gebhart/patrepeval huggingface dataset:
Abstract CT104: Evaluation of peripheral T cell subset proliferation as a pharmacodynamic assay to guide the development of anti-CTLA-4 and PD-1 antibody combinations in patients with solid tumors (2018)

Abstract The combination of anti-CTLA-4 and anti-PD-1 antibodies has demonstrated significant clinical efficacy in metastatic melanoma, but also significant toxicities. Pharmacodynamic (PD) markers are important tools in optimizing the safety and efficacy of anti-CTLA-4/anti-PD-1 combinations, but have remained elusive to date. To test the hypothesis that blockade of both CTLA-4 and PD-1 together results in increased expression of the proliferation marker Ki67 in CD4+ T cells, we studied two dose regimens of ipilimumab in combination with nivolumab in patients with advanced or metastatic solid tumors, using a validated assay. Subjects received either 1.0 mg or 0.3 mg /kg of ipilimumab every 6 weeks in combination with nivolumab 3mg/kg every 2 weeks for a maximum of 12 weeks (2 cycles). A total of 9 subjects were enrolled at the 1.0 mg/kg of ipilimumab cohort and 12 subjects in the 0.3 mg/kg cohort. Highly statistically significant increases of 4.56 fold (range 3.35-6.20) from baseline at cycle 1 day 8 post-treatment (p &amp;lt; 0.001) in cohort 1, and 3.13 fold (range 2.31-4.33) from baseline at cycle 1 day 8 post-treatment (p &amp;lt; 0.001) in cohort 2, in Ki67 expression were observed in CD4+ T cells. The absolute increase in Ki67 expression was also observed to be dose dependent numerically. Significant increases in Ki67 expression were also observed in CD8+ T cells, regulatory T cells, and natural killer T (NKT) cells following treatment. These results identify and support Ki67 expression as a PD biomarker in the context of CTLA-4 and PD-1 blockade. More work is required to correlate these finding with clinical outcomes in order to establish a benchmark biomarker assay for anti-CTLA-4 and anti-PD-1 combinations. (ACTRN12617001059358) Citation Format: Paul De Souza, Agnieszka Malczewski, Igor Proscurshim, Guojun Yuan, Elisabeth Coart, Christopher Dupont, Mariana Manrique, Elise Drouin, Ana Gonzalez, Meg Carini, Olga Shebanova, Jean-Marie Cuillerot. Evaluation of peripheral T cell subset proliferation as a pharmacodynamic assay to guide the development of anti-CTLA-4 and PD-1 antibody combinations in patients with solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT104.
Organization of the Herpes Simplex Virus Type 1 Transcription Unit Encoding Two Early Proteins with Molecular Weights of 140000 and 40000 (1983)

The 5' ends of two early herpes simplex virus type 1 mRNAs have been identified by nuclease S1 and exonuclease VII analysis using cloned virus DNA probes. These mRNAs (5.0 kb and 1.2 kb), located within the genome region between map coordinates 0.56 and 0.60, are unspliced and share a 3' terminus. Genomic DNA at the 5' ends has been sequenced and the 5' termini have been located on the virus DNA sequence. The DNA sequence has revealed signals involved in the initiation of transcription of both mRNAs, and the 5' end of the 1.2 mRNA is encoded within the internal sequences of the 5.0 kb mRNA. The probable translational initiation codons for the polypeptides specified by these mRNAs have been identified, and the results indicate that the coding regions of the two mRNAs do not overlap.
Room-Temperature Synthesis and Characterization of Nanocrystalline CdS, ZnS, and Cd<i><sub>x</sub></i>Zn<sub>1</sub><sub>-</sub><i><sub>x</sub></i>S (2002)

A novel and simple chemical reduction route at room temperature is described to synthesize nanocrystalline CdS, ZnS, and CdxZn1-xS. In the method, anhydrous CdCl2, or ZnCl2, S, and KBH4 powders react at room temperature in various organic solvents, and the effect of the solvent on the quality of the nanoparticle product is investigated. Among the solvents used, tetrahydrofuran is shown to produce the highest quality single-phase nanoparticles. The nanoparticles are characterized by X-ray diffraction, transmission electron microscopy, UV−vis absorption, and photoluminescence. The particle size ranges from 4 to 8 nm. In the CdxZn1-xS, the lattice structure gradually changes from cubic to hexagonal with increasing percentage of Zn in the ternary compound CdxZn1-xS. The nanoparticles exhibit broad emission peaks that shift to shorter wavelength with increasing percentage of Zn in the ternary compound CdxZn1-xS. The control of the composition of CdxZn1-xS nanoparticles may lead to the development of ideal materials for short wavelength diode laser applications.
Live Attenuated Chimeric Yellow Fever Dengue Type 2 (ChimeriVax™-DEN2) Vaccine: Phase I Clinical Trial for Safety and Immunogenicity: Effect of Yellow Fever Pre-immunity in Induction of Cross Neutralizing Antibody Responses to All (2006)

A randomized double-blind Phase I Trial was conducted to evaluate safety, tolerability, and immunogenicity of a yellow fever (YF)-dengue 2 (DEN2) chimera (ChimeriVax-DEN2) in comparison to that of YF vaccine (YF-VAX). Forty-two healthy YF naïve adults randomly received a single dose of either ChimeriVax-DEN2 (high dose, 5 log plaque forming units [PFU] or low dose, 3 log PFU) or YF-VAX by the subcutaneous route (SC). To determine the effect of YF preimmunity on the ChimeriVax-DEN2 vaccine, 14 subjects previously vaccinated against YF received a high dose of ChimeriVax-DEN2 as an open-label vaccine. Most adverse events were similar to YF-VAX and of mild to moderate intensity, with no serious side-effects. One hundred percent and 92.3% of YF naïve subjects inoculated with 5.0 and 3.0 log10 PFU of ChimeriVax-DEN2, respectively, seroconverted to wt DEN2 (strain 16681); 92% of subjects inoculated with YF-VAX seroconverted to YF 17D virus but none of YF naïve subjects inoculated with ChimeriVax-DEN2 seroconverted to YF 17D virus. Low seroconversion rates to heterologous DEN serotypes 1, 3 and 4 were observed in YF naïve subjects inoculated with either ChimeriVax-DEN2 or YF-VAX. In contrast, 100% of YF immune subjects inoculated with ChimeriVax-DEN2 seroconverted to all 4 DEN serotypes. Surprisingly, levels of neutralizing antibodies to DEN 1, 2 and 3 viruses in YF immune subjects persisted after 1 year. These data demonstrated that (1) the safety and immunogenicity profile of the ChimeriVax-DEN2 vaccine is consistent with that of YF-VAX, and (2) preimmunity to YF virus does not interfere with ChimeriVax-DEN2 immunization, but induces a long lasting and cross neutralizing antibody response to all 4 DEN serotypes. The latter observation can have practical implications toward development of a dengue vaccine.
Removing Noise From Pyrosequenced Amplicons (2011)

AmpliconNoise followed by Perseus is a very effective pipeline for the removal of noise. In addition the principles behind the algorithms, the inference of true sequences using Expectation-Maximization (EM), and the treatment of chimera detection as a classification or 'supervised learning' problem, will be equally applicable to new sequencing technologies as they appear.
Replication of non-hydrogen bonded bases by DNA polymerases: A mechanism for steric matching (1998)

Recent experiments have presented evidence that Watson-Crick hydrogen bonds in a base pair are not absolute requirements for efficient synthesis of that pair by DNA polymerase enzymes. Here we examine quantitative steady-state kinetic data from several published studies involving poorly hydrogen-bonding DNA base analogues and adducts, and analyze the results in terms of solvation, hydrogen bonding, and steric effects. We propose a mechanism that can explain the surprising lack of hydrogen-bonding requirement accompanied by significant selectivity in pairing. This hypothesis makes use of steric matching, enforced both by the tightly confined polymerase active site and by the DNA backbone, as a chief factor determining nucleotide selection during DNA synthesis. The results also suggest that hydrogen bonds from bases to water (solvation) may be important in increasing the effective size of DNA bases, which may help prevent misinsertion of small bases opposite each other.
Role of Hyperhomocystinemia in Retinal Vascular Occlusive Disease (2007)

Elevated plasma homocysteine (Hcy) level is considered a risk factor for vascular diseases. In recent years, many scientific reports have suggested that hyperhomocystinemia may be associated with an increased risk of retinal vascular occlusive disease (RVOD). The prevalence of elevation of homocysteine in patients with a recent retinal vascular occlusion was compared to a health control group in this study. Forty-nine consecutive patients (22 M; 27 F) (age 26-85 years, mean 69) with diagnosis of retinal vascular occlusion were compared with 71 healthy controls. These patients underwent laboratory evaluation for plasma fasting total homocysteine, activated protein C resistance, protein C, protein S, antithrombin III, and antiphospholipid and anticardiolipin antibodies. The G20210 prothrombin gene mutation (FII G20210A) and Factor V Leiden mutation (FVL) were evaluated. None of these enrolled subjects had other prothrombic risk factors. The health control group consisted of healthy subjects from the general population, with no history or clinical evidence of retinal vascular disease, recruited during the same 2-year period. High fasting homocystinemia (higher than 15 mumol/L) was detected in 24/49 subjects (48.9%) (P < .0005). There was a high prevalence of hyperhomocystinemia: these data suggest an association between RVOD and high fasting homocystinemia. Elevated homocysteine may be an independent risk factor, and its assessment may be important in the investigation, management, and follow-up of patients with RVOD. Further controlled studies are necessary to clarify the exact role of hyperhomocystinemia in RVOD and to evaluate the appropriate therapeutic approach.
Transistors made in single-crystal SOI films (1983)

Test transistors with gate lengths ranging from 10 to 4 µm were made in laser-recrystallized silicon on insulator films. A capping layer of patterned antireflecting stripes of Si <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</inf> N <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</inf> was used to grow large single-crystals of silicon. MOS transistors show good electrical characteristics and a surface mobility up to 650 cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> /V.s for electrons. With the exception of the recrystallization procedure, the wafers followed a fully standard NMOS process, including the growth of a LOCOS field oxide.
New edge dependent deinterlacing algorithm based on horizontal edge pattern (2003)

In this paper, we propose a new deinterlacing algorithm, which is an edge dependent interpolation (EDI) algorithm based on a horizontal edge pattern. Generally, a conventional EDI algorithm has a visually better performance than any other deinterlacing algorithms using one field. However, it produces unpleasant results due to the failure of estimating edge direction. In order to exactly detect edge direction, we use not only simple difference but also edge patterns. Experimental results indicate that the proposed algorithm outperforms conventional approaches with respect to both objective and subjective criteria.
RPCELP: a high quality and low complexity scheme for narrow band coding of speech (2003)

Code-excited linear prediction (CELP), a powerful technique for low-bit-rate speech coding, leads to a huge computational load. A related scheme that replaces the conventional stochastic excitation by an efficient regular pulse excitation is introduced. This method, called regular pulse CELP (RPCELP), takes advantage of the codebook structure together with a convenient perceptual criterion to achieve a very low complexity while maintaining high-quality output speech. The algorithm can be implemented easily in real-time and can provide good communication quality at 6 Kb/s, even over noisy transmission channels. Objective performance results are reported for several configurations.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A Review and Evaluation of Logistics Metrics (1994)

Abstract Performance measurement in the logistics function, like all business functions, begins at the individual metric level. A performance measurement system that is well designed at the strategic level can be flawed at the individual metric level; the Achilles' Heel of any measurement system. The pressing need is not for the development of novel performance metrics: there is a great abundance of sufficient metrics already in existence. Rather, there is a need for a method with which to evaluate existing metrics. This paper addresses this need by suggesting a set of evaluation criteria for individual logistics performance metrics and identifying the inherent trade‐offs. A taxonomy of logistics performance metrics, organized by process rather than by function, is also presented and the metrics are evaluated using the established criteria.
Surface plasmon propagation in microscale metal stripes (2001)

Addressing the fundamental question of miniaturization of light guiding and routing towards nanoscale optics, we study experimentally surface plasmon propagation in silver and gold thin films of finite widths in the micrometer range. Spatially confined excitation of surface plasmons is realized by a prism coupling arrangement involving an opaque aluminum screen for a distinct separation of excitation and propagation (measurement) region. The surface plasmon propagation length as a function of film widths is measured by detecting stray light due to surface plasmon scattering with a conventional optical microscope.
On the use of a modified fast affine projection algorithm in subbands for acoustic echo cancelation (1996)

The fast affine projection (FAP) has been proposed recently as a new adaptive filtering algorithm which possesses LMS like complexity but may achieve RLS like convergence. We investigate the use of FAP algorithms in subbands for acoustic echo cancellation (AEC). To this end, some modifications are first made on the FAP based on the consideration of the numerical stability. The modified FAP algorithm is then used in a complex adaptive subband filter structure for AEC. Advantages of the resulting subband FAP over the full-band NLMS scheme in terms of both complexity and performance are demonstrated by simulations.
The entry of diphtheria toxin into the mammalian cell cytoplasm: evidence for lysosomal involvement. (1980)

Lysosomotropic amines, such as ammonium chloride, are known to protect cells from the cytotoxic effects of diphtheria toxin. These drugs are believed to inhibit the transport of the toxin from a receptor at the cell exterior into the cytoplasm where a fragment of the toxin arrests protein synthesis. We studied the effects of lysosomotropic agents on the cytotoxic process to better understand how the toxin enters the cytoplasm. The cytotoxic effects of diphtheria toxin were not inhibited by antitoxin when cells were preincubated at 37 degrees C with toxin and ammonium chloride, exposed to antitoxin at 4 degrees C, washed to relieve the ammonium chloride inhibition, and finally warmed to 37 degrees C. The antigenic determinants of the toxin were, therefore, either altered or sheltered. It is likely that the combination of ammonium chloride and a low temperature trapped the toxin in an intracellular vesicle from which the toxin could proceed to the cytoplasm. Because lysosomotropic amines raise the pH within acidic intracellular vesicles, such as lysosomes, they could trap the toxin within such a vesicle if an acidic environment were necessary for the toxin to penetrate into the cytoplasm. We simulated acidic conditions which the toxin might encounter by exposing cells with toxin bound to their surface to acidic medium. We then measured the effects of lysosomotropic amines on the activity of the toxin to see if the acidic environment substituted for the function normally inhibited by the drugs. The drugs no longer protected the cells. This suggests that exposing the toxin to an acidic environment, such as that found within lysosomes, is an important step in the penetration of diphtheria toxin into the cytoplasm.
“Deceptive Equivalence” in C-E Fictional Translation: A Literary Stylistic Approach (2014)

Literary stylistics is an intermediary discipline mediating between linguistics and literary criticism. With the precision of linguistics, it can help fend off the general impressionistic comments and intuitive analysis. Chinese and English are two vastly different languages and deceptive equivalence is not uncommon in fictional translation. Literary linguistics is an effective tool in C-E fictional translation to help identify the “artistically or thematically motivated stylistic choices” in the original and thus help avoid deceptive equivalence and reduce stylistic losses in the translation.
Covalent and Selective Labeling of Proteins with Heavy Metals. Synthesis, X-ray Structure, and Reactivity Studies of <i>N</i>-Succinimidyl and <i>N</i>-Sulfosuccinimidyl Ester Organotungsten Complexes (1996)

New functionally substituted η5-cyclopentadienyl and 2-oxaallyl (η1-enolate) tungsten complexes bearing an N-succinimidyl or an N-sulfosuccinimidyl ester have been prepared and fully characterized. The molecular structures of [η5-((succinimidooxy)carbonyl)cyclopentadienyl]methyltricarbonyltungsten(II) (2) and [η5-((succinimidooxy)carbonyl)cyclopentadienyl]iodotricarbonyltungsten(II) (5) were solved by X-ray crystallography. The reactivity of these activated esters toward a range of amines and amino acids has been studied. While the N-succinimidyl ester enolate was found to be unreactive, N-succinimidyl-substituted cyclopentadienyl complexes were quite reactive, leading to the expected stable organometallic amides. Bovine serum albumin (BSA), a 66 kDa molecular mass globular protein, could be labeled with fair yields, and conjugates were characterized by IR spectroscopy of the CO ligands. Organotungsten N-succinimidyl esters thus appear as promising reagents for the labeling of proteins with heavy metals.
Anti-Human Immunodeficiency Virus Activity and Cellular Metabolism of a Potential Prodrug of the Acyclic Nucleoside Phosphonate 9- <i>R</i> -(2-Phosphonomethoxypropyl)adenine (PMPA), Bis(isopropyloxymethylcarbonyl)PMPA (1998)

Bis(isopropyloxymethylcarbonyl) 9-R-(2-phosphonomethoxypropyl)adenine [bis(POC)PMPA] has been identified as a novel prodrug of PMPA. The anti-human immunodeficiency virus activity of bis(POC)PMPA was >100-fold greater than that of PMPA in both an established T-cell line and primary peripheral blood lymphocytes. This improved efficacy was shown to be due to a rapid intracellular uptake of the prodrug resulting in an increased intracellular accumulation of PMPA diphosphate (PMPApp), the pharmacologically active metabolite. PMPApp levels in bis(POC)PMPA-treated cells exceeded by >1,000-fold the levels seen in cells treated with unmodified PMPA in both resting and activated peripheral blood lymphocytes. Significant differences in the intracellular catabolism of PMPA metabolites were noted between the resting and activated lymphocytes. The half-life for the disappearance of PMPApp, derived from either bis(POC)PMPA or PMPA, was 12 to 15 h in the activated lymphocytes and 33 to 50 h in the resting lymphocytes. This long persistence of PMPApp, particularly in resting lymphocytes, may be unique to the nucleoside phosphonate analogs and indicates that effective levels of the active metabolite can be achieved and maintained with relatively infrequent administration of the parent drug.
Treatments for common and plantar warts (2011)

Salicylic acid or liquid nitrogen is probably no more effective than a wait and see policy



Chassenet/SPL

Cutaneous warts are common, benign, and usually self limiting papillomas.1 2 They present in various forms and sizes and are caused by infection with human papillomavirus (HPV).1 2 The two most common types are common warts (verrucae vulgaris), which usually occur on the hands, and plantar warts (verrucae plantares), which are usually found on the soles of the feet. Between 10% and 30% of primary school children have cutaneous warts, of which two thirds resolve within two years.3 In the linked randomised controlled trial (doi:10.1136/bmj.d3271), Cockayne and colleagues compare the effectiveness of cryotherapy versus salicylic acid for the treatment of plantar warts⇑.4 

Treatments have been based on destruction (cryotherapy, photodynamic treatment, pulsed dye laser), keratolysis (salicylic acid), immunostimulation (dinitrochlorobenzene, interferons), or antimitotic effects (bleomycin, fluorouracil).1 5 A systematic review of topical treatments for cutaneous warts was published in 2006 and updated in 2009 to include subsequent randomised controlled trials.5 6 The authors identified 78 …
Natural Killer Cell Protocols (2009)

As the research has continued, it has become increasingly clear that natural killer (NK) cells are critical sentinels of the innate immune response, playing important roles in protecting the body from
Characterisation of monodisperse poly(N-isopropylacrylamide) microgel particles (2000)

Poly(N-isopropylacrylamide) microgel particles prepared by emulsion polymerisation in the presence of anionic surfactant have been investigated in different media in the swollen and collapsed state by static and dynamic light scattering measurements. The microgel latex was found to be highly monodisperse. The particle scattering function fits well to the theoretical function of a sphere. The hydrodynamic diameter of the particles is significantly higher than the diameter calculated from the measured radius of gyration for a sphere of constant density. The discrepancy was interpreted by a core/shell structure of the microgel particles. If the particles are in the collapsed state the two kinds of diameter coincide with each other, indicating that the microgel particles are compact spheres. In the globular state the gel still has 39% (w/w) water content. The particles bear a small surface charge resulting in a long-range electrostatic interaction between the particles in an aqueous environment. It was observed for the first time that at a sufficiently low ionic strength the aqueous microgel particle system undergoes an ordered/disordered phase transition.