gebhart/patrepeval huggingface dataset:
Development of a genome-scale metabolic model of Clostridium thermocellum and its applications for integration of multi-omics datasets and strain design (2020)

Abstract Solving environmental and social challenges such as climate change requires a shift from our current non-renewable manufacturing model to a sustainable bioeconomy. To lower carbon emissions in the production of fuels and chemicals, plant biomass feedstocks can replace petroleum using microorganisms as catalysts. The anaerobic thermophile Clostridium thermocellum is a promising bacterium for bioconversion due to its capability to efficiently degrade untreated lignocellulosic biomass. However, the complex metabolism of C. thermocellum is not fully understood, hindering metabolic engineering to achieve high titers, rates, and yields of targeted molecules. In this study, we developed an updated genome-scale metabolic model of C. thermocellum that accounts for recent metabolic findings, has improved prediction accuracy, and is standard-conformant to ensure easy reproducibility. We illustrated two applications of the developed model. We first formulated a multi-omics integration protocol and used it to understand redox metabolism and potential bottlenecks in biofuel (e.g., ethanol) production in C. thermocellum . Second, we used the metabolic model to design modular cells for efficient production of alcohols and esters with broad applications as flavors, fragrances, solvents, and fuels. The proposed designs not only feature intuitive push-and-pull metabolic engineering strategies, but also novel manipulations around important central metabolic branch-points. We anticipate the developed genome-scale metabolic model will provide a useful tool for system analysis of C. thermocellum metabolism to fundamentally understand its physiology and guide metabolic engineering strategies to rapidly generate modular production strains for effective biosynthesis of biofuels and biochemicals from lignocellulosic biomass.
Inhibition of the placental growth factor decreases burden of cholangiocarcinoma and hepatocellular carcinoma in a transgenic mouse model (2012)

The use of monoclonal antibodies targeting PlGF could thus offer a potential systemic treatment for patients who suffer from primary liver tumours.
Elliptical Pipette Generated Large Microdroplets for POC Visual ddPCR Quantification of Low Viral Load (2021)

Rapid point-of-care (POC) quantification of low virus RNA load would significantly reduce the turn-around time for the PCR test and help contain a fast-spreading epidemic. Herein, we report a droplet digital PCR (ddPCR) platform that can achieve this sensitivity and rapidity without bulky lab-bound equipment. The key technology is a flattened pipette tip with an elliptical cross-section, which extends a high aspect-ratio microfluidic chip design to pipette scale, for rapid (<5 min) generation of several thousand monodispersed droplets ∼150 to 350 μm in size with a CV of ∼2.3%. A block copolymer surfactant (polyoxyalkylene F127) is used to stabilize these large droplets in oil during thermal cycling. At this droplet size and number, positive droplets can be counted by eye or imaged by a smartphone with appropriate illumination/filtering to accurately quantify up to 100 target copies. We demonstrate with 2019 nCoV-PCR assay LODs of 3.8 copies per 20 μL of sample and a dynamic range of 4-100 copies. The ddPCR platform is shown to be inhibitor resistant with spiked saliva samples, suggesting RNA extraction may not be necessary. It represents a rapid 1.5-h POC quantitative PCR test that requires just a pipette equipped with elliptical pipette tip, a commercial portable thermal cycler, a smartphone, and a portable trans-illuminator, without bulky and expensive micropumps and optical detectors that prevent POC application.
An Axiomatic Theory of Fairness (2009)

The tradeoff between fairness and throughput has been widely observed in network analysis and protocol design. Despite many existing fairness metrics (from simple ones like Jain’s index to more complex ones like α-fair utility), the meaning of fairness is largely based on problemoriented interpretations and judgments, with no well-established framework. To tackle this challenging problem, we presented a set of five axioms for fairness, and showed that a wide range of fairness measures satisfying the axioms can be constructed in a unifying framework. The construction incorporates as special cases many existing metrics, such as Jain’s index, entropy, and α-fair utility, and also reveals a new family of fairness measures. Our axiomatic theory illuminates many issues in network resource allocation research, among which is a novel tradeoff between efficiency and fairness. The parallelism of our framework and well-known theories in other fields, e.g., Renyi Entropy, Lorenz Curve, Nash Bargaining Solutions, and Rawls’ Theory of Justice, greatly sharpens our understanding of the notion of fairness.
Byte-focal: a practical load balanced switch (2005)

Recently, a novel switch architecture, the load balanced (LB) switch proposed by C.S. Chang et al. (2000, 2002) opened a new avenue for designing a large-capacity packet switch. The load balanced switch consists of two stages. First, a load-balancing stage spreads arriving packets equally among all linecards. Then, a forwarding stage transfers packets from the linecards to their final output destination. The load balanced switch does not need any centralized scheduler and can achieve 100% throughput under a broad class of traffic distributions. However, the load balanced switch may cause packets at the output port to be out of sequence. Several schemes have been proposed to tackle the out-of-sequence problem of the load balanced switch. However, they are either too complex to implement, or introduce a large additional delay. In this paper, we present a practical load balanced switch, called the byte-focal switch, which uses packet-by-packet scheduling to significantly improve the delay performance over switches of comparable complexity.
Screening for gastric cancer using exhaled breath samples (2019)

This first validation of a nanomaterial sensor array-based algorithm for gastric cancer detection from breath samples in a large screening population supports the potential of this technology for the early detection of gastric cancer.
Continuous Intravesical Lidocaine Treatment for Interstitial Cystitis/Bladder Pain Syndrome: Safety and Efficacy of a New Drug Delivery Device (2012)

Limited treatment options exist for patients who suffer from a painful bladder condition known as interstitial cystitis/bladder pain syndrome (IC/BPS). Whether given systemically (orally) or by short-duration (1 to 2 hours) exposure via intravesical instillation, therapeutic agents have exhibited poor efficacy because their concentrations in the bladder are low. A previous attempt to develop a drug delivery device for use in the bladder was unsuccessful, likely as a result of poor tolerability. A continuous lidocaine-releasing intravesical system (LiRIS) was designed to be retained in the bladder and release therapeutic amounts of the drug into urine over a period of 2 weeks. The device was tested in healthy volunteers and IC/BPS patients and was found to be well tolerated in both subject groups because of its small size and freedom of movement within the bladder. The 16 women with IC/BPS who were enrolled in the study met the National Institute of Diabetes and Digestive and Kidney Diseases criteria for bladder hemorrhages or Hunner's lesions. Subjects received either LiRIS 200 mg or LiRIS 650 mg for 2 weeks. Safety, efficacy, cystoscopic appearance of the bladder, and limited pharmacokinetic data were collected. Both doses were well tolerated, and clinically meaningful reductions were seen in pain, urgency, voiding frequency, and disease questionnaires. Cystoscopic examinations showed improvement on day 14 (day of removal) compared with day 1, including resolution of Hunner's lesions in five of six subjects with baseline lesions. Global response assessment showed an overall responder rate of 64% at day 14 and a sustained overall responder rate of 64% 2 weeks later. Extended follow-up suggests that the reduction in pain was maintained for several months after the device was removed.
Asymptotic series solution of singularly perturbed free time optimal control problems (1975)

Optimal control of singularly perturbed systems with free terminal time is considered. A reduction in system order is achieved by perturbing a small scalar parameter in the system equations. Using the solution of this reduced order problem, an asymptotic series approximation method is presented for obtaining the solution to the complete problem. A backward sweep approach on the reduced model is used in determining the asymptotic series terms. Numerical results on an example show the applicability of the method.
Figure S4 from The Transcriptional Regulator Sin3A Contributes to the Oncogenic Potential of STAT3 (2023)

&lt;p&gt;Data describe the effect of Resveratrol inhibits STAT3 acetylation and binding to Sin3A in LIF-stimulated cells.&lt;/p&gt;
Defects in electron-irradiated Si studied by positron-lifetime spectroscopy (1998)

Differently doped and undoped silicon was irradiated with electrons to study the formation of nonequilibrium defects and their annealing behavior. The annealing curves, measured by positron lifetime and also partly by the shape parameters of the Doppler-broadened annihilation line, depend strongly on the doping concentration and the oxygen content. In addition, temperature-dependent positron-lifetime measurements starting at 15 K were performed after low-temperature and room-temperature irradiation with different doses and in different annealing states. Shallow positron traps were detected for all conductivity types of irradiated Si. However, the concentration of shallow traps depends on the crystal-growth procedure. Electron-irradiated Czochralski-grown samples contain a higher number of shallow traps than electron-irradiated floating-zone-grown material. Due to the different concentrations of oxygen in these differently grown Si, we conclude that the oxygen atoms are a part of these traps. A possible candidate is the irradiation-induced A center. Correlated infrared-absorption investigations were carried out to support this interpretation.
The GSK Bioanalytical Hub Model in Bioanalysis: Maximizing the Synergies of Co-Locating Various Platforms in Support of Regulated and Nonregulated Study end Points (2023)

The term "bioanalytical" encompasses a much greater breadth of analytical deliverables than ever before. Circulating drug concentration data are complemented by experimental evidence of drug in biophase, immunogenicity, target engagement and subsequent pathway modulation. Many bioanalytical assays bridge the traditional divide across discovery and development. Our approach is the Bioanalytical Hub model bringing together a wide breadth of bioanalytical support (GxP and non-GxP), multiple end points (pharmacokinetics, anti-drug antibodies and biomarkers) and analytical platforms (LC/MS, immunoassay, flow cytometry, genomics, immunohistochemistry) onto a common lab footprint. This maximizes instrument utilization, facilitates workforce agility and enhances data interpretation capability while reducing the number of hand-offs as assays evolve from their origins as exploratory end points to fully characterized to support primary and secondary end points.
Iminosugars as Possible Broad Spectrum anti Hepatitis Virus Agents: The Glucovirs and Alkovirs (2001)

Glucosidases in the endoplasmic reticulum (ER) mediate the first step in processing N-linked oligosaccharides. Recent evidence suggests that morphogenesis and secretion of members of the hepatitis B and flavivirus families are more dependent on these enzymes than are most host glycoproteins. Thus, it is possible that glucosidase inhibitors can be designed that are safe and selective for the treatment of hepatitis B and possibly C (since hepatitis C virus is a member of the flavivirus family), making them broad spectrum with respect to hepatitis viruses. Numerous pharmacological and genetic dissections support the notion that glucosidase inhibition can have an antiviral effect, and imino sugars that competitively inhibit ER glucosidases have been proposed as anti-hepatitis drug candidates. We call this family of compounds 'glucovirs'. Recently, however, alkylated imino sugars that retain substantial antiviral activity but lack glucosidase inhibitory activity have been described. These compounds are called 'alkovirs' and their mechanism of action is unknown. This review considers the rationale of the glucovir and alkovir approach to the treatment of hepatitis B and C.
Aircraft EMP isolation study (1980)

This report presents the results of a preliminary study into methods for electrically isolating the E-4B, the EC-135, and the EC-130 aircraft during EMP tests where the aircraft under test is directly driven by a high-voltage pulser.
Reconstructing dense light field from a multi-focus images array (2005)

The work presents a novel method for synthesizing a novel view from two sets of differently focused images taken by a sparse camera array for a scene of two approximately constant depths. The proposed method consists of two steps. The first step is a view interpolation to reconstruct an all-focused dense light field of the scene. The second step is to synthesize a novel view by a light-field rendering technique from the reconstructed dense light field. The view interpolation can be achieved simply by linear filters that are designed to convert defocus effects to parallax effects without estimating the depth map of the scene. The proposed method can effectively create a dense array of pin-hole cameras (i.e., all-focused images), so that the final novel view is better than traditional method using a sparse array of cameras. Experimental results on real images from four aligned cameras are shown.
Stimulant Drugs of Abuse and Cardiac Arrhythmias (2021)

Nonmedical use of prescription and nonprescription drugs is a worldwide epidemic, rapidly growing in magnitude with deaths because of overdose and chronic use. A vast majority of these drugs are stimulants that have various effects on the cardiovascular system including the cardiac rhythm. Drugs, like cocaine and methamphetamine, have measured effects on the conduction system and through several direct and indirect pathways, utilizing multiple second messenger systems, change the structural and electrical substrate of the heart, thereby promoting cardiac dysrhythmias. Substituted amphetamines and cocaine affect the expression and activation kinetics of multiple ion channels and calcium signaling proteins resulting in EKG changes, and atrial and ventricular brady and tachyarrhythmias. Preexisting conditions cause substrate changes in the heart, which decrease the threshold for such drug-induced cardiac arrhythmias. The treatment of cardiac arrhythmias in patients who take drugs of abuse may be specialized and will require an understanding of the unique underlying mechanisms and necessitates a multidisciplinary approach. The use of primary or secondary prevention defibrillators in drug abusers with chronic systolic heart failure is both sensitive and controversial. This review provides a broad overview of cardiac arrhythmias associated with stimulant substance abuse and their management.
Sonochemical Synthesis of Layered and Hexagonal Yttrium−Zirconium Oxides (2001)

Layered and hexagonal mesostructures of yttrium−zirconium oxides have been synthesized using a sonochemical method. Sodium dodecyl sulfate is used as the templating agent and urea as the precipitant agent. There is a transformation from layered to hexagonal mesostructure with a prolonged sonication time of 6 h. The surface areas of the sample with hexagonal mesostructure before and after extraction with sodium acetate were 98 and 245 m2/g, respectively. Low-angle X-ray diffraction, transmission electron microscopy, Brunauer−Emmett−Teller, energy-dispersive X-ray analysis, thermogravimetric analysis, and Fourier transform infrared were used to characterize these mesostructures.
Resonant InGaAs Detectors and Emitters for Passive and Active Imaging Application (2022)

In this work, we design an InGaAs avalanche photodiode (APD) with a higher photocurrent to dark current ratio than a conventional APD. The improvement is based on optical confinement in an optical resonator, which increases the optical intensity in the detector volume and thus its quantum efficiency. With optical confinement, the absorbing layer can be 20 times thinner than the conventional APD, reducing the intrinsic generation-recombination dark current by the same amount and still be able to produce 90.9% of the photocurrent. The photocurrent to intrinsic dark current ratio can thus be increased theoretically by 18.2 times in concomitant with a lower operating voltage. Higher photocurrent can also be obtained using a thicker absorber. Besides APDs, the optical resonator structure can also be applied to p-i-n photodiodes for similar improvement. To further increase the detection sensitivity, we design an efficient InGaAsP light emitting diode (LED) having a similar resonator geometry. The resonator geometry enables more collimated emission and increases the optical power theoretically by more than 36 times compared to a conventional LED. Integrating the resonant APD and LED together will yield a powerful SWIR transceiver for various low light, LIDAR, and 3-dimensional imaging applications.
Endothelial cell modulation of bone marrow stromal cell osteogenic potential (2005)

In the context of bone development and regeneration, the intimate association of the vascular endothelium with osteogenic cells suggests that endothelial cells (ECs) may directly regulate the differentiation of osteoprogenitor cells. To investigate this question, bone marrow stromal cells (BMSCs) were cultured: in the presence of EC-conditioned medium, on EC extracellular matrix, and in EC cocultures with and without cell contact. RNA and protein were isolated from ECs and analyzed by reverse transcriptase-polymerase chain reaction and Western blotting, respectively, for expression of bone morphogenetic protein 2 (BMP-2). In animal studies, BMSCs and ECs were cotransplanted into severe combined immunodeficient mice on biodegradable polymer matrices, and histomorphometric analysis was performed to determine the extent of new bone and blood vessel formation. ECs significantly increased BMSC osteogenic differentiation in vitro only when cultured in direct contact. ECs expressed BMP-2, and experiments employing interfering RNA inhibition confirmed its production as contributing to the increased BMSC osteogenic differentiation. In vivo, cotransplantation of ECs with BMSCs resulted in greater bone formation than did transplantation of BMSCs alone. These data suggest that ECs function not only to form the microvasculature that delivers nutrients to developing bone but also to modulate the differentiation of osteoprogenitor cells in vitro and in vivo.
Suboptimal Inspiratory Flow Rates With Passive Dry Powder Inhalers: Big Issue or Overstated Problem? (2022)

The premise that subjects must overcome the internal resistance of a DPI to achieve a peak inspiratory flow rate of 60 L min-1 12 for effective powder fluidization and deagglomeration of inhaled bronchodilators for the treatment of COPD is fundamentally incorrect. This reliance on a 60 L min-1 13 14 minimum flow leads to a significant overestimate of the percentage of patients with suboptimal flow 15 rates, and this criterion should not be used as a biomarker to guide transition of patients to an active 16 device. Alternatively, the minimum threshold energy for effective drug delivery with passive dry 17 powder inhalers (DPI) occurs at peak inspiratory pressures greater than or equal to about 1 kPa, 18 independent of the internal resistance of the device. Most patients can achieve the threshold 1 kPa 19 pressure drop even during periods of acute wheeze.
Electrostriction effect contribution to high dynamic range optical limiters (2000)

We show that electrostriction can dominate the nonlinear refraction in CS2 for nanosecond pulses. We use this effect in a new cascaded limiter geometry to make an extremely high performance optical limiter.
Nitroimidazoles, Part 2 (2006)

A series of 5-alkylamino and 5-alkylsulfanyl derivatives of 1-aryl-2-alkyl-4-nitro-1H-imidazoles 12-21, 31, and 34 were synthesized by a simple method with the aim to develop novel HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs). All the new compounds were tested against HIV-1 and HIV-2 in MT-4 cells. Compound 21, with an arylsulfanyl group at C(5) of the 4-nitro-1H-imidazole backbone showed an EC(50) value of 0.22 microg/ml against HIV-1 with a therapeutic index of 13. This means that compound 21 was cytotoxic to MT-4 cells at a CC(50) value of 2.57 microg/ml; also compounds 8, 22-25, 28, and 29 were cytotoxic to MT-4 cells within the 0.4-4 microg/ml concentration range. Compounds 8, and 12-21 were evaluated, as a rule, but found inactive at non-toxic concentrations against hepatitis C virus, herpes simplex type 1 and 2, cytomegalovirus (CMV), varicella-zoster virus (VZV), vaccinia virus, and vesicular stomatitis virus, and a number of other viruses. Yet, the therapeutic index of compounds 17 and 21 for CMV and VZV approached the tenfold cut-off point. Compounds 8 and 21 exhibited some cytostatic activity against leukemia and melanoma cell lines.
EFFECT OF TWELVE WEEKS OF MEDICINE BALL TRAINING ON HIGH SCHOOL BASEBALL PLAYERS (2007)

This study examined the effect of 12 weeks of medicine ball training on high school baseball players. Forty-nine baseball players (age 15.4 ± 1.2 years) were randomly assigned using a stratified sampling technique to 1 of 2 groups. Group 1 (n = 24) and group 2 (n = 25) performed the same full-body resistance exercises according to a stepwise periodized model and took 100 bat swings a day, 3 days per week, with their normal game bat for 12 weeks. Group 2 performed additional rotational and full-body medicine ball exercises 3 days per week for 12 weeks. Pre- and post-testing consisted of a 3 repetition maximum (RM) dominant and nondominant torso rotational strength and sequential hip-torso-arm rotational strength (medicine ball hitter's throw). A 3RM parallel squat and bench press were measured at 0 and after 4, 8, and 12 weeks of training. Although both groups made statistically significant increases (p > 0.05) in dominant (10.5 vs. 17.1%) and nondominant (10.2 vs. 18.3%) torso rotational strength and the medicine ball hitter's throw (3.0 vs. 10.6%), group 2 showed significantly greater increases in all 3 variables than group 1. Furthermore, both groups made significant increases in predicted 1RM parallel squat and bench press after 4, 8, and 12 weeks of training; however, there were no differences between groups. These data indicate that performing a 12-week medicine ball training program in addition to a stepwise periodized resistance training program with bat swings provided greater sport-specific training improvements in torso rotational and sequential hip-torso-arm rotational strength for high school baseball players.
Single-Slice Nanoworlds Online (2016)

Although general multi-slice calculations remain too slow, web-browsers on many platforms now make possible real-time single-slice (strong phase/amplitude object) simulation, with live image, diffraction, image power-spectrum, and darkfield-image modes, including specimen rotation e.g. for atomicresolution images with specimens having several tens of thousands of atoms. Moreover, a wide range of qualitative phenomena emerge that include diffraction-contrast effects associated with thickness, orientation changes, and defect strain. Hence students with no math background can get a visceral feel for the way 2-D lattice-projections, diffraction-patterns, image power-spectra, aperture size/position, and darkfield images relate to a specimen's structure & orientation, as well as microscope contrast-transfer, well before access to a real electron microscope is available.