gebhart/patrepeval huggingface dataset:
Inactivation of the IL-6 gene prevents development of multicentric Castleman's disease in C/EBP beta-deficient mice. (1996)

Castleman's disease is a lymphoproliferative disorder thought to be related to deregulated production of IL-6. We have previously shown that mice lacking the trans-acting factor C/EBP beta, a transcriptional regulator of IL-6 and a mediator of IL-6 intracellular signaling, develop a pathology nearly identical to multicentric Castleman's disease, together with increasingly high levels of circulating IL-6. We describe here how the simultaneous inactivation of both IL-6 and C/EBP beta genes prevents the development of pathological traits of Castleman's disease observed in C/EBP beta-deficient mice. Histological and phenotypic analysis of lymph nodes and spleen of double mutant mice did not show either the lymphoadenopathy and splenomegaly or the abnormal expansion of myeloid, B and plasma cell compartments observed in C/EBP beta-/- mice, while B cell development, although delayed, was normal. Our data demonstrate that IL-6 is essential for the development of multicentric Castleman's disease in C/EBP beta-/- mice.
Induction of intratumoral tumor necrosis factor (TNF) synthesis and hemorrhagic necrosis by 5,6-dimethylxanthenone-4-acetic acid (DMXAA) in TNF knockout mice. (1999)

5,6-Dimethylxanthenon-4-acetic acid (DMXAA) is a new antitumor drug currently undergoing clinical trial. Administration of DMXAA to mice with tumors leads to cessation of tumor blood flow and the onset of tumor hemorrhagic necrosis, accompanied by the production of the cytokine tumor necrosis factor (TNF). Previous studies have shown that DMXAA induces both tumor and host cells to synthesize TNF and that induced intratumoral TNF production correlates with the antitumor activity of DMXAA. To explore the hypothesis that TNF production by tumor cells contributed to the induction of hemorrhagic necrosis by DMXAA, TNF-/- (C57Bl/6 background) mice were used as recipients for the s.c. implantation of (TNF positive) colon 38 adenocarcinoma. Tumors removed 24 h after treatment with DMXAA (66 or 100 micromol/kg) were found to be hemorrhagic and necrotic. Cells expressing TNF mRNA in tumors removed 2 h after treatment with DMXAA (160 micromol/kg) were found by in situ hybridization to be comparable in frequency and distribution with those in tumors from C57Bl/6 TNF-positive mice. However, the amount of TNF protein extracted from tumors from TNF knockout mice was lower than that from TNF-positive mice. Spleen and liver tissue from TNF knockout mice, in contrast to that from TNF-positive mice, produced no TNF mRNA. TNF protein was undetectable in liver and spleen tissue from TNF knockout mice, but was evident in tissue from TNF-positive mice. These results confirm that DMXAA has the novel ability of inducing tumors to synthesize TNF in situ.
Efficient hardware implementations of high throughput SHA-3 candidates keccak, luffa and blue midnight wish for single- and multi-message hashing (2010)

In November 2007 NIST announced that it would organize the SHA-3 competition to select a new cryptographic hash function family by 2012. In the selection process, hardware performances of the candidates will play an important role. Our analysis of previously proposed hardware implementations shows that three SHA-3 candidate algorithms can provide superior performance in hardware: Keccak, Luffa and Blue Midnight Wish (BMW). In this paper, we provide efficient and fast hardware implementations of these three algorithms. Considering both single- and multi-message hashing applications with an emphasis on both speed and efficiency, our work presents more comprehensive analysis of their hardware performances by providing different performance figures for different target devices. To our best knowledge, this is the first work that provides a comparative analysis of SHA-3 candidates in multi-message applications. We discover that BMW algorithm can provide much higher throughput than previously reported if used in multi-message hashing. We also show that better utilization of resources can increase speed via different configurations. We implement our designs using Verilog HDL, and map to both ASIC and FPGA devices (Spartan3, Virtex2, and Virtex 4) to give a better comparison with those in the literature. We report total area, maximum frequency, maximum throughput and throughput/area of the designs for all target devices. Given that the selection process for SHA3 is still open; our results will be instrumental to evaluate the hardware performance of the candidates.
Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma (2016)

The addition of daratumumab to lenalidomide and dexamethasone significantly lengthened progression-free survival among patients with relapsed or refractory multiple myeloma. Daratumumab was associated with infusion-related reactions and a higher rate of neutropenia than the control therapy. (Funded by Janssen Research and Development; POLLUX ClinicalTrials.gov number, NCT02076009 .).
Expression and Characterization of Herpes Simplex Virus Type 1 (HSV-1) Glycoprotein G (gG) by Recombinant Vaccinia Virus: Neutralization of HSV-1 Infectivity with Anti-gG Antibody (1987)

A recombinant vaccinia virus expressing herpes simplex virus type 1 (HSV-1) glycoprotein G (gG) has been constructed. Cells infected with this recombinant virus (gG-VAC) synthesized glycosylated proteins of 48K, 57K and 61K mol. wt. that were recognized by anti-HSV-1 sera. Rabbits and mice vaccinated with the live recombinant virus produced antibodies that recognized 48K, 57K and 61K mol. wt. proteins in HSV-1-infected cells. The gG polypeptides were present on cytoplasmic and nuclear membranes during infection with both HSV-1 and recombinant vaccinia virus gG-VAC. The 57K and 61K mol. wt. gG polypeptides were present in purified HSV-1 virions and were targets for antibody-mediated complement-dependent virus neutralization.
PPARs and Mitochondrial Metabolism: From NAFLD to HCC (2016)

Metabolic related diseases, such as type 2 diabetes, metabolic syndrome, and nonalcoholic fatty liver disease (NAFLD), are widespread threats which bring about a significant burden of deaths worldwide, mainly due to cardiovascular events and cancer. The pathogenesis of these diseases is extremely complex, multifactorial, and only partially understood. As the main metabolic organ, the liver is central to maintain whole body energetic homeostasis. At the cellular level, mitochondria are the metabolic hub connecting and integrating all the main biochemical, hormonal, and inflammatory signaling pathways to fulfill the energetic and biosynthetic demand of the cell. In the liver, mitochondria metabolism needs to cope with the energetic regulation of the whole body. The nuclear receptors PPARs orchestrate lipid and glucose metabolism and are involved in a variety of diseases, from metabolic disorders to cancer. In this review, focus is placed on the roles of PPARs in the regulation of liver mitochondrial metabolism in physiology and pathology, from NAFLD to HCC.
Determination of 3D cartilage thickness data from MR imaging: Computational method and reproducibility in the living (1999)

The objective of this work was to develop a computational approach for quantifying the three-dimensional (3D) thickness distribution of articular cartilage with magnetic resonance (MR) imaging, independent of the imaging plane, and to test the reproducibility of the method in the living. An algorithm was implemented, based on a 3D Euclidean distance transformation, and its accuracy was assessed in geometric test objects, for which an analytic solution was available. The precision of the method was evaluated in six replicated MR data sets of the knee joint cartilage of eight volunteers. The algorithm produced 3D thickness values identical to those of the analytic solutions in the test objects. The reproducibility of the mean cartilage thickness in the patellar and tibial cartilages was 1.5–3.4% (root-mean-square average of the individual coefficient of variation percent), that of the maximal thickness 2.1–7.9%, and that of the thickness distribution 2.3–6.1%. The method presented allows for noninvasive analysis of 3D cartilage thickness from MR images in biomechanical and clinical investigations. Magn Reson Med 41:529–536, 1999. © 1999 Wiley-Liss, Inc.
Image Manipulation Detection With Binary Similarity Measures (2005)

Publication in the conference proceedings of EUSIPCO, Antalya, Turkey, 2005
Ionospheric constraints on VHF/UHF communications links during solar maximum and minimum periods (1988)

An extensive VHF/UHF scintillation data base covering the frequency range of VHF to a few gigahertz has been utilized to determine the magnitudes of phase and intensity scintillations and their temporal/spatial structures during the sunspot maximum and minimum periods. The equatorial portion of the study has been based on geostationary satellite observations at Huancayo, a station on the magnetic equator, and at Ascension Island, which is an equatorial anomaly station having an extremely disturbed irregularity environment. The high‐latitude part of the study is based on quasistationary satellite measurements at a polar cap location (Thule) and two auroral locations (Goose Bay and Tromsø). The Tromsø observations are augmented with the Defense Nuclear Agency HiLat satellite beacon measurements during the solar minimum period. The data indicate a strong solar cycle control of scintillation activity at all locations, resulting in a drastic reduction of the magnitudes and occurrence of scintillations during the current solar minimum period. This pattern is consistent with both a reduction of F region ionization density and a reduction of irregularity generation in the solar minimum period. At the magnetic equator the magnitude of scintillations at 1.5 GHz seldom exceeds 3 dB with the percentage occurrence &gt; 2 dB varying from 70% during high sunspot conditions to 30% during low sunspot conditions. At the crest of the equatorial anomaly, on the other hand, during the solar maximum in 1979, fades of 20 dB at 1.5 GHz are observed 30% of the time. At a decreased level of solar activity in 1982, a similar occurrence level is obtained at 1.5 GHz for fade levels of only 5 dB. During the solar minimum period, 1.5‐GHz scintillations are virtually absent. Phase scintillation measurements made at Ascension Island indicate that the median value of rms phase deviation is about 5 rad for detrend intervals of 100 s. In the auroral region, during the solar maximum period under magnetically disturbed conditions, the median values of scintillation fades and rms phase deviation (82‐s detrend) at 250 MHz are observed to be 15 dB and 3 rad, respectively. At Thule, located deep within the polar cap, the median values of scintillation fades and rms phase deviation at 250 MHz attain values as large as 20 dB and 4 rad during the sunspot maximum period. Unlike Ascension Island the scintillation activity at high‐latitude stations exhibits a threshold effect and does not decrease until 1983. However, in 1986 with sunspot numbers in the vicinity of 10, fade levels as low as 5 dB at 250 MHz are recorded in the polar cap and auroral stations only 5% of the time. It is noted that at auroral locations the most prominent feature, namely the existence of magnetic L shell‐aligned irregularity sheets, is equally evident at both sunspot maximum and minimum.
L-687,908, a potent hydroxyethylene containing HIV protease inhibitor (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTL-687,908, a potent hydroxyethylene containing HIV protease inhibitorJoseph P. Vacca, J. P. Guare, S. J. DeSolms, W. M. Sanders, E. A. Giuliani, S. D. Young, P. L. Darke, I. S. Sigal, W. A. Schleif, and Cite this: J. Med. Chem. 1991, 34, 3, 1225–1228Publication Date (Print):March 1, 1991Publication History Published online1 May 2002Published inissue 1 March 1991https://pubs.acs.org/doi/10.1021/jm00107a050https://doi.org/10.1021/jm00107a050research-articleACS PublicationsRequest reuse permissionsArticle Views299Altmetric-Citations95LEARN 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
The Nrf2/ARE Pathway: A Promising Target to Counteract Mitochondrial Dysfunction in Parkinson's Disease (2011)

Mitochondrial dysfunction is a prominent feature of various neurodegenerative diseases as strict regulation of integrated mitochondrial functions is essential for neuronal signaling, plasticity, and transmitter release. Many lines of evidence suggest that mitochondrial dysfunction plays a central role in the pathogenesis of Parkinson's disease (PD). Several PD-associated genes interface with mitochondrial dynamics regulating the structure and function of the mitochondrial network. Mitochondrial dysfunction can induce neuron death through a plethora of mechanisms. Both mitochondrial dysfunction and neuroinflammation, a common denominator of PD, lead to an increased production of reactive oxygen species, which are detrimental to neurons. The transcription factor nuclear factor E2-related factor 2 (Nrf2, NFE2L2) is an emerging target to counteract mitochondrial dysfunction and its consequences in PD. Nrf2 activates the antioxidant response element (ARE) pathway, including a battery of cytoprotective genes such as antioxidants and anti-inflammatory genes and several transcription factors involved in mitochondrial biogenesis. Here, the current knowledge about the role of mitochondrial dysfunction in PD, Nrf2/ARE stress-response mechanisms, and the evidence for specific links between this pathway and PD are summarized. The neuroprotection of nigral dopaminergic neurons by the activation of Nrf2 through several inducers in PD is also emphasized as a promising therapeutic approach.
Velocity-dependent curvature gain and avatar use for Redirected Walking (2010)

We investigated in a study whether humans sensitivity to curved walking is affected by their walking velocity.\nAmongst other techniques, redirecting users of an immersive virtual environment on a curved path is part of the\nso-called Redirected Walking. We conducted an experiment in which 12 participants walked specific curvatures\nat given speeds in a VR. We found that people are significantly less sensitive to walking on a curve when walking\nslower. Moreover, we assume the possibility of using avatars to support redirection algorithms as it was shown\nby Llobera et al. ([LSRS10]) that proxemics holds true for avatars in virtual environments, too. In this work, we\ndepict three possible applications of how avatars could be used to achieve a better redirection.
Viscoelastic Properties of Polymers (1961)

The Nature of Viscoelastic Behavior. Illustrations of Viscoelastic Behavior of Polymeric Systems. Exact Interrelations among the Viscoelastic Functions. Approximate Interrelations among the Linear Viscoelastic Functions. Experimental Methods for Viscoelastic Liquids. Experimental Methods for Soft Viscoelastic Solids and Liquids of High Viscosity. Experimental Methods for Hard Viscoelastic Solids. Experimental Methods for Bulk Measurements. Dilute Solutions: Molecular Theory and Comparisons with Experiments. Molecular Theory for Undiluted Amorphous Polymers and Concentrated Solutions Networks and Entanglements. Dependence of Viscoelastic Behavior on Temperature and Pressure. The Transition Zone from Rubberlike to Glasslike Behavior. The Plateau and Terminal Zones in Uncross-Linked Polymers. Cross-Linked Polymers and Composite Systems. The Glassy State. Crystalline Polymers. Concentrated Solutions, Plasticized Polymers, and Gels. Viscoelastic Behavior in Bulk (Volume) Deformation. Applications to Practical Problems. Appendices. Author & Subject Indexes.
Acidities of carboxamides, hydroxamic acids, carbohydrazides, benzenesulfonamides, and benzenesulfonohydrazides in DMSO solution (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAcidities of carboxamides, hydroxamic acids, carbohydrazides, benzenesulfonamides, and benzenesulfonohydrazides in DMSO solutionF. G. Bordwell, Herbert E. Fried, David L. Hughes, Tsuei Yun Lynch, A. V. Satish, and Young E. WhangCite this: J. Org. Chem. 1990, 55, 10, 3330–3336Publication Date (Print):May 1, 1990Publication History Published online1 May 2002Published inissue 1 May 1990https://doi.org/10.1021/jo00297a063RIGHTS & PERMISSIONSArticle Views1193Altmetric-Citations98LEARN 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 (963 KB) Get e-Alerts Get e-Alerts
Once daily intranasal fluticasone propionate is effective for perennial allergic rhinitis. (1994)

The efficacy of intranasal fluticasone propionate 200 micrograms once daily or 100 micrograms twice daily in treating perennial allergic rhinitis was evaluated in a randomized, double-blind, placebo-controlled study of 24 weeks' duration in 365 patients. Clinician-rated and patient-rated total nasal symptom severity scores were improved within 1 week of treatment with either regimen of fluticasone propionate and improvement was maintained over the 24-week treatment period. Clinician-rated overall evaluation indicated a significantly better response in the two fluticasone propionate groups compared with the placebo group. All efficacy evaluations indicated no difference in response between the fluticasone propionate 200 micrograms once-daily and 100 micrograms twice-daily groups. Patients in both fluticasone propionate groups had significantly less nasal obstruction upon awakening than the placebo group at all assessment periods. Fewer patients in either fluticasone propionate group used antihistamine rescue medication compared with the placebo group. The percentage of patients with nasal eosinophils and basophils at the end of the 24-week treatment period was significantly lower in both fluticasone propionate groups compared with the placebo group. Safety evaluations indicated that intranasal fluticasone propionate was as safe as placebo when given as 200 micrograms once daily or 100 micrograms twice daily. The incidence of drug-related adverse events was similar among the fluticasone propionate and placebo groups except for the incidence of epistaxis and blood in nasal mucus which was somewhat higher in the fluticasone propionate twice-daily group. There was no changes in the opthalmic examinations to suggest corticosteriod-induced posterior subcapsular cataract formation.(ABSTRACT TRUNCATED AT 250 WORDS)
A novel antibody targeting ICOS increases intratumoural cytotoxic to regulatory T cell ratio and induces tumour regression (2019)

Abstract The immunosuppressive tumour microenvironment constitutes a significant hurdle to the response to immune checkpoint inhibitors. Both soluble factors and specialised immune cells such as regulatory T cells (T Reg ) are key components of active intratumoural immunosuppression. Previous studies have shown that Inducible Co-Stimulatory receptor (ICOS) is highly expressed in the tumour microenvironment, especially on T Reg , suggesting that it represents a relevant target for preferential depletion of these cells. Here, we used immune profiling of samples from tumour bearing mice and cancer patients to characterise the expression of ICOS in different tissues and solid tumours. By immunizing an Icos knockout transgenic mouse line expressing antibodies with human variable domains, we selected a fully human IgG1 antibody called KY1044 that binds ICOS from different species. Using KY1044, we demonstrated that we can exploit the differential expression of ICOS on T cell subtypes to modify the tumour microenvironment and thereby improve the anti-tumour immune response. We showed that KY1044 induces sustained depletion of ICOS high T Reg cells in mouse tumours and depletion of ICOS high T cells in the blood of non-human primates, but was also associated with secretion of pro-inflammatory cytokines from ICOS low T EFF cells. Altogether, KY1044 improved the intratumoural T EFF :T Reg ratio and increased activation of T EFF cells, resulting in monotherapy efficacy or in synergistic combinatorial efficacy when administered with the immune checkpoint blocker anti-PD-L1. In summary, our data demonstrate that targeting ICOS with KY1044 can favourably alter the intratumoural immune contexture, promoting an anti-tumour response.
Pancreatic Ductal Adenocarcinoma Mice Lacking Mucin 1 Have a Profound Defect in Tumor Growth and Metastasis (2011)

MUC1 is overexpressed and aberrantly glycosylated in more than 60% of pancreatic ductal adenocarcinomas. The functional role of MUC1 in pancreatic cancer has yet to be fully elucidated due to a dearth of appropriate models. In this study, we have generated mouse models that spontaneously develop pancreatic ductal adenocarcinoma (KC), which are either Muc1-null (KCKO) or express human MUC1 (KCM). We show that KCKO mice have significantly slower tumor progression and rates of secondary metastasis, compared with both KC and KCM. Cell lines derived from KCKO tumors have significantly less tumorigenic capacity compared with cells from KCM tumors. Therefore, mice with KCKO tumors had a significant survival benefit compared with mice with KCM tumors. In vitro, KCKO cells have reduced proliferation and invasion and failed to respond to epidermal growth factor, platelet-derived growth factor, or matrix metalloproteinase 9. Further, significantly less KCKO cells entered the G(2)-M phase of the cell cycle compared with the KCM cells. Proteomics and Western blotting analysis revealed a complete loss of cdc-25c expression, phosphorylation of mitogen-activated protein kinase (MAPK), as well as a significant decrease in nestin and tubulin-α2 chain expression in KCKO cells. Treatment with a MEK1/2 inhibitor, U0126, abrogated the enhanced proliferation of the KCM cells but had minimal effect on KCKO cells, suggesting that MUC1 is necessary for MAPK activity and oncogenic signaling. This is the first study to utilize a Muc1-null PDA mouse to fully elucidate the oncogenic role of MUC1, both in vivo and in vitro.