gebhart/patrepeval huggingface dataset:
Ezetimibe and other Azetidinone Cholesterol Absorption Inhibitors (2005)

Atherosclerotic coronary artery disease remains a major healthcare concern especially in developed countries. While lowering plasma cholesterol levels via diet, exercise, and pharmacotherapy can reduce this risk of developing coronary artery disease, there remains a need for more effective drug therapies. The azetidinone cholesterol absorption inhibitors typified by ezetimibe represent the first new approach to lipid lowering therapy in more than a decade. This review summarizes the medicinal chemistry of the azetidinone cholesterol absorption inhibitors as a class, with emphasis on factors that contributed both to the discovery of ezetimibe as well as to our overall understanding of S.A.R. trends in this area.
The K666N mutation in SF3B1 is associated with increased progression of MDS and distinct RNA splicing (2020)

Key Points The K666N mutation of SF3B1 has distinct clinicopathologic features in MDS. The K666N mutation of SF3B1 has a distinct RNA splicing profile.
Denoising-Enhancing Images on Elastic Manifolds (2011)

The conflicting demands for simultaneous low-pass and high-pass processing, required in image denoising and enhancement, still present an outstanding challenge, although a great deal of progress has been made by means of adaptive diffusion-type algorithms. To further advance such processing methods and algorithms, we introduce a family of second-order (in time) partial differential equations. These equations describe the motion of a thin elastic sheet in a damping environment. They are also derived by a variational approach in the context of image processing. The new operator enables better edge preservation in denoising applications by offering an adaptive lowpass filter, which preserves high-frequency components in the pass-band better than the adaptive diffusion filter, while offering slower error propagation across edges. We explore the action of this powerful operator in the context of image processing and exploit for this purpose the wealth of knowledge accumulated in physics and mathematics about the action and behavior of this operator. The resulting methods are further generalized for color and/or texture image processing, by embedding images in multidimensional manifolds. A specific application of the proposed new approach to superresolution is outlined.
Multiphoton ionization spectroscopy measurements of silicon atoms during vapor-phase synthesis of ceramic particles (1990)

Resonance-enhanced multiphoton ionization spectroscopy has been applied to the problem of detection of gas-phase species in a dense particle-forming flow. Relative silicon atom profiles in an atmospheric pressure flame reactor producing silica particles have been made using a 2+1 ionization scheme. The results have shown that silicon atoms are confined to a very narrow time window in the reactor (&amp;lt;15 ms). In addition, the nonresonant background indicated the presence of ionizable clusters and could be a valuable tool for observing the presence and location of small clusters. The effect of varying silane loading changed both the location and magnitude of the silicon concentration observed. The results suggest that chain branching chemistry is important in the production of silicon and that enhancement of pyrolytic relative to oxidative processes occurs as the silane loading is increased. Finally, the role of charged particles on electron capture was investigated. It was found that significant attenuation of the electron current can lead to highly erroneous results.
BMP-SMAD-ID promotes reprogramming to pluripotency by inhibiting p16/INK4A-dependent senescence (2016)

Fibrodysplasia ossificans progressiva (FOP) patients carry a missense mutation in ACVR1 [617G > A (R206H)] that leads to hyperactivation of BMP-SMAD signaling. Contrary to a previous study, here we show that FOP fibroblasts showed an increased efficiency of induced pluripotent stem cell (iPSC) generation. This positive effect was attenuated by inhibitors of BMP-SMAD signaling (Dorsomorphin or LDN1931890) or transducing inhibitory SMADs (SMAD6 or SMAD7). In normal fibroblasts, the efficiency of iPSC generation was enhanced by transducing mutant ACVR1 (617G > A) or SMAD1 or adding BMP4 protein at early times during the reprogramming. In contrast, adding BMP4 at later times decreased iPSC generation. ID genes, transcriptional targets of BMP-SMAD signaling, were critical for iPSC generation. The BMP-SMAD-ID signaling axis suppressed p16/INK4A-mediated cell senescence, a major barrier to reprogramming. These results using patient cells carrying the ACVR1 R206H mutation reveal how cellular signaling and gene expression change during the reprogramming processes.
Whose 'City of Tomorrow' is It? On Urban Computing, Utopianism, and Ethics (2013)

In this article I discuss some ethical and moral ramifications of the future envisioned by urban computing. In doing so, I make analogies to twentieth century utopian visions of the “city of tomorrow,” so that we might see the historical context of a similar field with similar utopian instincts. I hope this context helps us better understand how our work might affect the lives of city dwellers in profound ways that we may never fully foresee. I discuss ethical questions related to using urban computing for policy making, for real-estate development, and for surveillance. I also define the concept of distributed sensing, and discuss some difficult regulatory questions that surround it. I hope this work inspires urban computing researchers to think critically in order to assess societal implications of the technologies they develop.
Recent progress in thin wafer processing (2013)

The ability to process thin wafers with thicknesses of 20-50um on front- and backside is a key technology for 3D IC. The most obvious reason for thin wafers is the reduced form factor, which is especially important for handheld devices. However, probably even more important is that thinner wafers enable significant cost reduction for TSVs. The silicon real estate consumed by the TSVs has to be minimized in order that the final device provides a performance advantage compared to traditional 2D devices. The only way to reduce area consumption by the TSVs is to reduce their diameter. For a given wafer thickness the reduction of TSV diameter increases the TSV aspect ratio. Consensus has developed on the use of Temporary Bonding / Debonding Technology as the solution of choice for reliably handling thin wafers through backside processing steps. While the majority of the device manufacturing steps on the front side of the wafer will be completed with the wafer still at full thickness, it will be temporarily mounted onto a carrier before thinning and processing of the features on its backside. Once the wafer reaches the temporary bonding step, it already represents a significant value, as it has already gone through numerous processing steps. For this reason, inspection of wafers prior to non-reworkable process steps is of great interest. Within the context of Temporary Bonding this consideration calls for inline metrology that allows for detection of excursions of the temporary bonding process in terms of adhesive thickness, thickness uniformity as well as bonding voids prior to thinning of the product wafer. This paper introduces a novel metrology solution capable of detecting all quality relevant parameters of temporarily bonded stacks in a single measurement cycle using an Infrared (IR) based measurement principle. Thanks to the IR based measurement principle, the metrology solution is compatible with both silicon and glass carriers. The system design has been developed with the inline metrology task in mind. This has led to a unique system design concept that enables scanning of wafers at a throughput rate sufficient to enable 100% inspection of all bonded wafers inline in the Temporary Bonding system. Both, current generation temporary bonding system throughputs and future high volume production system throughputs as required by the industry for cost effective manufacturing of 3D stacked devices were taken into account as basic specifications for the newly developed metrology solution. Sophisticated software algorithms allow for making pass/ fail decisions for the bonded stacks and triggering further inspection, processing and / or rework. Actual metrology results achieved with this novel system will be presented and discussed. In terms of adhesive total thickness variation (TTV) of bonded wafers, currently achieved performance values for postbond TTV will be reviewed in light of roadmaps as required by high volume production customers.
MORAb-009, a monoclonal antibody that specifically targets mesothelin, a cell surface tumor adhesion molecule over-expressed in pancreatic, ovarian, and lung cancer and mesothelioma. (2007)

654 Background: Mesothelin is a glycosyl-phosphatidyl inositol-linked membrane protein that is consistently over-expressed in pancreatic cancer and mesothelioma, and some ovarian, non-small cell lung and colorectal cancers. Mesothelin is involved in cellular attachment and binds to MUC16. MORAb-009 is an IgG1κ monoclonal antibody directed against mesothelin with demonstrated bimodal anti-tumor activity on mesothelin-bearing tumor cells, through prevention of adhesion of mesothelin bearing tumor cells to MUC16 positive cells, and through cytotoxic immune-effector functions. In preclinical studies, MORAb-009 has shown anti-tumor activity in xenograft models. Methods: MORAb-009 was tested in Antibody Dependent Cellular Cytotoxicity (ADCC) assays and heterotypic cell adhesion assays. For the ADCC assay, mesothelin bearing target cells were incubated with MORAb-009 or control antibody. Normal peripheral blood mononuclear cells (PBMC) were added in defined ratios. The amount of LDH release was measured to determine the percent of cytotoxicity. Non-mesothelin bearing target cells were used as a negative control. In the heterotypic cellular adhesion assay, mesothelin-bearing cells were loaded with fluorescein and allowed to bind to a confluent monolayer of either MUC16 positive or negative cells, in the presence of MORAb-009 or irrelevant control antibody. The amount of bound fluorescing cells was quantitated. MORAb-009 was also tested in xenograft experiments against mesothelin-bearing human tumors. Results: In ADCC experiments, MORAb-009 was very effective in mediating cellular cytotoxicity. Appropriate controls demonstrated that the effect was specific for MORAb-009 and mesothelin. In the heterotypic cell adhesion assay, MORAb-009 effectively blocked mesothelin-expressing cells from binding to a MUC16 positive monolayer. (See figure). In mouse xenograft experiments, MORAb-009 had anti-tumor effect as a single agent and caused dramatic tumor regressions in combination with gemcitabine. Non- human primate toxicology studies did not demonstrate any toxicity. Conclusions: MORAb-009, a monoclonal antibody against mesothelin, has preclinical activity against mesothelin positive tumor cells in mediating ADCC, preventing adhesion to MUC16 positive monolayers, and in xenograft experiments. MORAb-009 is entering clinical studies in the treatment of mesothelin positive tumors. Preliminary data will be presented.
Risks Involved in the Use of Enrofloxacin for Salmonella Enteritidis or Salmonella Heidelberg in Commercial Poultry (2016)

The objectives of the present study were to evaluate the risks involved in the use of Enrofloxacin for Salmonella Enteritidis (SE) or Salmonella Heidelberg (SH) in commercial poultry and determine the effects of a probiotic as an antibiotic alternative. Two experiments were conducted to evaluate the risks involved in the use of Enrofloxacin for SE or SH in commercial poultry. Experiment 1 consisted of two trials. In each trial, chickens were assigned to one of three groups; control + SE challenged; Enrofloxacin 25 mg/kg + SE; and Enrofloxacin 50 mg/kg + SE. Chickens received Enrofloxacin in the drinking water from days 1 to 5 of age. On day 6, all groups received fresh water without any treatment. All chickens were orally gavaged with 10(7) cfu/chick of SE at 7 days of age and euthanized on 8 days of age. In Experiment 2, turkey poults were assigned to one of the three groups; control + SH; probiotic + SH; and Enrofloxacin 50 mg/kg + SH. Poults received probiotic or Enrofloxacin in the drinking water from days 1 to 5 of age. On day 6, poults received fresh water without any treatment. Poults were orally gavaged with 10(7) cfu/poult of SH at 7 days of age. Poults were weighed and humanely killed 24 h post-SH challenge to evaluate serum concentration of fluorescein isothiocyanate-dextran to evaluate intestinal permeability, metagenomics, and SH infection. In both trials of Experiment 1, chickens treated with Enrofloxacin were more susceptible to SE organ invasion and intestinal colonization when compared with control non-treated chickens (P < 0.05). In Experiment 2, poults treated with 50 mg/kg of Enrofloxacin showed an increase in body weight, however, this group also showed an increase in SH susceptibility, intestinal permeability, and lower proportion of Firmicutes and Bacteroidetes, but with control group had the highest proportion of Proteobacteria. By contrast, poults that received the probiotic had the highest proportion of Firmicutes and Bacteroidetes, but lowest Proteobacteria. The results of the present study suggest that prophylactic utilization of Enrofloxacin at five times the recommended dose in poultry increases the susceptibility to salmonellae infections, and confirms that probiotics may be an effective tool in salmonellae infections.
Proceedings of the third ACM international workshop on Wireless network testbeds, experimental evaluation and characterization (2008)

Welcome to the Third ACM International Workshop on Wireless Network Testbeds, Experimental Evaluation and CHaracterization (WiNTECH'08), held in conjunction with ACM MobiCom 2008 in San Francisco, California. Three years ago, WiNTECH was created to promote experimental evaluation of wireless network protocols/applications using realistic testbeds and characterization using traces from operational wireless networks of which the importance has been increasingly recognized by the research community. Following the success of WiNTECH'06 and WiNTECH'07, also held in conjunction with MobiCom, WiNTECH'08 continues as a forum focusing on research issues concerning the experimental wireless network community.

WiNTECH'08 received 22 regular paper submissions from around the world. Members of the Technical Program Committee reviewed the submissions rigorously, with the help of a few external reviewers. Each paper had three reviews on average. Twelve regular were accepted for publication. The accepted papers cover a wide range of topics from tools and methodologies to metro-area testbeds. In addition, we are holding a contest for technical demonstrations, which will have at least ten participants. Cash prizes for the demo contest are being sponsored by Nokia Siemens Networks, BBN Technologies and ViaSat. We hope that the demo contest will spark more creative uses of testbeds and also serve as a conduit for increased awareness in the research and development community of new innovations. Finally, we are very pleased that the workshop will feature a keynote speech by Professor Nitin Vaidya. The talk is titled Can theory meet practice? The case of multi-channel wireless networks.
PRIMARY LIVER CELL CARCINOMA New Insight for a More Correct Approach to its Classification (1987)

Hepatocellular carcinomas, cholangiocellular carcinomas, and "indeterminate" forms have been studied by immunohistochemical detection of several antigens: alpha-fetoprotein and CEA, as well as type IV collagen, laminin, and keratin. While the first two antigens were variably detectable in different samples, in the poorly differentiated areas of hepatocellular carcinoma type IV collagen and laminin were both absent. These basement membrane glycoproteins constantly surrounded the cholangiocellular carcinoma tubular structures and were always present in those areas of the "indeterminate" group where the cells were organized as pseudoglandular or ductular aggregates. Keratin was absent in all cases of hepatocellular carcinoma, was variably detectable in the "indeterminate" neoplasms and was always present in cholangiocellular tumors. The neoplasias with mixed histopathological features usually showed morphological and biochemical biliary differentiation at the periphery, in contact with the collagenous stroma. We postulate that in some cases hepatocarcinoma cells undergo metaplastic transformation giving rise to cholangiocellular forms. Type IV collagen, laminin, and keratin seem to be accurate markers of phenotypical differentiation and show that a continuous phenotypical spectrum exists between hepatocellular and cholangiocellular entities.
Telomeres are favoured targets of a persistent DNA damage response in ageing and stress-induced senescence (2012)

Telomeres are specialized nucleoprotein structures, which protect chromosome ends and have been implicated in the ageing process. Telomere shortening has been shown to contribute to a persistent DNA damage response (DDR) during replicative senescence, the irreversible loss of division potential of somatic cells. Similarly, persistent DDR foci can be found in stress-induced senescence, although their nature is not understood. Here we show, using immuno-fluorescent in situ hybridization and ChIP, that up to half of the DNA damage foci in stress-induced senescence are located at telomeres irrespective of telomerase activity. Moreover, live-cell imaging experiments reveal that all persistent foci are associated with telomeres. Finally, we report an age-dependent increase in frequencies of telomere-associated foci in gut and liver of mice, occurring irrespectively of telomere length. We conclude that telomeres are important targets for stress in vitro and in vivo and this has important consequences for the ageing process.
Chlorotrioxorhenium. Neue Synthesen, Reaktionen und Derivate (1994)

Multiple Bonds between Main Group Elements and Transition Metals, CXXIX [1] . — Chlorotrioxorhenium. Novel Syntheses, Reactions, and Derivatives Chlorotrioxorhenium ( 1a ) and homologs of formula X‐ReO 3 ( 1b–e ) are generated from Re 2 O 7 and either ZnX 2 , ( n ‐ C 4 H 9 ) 3 SnX, [( n ‐C 4 H 9 ) 4 N]X, or [(C 6 H 5 ) 4 P]X in clean reactions. Compounds 1a–f form with stable six‐coordinate adducts XReO 3 ·L ( 2a–f, 3a, 4a, 5a : L = N,N ′‐ligand) upon addition of the free ligand L, e.g. 2,2′‐bipyridine. 1a is readily alkylated by means of SnR 4 or ZnR 2 to form organorhenium(VII) oxides in good yields. These synthetic routes have the advantage to proceed under very mild conditions. The adducts of 2,2′‐bipyridine with halorhenium(VII) oxides show characteristic thermogravimetric (TG) behavior that reflects the volatility of the uncoordinated complexes X‐ReO 3 .
Supported Ionic Liquid Membranes and Facilitated Ionic Liquid Membranes (2002)

Abstract For Abstract see ChemInform Abstract in Full Text.
Thiol-Catalyzed Radical Decyanation of Aliphatic Nitriles with Sodium Borohydride (2018)

Radical decyanation of aliphatic nitriles was achieved in the presence of NaBH<sub>4</sub> and a thiol. The reaction proceeds via a radical mechanism involving borane radical anion addition to nitrile to form an iminyl radical, which undergoes carbon-carbon cleavage. Reductive radical addition to acrylonitrile is followed by decyanation to give a two-carbon homologated product in a net radical ethylation reaction.
Intranasal lipopeptide primes lung‐resident memory CD8+ T cells for long‐term pulmonary protection against influenza (2006)

The longevity of the influenza virus-specific CD8+ T cell response following intranasal delivery of a synthetic lipopeptide was investigated and the characteristics and location of the cells associated with viral clearance examined. The lipopeptide, incorporating an epitope for CD8+ T cells and another for CD4+ T cells with the lipid moiety S-[2,3-bis(palmitoyloxy)propyl]cysteine (Pam2Cys) attached, induced potent and long-lived pulmonary protection. Both the lipopeptide and its largely unprotective non-lipidated counterpart elicited comparable numbers of CD8+ T cells in the spleen, which was the main location of the memory pool. However, the lipopeptide, unlike the non-lipidated peptide, also induced a substantial memory population that remained in the lungs and was rapidly activated upon viral challenge months later. These lipopeptide-induced lung-resident CD8+ T cells were also very similar in number and IFN-gamma-secreting potential to those induced by prior exposure to the virus itself and are likely mediators of initial viral clearance prior to recruitment from the expanding lymph node T cell pool. Significant clearing responses were demonstrated as late as 9 months post-lipopeptide vaccination. This study shows that CD8+ T cells primed by the lipopeptide are not only long-lived but can take up residence in the lung where they are important early mediators of pulmonary protection.
Topical Application of Soluble CD83 Induces IDO-Mediated Immune Modulation, Increases Foxp3+ T Cells, and Prolongs Allogeneic Corneal Graft Survival (2013)

Modulation of immune responses is one of the main research aims in transplant immunology. In this study, we investigate the local immunomodulatory properties of soluble CD83 (sCD83) at the graft-host interface using the high-risk corneal transplantation model. In this model, which mimics the inflammatory status and the preexisting vascularization of high-risk patients undergoing corneal transplantation, allogeneic donor corneas are transplanted onto sCD83-treated recipient animals. This model allows the direct and precise application of the immune modulator at the transplantation side. Interestingly, sCD83 was able to prolong graft survival after systemic application as well as after topical application, which is therapeutically more relevant. The therapeutic effect was accompanied by an increase in the frequency of regulatory T cells and was mediated by the immune-regulatory enzyme IDO and TGF-β. In vitro, sCD83 induced long-term IDO expression in both conventional and plasmacytoid dendritic cells via autocrine or paracrine production of TGF-β, a cytokine previously shown to be an essential mediator of IDO-dependent, long-term tolerance. These findings open new treatment avenues for local immune modulation after organ and tissue transplantation.
Reduced Folate Carrier and Dihydrofolate Reductase Expression in Acute Lymphocytic Leukemia May Predict Outcome: A Children's Cancer Group Study (2003)

These results suggest that impaired transport may be an important mechanism of intrinsic methotrexate resistance in ALL, and DHFR expression also may be an important prognostic factor in ALL. Additional studies are necessary to clarify the mechanism for the correlation of low DHFR expression with poor outcome.