gebhart/patrepeval huggingface dataset:
Preclinical Development of Inactivated Rabies Virus–Based Polyvalent Vaccine Against Rabies and Filoviruses (2015)

We previously described the generation of a novel Ebola virus (EBOV) vaccine based on inactivated rabies virus (RABV) containing EBOV glycoprotein (GP) incorporated in the RABV virion. Our results demonstrated safety, immunogenicity, and protective efficacy in mice and nonhuman primates (NHPs). Protection against viral challenge depended largely on the quality of the humoral immune response against EBOV GP.Here we present the extension and improvement of this vaccine by increasing the amount of GP incorporation into virions via GP codon-optimization as well as the addition of Sudan virus (SUDV) and Marburg virus (MARV) GP containing virions. Immunogenicity studies in mice indicate similar immune responses for both SUDV GP and MARV GP compared to EBOV GP. Immunizing mice with multiple antigens resulted in immune responses similar to immunization with a single antigen. Moreover, immunization of NHP with the new inactivated RABV EBOV vaccine resulted in high titer neutralizing antibody levels and 100% protection against lethal EBOV challenge when applied with adjuvant.Our results indicate that an inactivated polyvalent vaccine against RABV filoviruses is achievable. Finally, the novel vaccines are produced on approved VERO cells and a clinical grade RABV/EBOV vaccine for human trials has been produced.
Disjunctive Program Synthesis: A Robust Approach to Programming by Example (2018)

Programming by example (PBE) systems allow end users to easily create programs by providing a few input-output examples to specify their intended task. The system attempts to generate a program in a domain specific language (DSL) that satisfies the given examples. However, a key challenge faced by existing PBE techniques is to ensure the robustness of the programs that are synthesized from a small number of examples, as these programs often fail when applied to new inputs. This is because there can be many possible programs satisfying a small number of examples, and the PBE system has to somehow rank between these candidates and choose the correct one without any further information from the user. In this work we present a different approach to PBE in which the system avoids making a ranking decision at the synthesis stage, by instead synthesizing a disjunctive program that includes the many top-ranked programs as possible alternatives and selects between these different choices upon execution on a new input. This delayed choice brings the important benefit of comparing the possible outputs produced by the different disjuncts on a given input at execution time. We present a generic framework for synthesizing such disjunctive programs in arbitrary DSLs, and describe two concrete implementations of disjunctive synthesis in the practical domains of data extraction from plain text and HTML documents. We present an evaluation showing the significant increase in robustness achieved with our disjunctive approach, as illustrated by an increase from 59% to 93% of tasks for which correct programs can be learnt from a single example.
Optimized Li-Ion Electrolytes Containing Triphenyl Phosphate as a Flame-Retardant Additive (2011)

A number of future NASA missions involving the exploration of the Moon and Mars will be human-rated and thus require high-specific-energy rechargeable batteries that possess enhanced safety characteristics. Given that Li-ion technology is the most viable rechargeable energy storage device for near-term applications, effort has been devoted to improving the safety characteristics of this system. There is also a strong desire to develop Li-ion batteries with improved safety characteristics for terrestrial applications, most notably for hybrid electric vehicle (HEV) and plug-in hybrid electric vehicle (PHEV) automotive applications. Therefore, extensive effort has been devoted recently to developing non-flammable electrolytes to reduce the flammability of the cells/battery. A number of electrolyte formulations have been developed, including systems that (1) incorporate greater concentrations of the flame-retardant additive (FRA); (2) use di-2,2,2-trifluoroethyl carbonate (DTFEC) as a co-solvent; (3) use 2,2,2- trifluoroethyl methyl carbonate (TFEMC); (4) use mono-fluoroethylene carbonate (FEC) as a co-solvent and/or a replacement for ethylene carbonate in the electrolyte mixture; and (5) utilize vinylene carbonate as a SEI promoting electrolyte additive, to build on the favorable results previously obtained. To extend the family of electrolytes developed under previous work, a number of additional electrolyte formulations containing FRAs, most notably triphenyl phosphate (TPP), were investigated and demonstrated in experimental MCMB (mesocarbon micro beads) carbon- LiNi(0.8)Co(0.2)O2 cells. The use of higher concentrations of the FRA is known to reduce the flammability of the electrolyte solution, thus, a concentration range was investigated (i.e., 5 to 20 percent by volume). The desired concentration of the FRA is the highest amount tolerable without adversely affecting the performance in terms of reversibility, ability to operate over a wide temperature range, and the discharge rate capability. The use of fluorinated carbonates, much in the same manner as the incorporation of fluorinated ester-based solvents, was employed to reduce the inherent flammability of mixtures. Thus, electrolyte formulations that embody both approaches are anticipated to have much lower flammability, resulting in enhanced safety.
Rate-adaptive OFDM MIMO VLC system (2017)

In this paper, we investigate link adaptation for an orthogonal frequency division multiplexing (OFDM)-based multiple-input multiple-output (MIMO) visible light communication (VLC) system. The MIMO system under consideration employs repetition coding, therefore all the transmitters emit the same information. We propose a rate adaptation algorithm where the modulation size is selected among the available constellation sets. The receiver first calculates the instantaneous signal-to-noise ratio per subcarrier, then determines the maximum constellation size on each subcarrier that can be supported while satisfying a predefined target bit error rate. Our numerical results reveal that a peak data rate of more than 1.14 Gbits/sec can be achieved using LEDs with cut-off frequency of 10 MHz in typical office spaces.
Fiber Optic Spectrochemical Emission Sensors: A Detector For Chlorinated And Fluorinated Compounds (1990)

Prior work on fiber optic spectrochemical emission sensor (FOSES) concepts1,2 has been extended to the design and fabrication of a prototype fiber optic chemical sensor system for chlorinated compounds. The sensor performs analyte dissociation and atomic excitation via a radio-frequency-excited helium plasma. The device has been configured for field measurements of vadose-zone concentrations of carbon tetrachloride on the Hanford Reservation in southeastern Washington state. Detection and quantification of other atomic species may be achieved by varying the analytical wavelength. The sensor system design incorporates an RF excitation source; a metered, sub-atmospheric pressure helium supply system; an optical detection system; and a fiber optic umbilical to transmit analyte emissions to a central detection/data acquisition system. Sensor system design is summarized as well as performance data relating to detection limits and dynamic range.
Oral polymeric N-acetyl-D-glucosamine and osteoarthritis. (2001)

Many patients with arthritis are using alternative modes of therapy, including nutritional supplements, to treat their arthritis. Most patients never tell their doctors that they are taking alternative medications, and few doctors even ask about such activities. Over-the-counter supplements are expensive and consume large amounts of patients' healthcare dollars. Glucosamine has been widely touted as being an effective arthritis treatment. The authors designed and undertook a study to test the efficacy of a polymer of N-acetyl-D-glucosamine (NAG), or POLY-Nag, in a double-blind, placebo-controlled study in patients with osteoarthritis. Results indicate that POLY-Nag may be useful in treating patients with osteoarthritis.
Acquired resistance to EGFR tyrosine kinase inhibitors in lung cancer. (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

SY10-01 

The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), gefitinib (Iressa) and erlotinib (Tarceva), induce dramatic responses in certain patients with non-small cell lung cancer (NSCLC). Unfortunately, most patients who initially respond to these drugs eventually develop progression of disease. We previously reported that in 2 of 5 patients with clinically acquired resistance to either gefitinib or erlotinib and in 1 patient who progressed on adjuvant gefitinib, tumors contained a second site mutation in the kinase domain after progression, in addition to a primary drug-sensitive EGFR mutation (exon 19 deletion or L858R point mutation) (Pao et al, PLoS Med ‘05b). The second site T790M amino acid change is predicted to block binding of drug to the ATP pocket via steric clash resulting from introduction of the bulky methionine residue. We will present updated information on more patients examined for mechanisms of acquired resistance to EGFR TKIs; such patients received gefitinib or erlotinib as monotherapy or in combination with chemotherapy. In addition, we are establishing tetracycline-inducible mouse models of EGFR-dependent lung adenocarcinomas responsive (K Politi, M Zakowski, W Pao, and H Varmus, manuscript in preparation) and resistant to erlotinib. Such animals should be useful for testing new strategies to overcome acquired resistance in the clinic. We acknowledge funding from the Joan's Legacy Foundation, the Doris Duke Charitable Foundation, NCI K08-CA097980-01A2, and an anonymous donor.
Base Station Ordering for Emergency Call Localization in Ultra-Dense Cellular Networks (2017)

This paper proposes the base station ordering localization technique (BoLT) for emergency call localization in cellular networks. Exploiting the foreseen ultra-densification of the next-generation (5G and beyond) cellular networks, we utilize higher order Voronoi tessellations to provide ubiquitous localization services that are in compliance to the public safety standards in cellular networks. The proposed localization algorithm runs at the base stations (BSs) and requires minimal operation from agents (i.e., mobile users). Particularly, BoLT requires each agent to feedback a neighbor cell list that contains the order of neighboring BSs based on the received signal power in the pilots sent from these BSs. Moreover, this paper utilizes stochastic geometry to develop a tractable mathematical model to assess the performance of BoLT in a general network setting. The goal of this paper is to answer the following two fundamental questions: 1) how many BSs should be ordered and reported by the agent to achieve a desirable localization accuracy? and 2) what is the localization error probability given that the pilot signals are subject to shadowing? Assuming that the BSs are deployed according to a Poisson point process, we answer these two questions via characterizing the tradeoff between the area of location region and the localization error probability in terms of the number of BSs ordered by the agent. The results show that reporting the order of six neighboring BSs is sufficient to localize the agent within 10% of the cell area. Increasing the number of reported BSs to ten confines the location region to 1% of the cell area. This would translate to the range of a few meters to decimeters in the foreseen ultra-dense 5G networks.
Enhancement of Retroviral Gene Transduction on a Dish Coated with a Cocktail of Two Different Polypeptides: One Exhibiting Binding Activity toward Target Cells, and the Other toward Retroviral Vectors (1998)

CH-296, a recombinant fragment of human fibronectin (FN) composed of the cell-binding domain (C-domain), heparin-binding domain II (H-domain), and CS1 site, enhances the retrovirus-mediated gene transduction (GT) of hematopoietic stem cells. The RGD sequence in the C-domain is recognized by a variety of cell types through integrin VLA-5, and the LDV sequence in the CS1-site is recognized by integrin VLA-4. Retrovirus particles were also found to bind to the H-domain. Consequently, the CH-296 fragment can enhance GT through binding to both retrovirus particles and target cells that express integrins VLA-5 and/or VLA-4. In this study, we found that the GT efficiency can be maintained at levels comparable to that of CH-271, a FN fragment similar to CH-296 but lacking the CS1 site, when a cocktail of separated functional domains of CH-271 is used. When a dish was coated with a mixture of the C-domain and H-domain (molar ratio, 1:10), the GT efficiency of NIH3T3 cells reached the same level as that of the mother fragment, CH-271. The H-domain in the cocktail can be replaced with other virus-binding components, polylysine, FGF, and the insulin-binding domain of ColV, without the loss of GT efficiency. With other than FN fragments, a cocktail of erythropoietin and polylysine caused higher GT efficiency of Epo-receptor expressing TF-1 cells than in the case of each component alone.
ICD lead failure detection in chronic soaked leads (2015)

Abrasion-induced insulation breach is a common failure mode of silicone-body, transvenous, implantable cardioverter defibrillator leads. It is caused either by external compression or internal motion of conducting cables. The present method of monitoring lead integrity measures low frequency conductor impedance. It cannot detect insulation failures until both the silicone lead body and inner fluoropolymer insulation have been breached completely, exposing conductors directly to blood or tissue. Even then the resistance changes are usually swamped by the baseline values. Thus the first clinical presentation may be either failure to deliver a life-saving shock or painful, inappropriate shocks in normal rhythm. We have previously presented a method for identifying early lead failure based on high frequency transmission line impedance measurements. That work used fresh leads in a liquid simulation bath; we have now demonstrated similar effects in leads soaked for 32 days and hence with saline-saturated silicone lead bodies.
A Simple and Facile Approach to Aliphatic <i>N</i>-Substituted Functional Eight-Membered Cyclic Carbonates and Their Organocatalytic Polymerization (2015)

Aliphatic N-substituted functional eight-membered cyclic carbonates were synthesized from N-substituted diethanolamines by intramolecular cyclization. On the basis of the N-substituent, three major subclasses of carbonate monomers were synthesized (N-aryl, N-alkyl and N-carbamate). Organocatalytic ring opening polymerization (ROP) of eight-membered cyclic carbonates was explored as a route to access narrowly dispersed polymers of predictable molecular weights. Polymerization kinetics was highly dependent on the substituent on the nitrogen atom and the catalyst used for the reaction. The use of triazabicyclodecene (TBD), instead of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), as the catalyst for the N-alkyl substituted monomers significantly enhanced the rate of polymerizations. Computational studies were performed to rationalize the observed trends for TBD catalyzed polymerizations. With the optimal organocatalyst all monomers could be polymerized generating well-defined polymers within a timespan of ≤2 h with relatively high monomer conversion (≥80%) and low molar-mass dispersity (Đ(M) ≤ 1.3). Both the glass transition temperatures (T(g)) and onset of degradation temperatures (T(onset)) of these polymers were found to be N-substituent dependent and were in the range of about -45 to 35 °C and 230 to 333 °C, respectively. The copolymerization of the eight membered monomers with 6-membered cyclic comonomers including commercially available l-lactide and trimethylene carbonate produced novel copolymers. The combination of inexpensive starting materials, ease of ring-closure and subsequent polymerization makes this an attractive route to functional polycarbontes.
Depolymerization of Post-Consumer Polylactic Acid Products (2014)

Presented in this study is a novel recycling strategy for poly(lactic acid) (PLA) in which the depolymerization is rapidly promoted by the base–catalyzed hydrol–/alcohol–ysis of the terminal ester bonds under mild conditions. Post–consumer PLA water bottles were cut into approximately 6 × 2 mm plastic chips and heated to 50–60×C in water, ethanol, or methanol as the depolymerization medium. A variety of carbonate salts and alkaline metal oxides were screened as potential catalysts. High–power ultrasound was also investigated as a means to accelerate the PLA decomposition. Both mass loss and HPLC analysis of the treated suspensions showed that the conversion of PLA to lactic acid/lactic esters was achieved with yields over 90% utilizing either ultrasonics or a hot bath. It was found that the most rapid decomposition occurred in solution of sodium hydroxide in methanol at 50oC, in which maximum depolymerization was complete in 5 min. It was also seen that the degree of crystallinity affected the rate of depolymerization.
Development and Engine Testing of a Dry Low Emissions Combustor for Allison 501-K Industrial Gas Turbine Engines (1995)

The Allison Engine Company has been developing a low emission, can-annular combustion system for the 501K industrial gas turbine engine to satisfy increasingly stringent environmental requirements. This paper describes the progress achieved, over that previously reported by Razdan et al. (1994), through subsequent design evolution, bench testing, and engine evaluation. Allison’s goal is to develop a retrofittable, can-annular combustion system that limits emission levels to less than 25 ppm nitrogen oxide (NOx), 50 ppm carbon monoxide (CO), and 20 ppm unburned hydrocarbon (UHC), while operating at full load conditions. The interim emissions goals for the combustion system are 37 ppm NOx, 80 ppm CO, and 20 ppm UHC (all dry 15% O2 corrected). The combustion system under development employs a dual mode combustion approach to meet engine operability requirements and high power emission targets without the use of combustor diluent injection or postcombustor exhaust treatment. A lean premixed combustion mode is used to minimize combustion zone temperature and limit NOx production during high power engine operation. The lean premix mode is augmented with a diffusion flame pilot mode for engine starting and low power operation. Initial engine testing showed a dry low NOx combustion system, designed to meet a 37 ppm NOx limit, produced less than 34 ppm NOx and less than 10 ppm CO and UHC in test stand verification test. Continued burner rig testing with modified primary combustion zone stoichiometry has demonstrated NOx less than 25 ppm, CO less than 50 ppm, and UHC less than 20 ppm with simulated engine conditions representing 20 to 100% power. Development activity continues on the combustion system as engine field evaluation trials proceed.
Minor Histocompatibility Antigen-Specific T Cells (2020)

Minor Histocompatibility (H) antigens are major histocompatibility complex (MHC)/Human Leukocyte Antigen (HLA)-bound peptides that differ between allogeneic hematopoietic stem cell transplantation (HCT) recipients and their donors as a result of genetic polymorphisms. Some minor H antigens can be used as therapeutic T cell targets to augment the graft-vs.-leukemia (GVL) effect in order to prevent or manage leukemia relapse after HCT. Graft engineering and post-HCT immunotherapies are being developed to optimize delivery of T cells specific for selected minor H antigens. These strategies have the potential to reduce relapse risk and thereby permit implementation of HCT approaches that are associated with less toxicity and fewer late effects, which is particularly important in the growing and developing pediatric patient. Most minor H antigens are expressed ubiquitously, including on epithelial tissues, and can be recognized by donor T cells following HCT, leading to graft-vs.-host disease (GVHD) as well as GVL. However, those minor H antigens that are expressed predominantly on hematopoietic cells can be targeted for selective GVL. Once full donor hematopoietic chimerism is achieved after HCT, hematopoietic-restricted minor H antigens are present only on residual recipient malignant hematopoietic cells, and these minor H antigens serve as tumor-specific antigens for donor T cells. Minor H antigen-specific T cells that are delivered as part of the donor hematopoietic stem cell graft at the time of HCT contribute to relapse prevention. However, in some cases the minor H antigen-specific T cells delivered with the graft may be quantitatively insufficient or become functionally impaired over time, leading to leukemia relapse. Following HCT, adoptive T cell immunotherapy can be used to treat or prevent relapse by delivering large numbers of donor T cells targeting hematopoietic-restricted minor H antigens. In this review, we discuss minor H antigens as T cell targets for augmenting the GVL effect in engineered HCT grafts and for post-HCT immunotherapy. We will highlight the importance of these developments for pediatric HCT.
Mimicry of an HIV broadly neutralizing antibody epitope with a synthetic glycopeptide (2017)

A goal for an HIV-1 vaccine is to overcome virus variability by inducing broadly neutralizing antibodies (bnAbs). One key target of bnAbs is the glycan-polypeptide at the base of the envelope (Env) third variable loop (V3). We have designed and synthesized a homogeneous minimal immunogen with high-mannose glycans reflective of a native Env V3-glycan bnAb epitope (Man<sub>9</sub>-V3). V3-glycan bnAbs bound to Man<sub>9</sub>-V3 glycopeptide and native-like gp140 trimers with similar affinities. Fluorophore-labeled Man<sub>9</sub>-V3 glycopeptides bound to bnAb memory B cells and were able to be used to isolate a V3-glycan bnAb from an HIV-1-infected individual. In rhesus macaques, immunization with Man<sub>9</sub>-V3 induced V3-glycan-targeted antibodies. Thus, the Man<sub>9</sub>-V3 glycopeptide closely mimics an HIV-1 V3-glycan bnAb epitope and can be used to isolate V3-glycan bnAbs.
Development of biased agonists at the kappa opioid receptor. (2013)

Kappa opioid receptors (KOR) are the primary neuronal targets of the stress peptide, dynorphin, and regulation of the KOR may present a means to modulate responses to psychological stressors. Moreover, the development of therapeutics antagonizing the KOR may be useful for treating stress‐induced relapse in those suffering from substance addiction. βArrestins are key regulatory proteins of G protein‐coupled receptors (GPCR), such as the KOR. Given that there is some evidence to suggest that βarrestin‐mediated signaling may promote the negative aspects associated with dynorphin signaling, there is considerable interest in selectively dampening transduction via the KOR‐βarrestin signaling node, while potentially maintaining the G protein coupling of the receptor. Here we describe a number of newly synthesized KOR ligands that possess varying potency and efficacy profiles across multiple signaling assays. Our early efforts hold promise for biasing drug actions toward KOR‐mediated G protein coupling and ERK activation and away from inducing βarrestin recruitment in cell based assays. NIH/NIDA grant: 1R01DA031927–01
Direct Growth of Dense, Pristine Metal Nanoplates with Well-Controlled Dimensions on Semiconductor Substrates (2007)

Galvanic reactions between metal ions and semiconductor wafers provide a simple and fast approach to grow high-quality metal nanoplates with controlled sizes and thicknesses and clean surfaces. For example, the image shows an SEM image of silver nanoplates with thicknesses of ∼28 nm and edge lengths of 400–450 nm grown on an n-type (110) GaAs wafer.