gebhart/patrepeval huggingface dataset:
Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Single Domain Antibodies Are Potent Inhibitors of Low Density Lipoprotein Receptor Degradation (2016)

Single domain antibodies (sdAbs) correspond to the antigen-binding domains of camelid antibodies. They have the same antigen-binding properties and specificity as monoclonal antibodies (mAbs) but are easier and cheaper to produce. We report here the development of sdAbs targeting human PCSK9 (proprotein convertase subtilisin/kexin type 9) as an alternative to anti-PCSK9 mAbs. After immunizing a llama with human PCSK9, we selected four sdAbs that bind PCSK9 with a high affinity and produced them as fusion proteins with a mouse Fc. All four sdAb-Fcs recognize the C-terminal Cys-His-rich domain of PCSK9. We performed multiple cellular assays and demonstrated that the selected sdAbs efficiently blocked PCSK9-mediated low density lipoprotein receptor (LDLR) degradation in cell lines, in human hepatocytes, and in mouse primary hepatocytes. We further showed that the sdAb-Fcs do not affect binding of PCSK9 to the LDLR but rather block its induced cellular LDLR degradation. Pcsk9 knock-out mice expressing a human bacterial artificial chromosome (BAC) transgene were generated, resulting in plasma levels of ∼300 ng/ml human PCSK9. Mice were singly or doubly injected with the best sdAb-Fc and analyzed at day 4 or 11, respectively. After 4 days, mice exhibited a 32 and 44% decrease in the levels of total cholesterol and apolipoprotein B and ∼1.8-fold higher liver LDLR protein levels. At 11 days, the equivalent values were 24 and 46% and ∼2.3-fold higher LDLR proteins. These data constitute a proof-of-principle for the future usage of sdAbs as PCSK9-targeting drugs that can efficiently reduce LDL-cholesterol, and as tools to study the Cys-His-rich domain-dependent sorting the PCSK9-LDLR complex to lysosomes.
Impedance of Hydraulic Fractures: Its Measurement and Use for Estimating Fracture Closure Pressure and Dimensions (1985)

ABSTRACT The growth of a hydraulic fracture increases the period of free oscillations in a well. Simultaneously, the decay rate of free oscillations decreases. The properties of forced oscillations in a well also change during fracture growth. All of these effects result from the changing impedance of the hydraulic fracture that intersects the well. Fracture impedance can be determined directly by measuring the ratio of downhole pressure and flow oscillations, or determined indirectly from wellhead measurements using impedance transfer functions. Because impedance is a function of fracture dimensions and the elasticity of the surrounding rock, impedance analysis offers a promising new approach for evaluating fracture geometry. Because oscillatory flow conditions occur continuously a hydraulic-fracturing treatment, data collection is simple and economical, adding to the attractiveness of this technique.
Noble-metal catalyzed hydrodeoxygenation of biomass-derived lignin to aromatic hydrocarbons (2013)

Conversion of biomass derived lignin to liquid fuels has the promising potential to significantly improve carbon utilization and economic competitiveness of biomass refineries. In this study, an aqueous phase catalytic process was developed to selectively depolymerize the lignin polymeric framework and remove oxygen via hydrodeoxygenation (HDO) reactions. Efficient methods (ethanol and dilute alkali extraction) for selectively producing reactive lignin oligomers with high yields from corn stover were established. Characteristic structural features of the technical lignins employed for hydrocarbon production were elucidated with the aid of advanced analytical techniques, such as 2D HSQC NMR spectroscopy and gel permeation chromatography (GPC). Combinations of noble metal catalysts in the presence of various solid acid zeolites were tested for HDO activity of the oligomeric technical lignins predominantly containing 8–O–4′ inter-unit linkages. Results showed 35%–60% conversion of lignin with 65%–70% product selectivity for aromatic hydrocarbons (e.g. toluene) under various HDO conditions in the presence of noble metals (Ru, Rh and Pt) over Al2O3 (or C) supports and solid acid zeolites (e.g., NH4+ Z-Y 57277-14-1) catalyst matrices.
Design and analysis of a traveling-wave MESFET with enhanced shielding capabilities (1994)

The Concentric MESFET (CMESFET) is a small-signal, traveling-wave transistor in which a grounded source electrode surrounds and shields the gate and drain electrodes from electromagnetic fields generated by other nearby circuit elements. S-parameters for the transistor are computed to obtain gain curves for several design configurations. For a gate length of 2 /spl mu/m, maximum gain occurs with a gate width of 3.0 mm. The CMESFET has a calculated bandwidth of 17 GHz for this gate length and a gate width of 300 /spl mu/m. Coupling capacitances between device electrodes and a nearby transmission line are calculated to demonstrate how the shielding source electrode isolates the device from interference and crosstalk originating in the surrounding circuit. The CMESFET geometry exhibits shielding characteristics better than those of conventional small-signal FET geometries.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Inhibitory Effect of Topical Applications of Nondenatured Soymilk on the Formation and Growth of UVB-Induced Skin Tumors (2004)

Treatment of female SKH-1 hairless mice with ultraviolet B light twice a week for 20 weeks resulted in a population of tumor-free mice with a high risk of developing skin tumors during the next several months in the absence of additional UVB treatment (high-risk mice). Topical applications of nondenatured soymilk but not heat-denatured soymilk once a day, 5 days a week to these high-risk mice inhibited the formation and growth of skin tumors. Similar topical applications of soybean trypsin inhibitor or Bowman-Birk inhibitor also inhibited the formation and growth of skin tumors, but these agents were less active than nondenatured soymilk. Treatment of miniswine skin with nondenatured soymilk once a day for 5 days prior to UVB irradiation reduced or completely eliminated UVB-induced formation of thymine dimers and apoptotic cells in the epidermis. These data suggest that nondenatured soymilk could be applied to humans to prevent sunlight-induced skin damage and to reduce the risk of skin tumor formation and progression.
Metabolic loss of deuterium from isotopically labeled glucose (1994)

The isotopically substituted molecule (6-13C, 1, 6, 6-2H3)glucose was evaluated to determine whether metabolic 2H loss would prevent its use in quantitating pentose phosphate pathway (PPP) activity. PPP activity causes the C1 of glucose to be lost as CO2, while C6 can appear in lactate. 2H NMR analysis of the lactate produced from this glucose can distinguish (3-2H)-lactate (from C1 of glucose) from (3-13C, 3, 3-2H2)lactate (from C6 of glucose). 2H NMR spectroscopic analysis of medium containing (6-13C, 1, 6, 6-2H3)glucose after incubation with cultured rat 9L glioma cells suggested a 30.8 +/- 2.1% PPP activity as compared with 6.0 +/- 0.8% from separate, parallel incubations with (1-13C)glucose and (6-13C)glucose. Subsequent experiments with other isotopically labeled glucose molecules suggest that this discrepancy is due to selective loss of 2H from the C1 position of glucose, catalyzed by phosphomannose isomerase. Failure to consider 2H exchange from the C1 and C6 positions of glucose can lead to incorrect conclusions in metabolic studies utilizing this and other deuterated or tritiated glucose molecules.
Genetic mouse embryo assay: improving performance and quality testing for assisted reproductive technology (ART) with a functional bioassay (2016)

This novel approach provides a superior MEA that is more meaningful and sensitive for detection of embryotoxicity than morphological assessment alone.
Large Eddy Simulation Using a Wall-damping Function Based on Kolmogorov Velocity Scale (2005)

The usage of a wall-damping function based on Kolmogorov velocity scale in large eddy simulation (LES) is investigated. To calculate Kolmogorov velocity scale, the dissipation rate of turbulent energy, ε, is needed. In LES, however, the dissipation rate is not solved unlike in the k-ε model, and we have to take the statistics of the calculated unsteady data to obtain it. Therefore, the usage of the wall-damping function in LES is not straightforward. In some studies, the dissipation rate of the subgrid-scale (SGS) turbulent energy, εSGS, is used instead of ε. However, since the SGS components contain only the turbulent components in the scale smaller than the grid-filter width, the damping effect becomes inappropriate and dependent on the grid resolution employed. To overcome this problem, we propose a method for estimating ε from εSGS, where the ratio of two length scales, one in LES and the other in the k-ε model, is used. The revised wall-damping function using the estimated ε is tested in canonical channel flows, and the results show that it gives proper near-wall damping effect in every case with considerably wide range of grid resolutions.
<i>De Novo</i> Design and Synthesis of Cyclic and Linear Peptides to Mimic the Binding Cassette of Human Relaxin (2009)

A synthetic cyclic regioselectively addressable functionalized template was used to prepare six analogs that presented the side chains of the key receptor-binding residues of each of H2 and H3 relaxins and insulin-like peptide 3. None showed any binding affinity for RXFP1, RXFP2, or RXFP3, indicating that the key residues were either incorrectly oriented or that additional residues are required for receptor binding.
Molecular Dynamics Simulation Study of Permeation of Molecules through Skin Lipid Bilayer (2016)

Stratum Corneum (SC), the outermost layer of skin, is mainly responsible for skin's barrier function. The complex lipid matrix of SC determines these barrier properties. In this study, the lipid matrix is modeled as an equimolar mixture of ceramide (CER), cholesterol (CHOL), and free fatty acid (FFA). The permeation of water, oxygen, ethanol, acetic acid, urea, butanol, benzene, dimethyl sulfoxide (DMSO), toluene, phenol, styrene, and ethylbenzene across this layer is studied using a constrained MD simulations technique. Several long constrained simulations are performed at a skin temperature of 310 K under NPT conditions. The free energy profiles and diffusion coefficients along the bilayer normal have been calculated for each molecule. Permeability coefficients are also calculated and compared with experimental data. The main resistance for the permeation of hydrophilic and hydrophobic permeants has been found to be in the interior of the lipid bilayer and near the lipid-water interface, respectively. The obtained permeability is found to be a few orders of magnitude higher than experimental values for hydrophilic molecules while for hydrophobic molecules more discrepancy was observed. Overall, the qualitative ranking is consistent with the experiments.
Chitosan Nanoparticle-Mediated Gene Transfer (2008)

Recent advances in genomics and proteomics have led to the evolution of DNA-based therapeutics and the use of gene therapy for treatment of a wide range of human diseases. However, poor cellular uptake and rapid in vivo degradation of DNA-based therapeutics are the major drawbacks of gene therapy. Viral and nonviral gene transfer vectors have been developed to facilitate the cellular internalization and preserve their activity until the successful transgene expression. Chitosan, a natural polysaccharide, is biocompatible and biodegradable. Chitosan has been reported to form nanocomplexes with DNA to protect them against DNase degradation and transfer DNA effectively and safely into cells in culture cell as well as in vivo.
Complete Characterization of Polarization-Maintaining Fibers Using Distributed Polarization Analysis (2014)

We present methods and processes of using a ghost-peak-free distributed polarization crosstalk analyzer (DPXA) to accurately obtain all polarization related parameters of polarization-maintaining (PM) fibers. We show that by first inducing a series equidistant periodic polarization crosstalk peaks along a PM fiber and then measuring the positions and the widths of these peaks using the analyzer, all birefringence related parameters of the PM fiber, including group birefringence, group birefringence variation along the fiber, group birefringence dispersion, and group birefringence temperature coefficient, can be accurately obtained. We further show that the DPXA has the ability to identify and eliminate polarization crosstalk contributions of connectors or splices in the measurement system and therefore can be used to obtain high accuracy measurement of the polarization extinction ratio (PER) of PM fibers. Finally, we propose a set of parameters based on the distributed polarization analysis to quantitatively evaluate the quality of PM fibers. We believe that the methods and processes described in this paper can be widely applied in the industry for the complete characterization of PM optical fibers.
Unipolar spin diodes and transistors (2001)

Unipolar devices constructed from ferromagnetic semiconducting materials with variable magnetization direction are shown theoretically to behave very similarly to nonmagnetic bipolar devices such as the p-n diode and the bipolar (junction) transistor. Such devices may be applicable for magnetic sensing, nonvolatile memory, and reprogrammable logic.
Cloning and Expression of the Creatinase Gene from<i>Flavobacterium</i>sp. U-188 in<i>Escherichia coli</i> (1990)

The gene coding for creatinase (creatine amidinohydrolase, EC 3.5.3.3) was isolated from Flavobacterium sp. U-188. The primary structure of creatinase deduced from the nucleotide sequence showed a protein (molecular weight, 42, 651) composed of 378 amino acids. The creatinase gene was over-expressed in Escherichia coli under the control of the lac promoter and the amount of this enzyme was over 20 % of the soluble protein in the cell.
Characterization of partially saturated poly(propylene fumarate) for orthopaedic application (1997)

A partially saturated linear polyester based on poly(propylene fumarate) (PPF) was synthesized for potential application in filling skeletal defects. The synthesis was carried out according to a two-step reaction scheme. Propylene glycol and fumaryl chloride were first combined to form an intermediate fumaric diester. The intermediate was then subjected to a transesterification to form the PPF-based polymer. This method allowed for production of a polymer with a number average molecular weight up to 1500 and a polydispersity index of 2.8 and below. The polymeric backbone structure was investigated through the use of FTIR and NMR. Kinetic studies of the transesterification allowed mapping of the molecular weight increase with reaction time. The final product was also characterized by thermal and solubility analysis.
Assessment of Various Low Temperature Electrolytes in Prototype Li-Ion Cells Developed for ESMD Applications (2008)

Due to their attractive properties and proven success, Li-ion batteries have become identified as the battery chemistry of choice for a number of future NASA missions. A number of these applications would be greatly benefited by improved performance of Li-ion technology over a wider operating temperature range, especially at low temperatures, such as future ESMD missions. In many cases, these technology improvements may be mission enabling, and at the very least mission enhancing. In addition to aerospace applications, the DoE has interest in developing advanced Li-ion batteries that can operate over a wide temperature range to enable terrestrial HEV applications. Thus, our focus at JPL in recent years has been to extend the operating temperature range of Li-ion batteries, especially at low temperatures. To accomplish this, the main focus of the research has been devoted to developing improved lithium-ion conducting electrolytes. In the present paper, we would like to present some of the results we have obtained with six different ethylene carbonate-based electrolytes optimized for low temperature. In addition to investigating the behavior in experimental cells initially, the performance of these promising low temperature electrolytes was demonstrated in large capacity, aerospace quality Li-ion prototype cells, manufactured by Yardney Technical Products and Saft America, Inc. These cells were subjected to a number of performance tests, including discharge rate characterization, charge rate characterization, cycle life performance at various temperatures, and power characterization tests.
Analysis and design of AT&T's global PNNI network (2005)

This paper presents work done in the development and operation of the layer 2 infrastructure in AT&T's global network, one of the largest in size and geographic coverage. While conforming to ATM forum's private network-network interface (PNNI) standard, additional features were built in to ensure low latency, among other network objectives. The network uses preferred routing, connection mastership, and delay-based administrative-weights for optimal path selection. Peer-group splits are utilized to deal with network growth. Overbooking rules are used for capacity management to improve efficiency. Extensive modeling and analysis of the network was performed to validate these design features. Some of the techniques described herein would also be applicable to other technologies such as OSPF and MPLS.
Persistent Middle Tier Components Without Logging (2006)

Enterprise applications need to be highly available and scalable. In the past, this has required "stateless" applications, which essentially require the application to manage its state explicitly by storing it in transactional resource managers. Despite "stateful" applications being more natural and hence easier to write and get correct, having the system manage this state automatically has been considered too difficult and too costly. The Phoenix/App system showed how to manage state in stateful applications transparently, by logging interactions between components, guaranteeing "exactly once" execution of the application. By introducing some minor restrictions on Phoenix/App components, no logging need be done for middle tier components, thus making it easy to provide both availability and scalability. Because there is no logging, the performance of failure free application executions is excellent.
Effects of American ginseng (Panax quinquefolius) on neurocognitive function: an acute, randomised, double-blind, placebo-controlled, crossover study (2010)

This preliminary study has identified robust working memory enhancement following administration of American ginseng. These effects are distinct from those of Asian ginseng and suggest that psychopharmacological properties depend critically on ginsenoside profiles. These results have ramifications for the psychopharmacology of herbal extracts and merit further study using different dosing regimens and in populations where cognition is fragile.
Ibrutinib discontinuation in Waldenström macroglobulinemia: Etiologies, outcomes, and IgM rebound (2017)

Ibrutinib is the first approved therapy for symptomatic patients with Waldenström macroglobulinemia (WM). The reasons for discontinuing ibrutinib and subsequent outcomes have not been previously evaluated in WM patients. We therefore conducted a retrospective review of 189 WM patients seen at our institution who received treatment with ibrutinib, of whom 51 (27%) have discontinued therapy. Reasons for discontinuation include: disease progression (n = 27; 14%), toxicity (n = 15; 8%), nonresponse (n = 5; 3%), and other unrelated reasons (n = 4; 2%). The cumulative incidence of ibrutinib discontinuation at 12, 24, 36, and 48 months from treatment initiation was 22%, 26%, 35%, and 43%, respectively. A baseline platelet count ≤100 K/µL and presence of tumor CXCR4 mutations were independently associated with 4-fold increased odds of ibrutinib discontinuation. An IgM rebound (≥25% increase in serum IgM) was observed in 37 patients (73%) following ibrutinib discontinuation and occurred within 4 weeks for nearly half of patients. The response rate to salvage therapy was 71%; responses were higher in patients without an IgM rebound and when salvage therapy was initiated within 2 weeks of stopping ibrutinib. Patients who discontinued ibrutinib due to disease progression versus nonprogression events had significantly shorter overall survival (21 versus 32 months; P = .046). Response to salvage therapy was associated with an 82% reduction in the risk of death following ibrutinib discontinuation. WM patients who discontinue ibrutinib require close monitoring, and continuation of ibrutinib until the next therapy should be considered to maintain disease control.
The Arabidopsis Abscisic Acid Response Gene <i>ABI5</i> Encodes a Basic Leucine Zipper Transcription Factor (2000)

The Arabidopsis abscisic acid (ABA)-insensitive abi5 mutants have pleiotropic defects in ABA response, including decreased sensitivity to ABA inhibition of germination and altered expression of some ABA-regulated genes. We isolated the ABI5 gene by using a positional cloning approach and found that it encodes a member of the basic leucine zipper transcription factor family. The previously characterized abi5-1 allele encodes a protein that lacks the DNA binding and dimerization domains required for ABI5 function. Analyses of ABI5 expression provide evidence for ABA regulation, cross-regulation by other ABI genes, and possibly autoregulation. Comparison of seed and ABA-inducible vegetative gene expression in wild-type and abi5-1 plants indicates that ABI5 regulates a subset of late embryogenesis-abundant genes during both developmental stages.
Testing high resolution ADCs using deterministic dynamic element matching (2004)

Dynamic element matching (DEM) is an effective approach to achieving good average performance in the presence of major mismatch in matching-critical circuits. This paper presents a deterministic DEM (DDEM) strategy for ADC testing that offers substantial reductions in testing cost. The approach is mathematically formulated and validated with simulation results that show the number of test vectors needed is comparable to what are concurrently used with standard code density linearity testing. It is demonstrated that the DDEM method can be used to accurately test ADCs with linearity that far exceeds that of the DAC used as a signal generator. This technique offers potential for use in both production test and BIST environments where high linearity devices are difficult to test and characterize.
Transgenic expression and recovery of biologically active recombinant human insulin from <i>Arabidopsis thaliana</i> seeds (2005)

The increased incidence of diabetes, coupled with the introduction of alternative delivery methods that rely on higher doses, is expected to result in a substantial escalation in the demand for affordable insulin in the future. Limitations in the capacity and economics of production will make it difficult for current manufacturing technologies to meet this demand. We have developed a novel expression and recovery technology for the economical manufacture of biopharmaceuticals from oilseeds. Using this technology, recombinant human precursor insulin was expressed in transgenic plants. Plant-derived insulin accumulates to significant levels in transgenic seed (0.13% total seed protein) and can be enzymatically treated in vitro to generate a product with a mass identical to that of the predicted product, DesB(30)-insulin. The biological activity of this product in vivo and in vitro was demonstrated using an insulin tolerance test in mice and phosphorylation assay performed in a mammalian cell culture system, respectively.