gebhart/patrepeval huggingface dataset:
First‐line treatment of chronic hepatitis B with entecavir or tenofovir in ‘real‐life’ settings: from clinical trials to clinical practice (2012)

Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are potent nucleos(t)ide analogues (NUCs) recommended as first-line monotherapies for chronic hepatitis B. In Phase III trials, ETV and TDF demonstrated superior efficacy, and comparable safety compared with other NUCs. In long-term clinical studies, both drugs achieved virologic response rates of around 95%, with very low rates of resistance development and good safety profiles. Clinical trials are conducted under standardized conditions with strict enrolment criteria that limit the heterogeneity of study populations. 'Real-life' populations tend to be composed of a wider range of patients, often older and with different morbidities, comorbidities that may impact treatment efficacy and co-factors, such as smoking and alcohol intake, which can have a direct impact on disease progression. Real-life studies provide better representations of everyday clinical practice and are important to confirm the results reported in clinical studies and to identify rare or late-emerging adverse events. In five 'real-life' studies of ETV in more than 1000 patients, up to 4 years of treatment resulted in virologic responses in 76-96% of patients. Two real-life studies of TDF reported response rates of 71-92% after up to 21 months of treatment. Low incidences of drug resistance and favourable tolerabilities were reported for both drugs, thus confirming the results from registration trials.
Adaptive Procedural Task Generation for Hard-Exploration Problems (2020)

We introduce Adaptive Procedural Task Generation (APT-Gen), an approach to progressively generate a sequence of tasks as curricula to facilitate reinforcement learning in hard-exploration problems. At the heart of our approach, a task generator learns to create tasks from a parameterized task space via a black-box procedural generation module. To enable curriculum learning in the absence of a direct indicator of learning progress, we propose to train the task generator by balancing the agent's performance in the generated tasks and the similarity to the target tasks. Through adversarial training, the task similarity is adaptively estimated by a task discriminator defined on the agent's experiences, allowing the generated tasks to approximate target tasks of unknown parameterization or outside of the predefined task space. Our experiments on the grid world and robotic manipulation task domains show that APT-Gen achieves substantially better performance than various existing baselines by generating suitable tasks of rich variations.
ChemInform Abstract: An Improved Cu‐Based Catalyst System for the Reactions of Alcohols with Aryl Halides. (2008)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Expanding the HDAC druggable landscape beyond enzymatic activity (2022)

ABSTRACT Enzymatic pockets such as those of histone deacetylases (HDACs) are among the most favored targets for drug development. However, enzymatic inhibitors often exhibit low selectivity and high toxicity due to targeting multiple enzyme paralogs, which are often involved in distinct multisubunit complexes. Here, we report the discovery and characterization of a non-enzymatic small molecule inhibitor of HDAC transcriptional repression functions with comparable anti-tumor activity to the enzymatic HDAC inhibitor Vorinostat, and anti-psychedelic activity of an HDAC2 knockout in vivo . We highlight that these phenotypes are achieved while modulating the expression of 20- and 80-fold fewer genes than enzymatic and genetic inhibition in the respective models. Thus, by achieving the same biological outcomes as established therapeutics while impacting a dramatically smaller number of genes, inhibitors of protein-protein interactions can offer important advantages in improving the selectivity of epigenetic modulators. GRAPHICAL ABSTRACT
Tetravalent Antibody–scTRAIL Fusion Proteins with Improved Properties (2013)

We applied the immunoglobulin E (IgE) heavy-chain domain 2 (EHD2) as the covalently linked homodimerization module to generate antibody-scTRAIL fusion proteins. By fusing a humanized single-chain fragment variable (scFv) directed against EGFR to the N-terminus of the EHD2 and a single-chain derivative of TRAIL (scTRAIL) to the C-terminus of the EHD2, we produced a dimeric, tetravalent fusion protein. The fusion protein retained its binding activity for EGFR and TRAIL receptors. In vitro, the targeted antibody-scTRAIL fusion protein exhibited an approximately 8- to 18-fold increased cytotoxic activity compared with the untargeted EHD2-scTRAIL fusion protein. This resulted in increased antitumor activity in a subcutaneous Colo205 xenograft tumor murine model. In summary, the scFv-EHD2-scTRAIL fusion protein combines target cell selectivity with an increased TRAIL activity leading to improved antitumor activities.
P4‐108: Serum cystatin C and the risk of Alzheimer's disease (2008)

Multiple lines of basic research suggest that cystatin C in the brain may be neuroprotective against the development of Alzheimer's disease (AD). Yet, prospective studies relating circulating blood levels of cystatin C to the incidence of AD are lacking. Serum cystatin C was measured in a prospective, community-based, observational cohort of elderly men in Uppsala, Sweden (the ULSAM-study) at two different examination cycles (1990–95, age 70 years, n=1153 and 1997–2001, age 77 years, n=761) AD was diagnosed by standardized screening, clinical evaluation, and chart review. The primary outcome was hazard ratio of AD by baseline levels of cystatin C. On follow-up (median, 11.3 years), 82 subjects developed AD. At age 70, lower cystatin C was significantly associated with higher risk of AD independently of age, APOE4-genotype, glomerular filtration rate, diabetes, hypertension, stroke, cholesterol, body mass index, smoking, education level, plasma amyloid β-protein 40 and 42 levels (HR for lowest [<1.12 μmol/L] versus highest [>1.30 μmol/L] tertile; 2.67; 95% CI, 1.22–5.83, p<0.02). The results were similar at age 77 (43 participants developed AD during follow-up). Furthermore, a 0.1 μmol/L decrease of cystatin C between age 70 and 77 was associated with 29% higher risk of incident AD (HR 1.29 95% CI, 1.03–1.63, p<0.03). Sensitivity analysis indicated that these findings were not explained by competing risks. These findings suggest that low levels of serum cystatin C is a risk factor for AD.
George Eliot's "Middlemarch" (1953)

Book Review| December 01 1953 George Eliot's "Middlemarch" MiddlemarchGeorge Eliot Henry James Henry James Search for other works by this author on: This Site PubMed Google Scholar Nineteenth-Century Fiction (1953) 8 (3): 161–170. https://doi.org/10.2307/3044335 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Henry James; George Eliot's "Middlemarch". Nineteenth-Century Fiction 1 December 1953; 8 (3): 161–170. doi: https://doi.org/10.2307/3044335 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search nav search search input Search input auto suggest search filter All ContentNineteenth-Century Literature Search This content is only available via PDF. Article PDF first page preview Close Modal You do not currently have access to this content.
An assessment of photoacoustic and photon counting multispectral x-ray imaging techniques for imaging gold nanorods in vivo as part of predicting dose enhancing effects (2016)

Radiotherapy, whilst useful in the treatment of many cancers, suffers from the drawback of unavoidably delivering radiation doses to healthy tissue. Gold nanoparticles (GNPs) have been the subject of much interest as they are able to generate a local dose enhancing effect (DEE), allowing lower intensity beams to achieve a given effect, sparing healthy tissue. It is important that GNP distributions can be ascertained before radiotherapy begins so that accurate treatment plans can be made. Two imaging modalities that show great promise in being able to identify these GNPs in vivo without delivering excessive DEEs are photoacoustic imaging (PAI) and photon counting multi-spectral x-ray imaging (x-CSI). This work forms part of a larger project to assess the feasibility of using x-CSI and PAI to predict DEEs during radiotherapy planning. This work assessed the degradation of gold nanorods (GNRs) in a photoacoustic system sold by iThera, specifically comparing the protective effects against degradation afforded by a silica coating as opposed to GNR PEGylation. This coating is also hoped to prevent spectral broadening when the GNRs are endocytosed, allowing PAI to confirm uptake of GNRs by cells. With regards x-CSI, this work uses a combination of Monte Carlo and Finite Element modelling techniques to realistically model cylindrical phantoms of high-Z materials in order to demonstrate the potential improvements in imaging contrast that x-CSI can produce over traditional energy integrated x-ray imaging techniques. Results on the assessment of both techniques are discussed.
A mechanistic model explaining ligand affinity for, and partial agonism of, cannabinoid receptor 1 (2023)

CB1, a member of the G protein-coupled receptor class, is the putative protein target of THC, the psychoactive component of cannabis. To better identify new synthetic cannabinoids with increased activity, all cannabinoids with reported experimental binding to the CB1 receptor were modelled in silico to build a predictive model for CB1 affinity of small molecules. Computationally derived affinity is not sufficient in and of itself to predict binding, but coupled with the experimental evidence that ligands enter the receptor from the membrane rather than solvent, we provide a model that accurately describes the binding of these molecules by incorporating a correction factor for relative hydrophobicity. In addition, we propose a mechanism of action for partial CB1 agonists based on molecular dynamics simulations of THC homologues, modelling long time scale structural changes in the CB1 receptor. Together, the affinity model, and the mechanism of agonism/antagonism can allow for the computational prediction of both the effective behaviour and potency of novel cannabinoids, and several such predictions are made.
Fused-Pentagon-Configuration-Dependent Electron Transfer of Monotitanium-Encapsulated Fullerenes (2017)

We introduce monotitanium-based endohedral metallofullerenes (EMFs) using density functional theory calculations. Isomeric C<sub>64</sub> fullerenes are initially employed as hosts, and Ti@C<sub>64</sub> species show novel features on the electronic structures. Energetically, the preference of titanium residing on triple-fused-pentagon subunits is proposed in theory. More importantly, different from current knowledge on mono-EMFs, electron transfer between titanium and carbon cages is not unified but is essentially dependent on the pentagon distribution of the binding sites, giving rise to variations of the cationic titanium of Ti@C<sub>64</sub>. Such selective electron-transfer character is extended to the study of the encapsulation of other neighboring metal atoms (i.e., calcium and scandium). Because of their different capabilities to accept d electrons, fullerene cages with distinct fused-pentagon motifs show selective metal encapsulation characters. In addition, some other fullerenes (C<sub>44</sub>-C<sub>48</sub> and C<sub>82</sub>) are selected as hosts to study the electron-transfer behavior of titanium in smaller fullerenes and larger systems without pentagon adjacency.
The Mobility and Structure of Aerosol Agglomerates (1993)

The relation between the aerosol agglomerate structure and transition regime mobility can be explained with a simple model incorporating fractal geometry and results from computer simulations. The model is consistent with previous measurements of the shape factors and allows some structural information to be inferred from these measurements, although the data are insufficient for a rigorous comparison between theory and experiment. Experiments conducted here with well-characterized TiO2 and Si agglomerates support the model' assumption that the mobility diameter of a particle in the free-molecule regime is determined solely by the projected area of the particle. The correlation between the projected area and the mobility equivalent size remains remarkably good throughout the transition regime for the agglomerate particles studied here. The model predicts this result for particles with fractal dimensions of approximately D f = 2
Minimization of conical emission in gases for enhanced micromachining by ultrashort pulses (2009)

Parameters of conical emission are defined with respect to ambient gas, pulse-width and wavelength of focused radiation, which allows significant minimization of scattering in the case of ultra-short pulsed laser micromachining.
Synthesis of Copper Containing Zeolites: New, Simple and Efficient Method for Quantitative Exchange (1992)

A new technique is described which allows the quantitative exchange of copper(II) into ZSM-5 zeolites. The sequence consists of two steps: (i) impregnation of the zeolite with copper(II) in amounts higher than the exchange capacity; (ii) leaching of the copper in excess with respect to the exchange capacity with a chlorobenzene-water mixture at high temperature. The performances of the new materials in the hydrolysis of chlorobenzene, as well as preliminary informations on the nature of the catalyst and the type of mechanism are presented.
Mitochondrial Ribosome Dysfunction in Human Alveolar Type II Cells in Emphysema (2022)

Pulmonary emphysema is characterized by airspace enlargement and the destruction of alveoli. Alveolar type II (ATII) cells are very abundant in mitochondria. OXPHOS complexes are composed of proteins encoded by the mitochondrial and nuclear genomes. Mitochondrial 12S and 16S rRNAs are required to assemble the small and large subunits of the mitoribosome, respectively. We aimed to determine the mechanism of mitoribosome dysfunction in ATII cells in emphysema. ATII cells were isolated from control nonsmokers and smokers, and emphysema patients. Mitochondrial transcription and translation were analyzed. We also determined the miRNA expression. Decreases in ND1 and UQCRC2 expression levels were found in ATII cells in emphysema. Moreover, nuclear NDUFS1 and SDHB levels increased, and mitochondrial transcribed ND1 protein expression decreased. These results suggest an impairment of the nuclear and mitochondrial stoichiometry in this disease. We also detected low levels of the mitoribosome structural protein MRPL48 in ATII cells in emphysema. Decreased 16S rRNA expression and increased 12S rRNA levels were observed. Moreover, we analyzed miR4485-3p levels in this disease. Our results suggest a negative feedback loop between miR-4485-3p and 16S rRNA. The obtained results provide molecular mechanisms of mitoribosome dysfunction in ATII cells in emphysema.
Parallel space-time likelihood optimization for air pollution prediction on large-scale systems (2022)

Gaussian geostatistical space-time modeling is an effective tool for performing statistical inference of field data evolving in space and time, generalizing spatial modeling alone at the cost of the greater complexity of operations and storage, and pushing geostatistical modeling even further into the arms of high-performance computing. It makes inferences for missing data by leveraging space-time measurements of one or more fields. We propose a high-performance implementation of a widely applied space-time model for large-scale systems using a two-level parallelization technique. At the inner level, we rely on state-of-the-art dense linear algebra libraries and parallel runtime systems to perform complex matrix operations required to evaluate the maximum likelihood estimation (MLE). At the outer level, we parallelize the optimization process using a distributed implementation of the particle swarm optimization (PSO) algorithm. At this level, parallelization is accomplished using MPI sub-communicators, such that the nodes in each sub-communicator perform a single MLE iteration at a time. To evaluate the effectiveness of the proposed methodology, we assess the accuracy of the newly implemented space-time model on a set of large-scale synthetic space-time datasets. Moreover, we use the proposed implementation to model two air pollution datasets from the Middle East and US regions with 550 spatial locations X730 time slots and 945 spatial locations X500 time slots, respectively. The evaluation shows that the proposed approach satisfies high prediction accuracy on both synthetic datasets and real particulate matter (PM) datasets in the context of the air pollution problem. We achieve up to 757.16 TFLOPS/s using 1024 nodes (75% of the peak performance) using 490K geospatial locations on Shaheen-II Cray XC40 system.
Disruptive Technologies in Computer Graphics: Past, Present, and Future (1999)

The history and famous landmarks of computer graphics hardware are well known. Starting with Ivan Sutherlands Sketchpad system in the early 1960s, the first generation of computer graphics hardware consisted of calligraphic (vector) displays capable of drawing complex three-dimensional wireframe models at interactive rates. In the early 1970s expensive color frame buffers with the capability for displaying static color images were introduced. Although more and more intelligence was added to these frame buffers, Jim Clarks geometry engine and the first graphics workstations were not introduced until the 1980s. During the 1970s, only the very costly and specialized hardware used for military and aerospace simulations was capable of real-time surface color display.
Degradation of Cd-yellow Paints: ab initio study of the adsorption of oxygen and water on {10.0} CdS surface (2014)

The cadmium yellow paints (CdS) used in impressionist and modernist paintings in early 1900s are undergoing several deterioration processes including whitening and discoloration. A relevant effect produced at the surface of the paintings is the growth of discolored crusts formed mainly by white globular hydrated cadmium sulfate (CdSO4*nH2O) and cadmium carbonate (CdCO3). Recent studies [1,2] ascribe to an initial photo-oxidation process of CdS the input for the formation of such whitish compounds. &#13;\nIn order to understand the oxidation and hydration mechanisms, at atomic level, of these whitish globules, we present the early stages of a theoretical study on the interaction between the hexagonal (10-10) surface of CdS and O2 and H2O molecules to simulate the combined effects of exposure to air and humidity. More specifically, we determined the favorite adsorption sites and calculated the adsorption energies of the different molecules on top of the surface. The details of the electronic structure of the interactions are given via the bonding charge analysis along with a thorough description of the geometry.
Fast simulation for self-similar traffic in ATM networks (2002)

Self-similar (or fractal) stochastic processes were proposed as more accurate models of certain categories of traffic (e.g., Ethernet traffic, variable-bit-rate video) which will be transported in ATM networks. Existing analytical results for the tail distribution of the waiting time in a single server queue based on fractional Gaussian noise and large deviation theory, are valid under a steady-state regime and for an asymptotically large buffer size. However, the predicted performance based on steady-state regimes may be overly pessimistic for practical applications. Theoretical approaches used to obtain the transient queueing behavior and queueing distributions for a small buffer size become quickly intractable. The approach we followed was based on fast simulation techniques for the study of certain rare events such as cell losses with very small probability of occurrence. Our simulation experiments provide an insight on the transient behavior that is not possible to predict using current analytical results. Finally they show good agreement with existing results when approaching steady-state.
Nonlocal effects and shrinkage of the vortex core radius inYNi2B2Cprobed by muon spin rotation (2002)

The magnetic field distribution in the vortex state of ${\mathrm{YNi}}_{2}{\mathrm{B}}_{2}\mathrm{C}$ has been probed by muon spin rotation. The analysis based on the London model with nonlocal corrections shows that the vortex lattice has changed from hexagonal to square with increasing magnetic field H. At low fields the vortex core radius, ${\ensuremath{\rho}}_{v}(H),$ decreases with increasing H much steeper than what is expected from the $\sqrt{H}$ behavior of the Sommerfeld constant $\ensuremath{\gamma}(H),$ strongly suggesting that the anomaly in $\ensuremath{\gamma}(H)$ primarily arises from the quasiparticle excitations outside the vortex cores.
Federico García Lorca (2005)

Federico García Lorca (1898–1936) is Spain's most celebrated twentieth-century author. He achieved success and popularity as both poet and dramatist within Spain before his untimely death, and his international reputation has grown steadily since then, resulting in an extraordinary range of editions, translations, critical commentary, productions, and adaptations.
CLINICAL PERFORMANCE OF CONTEMPORARY TIBIAL POLYETHYLENE COMPONENTS (2009)

A post-clinical retrieval analysis was performed on 43 polyethylene tibial components of a contemporary total knee arthroplasty system with implantation duration between 12 and 80 months. Components were scored for eight potential modes of surface wear or damage on the top and back surfaces. Moderate backside wear of 4.1μm per year was documented by measuring the extent of manufacturer’s engraved lettering removal. Neither the topside nor backside score correlated with duration of in vivo function. No component experienced topside or backside delamination, cracking, or significant deformation. The greatest contribution to wear and damage score was pitting and scratching secondary to bone cement debris. The extent of both wear and damage experienced by these components was moderate, in comparison with that previously reported with older implant systems.
Molecular targeted drugs against ALK fusions (2011)

我々は独自の機能スクリーニング手法を開発し，それを用いて肺腺がん臨床検体から新しい融合型がん遺伝子EML4-ALK を発見した．本来ALK は受容体型チロシンキナーゼをコードするが，染色体転座inv（2）（p21p23）が生じた結果EML4 遺伝子とALK 遺伝子が融合し，EML4タンパク質のアミノ末端側約半分がALKのキナーゼドメインと融合したタンパク質が産生されるのである．EML4-ALKはEML4内のcoiled-coilドメインを介して恒常的に二量体化され活性化されて発がんを誘導することが明らかになった．実際EML4-ALK を肺胞上皮特異的に発現するトランスジェニックマウスを作成すると同マウスは生後すぐに両肺に多数の肺腺がんを発症し，しかもこれらマウスにALK活性の特異的阻害薬を投与すると肺腺がんは速やかに消失した．すなわちEML4-ALKこそが同キナーゼ陽性肺がんの主たる発がん原因であり，だからこそその酵素活性を阻害する薬剤はEML4-ALK陽性肺がんの全く新しい分子標的治療薬となる事が生体において証明されたのである．我々のEML4-ALK の論文公開は2007年であったが，翌年にはALK特異的阻害薬による初めての臨床試験が開始され，2010年にはその驚くべき治療効果が公表された．現在すでに世界中で計5種類のALK阻害薬による臨床試験が行われており，その数は増加の一途をたどっている．肺がんという極めて予後不良ながん腫に対して，この様な特効薬とも言うべき治療薬が開発されつつあることは臨床上極めて意義のあることであり，大規模な第III相試験を必要としない形で薬剤として認可され臨床に供されることが望ましい．そしてその時に最も重要なことは，正確かつ高感度にEML4-ALK陽性肺がんを診断することであろう．
A Bend-insensitive Ultra Low Loss and Large Aeff fibre for Long Haul transmission (2016)

A large effective area fiber (110μm2) with excellent bend-insensitive characteristics and attenuation lower than 0.160dB/km is presented. It’s excellent bend-insensitive performance is benefit for cable temperature cycling test and attenuation change during cabling process.