gebhart/patrepeval huggingface dataset:
Enhancer Reprogramming in Melanoma Immune Checkpoint Therapy Resistance (2022)

ABSTRACT Immune checkpoint blockade (ICB) therapy has improved long-term survival for patients with advanced melanoma. However, there is critical need to identify potential biomarkers of response and actionable strategies to improve response rates. Through generation and analysis of 148 chromatin modification maps for 36 melanoma samples from patients treated with anti-PD- 1, we identified significant enrichment of active enhancer states in non-responders at baseline. Analysis of an independent cohort of 20 samples identified a set of 437 enhancers that predicted response to anti-PD-1 therapy (Area Under the Curve of 0.8417). The activated non-responder enhancers marked a group of key regulators of several pathways in melanoma cells (including c- MET, TGFβ, EMT and AKT) that are known to mediate resistance to ICB therapy and several checkpoint receptors in T cells. Epigenetic editing experiments implicated involvement of c-MET enhancers in the modulation of immune response. Finally, inhibition of enhancers and repression of these pathways using bromodomain inhibitors along with anti-PD-1 therapy significantly decreased melanoma tumor burden and increased T-cell infiltration. Together, these findings identify a potential enhancer-based biomarker of resistance to anti-PD-1 and suggest enhancer blockade in combination with ICB as a potential strategy to improve responses.
A novel therapeutic approach with Caviunin-based isoflavonoid that en routes bone marrow cells to bone formation via BMP2/Wnt-β-catenin signaling (2014)

Recently, we reported that extract of Dalbergia sissoo made from leaves and pods have antiresorptive and bone-forming effects. The positive skeletal effect attributed because of active molecules present in the extract of Dalbergia sissoo. Caviunin 7-O-[β-D-apiofuranosyl-(1-6)-β-D-glucopyranoside] (CAFG), a novel isoflavonoid show higher percentage present in the extract. Here, we show the osteogenic potential of CAFG as an alternative for anabolic therapy for the treatment of osteoporosis by stimulating bone morphogenetic protein 2 (BMP2) and Wnt/β-catenin mechanism. CAFG supplementation improved trabecular micro-architecture of the long bones, increased biomechanical strength parameters of the vertebra and femur and decreased bone turnover markers better than genistein. Oral administration of CAFG to osteopenic ovariectomized mice increased osteoprogenitor cells in the bone marrow and increased the expression of osteogenic genes in femur and show new bone formation without uterine hyperplasia. CAFG increased mRNA expression of osteoprotegerin in bone and inhibited osteoclast activation by inhibiting the expression of skeletal osteoclastogenic genes. CAFG is also an effective accelerant for chondrogenesis and has stimulatory effect on the repair of cortical bone after drill-hole injury at the tissue, cell and gene level in mouse femur. At cellular levels, CAFG stimulated osteoblast proliferation, survival and differentiation. Signal transduction inhibitors in osteoblast demonstrated involvement of p-38 mitogen-activated protein kinase pathway stimulated by BMP2 to initiate Wnt/β-catenin signaling to reduce phosphorylation of GSK3-β and subsequent nuclear accumulation of β-catenin. Osteogenic effects were abrogated by Dkk1, Wnt-receptor blocker and FH535, inhibitor of TCF-complex by reduction in β-catenin levels. CAFG modulated MSC responsiveness to BMP2, which promoted osteoblast differentiation via Wnt/β-catenin mechanism. CAFG at 1 mg/kg(/)day dose in ovariectomy mice (human dose ∼0.081 mg/kg) led to enhanced bone formation, reduced bone resorption and bone turnover better than well-known phytoestrogen genistein. Owing to CAFG's inherent properties for bone, it could be positioned as a potential drug, food supplement, for postmenopausal osteoporosis and fracture repair.
1112 Characterization of Regenerative Heart Valve (2007)

The purpose in this study is to characterize a regenerative heart valve mechanically which was developed from a porcine aortic valve with our ultra-high pressure method. The result of tensile test on a porcine native valve showed anisotropy in a leaflet. A maximum stress on a circumferential direction was much greater than that on a radial direction. This difference of maximum stress in each direction may depend on orientation of collagen fibers. The tensile property of a human valvular leaflet was similar to the property of a porcine valve. A maximum stress of the regenerative valvelar leaflet was considerably stronger than that of the porcine and the human native leaflet. The thickness of the regenerative valvular leaflet decreased because glycosaminoglycan and other contents were removed from the inside through the decellularization process. Consequently the maximum stress increased although maximum load of the regenerative leaflet was not so different from the native one. This result means that the property of collagen was not affected by our decellularization treatment. The results of this study showed that the regenerative valve could be implanted to a human from the point of tensile property.
Easy Access to Amphiphilic Heterografted Poly(2-oxazoline) Comb Copolymers (2013)

A series of heterografted polymers with a polymethacrylate backbone and varying composition of oligomeric 2-oxazoline side chains was synthesized by copolymerization of oligo(2-ethyl-2-oxazoline)methacrylate and oligo(2-n-nonyl-2-oxazoline)methacrylate (ONonOx) macromonomers using the reversible addition–fragmentation chain transfer (RAFT) technique. Kinetic studies revealed pseudofirst order kinetics, PDI values below 1.3, and a slight enrichment of ONonOx side chains toward the end of the reaction. The heterografted comb polymers were characterized by means of 1H NMR spectroscopy (0 to 100 mol % ONonOx) and size exclusion chromatography. Differential scanning calorimetry and wide-angle X-ray scattering revealed partial crystallinity of the lateral n-nonyl chains within the ONonOx domains. Depending on the composition of the amphiphilic copolymer, the comb polymers either formed unimers or aggregated (super)structures in water, methanol, and ethanol, as investigated by dynamic light scattering and cryo-transmission electron microscopy.
<title>Design of psychovisual quantizers for a visual subband image coding</title> (1994)

In order to specify the optimal psychovisual quantizer associated to a given visual subband decomposition scheme, a new methodology has been developed. Psychovisual experiments based on the visibility of the quantization noise, have been conducted. The complex signals used, have been characterized by the local band-limited contrast. The main finding of this study is that the quantizers are, in the chosen space contrast, of a linear type. The quantization intervals contrast, obtained with a given observer, are of 0.039 for the subband called III-1 (radial selectivity 1.5 cy/d degree(s) to 5.7 cy/d degree(s), angular selectivity -22.5 d degree(s) to 22.5) 0.031 for the subband called IV-1 (radial selectivity 5.7 cy/d degree(s) to 14.1 cy/d degree(s), angular selectivity -15 d degree(s) to 15 d degree(s)) 0.117 for the subband called V-1 (radial selectivity 14.1 cy/d degree(s) to 28.2 cy/d degree(s), angular selectivity -15 d degree(s) to 15 d degree(s)). To evaluate the importance of the `angular' aspect in this approach, further measurements have been made with the subband IV-2 (radial selectivity 5.7 cy/d degree(s) to 14.1 cy/d degree(s), angular selectivity 15 d degree(s) to 30 d degree(s)). The linearity is also observed and the quantization interval contrast, for the same observer, is of 0.122.
Targeting BET bromodomain proteins in solid tumors (2016)

There is increasing interest in inhibitors targeting BET (bromodomain and extra-terminal) proteins because of the association between this family of proteins and cancer progression. BET inhibitors were initially shown to have efficacy in hematologic malignancies; however, a number of studies have now shown that BET inhibitors can also block progression of non-hematologic malignancies. In this Review, we summarize the efficacy of BET inhibitors in select solid tumors; evaluate the role of BET proteins in mediating resistance to current targeted therapies; and consider potential toxicities of BET inhibitors. We also evaluate recently characterized mechanisms of resistance to BET inhibitors; summarize ongoing clinical trials with these inhibitors; and discuss potential future roles of BET inhibitors in patients with solid tumors.
Low-damage dry-etched grating on an MQW active layer and dislocation-free InP regrowth for 1.55-/spl mu/m complex-coupled DFB lasers fabrication (1998)

A grating dry-etched through the upper wells of a multiquantum-well active layer has been characterized before and after regrowth. TEM observation and carrier lifetime measurements have shown growth-free defects of the epitaxial layers. As a consequence, quasi-100% monomode oscillation on /spl lambda/+1 mode has been achieved on complex-coupled distributed-feedback GaInAsP QW lasers fabricated with such grating.
Emergency preparedness for long lasting releases – accident scenarios (2016)

The Fukushima-Daiichi accident has demonstrated the possibility of long-lasting releases of radionuclides from a nuclear power plant (NPP) over several weeks, which has led to the need to review if current procedures of external emergency planning are suitable for these situations. Under the framework of the “PREPARE” project one work package focused on “Review of the emergency preparedness in case of long-term emissions”. The aim is to test the current off-site nuclear emergency planning along Europe and to derive recommendations on how to improve it. In this context, a statistical study has been proposed by using potential long lasting release scenarios in combination with different weather conditions over a significant period of time (for instance one year) in some selected locations. This paper presents the results obtained in the development of accidental scenarios for a range of meteorological conditions representative for NPP sites in several European countries, i.e. Germany, Slovakia, Finland and Spain.
A NEW TYPE OF SYNTHESIS. I. THE REACTION BETWEEN HALOGEN-ALKYL SULFONATES AND ORGANOMAGNESIUM HALIDES: Preliminary Note (1923)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA NEW TYPE OF SYNTHESIS. I. THE REACTION BETWEEN HALOGEN-ALKYL SULFONATES AND ORGANOMAGNESIUM HALIDES: Preliminary NoteHenry Gilman and N. J. BeaberCite this: J. Am. Chem. Soc. 1923, 45, 3, 839–842Publication Date (Print):March 1, 1923Publication History Published online1 May 2002Published inissue 1 March 1923https://doi.org/10.1021/ja01656a046Request reuse permissionsArticle Views175Altmetric-Citations9LEARN 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 (280 KB) Get e-Alertsclose Get e-Alerts
The role of activated carbon surface heterogeneity on the polymerization of adsorbed phenols (1995)

The role of GAC surface site energy distributions and the effects of prior adsorption of background organic macromolecules ({open_quotes}preloading{close_quotes}) on the polymerization of phenolic compounds in the presence of oxygen have been investigated using a theory developed to describe sorption of solutes on heterogeneous solid surfaces. GAC surface heterogeneity has been found to be the most important parameter controlling the polymerization reactions of adsorbed phenols, the extent of polymerization being greater on high energy sites than on low energy sites. Surface site energy distribution analysis under preloading conditions indicates that preferential and {open_quotes}irreversible{close_quotes} occupation of high energy sites by background organic macromolecules, which themselves can polymerize on such sites, markedly increases the adverse effects of preloading, decreasing the ability of the GAC both to subsequently adsorb and to polymerize target phenolic contaminants.
Selective Oxidation of 5-Hydroxymethylfurfural to 5-Hydroxymethyl-2-furancarboxylic Acid Using Gluconobacter oxydans (2019)

5-Hydroxymethylfurfural (HMF), an important biobased platform chemical, can be potentially oxidized to several products that can serve as versatile building blocks for polymers. 5-Hydroxymethyl-2-furan carboxylic acid (HMFCA) is formed by incomplete oxidation of HMF but the reaction often suffers from substrate inhibition and overoxidation to other products. In this study, resting cells of Gluconobacteroxydans DSM 50049 were shown to oxidize HMF quantitatively to HMFCA with exquisite selectivity. Complete conversion of 31.5 g L–1 crude HMF to HMFCA was achieved within 6 h under pH-controlled conditions. Initial productivity of 10 g L–1 h–1 was reduced to 2 g L–1 h–1 toward the end of the reaction. Thereafter, additional HMF added to the reaction mixture (12 g L–1) was converted up to 94% within 17 h with 100% selectivity resulting in final HMFCA concentration of 44.6 g L–1 and yield of 6.2 g g–1 cell dry weight. Recovery of HMFCA from the reaction could be achieved by adsorption to anion exchange resins Amberlite IRA-400 (Cl– form) and Ambersep 900 (OH– form), the former showing higher binding (169 mg/g resin) and product recovery. Alternatively, liquid–liquid extraction with ethyl acetate provided a facile separation technique for the recovery of pure HMFCA.
Stress Analysis of Tapered Composite Laminates Using Partial Hybrid Finite Elements (2004)

Two special partial hybrid finite elements have been developed for the stress analysis of tapered composite laminates. These are quasi three dimensional elements that can be used for plain strain analysis. Partial hybrid finite elements are efficient in the use of computer space with good accuracy for stress determination. The elements are used to calculate stresses in a tapered laminate. Results compare well with results obtained using another method.
The association between SCN5A, KCNQ1 and KCNE1 gene polymorphisms and complex ventricular arrhythmias in survivors of myocardial infarction. (2008)

The above polymorphisms were associated with abnormal repolarisation phase patterns in post-MI patients, which manifested in QT interval prolongation and QTd increase. There was no relationship between these polymorphisms and complex VA, SCA or SCD. The results show that not only exonic alterations but also intronic ones may affect the phenotype.
Algunas proyecciones del Vto informe del IPCC y sus implicaciones para Nicaragua (2014)

El 30 de Septiembre del 2013, fue publicado en Estocolmo, Suecia, el informe de consenso del grupo I del Vto informe del Panel Intergubernamental de Cambio Climatico (IPCC) titulado: Bases Cientificas del Cambio Climatico. 
A nivel global el informe califica las evidencias del cambio climatico como “inequivocas” y “sin precedentes”, destacando que este fenomeno obedece a la accion humana con un “95% de certeza”.
Consideration of the Environmental Cost in Construction Contracting for Public Works: A+C and A+B+C Bidding Methods (2012)

Growing concerns about sustainable development have brought about an urgent need to develop global efforts to mitigate environmental impact. Although construction projects and their related activities consume much energy and generate a significant amount of greenhouse gas (GHG) and other diesel emissions, the efforts to mitigate these emissions remain at an early stage. To address this issue, this paper explores opportunities to consider contractors’ green capabilities during the bid evaluation phase. Based on reviews of the success story of the A+B bidding method, this paper suggests a modified bidding system in which contractors bid on the cost (part A) and environmental cost (part C) or on the cost (part A), time (part B), and environmental cost (part C) for public projects. An application of the proposed bidding methods is described using a bid for a highway reconstruction project. This case study reveals the potential impact of environmental cost criteria on the selection of a winning bid. The result of this case study indicates that the proposed bidding methods can offer bidding incentives to create sustainability initiatives for public works contractors.
Flame balls - Past, present and future (1993)

This paper discusses analytical and numerical work that has been carried out in order to understand flame-balls and related phenomena that have been observed in microgravity experiments. The importance of heat losses is identified, whether from conduction, convection, or radiation. Accurate numerical simulations for hydrogen-air mixtures with radiation losses reveal a flammability limit of 3.5 percent of hydrogen by volume, a value close to the experimental one. The important role of stability analyses is emphasized, with particular attention to the role of three-dimensional instabilities in explaining unsteady spheroidal flames and flame-strings, objects that are observed in the experiments. We speculate that the dynamics of flame-strings is affected by in-depth radiation absorption for mixtures containing SF6, and report on some preliminary calculations in which this phenomenon is accounted for.
Expression and Localization of Nitrilase during Symptom Development of the Clubroot Disease in Arabidopsis (2000)

The expression of nitrilase in Arabidopsis during the development of the clubroot disease caused by the obligate biotroph Plasmodiophora brassicae was investigated. A time course study showed that only during the exponential growth phase of the clubs was nitrilase prominently enhanced in infected roots compared with controls. NIT1 and NIT2 are the nitrilase isoforms predominantly expressed in clubroot tissue, as shown by investigating promoter-beta-glucuronidase fusions of each. Two peaks of beta-glucuronidase activity were visible: an earlier peak (21 d post inoculation) consisting only of the expression of NIT1, and a second peak at about 32 d post inoculation, which predominantly consisted of NIT2 expression. Using a polyclonal antibody against nitrilase, it was shown that the protein was mainly found in infected cells containing sporulating plasmodia, whereas in cells of healthy roots and in uninfected cells of inoculated roots only a few immunosignals were detected. To determine which effect a missing nitrilase isoform might have on symptom development, the P. brassicae infection in a nitrilase mutant (nit1-3) of Arabidopsis was investigated. As a comparison, transgenic plants overexpressing NIT2 under the control of the cauliflower mosaic virus 35S promoter were studied. Root galls were smaller in nit1-3 plants compared with the wild type. The phenotype of smaller clubs in the mutant was correlated with a lower free indole-3-acetic acid content in the clubs compared with the wild type. Overexpression of nitrilase did not result in larger clubs compared with the wild type. The putative role of nitrilase and auxins during symptom development is discussed.
Simulation of Diffusion Phenomena by Cellular Automata (1998)

This paper describes a new simulation technique for diffusion phenomena over the sea surface using Cellular Automata (CA), which is capable of making prediction of oil dispersion from tankers come into collision or stranded on rocks. Automaton is known as an abstract expression of sequencial machine in the field of information science, and CA is recognized as one of the model of finite state automata with sectional analysis domain called “cell”. CA has also been applied to demonstrate various engineering phenomena, and one of the most promising application field is flow simulation of viscous fluid, percoration, multi-phase fluid, reaction diffusion problems and so on. In this field, CA is called Lattice Gas Automata (LGA) and the solutions by LGA has been proved to coinside those by Navier-Stokes equation. In the procedure of CA, the analytical area is devided into cells and all the state variables defined on each cell are made transition by local neighbor rule and transition rule along the discrete time steps without solving the governing equation.In the present paper, CA is applied to solve a diffusion problem in which the simulation results are compared to the analytical solution of diffusion equation, and possibility is shown in predicting the oil dispersion in the accident of tanker occured in Japan Sea in January, 1997, as an example. It is shown that the simulation by CA shows good agreement with the analytical solution of diffusion equation, and that the prediction of oil dispersion in Japan Sea can be made in a short time by a personal computer.
Fast algorithms for mutual information based independent component analysis (2004)

This paper provides fast algorithms to perform independent component analysis based on the mutual information criterion. The main ingredient is the binning technique and the use of cardinal splines, which allows the fast computation of the density estimator over a regular grid. Using a discretized form of the entropy, the criterion can be evaluated quickly together with its gradient, which can be expressed in terms of the score functions. Both offline and online separation algorithms have been developed. Our density, entropy, and score estimators also have their own interest.
Mast cell lines HMC‐1 and LAD2 in comparison with mature human skin mast cells – drastically reduced levels of tryptase and chymase in mast cell lines (2010)

To circumvent the costly isolation procedure associated with tissue mast cells (MC), two human MC lines, i.e. HMC-1 and LAD2, are frequently employed, but their relation to mature MC is unknown. Here, we quantitatively assessed their expression of MC markers in direct comparison to skin MC (sMC). sMC expressed all lineage markers at highest and HMC-1 cells at lowest levels. LAD2 cells expressed comparable high-affinity IgE receptor alpha (FcepsilonRIalpha) and FcepsilonRIgamma but less FcepsilonRIbeta than sMC and displayed slightly reduced, but robust FcepsilonRI-mediated histamine release. Only minor differences were found for total histamine content and c-Kit expression. Huge, and to this level unexpected, differences were found for MC tryptase and chymase, with sMC >>> LAD2 > HMC-1. Taken together, HMC-1 cells represent very immature malignantly transformed MC, whereas LAD2 cells can be considered intermediately differentiated. Because of the minute levels of MC proteases, MC lines can serve as surrogates of tissue MC to a limited degree only.
Robotic Gift Wrapping or a Glance at the Present State in Santa's Workshop (2016)

This work presents a robotic implementation of Christmas gift wrapping. Handling paper is a challenging task for an industrial robot as it easily tears and folds in unexpected ways. In this application, a dual-arm industrial robot with simple two-finger grippers was used, and the robot was programmed using a standard position-based approach. The wrapping was accomplished with the help of plastic spatulas, and although the speed of the final wrapping was slower than an average human, the gift wrapper application became a success on its tour around Sweden during the Christmas commerce 2015.