gebhart/patrepeval huggingface dataset:
Fundamental Considerations for GeneticallyGuided Pain Management with Opioids Basedon CYP2D6 and OPRM1 Polymorphisms (2018)

Background: A major challenge for effective pharmacotherapy in pain management is to provide the drug best suited to the patient’s innate characteristics. Objective: The article illustrates pharmacogenetic principles to optimize treatments for patients and increase the likelihood of pain relief without dependence. Genetic variances are particularly relevant to opioid drugs used in pain control, and can now be harvested for predictive clinical decision support. Study Design: Clinically actionable polymorphisms in CYP2D6 (cytochrome p450 2D6) and OPRM1 (μ1 opioid receptor), the most important gene coding, respectively, for a metabolizing enzyme and receptor for opioids are reviewed, and functional effects described. Methods: Risk of dysfunction is calculated from the frequency of the alleles with null function for CYP2D6, and from the low function polymorphism for OPRM1. Integration of genetic variability was performed for 9 combinatorial scenarios for CYP2D6 and OPRM1. Each combination was quantified in frequency and classified for clinical impact. A rational and pharmacological basis for personalized pain management based on pharmacokinetic and pharmacodynamic modeling is extracted from the frequency of the combinations. Results: Patients can be classified in 3 broad risk categories for opioid side effects and dependence. Patients at high-risk with dysfunctional CYP2D6 or OPRM1 account for ~14% of the population and are best managed with non-opioids. Patients at medium risk with subnormal CYP2D6 or OPRM1 account for ~48% of the population and can be managed with dose monitoring. Patients at low risk with functional CYP2D6 and OPRM1 account for ~38% of the population and should be availed to opioid therapy. Limitations: Heuristic clinical decision support considerations are not validated yet by deployment in large clinical practices. Environmental modifiers such as other drugs and dietary supplements interact with innate characteristics to modify the genetic predictions. Conclusion: Through clinical decision support interpreting the genotyping data, drug choices and doses can then be tailored to provide safe and effective therapy for individual patients. This precision affords personalized medicine to be practiced in pain treatment. Genetic factors could help determine why some patients seem more vulnerable than others to opioid side effects and dependence. Key words: Pain management, opioids, CYP2D6, OPRM1, clinical decision support, pharmacokinetics, pharmacodynamics, pharmacogenetics, combinatorial genotypes
Designing New Protoporphyrinogen Oxidase-Inhibitors Carrying Potential Side Chain Isosteres to Enhance Crop Safety and Spectrum of Activity (2023)

There are several methods to control weeds, which impose particular challenges for farmers in all parts of the world, although applying small molecular compounds still remains the most efficient technology to date. However, plants can evolve to become resistant toward active ingredients which is also the case for protoporphyrinogen oxidase (PPO) inhibitors, a class of highly effective herbicides in use for more than 50 years. Hence, it is essential to continuously discover and develop new herbicidal PPO inhibitors with enhanced intrinsic activity, an improved resistance profile, enhanced crop safety, favorable physicochemical properties, and a clean toxicological profile. By modifying structural key features from known PPO inhibitors such as tiafenacil, inspired by isostere and mix&match concepts in combination with modeling investigations based on a wild-type <i>Amaranthus</i> crystal structure, we have found new promising lead structures showing strong activity <i>in vitro</i> and <i>in vivo</i> against several notorious dicotyledon and monocotyledon weeds with emerging resistance (e.g., <i>Amaranthus palmeri</i>, <i>Amaranthus tuberculatus</i>, <i>Lolium rigidum</i>, and <i>Alopecurus myosuroides</i>). While several phenyl uracils carrying an isoxazoline motif in their thio-linked side chain showed promising resistance-breaking potential against different <i>Amaranthus</i> species, introducing a thioacrylamide side chain afforded outstanding efficacy against resistant grass weeds.
Measurement of the top-quark mass in the fully hadronic decay channel from ATLAS data at $$\sqrt{s}=7\mathrm{\,TeV}$$ s = 7 TeV (2015)

The mass of the top quark is measured in a data set corresponding to 4.6 [Formula: see text] of proton-proton collisions with centre-of-mass energy [Formula: see text] TeV collected by the ATLAS detector at the LHC. Events consistent with hadronic decays of top-antitop quark pairs with at least six jets in the final state are selected. The substantial background from multijet production is modelled with data-driven methods that utilise the number of identified [Formula: see text]-quark jets and the transverse momentum of the sixth leading jet, which have minimal correlation. The top-quark mass is obtained from template fits to the ratio of three-jet to dijet mass. The three-jet mass is calculated from the three jets produced in a top-quark decay. Using these three jets the dijet mass is obtained from the two jets produced in the [Formula: see text] boson decay. The top-quark mass obtained from this fit is thus less sensitive to the uncertainty in the energy measurement of the jets. A binned likelihood fit yields a top-quark mass of [Formula: see text].
SERUM COBALT AND CHROMIUM LEVELS IN PATIENTS WITH METAL-ON-METAL RESURFACING HIP PROSTHESES (2008)

Purpose: The purpose of this study was to monitor serum cobalt (Co) and chromium (Cr) levels in patients after metal-on-metal resurfacing hip arthroplasty with the Cormet 2000® prosthesis, and to evaluate the effect of patient characteristics, prosthesis characteristics, clinical and radiographic measures on metal levels. Methods: Serum Co and Cr levels were determined in 32 patients with Cormet resurfacing prostheses at 0.5, 1 and 2 years postoperatively using ICP-MS and are reported as g/L. Control levels were measured in 20 patients without implants. Results: Medium Co and Cr were 0.21 and 0.16 in controls without implants. Medium Co at 6 months (2.65), 1 year (3.62) and 2 years (2.80), and Cr at 6 months (3.74), 1 year (4.73) and 2 years (4.68) were signifi-cantly increased in the Cormet group when compared to control levels (p Conclusions: Significantly increased levels of cobalt and chromium were released from Cormet 2000 articulations at all time points. Excessive cup abduction was associated with markedly elevated ion levels indicating that accurate cup placement is an important consideration in resurfacing arthroplasty. The significantly increased trace metal levels following resurfacing with the Cormet prosthesis is a concern and warrants further monitoring.
A High-Speed Silicon Modulator Based on an Embedded-Ring-Resonator Structure (2009)

An embedded-ring-based modulator is proposed for 40-Gb/s signal generation, with compact chip-size and enhanced tolerance to cavity loss and fabrication-induced coupling variation. The modulated signal with negative chirp exhibits penalty-free transmission of 6.5 km, with a drive voltage lower by 40%.
Regulation of the jun B Gene by v- src (1992)

The proteins encoded by cellular and viral src genes are believed to be involved in the transmission of mitogenic signals, the nuclear recipients of which are largely unknown. In this work, we report that four different v-src-transformed cell lines from three different species possess elevated levels of junB transcripts. Transient expression of junB promoter-chloramphenicol acetyltransferase constructs in NIH 3T3 cells was used to demonstrate that the increase in junB transcripts was specifically associated with v-src expression and could not be recapitulated with a c-src, v-H-ras, or v-raf expression vector. Deletion mutants were used to localize the v-src-responsive region in the junB promoter to a 121-nucleotide region encompassing the CCAAT and TATAA elements. This region is distinct from one in the 5' untranslated region of the junB gene which is required to maintain its high-level basal expression. Point mutagenesis of the junB TATAA box completely abolished v-src responsiveness, suggesting that proteins which bind to this element are modified by src transformation. Several v-src and c-src mutants were used to demonstrate that elevated tyrosine kinase activity of src proteins is required for the observed effects on junB expression. Finally, homology between the TATAA box regions of junB and the unrelated but src-responsive gene 9E3/CEF-4 suggests that modulation of gene activity through proteins which bind to this region may be a recurrent, although not exclusive, theme in src transforming action. Our results suggest that src proteins may modulate some nuclear effectors through pathways not involving cellular ras or raf gene products.
A Study of Ceramic Bearing for Vertical Pumps : Friction Coefficients of Submersible Bearings in Air and Water (1990)

Friction coefficients in air and water of various sleeve-type submersible bearings for vertical pumps were investigated with respect to a variety of bearing materials including SiC-sintered ceramics, WC-cemented carbides, self-fluxing alloys and conventional bearing materials such as rubber, resins, PTFE # and soft sintered alloys. The test equipment simulated the frictional conditions of actual vertical pump shafts, that is, the shaft of the testing apparatus precessed against the bearing. The results showed that when silicon carbide was used as a stationary bearing, lower friction coefficients could be obtained, regardless of the material used for the rotating sleeve. In slurries, the abrasive particles adversely affected the friction coefficients of conventional bearings, however, owing to superior hardness, ceramic bearings maintained low friction coefficients. In air, a combination of silicon carbide and tungsten carbide displayed a low friction coefficient. Also, the results confirmed that dry starting of vertical pumps is also possible when using this combination of materials.
Fuzzy-Neural Network Traffic Prediction Framework with Wavelet Decomposition (2003)

The framework of a traffic prediction model that could eliminate noise caused by random travel conditions is investigated. This model also can quantitatively calculate the influence of special factors. The framework combined several artificial intelligence technologies, such as wavelet transform, neural network, and fuzzy logic. The wavelet denoising method is emphasized and analyzed.
<title>Front-illuminated full-frame charge-coupled-device image sensor achieves 85% peak quantum efficiency</title> (2002)

A high sensitivity front-illuminated charge-coupled device (CCD) technology has been developed by combining the transparent gate technology introduced by Kodak in 1999 with the microlens technology usually employed on interline CCDs. In this new architecture, the microlens is used to focus the incoming light onto the more transparent of the two electrodes. The new sensors offer significant increases in quantum efficiency while maintaining the performance advantages of front-illuminated full-frame CCDs including 3 pA/cm<SUP>2</SUP> typical dark current at 25 degree(s)C, and 55 ke full well in a 6.8 micrometers pixel.
On Backside Probing Techniques and Their Emerging Security Threats (2022)

Various probing methodologies have been developed in the semiconductor industry to perform failure analysis of an integrated circuit. However, these probing techniques can be misused to launch security attacks and extract sensitive information from the hardware. In this article, the authors provide an overview of such attacks and present probable countermeasures and their limitations.
Hepatic targeting of the centrally active cannabinoid 1 receptor (CB1R) blocker rimonabant via PLGA nanoparticles for treating fatty liver disease and diabetes (2022)

Over-activation of the endocannabinoid/CB<sub>1</sub>R system is a hallmark feature of obesity and its related comorbidities, most notably type 2 diabetes (T2D), and non-alcoholic fatty liver disease (NAFLD). Although the use of drugs that widely block the CB<sub>1</sub>R was found to be highly effective in treating all metabolic abnormalities associated with obesity, they are no longer considered a valid therapeutic option due to their adverse neuropsychiatric side effects. Here, we describe a novel nanotechnology-based drug delivery system for repurposing the abandoned first-in-class global CB<sub>1</sub>R antagonist, rimonabant, by encapsulating it in polymeric nanoparticles (NPs) for effective hepatic targeting of CB<sub>1</sub>Rs, enabling effective treatment of NAFLD and T2D. Rimonabant-encapsulated NPs (Rimo-NPs) were mainly distributed in the liver, spleen, and kidney, and only negligible marginal levels of rimonabant were found in the brain of mice treated by iv/ip administration. In contrast to freely administered rimonabant treatment, no CNS-mediated behavioral activities were detected in animals treated with Rimo-NPs. Chronic treatment of diet-induced obese mice with Rimo-NPs resulted in reduced hepatic steatosis and liver injury as well as enhanced insulin sensitivity, which were associated with enhanced cellular uptake of the formulation into hepatocytes. Collectively, we successfully developed a method of encapsulating the centrally acting CB<sub>1</sub>R blocker in NPs with desired physicochemical properties. This novel drug delivery system allows hepatic targeting of rimonabant to restore the metabolic advantages of blocking CB<sub>1</sub>R in peripheral tissues, especially in the liver, without the negative CB<sub>1</sub>R-mediated neuropsychiatric side effects.
A Flock of Birds (2012)

In this paper we describe A Flock of Birds, an interactive, robotic origami art installation. The art installation explores folding paper as a fusion of input, output and computation while simultaneously providing its audience with a fun and exciting experience.
Polygonophenone, the First MEM-Substituted Natural Product, from Polygonum maritimum (2009)

An unprecedented natural acetophenone, polygonophenone (1), and a new resorcinol, polygonocinol (2), were isolated from the dichloromethane and methanol extracts of Polygonum maritimum and identified as 2-hydroxy-4-[(2-methoxyethoxy)methoxy] acetophenone and 2-methyl-5-nonadecylresorcinol, respectively. In addition, 11 known compounds were identified, namely, the sesquiterpenoid (+)-8-hydroxycalamene, four ferulic acid esters (tetracosyl, hexacosyl, octacosyl, and triacontyl ferulate), the arylpropane broussonin B, the flavonoids quercetin, quercitrin, and (+)-catechin, the hydroquinone glucoside isotachioside, and beta-sitosterol. The structures of the new compounds were elucidated on the basis of their NMR and MS data. It is noteworthy that polygonophenone (1) is the first naturally methoxyethoxymethyl (MEM)-substituted natural product, and its isolation gives support for the use of MEM protection in biomimetic synthetic schemes.
Development of Transceiver LSI with On-chip Isolator and Regulator (2004)

The demand for effective production control and flexible manufacturing lines is increasing placing many kinds of products on the market promptly according to various needs. Therefore field networks that connect line controllers and field equipment like sensors and actuators have been spreading instead of separate conventional electrical wiring. We describe the development of a one-chip transceiver LSI for communication interface. High-voltage devices with SOI substrate and monolithic isolator technology were developed. Then, a 1 MHz transceiver circuit and discrete devices, including 1 kV isolators, and a 5 V switching regulator were integrated onto the one-chip that measures 4.5 mm x 4.3 mm. An LSI with a monolithic isolator and a switching regulator can provide a small, low-consumption communication interface for the DeviceNet of a representative field network. Consequently, the mounting space and power consumption of the interface were reduced by 50% and 80%, respectively. We confirmed that an interface circuit employing the LSI in a network control system for air conditioners had the same transmission waveforms as that of a conventional interface circuit.
Utilization of a Graphite Foam Radiator on a Natural Gas Engine-Driven Heat Pump (2002)

A natural gas engine-driven heat pump was outfitted with a graphite foam radiator to demonstrate its thermal efficiency and compare it with that of a conventional radiator. A sequence of tests was performed with the graphite foam radiator operating in series with the standard aluminum radiator. Most aluminum air-to-water radiators exhibit an overall heat transfer coefficient up to 100 W/(m2·K). Laboratory experiments have demonstrated that a graphite foam radiator can achieve an overall heat transfer coefficient up to an order of magnitude larger. The mesophase pitch derived graphite foam is a material that offers excellent thermal management capability. The foam has an accessible surface area of 4 m2/g and an open cell structure with graphitic ligaments aligned parallel to the cell walls, giving it an overall bulk thermal conductivity of up to 175 W/(m·K). The bulk thermal conductivity of aluminum is 180 W/(m·K). The density of the graphite foam is a fifth of that of aluminum and its thermal diffusivity is three times greater than aluminum. These properties allow the graphite foam to be utilized in radiator, or any other heat exchanger, designs that are more efficient than conventional radiators. A graphite foam radiator designed to reject a given amount of heat will be smaller in size, weigh less, require less cooling air, and be quicker at removing heat than a conventional aluminum radiator.
Role of copper-phthalocyanine in multilayer organic LEDs based on small molecules (2003)

The role of copper-phthalocyanine (CuPc) has intermediate layer between the anode and the hole-transport layer in multilayer organic light-emitting devices (OLEDs) was studied. The OLEDs consisted of CuPc, N,N'-di(naphtalene-1-yl)-N,N'-diphenyl-benzidine (NPB) as hole-transport layer and tris-(8-hydroxyquinolinato)-aluminum (Alq<sub>3</sub>) as electron-transport and emitting layer sandwiched between a high-work-function metal and a semi-transparent calcium cathode. A combinatorial approach that allows the simultaneous fabrication of 10 x 10 individual devices was used to vary the thicknesses of CuPc and NPB over a broad range from 0 to 45 nm and from 10 to 100 nm, respectively. Systematic current-voltage and impedance measurements revealed a redistribution of the internal electric field of the CuPc/NPB/Alq<sub>3</sub> three-layer structure compared to that of the NPB/Alq<sub>3</sub> bilayer OLED. It was demonstrated that the hole transport is mainly controlled by the internal energy barrier at the CuPc/NPB interface. The fact that CuPc strongly impedes hole injection into NPB also has a significant impact on the frequency-dependent behavior of the capacitance, especially the cutoff frequency.
Local transformation of ZIF-8 powders and coatings into ZnO nanorods for photocatalytic application (2013)

Silver nitrate induces spontaneous room temperature transformation of ZIF-8 into a composite of ZnO nanorods embedded in a ZIF-8 matrix. This first example of reverse transformation of ZIF-8 into ZnO is a convenient method for generating fixed ZnO nanoparticles in powders as well as films and coatings. The fabricated ZnO nanorod@ZIF-8 is photocatalytically active.
Predictive value of cytoplasmic granulation patterns during in vitro fertilization in metaphase II oocytes: Part I, poor-prognosis patients (2021)

We, for the first time, demonstrated that 4 distinct cytoplasmic granulation patterns in metaphase II oocytes had, largely independent of age and other variables, a predictive value for fertilization, pregnancy, and live birth outcomes in in vitro fertilization cycles of poor-prognosis patients. These data suggest that upstream ooplasm granulation patterns deserve closer attention in terms of embryo selection.
Ectopic expression of myc or myn down-regulates immunoglobulin transcription. (1994)

Co-transfection of expression vectors for c-myc or myn down-regulated the expression from a reporter plasmid containing the chloramphenicol-acetyl-transferase (CAT) gene, under the control of an immunoglobulin kappa promoter and the immunoglobulin heavy-chain enhancer. The effect was dose-dependent and an additive effect was seen when both expression vectors were transfected simultaneously. Deletion mutants lacking the leucine zipper region of c-myc were unable to down-regulate the transcription from the reporter construct. Reporter genes where the immunoglobulin enhancer had been exchanged with a SV40 enhancer or an immunoglobulin minimal enhancer were still down-regulated by a cotransfection with c-myc expression vectors. A minimal promoter containing an octamer motif responded to myc expression while a minimal promoter containing a SP1 motif did not. No direct interactions between myc, myn and Oct proteins could be detected either by band-shift analysis, or by co-translation in vitro followed by precipitation with SP6 kappa promoter bound to magnetic carriers. Furthermore, B cells from mice transgenic for myc showed aberrant expression of transcription factors.
Versatile RNA-sensing transcriptional regulators for engineering genetic networks (2011)

The widespread natural ability of RNA to sense small molecules and regulate genes has become an important tool for synthetic biology in applications as diverse as environmental sensing and metabolic engineering. Previous work in RNA synthetic biology has engineered RNA mechanisms that independently regulate multiple targets and integrate regulatory signals. However, intracellular regulatory networks built with these systems have required proteins to propagate regulatory signals. In this work, we remove this requirement and expand the RNA synthetic biology toolkit by engineering three unique features of the plasmid pT181 antisense-RNA-mediated transcription attenuation mechanism. First, because the antisense RNA mechanism relies on RNA-RNA interactions, we show how the specificity of the natural system can be engineered to create variants that independently regulate multiple targets in the same cell. Second, because the pT181 mechanism controls transcription, we show how independently acting variants can be configured in tandem to integrate regulatory signals and perform genetic logic. Finally, because both the input and output of the attenuator is RNA, we show how these variants can be configured to directly propagate RNA regulatory signals by constructing an RNA-meditated transcriptional cascade. The combination of these three features within a single RNA-based regulatory mechanism has the potential to simplify the design and construction of genetic networks by directly propagating signals as RNA molecules.