gebhart/patrepeval huggingface dataset:
Acquired Resistance to Fractionated Radiotherapy Can Be Overcome by Concurrent PD-L1 Blockade (2014)

Radiotherapy is a major part in the treatment of most common cancers, but many patients experience local recurrence with metastatic disease. In evaluating response biomarkers, we found that low doses of fractionated radiotherapy led to PD-L1 upregulation on tumor cells in a variety of syngeneic mouse models of cancer. Notably, fractionated radiotherapy delivered in combination with αPD-1 or αPD-L1 mAbs generated efficacious CD8(+) T-cell responses that improved local tumor control, long-term survival, and protection against tumor rechallenge. These favorable outcomes were associated with induction of a tumor antigen-specific memory immune response. Mechanistic investigations showed that IFNγ produced by CD8(+) T cells was responsible for mediating PD-L1 upregulation on tumor cells after delivery of fractionated radiotherapy. Scheduling of anti-PD-L1 mAb was important for therapeutic outcome, with concomitant but not sequential administration with fractionated radiotherapy required to improve survival. Taken together, our results reveal the mechanistic basis for an adaptive response by tumor cells that mediates resistance to fractionated radiotherapy and its treatment failure. With attention to scheduling, combination immunoradiotherapy with radiotherapy and PD-1/PD-L1 signaling blockade may offer an immediate strategy for clinical evaluation to improve treatment outcomes.
Membrane Assisted Simultaneous Extraction and Derivatization with Triphenylphosphine of Elemental Sulfur in Arabian Crude Samples by Gas Chromatography/Mass Spectrometry (2015)

Determination of trace level elemental sulfur from crude oil samples is a tedious task. Recently, several gas chromatographic methods were reported in which selective triphenylphosphine derivatization of sulfur was used to form triphenylphosphine sulfide. Direct quantitation of elemental sulfur from crude oil requires an efficient sample preparation method. This paper describes how simultaneous extraction derivatization of elemental sulfur was performed for the first time using porous hollow fiber membrane. A thick (0.25 um pore size; 1550 μ m wall thickness; and 5500 μ m inner diameter) hollow fiber membrane filled with triphenylphosphine (dissolved N‐methylpyrrolidone) is used as a solvent bar. The solvent bar is tumbled freely in the crude oil sample; the elemental sulfur was extracted and derivatized. Finally, the derivatized sulfur was analyzed by gas chromatography/mass spectrometry. Various experimental conditions of solvent bar microextraction (SBME) were optimized to achieve higher extraction. The linear range was established between 1 and 50 μ g/mL, while a squared regression coefficient was found to be 0.9959 μ g/mL. Relative standard deviation (RSD) was below 10%. Relative recoveries were calculated for SBME in crude oil samples and were in the range between 98.2% and 101.2%.
NEW TECHNIQUE AND RESULTS OF LASER WELDED SCRF CAVITY DEVELOPED AT RRCAT (2013)

A new technique to fabricate SCRF cavities with the help of laser welding process has been developed at Raja Ramanna Centre for Advanced Technology (RRCAT), Indore, Department of Atomic Energy, India. In this technique, an Nd:YAG laser has been used and welding was performed in inert gas environment in a specially designed welding rig. The advantages of this technique are reduced cost, small heat affected zone, no necessity to weld in vacuum and an enhanced rate of production. The paper describes the technique and fabrication method of a single-cell 1.3 GHz SCRF cavity which was fabricated at RRCAT with this new technique. It also discusses the test results of this cavity which was processed and tested at Fermi Lab, USA (FNAL). The cavity reached an Eacc of 17MV/m with a Q0 of 1.4 x10 10 at 2K after buffered chemical and electro-polishing processing sequence. The cavity was then barrel polished to remove a small weld defect and then electro-polished. In the next test the cavity achieved a quench field of 31.6 MV/m with a Q0 of 1.0 x10 10 .
QTL Mapping for Ovary- and Fruit-Related Traits in Cucumis sativus-C. hystrix Introgression Line IL52 (2023)

IL52 is a valuable introgression line obtained from interspecific hybridization between cultivated cucumber (<i>Cucumis sativus</i> L., 2n = 14) and the wild relative species <i>C. hystrix</i> Chakr. (2n = 24). IL52 exhibits high resistance to a number of diseases, including downy mildew, powdery mildew, and angular leaf spot. However, the ovary- and fruit-related traits of IL52 have not been thoroughly investigated. Here, we conducted quantitative trait loci (QTL) mapping for 11 traits related to ovary size, fruit size, and flowering time using a previously developed 155 F<sub>7:8</sub> RIL population derived from a cross between CCMC and IL52. In total, 27 QTL associated with the 11 traits were detected, distributed on seven chromosomes. These QTL explained 3.61% to 43.98% of the phenotypic variance. Notably, we identified a major-effect QTL (<i>qOHN4.1</i>) on chromosome 4 associated with the ovary hypanthium neck width and further delimited it into a 114-kb candidate region harboring 13 candidate genes. Furthermore, the QTL <i>qOHN4.1</i> is co-localized with the QTL detected for ovary length, mature fruit length, and fruit neck length, all residing within the consensus QTL <i>FS4.1</i>, suggesting a plausible pleiotropic effect.
A single-layer tilting actuator with multiple close-gap electrodes (2009)

We report on the design, fabrication and characterization of a novel tilting electrostatic actuator, fabricated by using a single layer of a silicon on insulator (SOI) wafer and investigate, both theoretically and experimentally, the electromechanical behavior of the device. The actuator incorporates high aspect ratio comb-like electrodes oriented in the direction parallel to the rotation axis of the tilting element. An increase in the tilting angle is accompanied by a decrease in the distance between the electrodes and by an increase of the actuating torque. Simultaneously, the overlap area between electrodes located farther apart the axis shrinks, resulting in a 'restoring' torque in the opposite direction. The electromechanical behavior and stability of the device were investigated using a simplified model of the actuator and verified by a coupled three-dimensional simulation. Model results suggest that by changing the design parameters, the actuator characteristic can be tailored in a large range. Devices of three different configurations incorporating elastic torsion axes or bending flexures were fabricated and characterized and both static and resonant responses, typical for parametrically excited nonlinear oscillators, were registered. Theoretical and experimental results indicate that the suggested architecture can be efficiently used for the static and dynamic operation of electrostatic tilting devices.
Efforts Toward Synthesis of Oligonucleotides for Commercialization (1997)

Abstract Recent progress on the development of oligonucleotide phosphorothioates to meet market demands is reported.
Fundamental Limits on Gas-Phase Chemical Reduction of NOx in a Plasma (1997)

In the plasma, the electrons do not react directly with the NOx molecules. The electrons collide mainly with the background gas molecules like N{sub 2}, O{sub 2} and H{sub 2}O. Electron impact on these molecules result partly in dissociation reactions that produce reactive species like N, O and OH. The NOx in the engine exhaust gas initially consist mostly of NO. The ground state nitrogen atom, N, is the only species that could lead to the chemical reduction of NO to N{sub 2}. The O radical oxidizes NO to NO{sub 2} leaving the same amount of NOx. The OH radical converts NO{sub 2} to nitric acid. Acid products in the plasma can easily get adsorbed on surfaces in the plasma reactor and in the pipes. When undetected, the absence of these oxidation products can often be mistaken for chemical reduction of NOx. In this paper the authors will examine the gas-phase chemical reduction of NOx. They will show that under the best conditions, the plasma can chemically reduce 1.6 grams of NOx per brake-horsepower-hour [g(NOx)/bhp-hr] when 5% of the engine output energy is delivered to the plasma.
Cellular Biochemistry Methods for Investigating Protein Tyrosine Phosphatases (2013)

Further development of approaches to investigate the intracellular PTP activity and functions will provide specific insight into their mechanisms of action and control of diverse signaling pathways.
Modulation Bandwidth Enhancement Beyond 100 GHz in Strongly Injection-Locked Cascaded Semiconductor Ring Lasers (2012)

A novel scheme for modulation bandwidth enhancement is presented, involving a DBR master laser monolithically integrated with two cascaded strongly injection-locked whistle-geometry semiconductor microring lasers. Enhanced performance of the novel scheme is confirmed through numerical modeling.
Formation of rhinovirus-soluble ICAM-1 complexes and conformational changes in the virion (1993)

Viral receptors serve both to target viruses to specific cell types and to actively promote the entry of bound virus into cells. Human rhinoviruses (HRVs) can form complexes in vitro with a truncated soluble form of the HRV cell surface receptor, ICAM-1. These complexes appear to be stoichiometric, with approximately 60 ICAM molecules bound per virion or 1 ICAM-1 molecule per icosahedral face of the capsid. The complex can have two fates, either dissociating to yield free virus and free ICAM-1 or uncoating to break down to an 80S empty capsid which has released VP4, viral RNA, and ICAM-1. This uncoating in vitro mimics the uncoating of virus during infection of cells. The stability of the virus-receptor complex is dependent on temperature and the rhinovirus serotype. HRV serotype 14 (HRV14)-ICAM-1 complexes rapidly uncoat, HRV16 forms a stable virus-ICAM complex which does not uncoat detectably at 34 degrees C, and HRV3 has an intermediate phenotype. Rhinovirus can also uncoat after exposure to mildly acidic pH. The sensitivities of individual rhinovirus serotypes to ICAM-1-mediated virus uncoating do not correlate with uncoating promoted by incubation at low pH, suggesting that these two means of virus destabilization occur by different mechanisms. Soluble ICAM-1 and low pH do not act synergistically to promote uncoating. The rate of uncoating does appear to be inversely related to virus affinity for its receptor.
Properties of Calcium Phosphate Cements With Different Tetracalcium Phosphate and Dicalcium Phosphate Anhydrous Molar Ratios (2008)

Calcium phosphate cements (CPCs) were prepared using mixtures of tetracalcium phosphate (TTCP) and dicalcium phosphate anhydrous (DCPA), with TTCP/DCPA molar ratios of 1/1, 1/2, or 1/3, with the powder and water as the liquid. Diametral tensile strength (DTS), porosity, and phase composition (powder x-ray diffraction) were determined after the set specimens have been immersed in a physiological-like solution (PLS) for 1 d, 5 d, and 10 d. Cement dissolution rates in an acidified PLS were measured using a dual constant composition method. Setting times ((30 ± 1) min) were the same for all cements. DTS decreased with decreasing TTCP/DCPA ratio and, in some cases, also decreased with PLS immersion time. Porosity and hydroxyapatite (HA) formation increased with PLS immersion time. Cements with TTCP/DCPA ratios of 1/2 and 1/3, which formed calcium-deficient HA, dissolved more rapidly than the cement with a ratio of 1/1. In conclusion, cements may be prepared with a range of TTCP/DCPA ratios, and those with lower ratio had lower strengths but dissolved more rapidly in acidified PLS.
Clinical Pharmacokinetic Evaluation of Optimized Liquisolid Tablets as a Potential Therapy for Male Sexual Dysfunction (2020)

The study aimed at developing a liquisolid tablet (LST) containing tadalafil (TDL) and dapoxetine (DPX) with improved bioavailability as a potential therapy for male sexual dysfunction. A mixture of nonvolatile solvents, namely PEG 200 and Labrasol®, was utilized to prepare LSTs that were assessed for their quality characteristics. The Box-Behnken design (BBD) was employed to statistically explore the effect of the formulation factors on the quality attributes of LSTs. Furthermore, an in vivo pharmacokinetic study was carried out for the optimized LST in comparison with the marketed tablets on healthy human volunteers. The optimized LST revealed acceptable quality limits with enhanced dissolution for both APIs. The pharmacokinetic parameters after oral administration of the optimized LST indicated that the Cmax of TDL in LSTs was 122.61 ng/mL within 2h compared to the marketed tablets, which reached 91.72 ng/mL after 3 h, indicating the faster onset of action. The AUC was improved for TDL in LST (4484.953 vs. 2994.611 ng/mL∙h in the marketed tablet) and DPX in LST (919.633 vs. 794.699 ng/mL∙h in the marketed tablet). This enhancement in bioavailability potentially minimizes the associated side effects and improves the treatment of male sexual dysfunction, particularly for diabetic patients.
Salt Sensitivity of Blood Pressure Is Associated With Polymorphisms in the Sodium-Bicarbonate Cotransporter (2012)

Previous studies have demonstrated that single nucleotide polymorphisms (SNPs) of the sodium-bicarbonate co-transporter gene (SLC4A5) are associated with hypertension. We tested the hypothesis that SNPs in SLC4A5 are associated with salt sensitivity of blood pressure in 185 whites consuming an isocaloric constant diet with a randomized order of 7 days of low Na(+) (10 mmol/d) and 7 days of high Na(+) (300 mmol/d) intake. Salt sensitivity was defined as a ≥ 7-mm Hg increase in mean arterial pressure during a randomized transition between high and low Na(+) diet. A total of 35 polymorphisms in 17 candidate genes were assayed, 25 of which were tested for association. Association analyses with salt sensitivity revealed 3 variants that associated with salt sensitivity, 2 in SLC4A5 (P<0.001) and 1 in GRK4 (P=0.020). Of these, 2 SNPs in SLC4A5 (rs7571842 and rs10177833) demonstrated highly significant results and large effects sizes, using logistic regression. These 2 SNPs had P values of 1.0 × 10(-4) and 3.1 × 10(-4) with odds ratios of 0.221 and 0.221 in unadjusted regression models, respectively, with the G allele at both sites conferring protection. These SNPs remained significant after adjusting for body mass index and age (P=8.9 × 10(-5) and 2.6 × 10(-4) and odds ratios 0.210 and 0.286, respectively). Furthermore, the association of these SNPs with salt sensitivity was replicated in a second hypertensive population. Meta-analysis demonstrated significant associations of both SNPs with salt sensitivity (rs7571842 [P=1.2 × 10(-5)]; rs1017783 [P=1.1 × 10(-4)]). In conclusion, SLC4A5 variants are strongly associated with salt sensitivity of blood pressure in 2 separate white populations.
Generic inhibition of amyloidogenic proteins by two naphthoquinone–tryptophan hybrid molecules (2012)

Amyloid formation is associated with several human diseases including Alzheimer's disease (AD), Parkinson's disease, Type 2 Diabetes, and so forth, no disease modifying therapeutics are available for them. Because of the structural similarities between the amyloid species characterizing these diseases, (despite the lack of amino acid homology) it is believed that there might be a common mechanism of toxicity for these conditions. Thus, inhibition of amyloid formation could be a promising disease-modifying therapeutic strategy for them. Aromatic residues have been identified as crucial in formation and stabilization of amyloid structures. This finding was corroborated by high-resolution structural studies, theoretical analysis, and molecular dynamics simulations. Amongst the aromatic entities, tryptophan was found to possess the most amyloidogenic potential. We therefore postulate that targeting aromatic recognition interfaces by tryptophan could be a useful approach for inhibiting the formation of amyloids. Quinones are known as inhibitors of cellular metabolic pathways, to have anti- cancer, anti-viral and anti-bacterial properties and were shown to inhibit aggregation of several amyloidogenic proteins in vitro. We have previously described two quinone-tryptophan hybrids which are capable of inhibiting amyloid-beta, the protein associated with AD pathology, both in vitro and in vivo. Here we tested their generic properties and their ability to inhibit other amyloidogenic proteins including α-synuclein, islet amyloid polypeptide, lysozyme, calcitonin, and insulin. Both compounds showed efficient inhibition of all five proteins examined both by ThT fluorescence analysis and by electron microscope imaging. If verified in vivo, these small molecules could serve as leads for developing generic anti-amyloid drugs.
High Holding Voltage Cascoded LVTSCR Structures for 5.5-V Tolerant ESD Protection Clamps (2004)

This paper presents a new design concept for the control of the holding voltage of LVTSCR ESD protection structures by realizing a negative feedback in the p emitter. The negative feedback is implemented by the creation of a voltage drop using embedded circuit elements. The final clamp voltage is tuned to exceed the power supply level, thus eliminating the potential for latchup. The design is validated by ESD pulse measurements performed on test structures with cascoded, triggered LVTSCRs for 5.5-V tolerant I/O pins in an 0.18-/spl mu/m CMOS process. The results of the first part of the study were used to propose another design for the LVTSCR with a high holding voltage based on emitter area reduction. The proposed device is validated using three-dimensional simulations and experimental analysis.
Electrodeposition of Low Stress Nickel Phosphorous Alloys for Precision Component Fabrication (2001)

Nickel alloys are favored for electroforming precision components. Nickel phosphorous and nickel cobalt phosphorous are studied in this work. A completely new and innovative electrolytic process eliminates the fumes present in electroless processes and is suitable for electroforming nickel phosphorous and nickel cobalt phosphorous alloys to any desirable thickness, using soluble anodes, without stripping of tanks. Solutions show excellent performance for extended throughput. Properties include, cleaner low temperature operation (40 - 45 C), high Faradaic efficiency, low stress, Rockwell C 52 - 54 hardness and as much as 2000 N per square millimeter tensile strength. Performance is compared to nickel and nickel cobalt electroforming.
Tomato fruits expressing a bacterial feedback-insensitive 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase of the shikimate pathway possess enhanced levels of multiple specialized metabolites and upgraded aroma (2013)

Tomato (Solanum lycopersicum) fruit contains significant amounts of bioactive compounds, particularly multiple classes of specialized metabolites. Enhancing the synthesis and accumulation of these substances, specifically in fruits, are central for improving tomato fruit quality (e.g. flavour and aroma) and could aid in elucidate pathways of specialized metabolism. To promote the production of specialized metabolites in tomato fruit, this work expressed under a fruit ripening-specific promoter, E8, a bacterial AroG gene encoding a 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase (DAHPS), which is feedback-insensitive to phenylalanine inhibition. DAHPS, the first enzyme of the shikimate pathway, links between the primary and specialized metabolism derived from aromatic amino acids. AroG expression influenced the levels of number of primary metabolites, such as shikimic acid and aromatic amino acids, as well as multiple volatile and non-volatile phenylpropanoids specialized metabolites and carotenoids. An organoleptic test, performed by trained panellists, suggested that the ripe AroG-expressing tomato fruits had a preferred floral aroma compare with fruits of the wild-type line. These results imply that fruit-specific manipulation of the conversion of primary to specialized metabolism is an attractive approach for improving fruit aroma and flavour qualities as well as discovering novel fruit-specialized metabolites.
Directional Pumping Performance of an Electrostatic Checkerboard Microvalve (2006)

This paper reports experimental characterization of directional gas pumping generated by MEMS-fabricated checkerboard-type electrostatic microvalves. It is found that the oscillatory motion of the checkerboard microvalve membrane provides both the pumping and valve functions of a pump, namely: 1) to cause the volume displacement and, thus, compression and transfer of gas, and 2) to direct gas flow in one direction by closing and opening air paths in the proper sequence. Here, we describe the microvalve-only design, and report the pumping performance producing a maximum flow rate of 1.8 sccm and a maximum pressure differential of 3.0 kPa for five microvalves driven simultaneously with a sinusoidal signal of ± 100V amplitude at 5.5 kHz.
Direct Raman imaging techniques for study of the subcellular distribution of a drug (2002)

Direct Raman imaging techniques are demonstrated to study the drug distribution in living cells. The advantage of Raman imaging is that no external markers are required, which simplifies the sample preparation and minimally disturbs the drug mechanism during imaging. The major challenge in Raman imaging is the weak Raman signal. In this study, we present a Raman image model to describe the degradation of Raman signals by imaging processes. Using this model, we demonstrate special-purpose image-processing algorithms to restore the Raman images. The processing techniques are then applied to visualize the anticancer agent paclitaxel in living MDA-435 breast cancer cells. Raman images were obtained from a cancer cell before, during, and after drug treatment. The paclitaxel distribution illustrated in these images is explained by means of the binding characteristics of the paclitaxel and its molecular target-the microtubules. This result demonstrates that direct Raman imaging is a promising tool to study the distribution of a drug in living cells.
Rapid Diagnosis of Pertussis (1990)

A rapid and sensitive method has been devised for the detection of Bordetella pertussis in clinical samples. The feasibility of the technique, which is based upon enzymatic assay of adenylate cyclase associated with the intact B. pertussis organisms, has been demonstrated in laboratory simulations. In the present study, we evaluated this novel diagnostic method using clinical specimens obtained from 120 children with suspected pertussis. Levels of adenylate cyclase activity in these specimens were highly correlated with culture results; intermediate and high levels in 28 samples predicted positive cultures in 23 (82%). Further, the adenylate cyclase assay results were obtained 2-7 days earlier than the results of cultures. Among 92 specimens with low levels of adenylate cyclase activity, only 11 were positive in culture. We conclude that adenylate cyclase assays may be suitable for rapid diagnosis of pertussis in children and might facilitate early and effective intervention.