gebhart/patrepeval huggingface dataset:
Stem cell-derived clade F AAVs mediate high-efficiency homologous recombination-based genome editing (2018)

The precise correction of genetic mutations at the nucleotide level is an attractive permanent therapeutic strategy for human disease. However, despite significant progress, challenges to efficient and accurate genome editing persist. Here, we report a genome editing platform based upon a class of hematopoietic stem cell (HSC)-derived clade F adeno-associated virus (AAV), which does not require prior nuclease-mediated DNA breaks and functions exclusively through BRCA2-dependent homologous recombination. Genome editing is guided by complementary homology arms and is highly accurate and seamless, with no evidence of on-target mutations, including insertion/deletions or inclusion of AAV inverted terminal repeats. Efficient genome editing was demonstrated at different loci within the human genome, including a safe harbor locus, AAVS1, and the therapeutically relevant IL2RG gene, and at the murine Rosa26 locus. HSC-derived AAV vector (AAVHSC)-mediated genome editing was robust in primary human cells, including CD34<sup>+</sup> cells, adult liver, hepatic endothelial cells, and myocytes. Importantly, high-efficiency gene editing was achieved in vivo upon a single i.v. injection of AAVHSC editing vectors in mice. Thus, clade F AAV-mediated genome editing represents a promising, highly efficient, precise, single-component approach that enables the development of therapeutic in vivo genome editing for the treatment of a multitude of human gene-based diseases.
Glycerol production by Dunaliella (1982)

Species of the unicellular alga Dunaliella possess outstanding tolerance of a wide range of salinities. They can adapt to grow in salt media which range from less than 0.5 M to saturated salt solutions and withstand enormous osmotic shocks through a unique osmotic adaptation. The osmoregulating mechanism depends on photosynthetic production of glycerol, whose intracellular concentration varies in direct proportion to the extracellular salt concentration and reaches values in excess of 50% of the total dry weight of the cells. Dunaliella, and another halotolerant glycerol producing alga, Asteromonas gracilis, osmoregulate biochemically by controlling glycerol biosynthesis and degradation. 3 new enzymes, NADPH-dihydroxyacetone-reductase, dihydroxyacetone kinase and glycerol-1-phosphatase seem to be involved in the osmoregulatory response via glycerol in Dunaliella and Asteromonas. A hypothetical scheme of glycerol metabolism in these algae utilizing these enzymes is presented. Growth studies of Dunaliella indoors and outdoors showed that salt concentrations favoring maximal glycerol productivity are not identical with those required for maximal algal productivity. Maximal yield of glycerol occurred around 2 M NaCl while maximal algal productivity occurred below 0.5 M NaCl. Observed yields of glycerol in Dunaliella culture outdoors are compared with theoretically calculated maximal yield.
Theoretical model of a piezoelectric composite spinal fusion interbody implant (2013)

Failure rates of spinal fusion are high in smokers and diabetics. The authors are investigating the development of a piezoelectric composite biomaterial and interbody device design that could generate clinically relevant levels of electrical stimulation to help improve the rate of fusion for these patients. A lumped parameter model of the piezoelectric composite implant was developed based on a model that has been utilized to successfully predict power generation for piezoceramics. Seven variables (fiber material, matrix material, fiber volume fraction, fiber aspect ratio, implant cross-sectional area, implant thickness, and electrical load resistance) were parametrically analyzed to determine their effects on power generation within reasonable implant constraints. Influences of implant geometry and fiber aspect ratio were independent of material parameters. For a cyclic force of constant magnitude, implant thickness was directly and cross-sectional area inversely proportional to power generation potential. Fiber aspect ratios above 30 yielded maximum power generation potential while volume fractions above 15% showed superior performance. This investigation demonstrates the feasibility of using composite piezoelectric biomaterials in medical implants to generate therapeutic levels of direct current electrical stimulation. The piezoelectric spinal fusion interbody implant shows promise for helping increase success rates of spinal fusion.
Exploiting Bacterial Iron Acquisition: Siderophore Conjugates (2012)

Siderophores are chelators synthesized by bacteria and fungi to sequester iron, which is essential for virulence and pathogenicity. Since the process involves active transport, which is highly regulated, remarkably efficient and often microbially selective, it has been exploited as a Trojan Horse method for development of microbe-selective antibiotics. Siderophores also have significant potential for the development of imaging contrast agents and diagnostics for pathogen-selective detection. These promising results demonstrate the versatility of natural and synthetic microbial iron chelators and their potential therapeutic applications.
Identification and Characterization of Allophenylnorstatine-Based Inhibitors of Plasmepsin II, an Antimalarial Target (2002)

Plasmepsin II is a key enzyme in the life cycle of the Plasmodium parasites responsible for malaria, a disease that afflicts more than 300 million individuals annually. Since plasmepsin II inhibition leads to starvation of the parasite, it has been acknowledged as an important target for the development of new antimalarials. In this paper, we identify and characterize high-affinity inhibitors of plasmepsin II based upon the allophenylnorstatine scaffold. The best compound, KNI-727, inhibits plasmepsin II with a K(i) of 70 nM and a 22-fold selectivity with respect to the highly homologous human enzyme cathepsin D. KNI-727 binds to plasmepsin II in a process favored both enthalpically and entropically. At 25 degrees C, the binding enthalpy (DeltaH) is -4.4 kcal/mol and the entropic contribution (-TDeltaS) to the Gibbs energy is -5.56 kcal/mol. Structural stability measurements of plasmepsin II were also utilized to characterize inhibitor binding. High-sensitivity differential scanning calorimetry experiments performed in the absence of inhibitors indicate that, at pH 4.0, plasmepsin II undergoes thermal denaturation at 63.3 degrees C. The structural stability of the enzyme increases with inhibitor concentration in a manner for which the binding energetics of the inhibitor can quantitatively account. The effectiveness of the best compounds in killing the malaria parasite was validated by performing cytotoxicity assays in red blood cells infected with Plasmodium falciparum. EC50s ranging between 6 and 10 microM (3-6 microg/mL) were obtained. These experiments demonstrate the viability of the allophenylnorstatine scaffold in the design of powerful and selective plasmepsin inhibitors.
MDL 72,974A: a selective MAO-B inhibitor with potential for treatment of Parkinson's disease. (1993)

MDL 72,974A [(E)-2-(4-fluorophenethyl)-3-fluoroallylamine, hydrochloride] was designed to be a selective, mechanism-based irreversible inhibitor of monoamine oxidase type B (MAO-B). The compound is a potent, selective MAO-B inhibitor in vitro and in vivo. In vitro studies revealed an IC50 value (MAO-B) of 3.6 nM with 189-fold selectivity compared to MAO-A. In rats, profound inhibition of MAO-B was achieved after a single oral dose with an ED50 of 0.18 mg/kg; a dose 44 times this amount was required to inhibit MAO-A by 50%. Selectivity was maintained following chronic dosing. MDL 72,974A had minimal sympathomimetic effects and did not potentiate the cardiovascular effects of tyramine, even at 50 times the MAO-B inhibiting dose. This inhibitor was equally effective and well-tolerated in man. In human volunteers, potent inhibition of platelet MAO-B activity was observed at submilligram doses (ED50 = 90 micrograms) following a single oral dose. Upon multiple oral doses of 100 micrograms, as much as 80% of MAO-B could be inhibited. In phase II studies, MDL 72,974A is proving to be a useful adjunct to conventional therapy. Patients (250) with Parkinson's disease, treated once daily with either 1 or 4 mg, together with L-Dopa and a decarboxylase inhibitor (MadoparR or SinemetR), saw significant improvements in symptoms compared with those on standard therapy without the inhibitor.
Resonant Laser Induced Breakdown for Fuel-Air Ignition (2010)

A resonant laser-induced breakdown scheme to provide precision spatial guidance and timing of fuel-air ignition is presented. This scheme could potentially provide a precision trigger leading to breakdown of a fuel-air flow within a high-voltage gap using a compact low power laser source. The laser scheme employs resonant enhanced multiphoton ionization to generate a pre-ionized path between the electrodes and thus spatially guiding the eventual spark, even when the laser path does not follow the electric field path directly. We present here experimental data that demonstrates precision laser induced breakdown on an air flow (no fuel) within a large scale high-voltage electrode system.
The Synergistic Effect of Combined Immunization with a DNA Vaccine and Chimeric Yellow Fever/Dengue Virus Leads to Strong Protection against Dengue (2013)

The dengue envelope glycoprotein (E) is the major component of virion surface and its ectodomain is composed of domains I, II and III. This protein is the main target for the development of a dengue vaccine with induction of neutralizing antibodies. In the present work, we tested two different vaccination strategies, with combined immunizations in a prime/booster regimen or simultaneous inoculation with a DNA vaccine (pE1D2) and a chimeric yellow fever/dengue 2 virus (YF17D-D2). The pE1D2 DNA vaccine encodes the ectodomain of the envelope DENV2 protein fused to t-PA signal peptide, while the YF17D-D2 was constructed by replacing the prM and E genes from the 17D yellow fever vaccine virus by those from DENV2. Balb/c mice were inoculated with these two vaccines by different prime/booster or simultaneous immunization protocols and most of them induced a synergistic effect on the elicited immune response, mainly in neutralizing antibody production. Furthermore, combined immunization remarkably increased protection against a lethal dose of DENV2, when compared to each vaccine administered alone. Results also revealed that immunization with the DNA vaccine, regardless of the combination with the chimeric virus, induced a robust cell immune response, with production of IFN-γ by CD8+ T lymphocytes.
Carbon Nanotubes as Nanotexturing Agents for High Power Supercapacitors Based on Seaweed Carbons (2011)

The advantages provided by multiwalled carbon nanotubes (CNTs) as backbones for composite supercapacitor electrodes are discussed. This paper particularly highlights the electrochemical properties of carbon composites obtained by pyrolysis of seaweed/CNTs blends. Due to the nanotexturing effect of CNTs, supercapacitors fabricated with electrodes from these composites exhibit enhanced electrochemical performances compared with CNT-free carbons. The cell resistance is dramatically reduced by the excellent conductivity of CNTs and by the good propagation of ions favored by the presence of opened mesopores. As a consequence, the specific power of supercapacitors based on these nanocomposites is very high. Another advantage related to the presence of CNTs is a better life cycle of the systems. The composite electrodes are resilient during the charge/discharge of capacitors; these are able to perfectly accommodate the dimensional changes appearing in the active material without mechanical damages.
ChemInform Abstract: CARBOXYLATION OF ORGANIC SUBSTRATES WITH CARBON DIOXIDE IN HYDROCARBON MEDIA (1978)

Abstract Durch Variation der Versuchsbedingungen (50 ,I00°C ; Na‐ anstelle K‐kresolat (II); andere K‐phenolate wie die von 2,6‐ oder 3,5‐Di‐tert.‐butyl‐, 2‐, 3‐, 4‐tert.‐Butyl‐ 2‐, 4‐Phenyl‐ und ‐Dodecyl‐phenol) wird ermittelt, daß die im Schema genannten Bedingungen die höchste Ausb. an Benzoylessigsäure (III) bringt.
Adult growth hormone treatment reduces hypertension and obesity induced by an adverse prenatal environment (2002)

The discovery of a link between an adverse in utero environment and the propensity to develop metabolic and cardiovascular disease in adult life is one of the most important advances in epidemiological research of recent Years. Increasing experimental evidence suggests that alterations in the fetal environment may have long-term consequences for the development of metabolic disorders in adult life. This process has been termed 'fetal programming' and we have shown that undernutrition of the mother during gestation leads to development of the metabolic syndrome X during adult life. Striking metabolic similarities exist between syndrome X and untreated GH deficiency (GHD). In the present study we have investigated the effects of GH treatment on blood pressure and metabolic parameters. Virgin Wistar rats (age 75+/-5 days, n=20 per group) were time-mated and randomly assigned to receive food either ad libitum (AD) or 30% of AD intake (UN) throughout pregnancy. At weaning, male offspring were assigned to one of two diets (control or hypercaloric (30% fat)). Systolic blood pressure was measured at day 100 and following twice daily treatment with recombinant bovine GH for 21 days. GH treatment increased body weights in all treated animals but significantly reduced retroperitoneal and gonadal fat pad weights. Following GH treatment, systolic blood pressure was markedly decreased in all UN offspring. Saline-treated animals showed no change in systolic blood pressure over the treatment period. GH treatment increased heart-to-body weight ratio in all GH-treated animals. Our data demonstrated that GH treatment reduces hypertension and improves cardiovascular function in animals exposed to adverse environmental conditions during fetal or postnatal life.
Advances in 1D and 2D thermoelectric materials (2003)

Recent advances in our understanding of 1D and 2D thermoelectric materials in the form of quantum wires (1D) and quantum wells (2D) are reviewed, with emphasis given to the physical mechanisms responsible for the enhanced thermoelectric figure of merit (ZT) in these low dimensional systems. Starting with 2D superlattices, progress in demonstrating proof-of-principle in the PbTe/Pb/sub 1-x/Eu/sub x/Te and Si/Si/sub 1-x/Ge/sub x/ systems is presented. The concept of carrier pocket engineering regarding improved thermoelectric performance for the whole superlattice Z/sub 3D/T, including both the quantum well and the barrier region, is reviewed. Particular attention is given to recent results obtained for 1D bismuth nanowire arrays and for individual Bi nanowires.
A fast on-chip decoupling capacitance budgeting algorithm using macromodeling and linear programming (2006)

We propose a novel and efficient charge-based decoupling capacitance budgeting algorithm. Our method uses the macromodeling technique and effective radius of decoupling capacitance to reduce the size of the problem. We formulate the nonlinear optimization into a linear program (LP) by integrating the nodal equations across a time period of interest and through certain approximations. To reduce the error caused by linearization, we do multiple iterations of the linear program. Experimental results demonstrate that, with the proposed algorithm, even very large power networks (eg. 5 million nodes) can be optimized in a couple of hours with 1-2 transient analyses. Comparison of our algorithm with another heuristic method shows area efficiency and run time advantage of our method.
Universal balancing controller for robust lateral stabilization of bipedal robots in dynamic, unstable environments (2014)

This paper presents a novel universal balancing controller that successfully stabilizes a planar bipedal robot in dynamic, unstable environments like seesaw and bongoboards, and also in static environments like curved and flat floors. These different dynamic systems have state spaces with different dimensions, and hence instead of using full state feedback, the universal controller is derived as a single output feedback controller that stabilizes them. This paper analyzes the robustness of the derived universal controller to disturbances and parameter uncertainties, and demonstrates its universality and superiority to similarly derived LQR and H <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">∞</sub> controllers. This paper also presents nonlinear simulation results of the universal controller successfully stabilizing a family of bongoboard, curved floor, seesaw, tilting and rocking floor models.
Confidentiality-preserving rank-ordered search (2007)

This paper introduces a new framework for confidentiality preserving rank-ordered search and retrieval over large document collections. The proposed framework not only protects document/query confidentiality against an outside intruder, but also prevents an untrusted data center from learning information about the query and the document collection. We present practical techniques for proper integration of relevance scoring methods and cryptographic techniques, such as order preserving encryption, to protect data collections and indices and provide efficient and accurate search capabilities to securely rank-order documents in response to a query. Experimental results on the W3C collection show that these techniques have comparable performance to conventional search systems designed for non-encrypted data in terms of search accuracy. The proposed methods thus form the first steps to bring together advanced information retrieval and secure search capabilities for a wide range of applications including managing data in government and business operations, enabling scholarly study of sensitive data, and facilitating the document discovery process in litigation.
ChemInform Abstract: Formation of Tertiary Amides and Dihydrogen by Dehydrogenative Coupling of Primary Alcohols with Secondary Amines Catalyzed by Ruthenium Bipyridine‐Based Pincer Complexes. (2014)

Abstract The direct amidation of primary alcohols with challenging secondary amines is achieved in the presence of small amounts of Ru‐catalysts.
Segmented illumination lenses for step lighting and wall washing (1999)

Many illumination situations involve a flat surface and an oblique luminaire placement. Today's commercially available luminaires give very uneven illumination here. A novel injection-moldable segmented lens is presented that will uniformly illuminate a rectangular zone, such as a stair- step or a picture on a wall. Its design is a development of prior methods of lens-surface generation that derived the array of surface normal vectors required to match a source with a particular illumination prescription. This matching is done via grids on the unit sphere: one for the source and one for the prescription. The cells of these two grids are sized so that they have the same flux of lumens, according to the source intensity and the prescribed illumination, respectively. The first development is the use of an equi- flux polar grid for the target rectangle, because most light sources have circular symmetry. The second development is the radial segmentation of the lens surface in order to approximate the non-irrotational array of surface normal vectors derived from the two grids. Designs are presented for step-lighting by LEDs and fiber-optic billboard lighting.
Precision aerosol divider (1976)

A precision aerosol divider with a 17 to 1 flow split has been designed and tested. The divider, primarily a mass monitor calibration device, collects 94.4% of the aerosol on a filter to serve as a standard and delivers 5.6% of the aerosol to the mass monitor to be calibrated.
A Cognitive Prioritization for Reports Generated in Resource Constrained Applications (2017)

In many resource constrained web/cloud applications, users are given the ability to generate different kinds of reports after selecting some criteria for each report to be produced. Such criteria could, for example, be filters on certain report attributes. With limited computing resources, it is critical to prioritize the reports requested by users at any certain period of time. Then, that prioritization can be fed into any of the known web services scheduling algorithms. In this paper, we provide a novel cognitive prioritization approach that takes into consideration the free-form user-input text about the criticality of the reports as well as their aforementioned structured attributes/filters. Our method consists of a predictive model that uses the structured data to predict the report completion time as well as another text-mining model that uses the user’s text to weight its importance. Then, both outputs are combined with the user profile to come up with the final prioritization. We apply our methodology to real data taken from the report generation of a real-world application of IT service deal pricing and show results that illustrate the effectiveness of our approach.
Electrochemical cell and method of assembly. [LiAl/LiCl-KCl/Li/sub 2/FeS/sub 2/] (1979)

A method of preparing an electrochemical cell is disclosed which permits the assembly to be accomplished in air. The cell includes a metal sulfide as the positive electrode reactant, lithium alloy as the negative electrode reactant, and an alkali metal; molten salt electrolyte. Positive electrode reactant is introduced as Li/sub 2/-FeS/sub 2/, a single-phase compound produced by the reaction of Li/sub 2/S and FeS. The use of this compound permits introduction of lithium in an oxidized form. Additional lithium can be introduced in the negative electrode structure enclosed within an aluminum foil envelope between layers of porous aluminum. Molten salt electrolyte is added after assembly and evacuation of the cell by including an interelectrode separator that has been prewet with an organic solution of KCl.
Time-Lapse Noise Modeling for Enhanced 4D Interpretation (2019)

Summary Since the start of 4D acquisition in the mid-90s, the time-lapse technology pushed geophysicists to 4D seismic data of very different quality. The 4D signal is a combination of 4D noise and reservoir production effects and results are not always straightforward to interpret. Thus, a good understanding of the 4D noise helps to provide a reliability attribute allowing better 4D evaluation to interpreters and reservoir engineers. A precise noise description is presented with the creation of a “confidence” parameter. It allows to rank seismic 4D signatures, to provide 4D seismic uncertainty evaluation and to discriminate 4D signal from 4D noise. The methodology was applied to various 4D signal and noise cases.