficacy of ISU104 in multiple xenograft models. Mice were treated with 10 mg/kg of ISU104 twice weekly. ISU104 regressed tumor growth in FaDu HNSCC model, and showed more than 70% tumor growth inhibition (TGI) in CAL27 (HNSCC), BxPC3 (pancreatic cancer), MDA-MB-468 (breast cancer), A549 (skin cancer), and BT474 (breast cancer) models. Our results suggest that ISU104 effectively blocks activation of ErbB3 and the downstream pathway by ErbB3, and may provide clinical benefit to ErbB3-activated patients. Citation Format: Miyoung Kim, Youngmi Hur, Sohyeon Seo, Heynjeong Lim, Kyungyong Kim, Youngsoo Sohn, Seung-Beom Hong, Donggoo Bae. ISU104, a fully human antibody targeting a specific epitope on the ErbB3, displays potent inhibition of tumor growth in multiple xenograft tumor models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 830.
Stem cell-related cardiac gene expression early after murine myocardial infarction (2006)

Genes that are generally considered to participate in stem cell-related processes and angiogenesis were not upregulated after MI, whereas the inflammatory gene expression dominated. Modulation of this imbalance might be of value for stem cell-mediated therapy.
Silicone-Suppressed 3D MRI of the Breast Using Rotating Delivery of Off-Resonance Excitation (1995)

Silicone-suppressed RODEO MRI of the breast can accurately identify free and intracapsular silicone and can distinguish silicone from other tissues. This provides unique information about the breast in a number of specific applications.
AN INFRARED SPECTROSCOPIC STUDY OF THE ADSORPTION OF WATER AND CARBON DIOXIDE BY LINDE MOLECULAR SIEVE X1 (1963)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAN INFRARED SPECTROSCOPIC STUDY OF THE ADSORPTION OF WATER AND CARBON DIOXIDE BY LINDE MOLECULAR SIEVE X1L. Bertsch and H. W. HabgoodCite this: J. Phys. Chem. 1963, 67, 8, 1621–1628Publication Date (Print):August 1, 1963Publication History Published online1 May 2002Published inissue 1 August 1963https://doi.org/10.1021/j100802a013RIGHTS & PERMISSIONSArticle Views782Altmetric-Citations164LEARN 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 PDF (1 MB) Get e-Alerts
Atomic SC for simple in-order processors (2014)

Sequential consistency is arguably the most intuitive memory consistency model for shared-memory multi-threaded programming, yet it appears to be a poor fit for simple, in-order processors that are most attractive in the power-constrained many-core era. This paper proposes an intuitively appealing and straightforward framework for ensuring sequentially consistent execution. Prior schemes have enabled similar reordering, but in ways that are most naturally implemented in aggressive out-of-order processors that support speculative execution or that require pervasive and error-prone revisions to the already-complex coherence protocols. The proposed Atomic SC approach adds a light-weight scheme for enforcing mutual exclusion to maintain proper SC order for reordered references, works without any alteration to the underlying coherence protocol and consumes minimal silicon area and energy. On an in-order processor running multithreaded PARSEC workloads, Atomic SC delivers performance that is equal to or better than prior SC-compatible schemes, which require much greater energy and design complexity.