gebhart/patrepeval huggingface dataset:
Clinical Use of Pediatric Bosentan in Japanese Children with Pulmonary Arterial Hypertension: Investigation of Efficacy, Pharmacokinetics, Safety, and Tolerability (2018)

背景：日本人小児PAH患者に対するボセンタン（BOS）新規小児用製剤の有効性，薬物動態，安全性，及び忍容性を検討する目的で治験を実施した．
1040Myocardial T1 mapping in iron overload. A comparison to the T2* technique (2013)

Objectives: To evaluate myocardial T1 mapping in patients with iron overload, comparing it to the non invasive gold standard of T2*. Methods: Eighty eight patients with the potenital for cardiac iron overloading underwent T1 mapping using the shortened modified look locker inversion (ShMOLLI) sequence in a mid short axis slice. Patients also underwent T2* assessment of the same slice. Regions of interest were drawn in the mid septum. Thirty five patients underwent a second study later on the same day in which both T1 and T2* were repeated, allowing interstudy reproducibility assessment. The studies were annonymised with inter and intra observer variabilty then assessed by two blinded physicians. As the results of the T2* interstudy reproducibility were inferior to previous published data, we asked a second group, not previously involved in the study, to re-analyse this data. Results: There was strong correlation between myocardial T1 and T2* (R = -0.87, P < 0.0001, Fig 1). However 30% of patients with a normal T2* (defined as >20ms), were found to have a T1 of at least 2 standard deviations (and upto 7 standard deviations) below the normal mean (968 ± 32ms). The T1 interstudy and interobserver variablity were significantly better than T2* (P < 0.0001 and P = 0.03). When the second research group re-analysed the T2* interstudy data, although there was a trend towards improvement, it was not statisitically significant compared to the original results (P = 0.74, fig 2). Furthermore, T1 remained statisitically better than T2* (P < 0.0001).
DOP074 Pharmacokinetics and exposure-response of tofacitinib in a Phase 3 maintenance study in ulcerative colitis patients (2017)

Background: Tofacitinib is an oral small molecule Janus kinase inhibitor that is being investigated for ulcerative colitis (UC). A recently completed 52-week (wk) Phase 3 maintenance study (NCT01458574) demonstrated efficacy of tofacitinib 5 and 10 mg twice daily (BID) in patients (pts) with moderately to severely active UC, who achieved clinical response following 8 wks of induction therapy. Here, we characterised the pharmacokinetics (PK) of tofacitinib and the relationships of tofacitinib exposure to efficacy endpoints, using exposure-response (E-R) modeling of data from the Phase 3 maintenance study. Methods: Plasma samples for population PK analysis were collected from all pts in the maintenance study. PK data from the induction and maintenance studies were pooled, and individual tofacitinib exposure metrics (average concentration [Cavg]; trough concentration [Ctrough]) were derived for pts in the maintenance study. Efficacy endpoints at Wk 24 and 52 were: remission (total Mayo score ≤2, no subscore >1, rectal bleeding subscore of 0), mucosal healing (Mayo endoscopic subscore ≤1), and sustained steroid-free remission. The E-R analysis evaluated linear and non-linear (Emax) relationships in a binomial model with Markov dependence, implemented in SAS v 9.2. Maintenance baseline (BL) disease (Mayo score, extent of disease, disease duration), TNF inhibitor (TNFi) failure and prior use of immunosuppressants, BL corticosteroid and aminosalicylate use, age, sex and race were evaluated as covariates. Results: Individual predicted Cavg and Ctrough did not show significant change over the 52-wk study duration. The PK was linear with a mean estimated clearance of 26.3 L/hr and a volume of distribution of 115.8 L. E-R modeling of remission at Wk 24 and 52 indicated that pts who were not in remission at BL in the study achieved greater incremental benefit with 10 vs 5 mg BID, compared to pts in remission (Figure 1) at BL. Dose-normalised Cavg values at each dose level were similar between pts irrespective of remission status. More refractory pts, such as those with higher BL Mayo score, who did not achieve remission during induction, and with previous TNFi failure, showed lower efficacy compared to other pts. Figure 1. Predicted probability of remission at Week 52 as a function of average tofacitinib concentration (Cavg) in patients not in remission (Panel A) or in remission (Panel B) at the start of the maintenance trial. Conclusions: Individual plasma concentrations remained stable through the 52-wk study, and monitoring of plasma tofacitinib concentrations is not needed during maintenance treatment. The incremental efficacy of 10 mg BID relative to 5 mg BID appeared to be more pronounced in pts with refractory disease.
Reduced infiltration of regulatory T cells in tumours from mice fed daily with gamma-tocotrienol supplementation (2021)

Gamma-tocotrienol (γT3) is an analogue of vitamin E with beneficial effects on the immune system, including immune-modulatory properties. This study reports the immune-modulatory effects of daily supplementation of γT3 on host T helper (Th) and T regulatory cell (T<sub>reg</sub> ) populations in a syngeneic mouse model of breast cancer. Female BALB/c mice were fed with either γT3 or vehicle (soy oil) for 2 weeks via oral gavage before they were inoculated with syngeneic 4T1 mouse mammary cancer cells (4T1 cells). Supplementation continued until the mice were euthanized. Mice (n = 6) were euthanized at specified time-points for various analysis (blood leucocyte, cytokine production and immunohistochemistry). Tumour volume was measured once every 7 days. Gene expression studies were carried out on tumour-specific T lymphocytes isolated from splenic cultures. Supplementation with γT3 increased CD4<sup>+</sup> (p < 0.05), CD8<sup>+</sup> (p < 0.05) T-cells and natural killer cells (p < 0.05) but suppressed T<sub>reg</sub> cells (p < 0.05) in peripheral blood when compared to animals fed with the vehicle. Higher interferon (IFN)-γ and lower transforming growth factor (TGF)-ꞵ levels were noted in the γT3 fed mice. Immunohistochemistry findings revealed higher infiltration of CD4<sup>+</sup> cells, increased expression of interleukin-12 receptor-beta-2 (IL-12ꞵ2R), interleukin (IL)-24 and reduced expression of cells that express the forkhead box P3 (FoxP3) in tumours from the γT3-fed animals. Gene expression studies showed the down-regulation of seven prominent genes in splenic CD4<sup>+</sup> T cells isolated from γT3-fed mice. Supplementation with γT3 from palm oil-induced T cell-dependent cell-mediated immune responses and suppressed T cells in the tumour microenvironment in a syngeneic mouse model of breast cancer.
Properties of very uniform InxGa1−xAs single crystals grown by liquid-phase electroepitaxy (1990)

InxGa1−xAs (0&amp;lt;x&amp;lt;0.09) crystals with excellent compositional and luminescence efficiency uniformity were grown on (100) GaAs substrates by liquid-phase electroepitaxy. Compositional variations in these ternary alloys, ΔX, parallel and perpendicular to the growth direction, did not exceed 0.001 over a 1 in. diameter. These ternary bulk crystals are superior to comparable melt-grown materials.
Carbonic anhydrase inhibition. Insight into the characteristics of zonisamide, topiramate, and the sulfamide cognate of topiramate (2008)

Some useful therapeutic agents inhibit certain carbonic anhydrase (CA) isozymes to varying degrees. We have conducted enzyme kinetics studies in a 4-nitrophenyl acetate (4-NPA) hydrolysis assay with the marketed antiepileptic drugs topiramate (1) and zonisamide (2) to determine if their full inhibition of human CA-II and CA-I requires extended preincubation conditions. We found that neither 1 nor 2 requires appreciable preincubation with either enzyme to manifest full inhibitory activity. We also examined the sulfamide cognate of topiramate (3) to characterize its CA inhibitory activity, and confirmed that it is a very weak inhibitor, unlike 1 or 2. In a CO(2) hydration assay, 3 behaved as a very weak, partial inhibitor of CA-II and CA-I. We conclude that topiramate (1), zonisamide (2), and sulfamide 3 do not require extended exposure to human CA-I or CA-II to manifest full inhibitory activity (4-NPA assay).
The field-effect modified transistor: a high-responsivity photosensor (1972)

A new photosensing device that can be described as a field-effect modified bipolar transistor, has been developed. A novel technique of reducing the effective collector capacitance without reducing the total primary photocurrent provides for a decade improvement in responsivity for the FEM phototransistor operating in the charge-storage mode. Other applications of this device include a high noise-immunity inverter, a light intensity-to-frequency converter, and a simple semiconductor memory element. FEM transistors can be fabricated using the same processing schedule used for conventional bipolar transistors; no additional steps are required.
Synthesis of 2’-O-Methyl-5-alkynyl and alkenyl Substituted Uridine Derivatives to Screen for Inhibitors of HCV (2006)

Using Sonogashira and Heck coupling reactions, a series of 5-alkynyl and 5-alkenyl substituted 2′-O-methyluridine derivatives were synthesized in high yields.These compounds were used to screen for inhibitors of HCV, however none of them showed significant HCV inhibitory activity under 300 µM.
Quantifying Interactions between DNA Oligomers and Graphite Surface Using Single Molecule Force Spectroscopy (2012)

In single molecule force spectroscopy experiments, force probes chemically modified with synthetic, single-stranded DNA oligomers produced characteristic steady-state forces connected by abrupt steps between plateaus, as the probes moved away from a graphite substrate. The force plateaus represent peeling of a small number of polymer molecules from the flat surface. The final force jump in the retraction region of the force–distance curves can be attributed to a single DNA molecule detaching from the graphite surface. Previously, Manohar et al. (Nano Lett.2008, 8, 4365) reported the peeling forces of the pyrimidine oligomers as 85.3 ± 4.7 and 60.8 ± 5.5 pN for polythymine and polycytosine, respectively. We measured the force–distance curves for purine oligomers on a graphite surface and found the peeling forces to be 76.6 ± 3.0 and 66.4 ± 1.4 pN for polyadenine and polyguanine, respectively. Using a refined model for peeling a single freely jointed polymer chain from a frictionless substrate, we determined a ranking of the effective average binding energy per nucleotide for all four bases as T ≥ A > G ≥ C (11.3 ± 0.8, 9.9 ± 0.5, 8.3 ± 0.2, and 7.5 ± 0.8 kBT, respectively). The binding energy determined from the peeling force data did not scale with the size of the base. The distribution of peeling forces of polyguanine from the graphite surface was unusually broad in comparison to the other homopolymers, and often with inconsistent chain extensions, possibly indicating the presence of secondary structures (intra- or intermolecular) for this sequence.
Conceptual Development of Impact Overload Detection Devices for Tank Car Service (2007)

The objective of this project was to develop concepts for mechanical and electronic systems that can detect yard or in-train impacts that exceed design load or other reasonable limits on tank cars. The project team developed some mechanical and electronic systems for detecting overload impacts. For the mechanical system, detection of draft gear travel and closeout offered the best chances for success. For electronic systems, this project identified the following methods for overload impact detection: (1) Measuring a combination of draft gear travel and draft gear velocity (2) Measuring impact force using piezo-electric film (3) Using acceleration measurements for overload detection Although the team developed a fairly accurate way to estimate overload impacts through acceleration measurements, the commercially available unit tested did not function well enough to do the same. It is possible that additional development will help the unit perform better. Therefore, it is recommended that this option not be used for electronic overload detection until additional developments are made. It might be possible for the manufacturer of the tested unit to make adjustments in its functionality that might in turn enable the unit to perform better at threshold detection and transmission.
Automatically Detecting Integrity Violations in Database-Centric Applications (2017)

Database-centric applications (DCAs) are widely used by many companies and organizations to perform various control and analytical tasks using large databases. Real-world databases are described by complex schemas that oftentimes contain hundreds of tables consisting of thousands of attributes. However, when software engineers develop DCAs, they may write code that can inadvertently violate the integrity of these databases. Alternatively, business analysts and database administrators can also make errors that lead to integrity violations (semantic bugs). To detect these violations, stakeholders must create assertions that check the validity of the data in the rows of the database tables. Unfortunately, creating assertions is a manual, laborious and error-prone task. Thus, a fundamental problem of testing DCAs is how to find such semantic bugs automatically. We propose a novel solution, namely DACITE, that enables stakeholders to automatically obtain constraints that semantically relate database attributes and code statements using a combination of static analysis of the source code and associative rule mining of the databases. We rely on SAT-solvers to validate if a solution to the combined constraints exists and issue warnings on possible semantic bugs to stakeholders. We evaluated our approach on eight open-source DCAs and our results suggest that semantic bugs can be found automatically with high precision. The results of the study with developers show that warnings produced by DACITE are useful and enable them to find semantic bugs faster.
Biomimetic sensory feedback through peripheral nerve stimulation improves dexterous use of a bionic hand (2019)

We describe use of a bidirectional neuromyoelectric prosthetic hand that conveys biomimetic sensory feedback. Electromyographic recordings from residual arm muscles were decoded to provide independent and proportional control of a six-DOF prosthetic hand and wrist-the DEKA LUKE arm. Activation of contact sensors on the prosthesis resulted in intraneural microstimulation of residual sensory nerve fibers through chronically implanted Utah Slanted Electrode Arrays, thereby evoking tactile percepts on the phantom hand. With sensory feedback enabled, the participant exhibited greater precision in grip force and was better able to handle fragile objects. With active exploration, the participant was also able to distinguish between small and large objects and between soft and hard ones. When the sensory feedback was biomimetic-designed to mimic natural sensory signals-the participant was able to identify the objects significantly faster than with the use of traditional encoding algorithms that depended on only the present stimulus intensity. Thus, artificial touch can be sculpted by patterning the sensory feedback, and biologically inspired patterns elicit more interpretable and useful percepts.
<title>Novel nonimaging lens for photodiode receivers with a prescribed angular response and maximum integrated sensitivity</title> (2001)

12 In this work we present a novel optical lens that can be designed to provide any specified angular sensitivity to a receiver, illuminating the sensitive area almost isotropically. This lens, which has been designed in the framework of nonimaging optics, consists in a single dielectric piece that encapsulates the receiver (as conventional epoxy packages of photodiodes), whose interface with air is an aspheric refractive surface. Several trial products have been manufactured with different angular sensitivities (linear response, cos<SUP>-1</SUP>(theta) and cos<SUP>-2</SUP>(theta) ). The experimental results have shown that the trial devices have the specified angular sensitivity with +/- 5% accuracy.
Abstract 4600: Analysis of clonal evolution in cancer using whole exome sequence data reveals that subclonal driver mutations predict poor prognosis in chronic lymphocytic leukemia. (2013)

Abstract Clonal evolution is a key feature of cancer progression and relapse. We present a computational technique for analyzing whole exome sequence data to measure the fraction of cancer cells harboring each somatic mutation and resolve subclonal cell populations. We applied our methods to 149 chronic lymphocytic leukemia (CLL) samples to classify driver mutations as predominantly clonal or subclonal, corresponding to initiating and progression events in CLL evolution. We identified driver mutations as predominantly clonal (e.g., MYD88, trisomy 12 and del(13q)) or subclonal (e.g., SF3B1, TP53), corresponding to earlier and later events in CLL evolution. We sampled leukemia cells from 18 patients at two timepoints and found that 10 of 12 CLL cases treated with chemotherapy (but only 1 of 6 without treatment) underwent clonal evolution, predominantly involving subclones with driver mutations (e.g., SF3B1, TP53) that expanded over time. Furthermore, presence of a subclonal driver mutation was an independent risk factor for rapid disease progression. Our methods uncover patterns of clonal evolution in cancer, providing insights into its stepwise transformation and linking the presence of subclones with adverse clinical outcome. Because our methods require only whole exome sequence data, they are readily applicable to a large corpus of approximately 6,000 sequenced cancer exomes, and are ideally suited for application in future exome-based clinical cancer sequencing pipelines. We present additional application of our methods to analysis of prostate cancer, multiple myeloma, and glioblastoma multiforme datasets. Citation Format: Scott L. Carter, Dan-Avi Landau, Petar Stojanov, Aaron McKenna, Kristian Cibulskis, Michael S. Lawrence, Jens Lohr, Kristen Stevenson, Donna Neuberg, Matthew Meyerson, Catherine J. Wu, Gad Getz. Analysis of clonal evolution in cancer using whole exome sequence data reveals that subclonal driver mutations predict poor prognosis in chronic lymphocytic leukemia. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4600. doi:10.1158/1538-7445.AM2013-4600
Central hemodynamic monitoring in a woman with acute respiratory insufficiency after evacuation of a complete molar pregnancy. A case report. (2001)

The majority of case reports of pulmonary complications after evacuation of a hydatidiform mole were either presumed or documented to be due to trophoblastic pulmonary embolism. Thyrotoxicosis, fluid overload with dilutional anemia, preeclampsia, sepsis, hypoalbuminemia or a combination of these factors may be more common than trophoblastic embolization.
Investigation of Using Various Quantities of Steelmaking Waste for Scavenging Hydrogen Sulfide in Drilling Fluids (2022)

Effective in situ scavenging of hydrogen sulfide (H2S) while drilling a sour formation is critical for limiting the prevalent related impacts and safety hazards. Thus, it is necessary to develop a specialized additive that can selectively react with H2S and remove it without generating harmful byproducts or impairing drilling fluid performance. Additionally, waste management and utilization will transfer the waste from being an environmental and economic burden to a valuable commodity. Accordingly, we report herein the management of steelmaking waste through its utilization as a novel H2S scavenger for water-based drilling fluids, as well as the evaluation of the effects of the steelmaking waste dosage (1, 2, and 3 g) on the mud H2S scavenging capability and key properties. The H2S scavenging capacity of the waste-containing mud was investigated and compared to that of the base mud and fluids containing the commercial scavengers (triazine- and iron gluconate-based materials). In addition, the mud rheology, alkalinity, and filtering performance were studied in the presence and absence of the waste, and the findings were compared to those of commercial scavengers. This study showed that adding 1, 2, and 3 g of the steelmaking waste to the base drilling fluid significantly improved the H2S scavenging capacity by 105, 399, and 503%, respectively, while the triazine- and iron gluconate-based materials increased the capacity by 179 and 131%. Similarly, when the proportion of the steelmaking waste increased, the rheological parameters, comprising apparent viscosity, plastic viscosity, and yield point, slightly increased. The inclusion of the steelmaking waste reduced mud pH to 10.4, 9.8, and 8.5 with a content of 1, 2, and 3 g, respectively, compared to 11.0 for the base mud, 11.1 for triazine-based material, and 7.9 for iron gluconate-based scavenger. When 1 and 2 g of the steelmaking waste were added, the obtained filtrated liquid volume was preferably lower than the base mud and even the commercial scavengers-contained muds. As a result, 2 g of steelmaking waste could be added for enhanced mud performance. Nevertheless, higher amounts of the steelmaking waste could be used instead to achieve maximal H2S scavenging capability, with an extra alkalinity controller added to ensure attaining the practical recommended properties.
3-Watt blue source based on 914-nm Nd:YVO4 passively-Q-switched laser amplified in cladding-pumped Nd:fiber (2004)

A cladding-pumped Nd:silica fiber with a fundamental-mode cut-off near 1000 nm was used to build an amplifier with gain over a range near 920 nm. Pulses from an Nd:YVO4 passively Q-switched laser were amplified and then frequency doubled in LBO to produce blue with 3-W average power.
Closed-loop optical stimulation and recording system with GPU-based real-time spike sorting (2014)

Closed-loop brain computer interfaces are rapidly progressing due to their applications in fundamental neuroscience and prosthetics. For optogenetic experiments, the integration of optical stimulation and electrophysiological recordings is emerging as an imperative engineering research topic. Optical stimulation does not only bring the advantage of cell-type selectivity, but also provides an alternative solution to the electrical stimulation-induced artifacts, a challenge in closedloop architectures. A closed-loop system must identify the neuronal signals in real-time such that a strategy is selected immediately (within a few milliseconds) for delivering stimulation patterns. Real-time spike sorting poses important challenges especially when a large number of recording channels are involved. Here we present a prototype allowing simultaneous optical stimulation and electro-physiological recordings in a closed-loop manner. The prototype was implemented with online spike detection and classification capabilities for selective cell stimulation. Real-time spike sorting was achieved by computations with a high speed, low cost graphic processing unit (GPU). We have successfully demonstrated the closed-loop operation, i.e. optical stimulation in vivo based on spike detection from 8 tetrodes (32 channels). The performance of GPU computation in spike sorting for different channel numbers and signal lengths was also investigated.