gebhart/patrepeval huggingface dataset:
310. Development of Generation X Recombinant AAV Vectors for Human Gene Therapy (2015)

We have previously reported the development of capsid-modified next generation (NextGen) AAV serotype vectors that transduce cells and tissues more efficiently at reduced vector doses (Proc. Natl. Acad. Sci., USA, 105: 7827-7832, 2008). More recently, we have also described the development of genome-modified generation X (GenX) AAV vectors that also transduce cells and tissues more efficiently (J. Virol, 89: 952-961, 2015). The recombinant AAV genome contains inverted terminal repeats (ITRs) of 145 nucleotides at both ends. In these studies, a 20-nucleotide sequence, termed the D-sequence, was replaced with a substitute sequence, which led to enhanced transgene expression in human cell lines in vitro an in murine hepatocytes in vivo (J. Virol., 89: 952-961, 2015). In our present studies, we observed that a sequence, GGTTCCT, at the end of the D-sequence, shares partial homology to the consensus glucocorticoid receptor-binding element (GRE) site, 5’-GGTACANNNTGTT/CCT-3’. The TGTTCT half-site is an essential core element, which has been reported to be sufficient to relay glucocorticoid signaling. In electrophoretic mobility-shift assays (EMSAs), we documented that purified GR protein could specifically bind to double-stranded D-sequence oligonucleotides, suggesting that the D-sequence potentially functions as a ½ GRE site. Based on these results, we hypothesized that replacement of the D-sequence with a full GRE binding-site in the ITR might further increase transgene expression from these GenX AAV genomes. To this end, recombinant AAV vectors were generated in which the D-sequence was replaced with a fully functional GRE site. Insertion of a full GRE binding-site in the ITR significantly increased the transgene expression from these GenX AAV genomes following encapsidation in the wild-type (WT) AAV2 capsid vectors in human cell lines in vitro, and the extent of the transgene expression was further increased by dexamethasone-treatment. When 1×1010 vgs of recombinant AAV2 vectors containing the Gaussia luciferase (Gluc) reporter gene in the unmodified AAV genome, or those containing the GRE sequence, were administered via tail-vein into C57BL6/J mice, the transduction efficiency of the AAV-GRE vectors was ~8-fold higher in murine hepatocytes in vivo up to 9-weeks post-vector administration. More interestingly, when AAV-GRE genomes containing the enhanced green fluorescence protein (EGFP) reporter gene were encapsidated in the optimal NextGen AAV capsid-modified quadruple-mutant (Y444F+Y500F+Y730F+T491V) AAV2 vectors, the transduction efficiency of these vectors was further increased by ~8-fold in murine hepatocytes in vivo at a dose as low as 5×108 vgs/mouse. Taken together, the availability of these novel GenX AAV vectors containing the D-sequence substitution, and the fully functional GRE site insertion, to achieve high-efficiency transgene expression, has implications in the use of these vectors in human gene therapy.
Liquid-Crystalline Assemblies Containing Ionic Liquids: An Approach to Anisotropic Ionic Materials (2002)

Abstract Amphiphilic ionic liquid derivatives form self-organized lamellar liquid crystals with room temperature ionic liquids. The ionic conductivities along the smectic layers have been obtained for the samples aligned in the cells with electrodes. The highest value is 4.3×10-2 S cm-1 at 139 °C.
Hand-Held Reader for Colorimetric Sensor Arrays (2015)

An inexpensive hand-held device for analysis of colorimetric sensor arrays (CSAs) has been developed. The device makes use of a contact image sensor (CIS), technology commonly used in business card scanners, to rapidly collect low-noise colorimetric data for chemical sensing. The lack of moving parts and insensitivity to vibration allow for lower noise and improved scan rates compared to other digital imaging techniques (e.g., digital cameras, flatbed scanners); signal-to-noise ratios are a factor of 3-10 higher than currently used methods, and scan rates are up to 250 times faster without compromising sensitivity. The device is capable of real-time chemical analysis at scan rates up to 48 Hz.
Effect of Hot Rolling on Mechanical Properties of Extra Low Carbon Cold Rolled Steel Sheet Containing Niobium (1983)

Effects of hot rolling conditions on the mechanical properties of extra low carbon cold rolled steel sheets containing niobium have been investigated. The mechanical properties of this steel depend on the hot working conditions and heat history after hot rolling, and the former effect is stronger than the latter. Hot rolling with high reductions, high speeds or low finishing temperatures (≥Ar3) improves the Lankford-value and the ductility of cold rolled and continuously annealed steel sheets. The reason can be explained as follows. When carbo-nitride precipitation is accelerated through the hot rolling with the above conditions, the grain size of the hot rolled sheets becomes amaller and the density of fine carbo-nitrides precipitating after hot rolling decreases extremely. The smaller grain size of hot rolled sheets contributes to the improvement of Lankford-value. The low density of fine carbo-nitrides in hot rolled sheets increases the ductility of cold rolled and rapidly heated steel sheets.
14.2: New Transparent Electrodes for Cholesteric Liquid Crystal Displays (2012)

Abstract Cholesteric liquid crystals are an important class of optical materials for bistable full‐color reflective displays. ITO and PEDOT are commonly used for transparent electrodes in ChLCD constructions. Both have limitations. Recent 3M work has shed light on new transparent electrodes for ChLCD displays that can give higher performing devices.
Cephalosporin 3‘-Phloroglucide Esters and 7-(Phloroglucidamido)cephalosporins as Novel Antibacterial Agents (1997)

Two series of new phloroglucide derivatives were synthesized that possessed antibacterial activities. The first series includes cephalosporin 3'-phloroglucide esters 19 and 20, which were obtained by condensation of cephalosporin 16 with bioactive phloroglucides 14 and 15, respectively. They exhibited a dual mode of antibacterial action. In comparison with cephalosporins 26 and 27, bearing an acetoxy unit at the C-3' position, the bifunctional cephalosporins 19 and 20 showed a broadened spectrum of activity. Results from the consistent valence force field (CVFF) calculations indicate that the most stable conformational isomer of phenolic acid 14, holding a cis-syn-syn geometry, possessed a cavity. It provides an ideal environment to accommodate metal ions of holoenzymes. Phenolic keto acid 15, however, possessed a trans-anti-syn conformation, which allowed chelation between metal ions and the phenolic hydroxyl groups as well as the carbonyl functionalities. Our biological results show that the cavity formed in phloroglucides plays an important role. The second series includes 7-(phloroglucidamido)cephalosporins 24 and 25, which were synthesized by condensation of cephalosporin 21 with 14 and 15, respectively. Results from the CVFF calculations indicate that cephalosporin 24 also possessed a cavity. Unlike cephalosporin 3'-phloroglucide esters 19 and 20, cephalosporins 24 and 25 were found resistant to beta-lactamases from Staphylococcus aureus 95 and Pseudomonas aeruginosa 18S-H. These new compounds, however, showed notable activities against S. aureus FDA 209P, S. aureus 95, Candida albicans, P. aeruginosa 1101-75, and P. aeruginosa 18S-H.
Synthesis and Reactions of Optically Active Cyanohydrins (1994)

Abstract Cyanohydrins have always held a place of importance both as technical products and as reagents in organic chemistry. It is surprising, therefore, that optically active Cyanohydrins have been extensively investigated and employed for syntheses relatively recently. This can be explained by the fact that only in the past few years have enzymatic methods made chiral Cyanohydrins readily available in high optical purity. Chiral Cyanohydrins are widespread in nature in the form of the respective glycosides and serve roughly 3000 plants and many insects as antifeedants. For the preparative organic chemist, this class of compounds offers an enormous synthetic potential for making other chiral compounds accessible. In a few instances, the pharmacological principle of a drug also incorporates a chiral cyanohydrin as constitutive structural element. In the development of novel, physiologically active compounds all possible stereo‐isomers must be synthesized and investigated with respect to their activity range and the pathway of their metabolic transformations and/or degradation. The development of simple synthetic procedures for such compounds, which also entail a high degree of stereoselectivity, therefore has prime importance. To this end chiral Cyanohydrins may serve as stereochemically pure starting materials. In the present review, the following topics will be addressed: enantioselective addition of hydrogen cyanide (HCN), catalysed by the enzymes ( R )‐and ( S )‐oxynitrilase, to aldehydes and Ketones yielding ( R ) and ( S ) cyanohydrins, respectivity; enantioselective addition of HCN to aldehydes catalyzed by cyclic dipeptides; enantioselective esterification of racemic ocyanohydrins and enantioselective hydrolysis of cyanohydrin esters caytalyzed by lipases and esterases, reprectively; transformation of the nitrile groups of chiral cyanohydrins to provide optically active α‐hydroxycarboxylic acids, aldehydes, and ketones, as well as 2‐amino alcohols; sulfonylation of the OH group of chiral cyanohydrins to furnish optically active α‐sulfonyloxynitriles which undergo S N 2 displacement of the activated OH group yielding α‐azido‐, α‐amino, and α‐fluoronitriles with inverted configuration.
Discovery of 3-({5-Chloro-1-[3-(methylsulfonyl)propyl]-1<i>H</i>-indol-2-yl}methyl)-1-(2,2,2-trifluoroethyl)-1,3-dihydro-2<i>H</i>-imidazo[4,5-<i>c</i>]pyridin-2-one (JNJ-53718678), a Potent and Orally Bioavailable Fusion Inhibitor of Respiratory Syncytial Virus (2020)

Respiratory syncytial virus (RSV) is a seasonal virus that infects the lungs and airways of 64 million children and adults every year. It is a major cause of acute lower respiratory tract infection and is associated with significant morbidity and mortality. Despite the large medical and economic burden, treatment options for RSV-associated bronchiolitis and pneumonia are limited and mainly consist of supportive care. This publication covers the medicinal chemistry efforts resulting in the identification of JNJ-53718678, an orally bioavailable RSV inhibitor that was shown to be efficacious in a phase 2a challenge study in healthy adult subjects and that is currently being evaluated in hospitalized infants and adults. Cocrystal structures of several new derivatives helped in rationalizing some of the structure–activity relationship (SAR) trends observed.
Methanobactin, a Copper-Acquisition Compound from Methane-Oxidizing Bacteria (2004)

Siderophores are extracellular iron-binding compounds that mediate iron transport into many cells. We present evidence of analogous molecules for copper transport from methane-oxidizing bacteria, represented here by a small fluorescent chromopeptide (C45N12O14H62Cu, 1216 daltons) produced by Methylosinus trichosporium OB3b. The crystal structure of this compound, methanobactin, was resolved to 1.15 angstroms. It is composed of a tetrapeptide, a tripeptide, and several unusual moieties, including two 4-thionyl-5-hydroxy-imidazole chromophores that coordinate the copper, a pyrrolidine that confers a bend in the overall chain, and an amino-terminal isopropylester group. The copper coordination environment includes a dual nitrogen- and sulfur-donating system derived from the thionyl imidazolate moieties. Structural elucidation of this molecule has broad implications in terms of organo-copper chemistry, biological methane oxidation, and global carbon cycling.
Efficient mRNA-Based Genetic Engineering of Human NK Cells with High-Affinity CD16 and CCR7 Augments Rituximab-Induced ADCC against Lymphoma and Targets NK Cell Migration toward the Lymph Node-Associated Chemokine CCL19 (2016)

For more than a decade, investigators have pursued methods to genetically engineer natural killer (NK) cells for use in clinical therapy against cancer. Despite considerable advances in viral transduction of hematopoietic stem cells and T cells, transduction efficiencies for NK cells have remained disappointingly low. Here, we show that NK cells can be genetically reprogramed efficiently using a cGMP-compliant mRNA electroporation method that induces rapid and reproducible transgene expression in nearly all transfected cells, without negatively influencing their viability, phenotype, and cytotoxic function. To study its potential therapeutic application, we used this approach to improve key aspects involved in efficient lymphoma targeting by adoptively infused ex vivo-expanded NK cells. Electroporation of NK cells with mRNA coding for the chemokine receptor CCR7 significantly promoted migration toward the lymph node-associated chemokine CCL19. Further, introduction of mRNA coding for the high-affinity antibody-binding receptor CD16 (CD16-158V) substantially augmented NK cell cytotoxicity against rituximab-coated lymphoma cells. Based on these data, we conclude that this approach can be utilized to genetically modify multiple modalities of NK cells in a highly efficient manner with the potential to improve multiple facets of their in vivo tumor targeting, thus, opening a new arena for the development of more efficacious adoptive NK cell-based cancer immunotherapies.
Evaluation of a Simple Lamination Stacking Method for the Teeth of an Axial Flux Permanent-Magnet Synchronous Machine With Concentrated Stator Windings (2012)

In this paper, a simple lamination stacking method for the teeth of an axial flux permanent-magnet synchronous machine with concentrated stator windings is proposed. In this simple lamination stacking method, only two lamination profiles are used and are stacked alternately. To evaluate the performance of this stacking method, a comparison is made between the proposed method with two profiles and a conventional stacking method that uses different profiles for each lamination layer, using a multilayer 2-D finite element model.
TeleMIP: telecommunications-enhanced mobile IP architecture for fast intradomain mobility (2000)

This article first surveys existing protocols for supporting IP mobility and then proposes an extension to the mobile IP architecture, called TeleMIP. Our architecture attempts to achieve smaller handoff latency by localizing the scope of most location update messages within an administrative domain or a geographical region. TeleMIP is intended for use in evolving third-generation wireless networks, and introduces a new logical entity, called the mobility agent, which provides a mobile node with a stable point of attachment in a foreign network. While the MA is functionally similar to conventional foreign agents, it is located at a higher level in the network hierarchy than the subnet-specific FAs. Location updates for intradomain mobility are localized only up to the MA; transmission of global location updates are necessary only when the mobile changes administrative domains and/or geographical regions. By permitting the use of private or locally scoped addresses for handling intradomain mobility, TeleMIP allows efficient use of public address space. Also, by reducing the frequency of global update messages, our architecture overcomes several drawbacks of existing protocols, such as large latencies in location updates, higher likelihood of loss of binding update messages, and loss of inflight packets, and thus provides better mobility support for real-time services and applications. The dynamic creation of mobility agents (in TeleMLP) permits the use of load balancing schemes for the efficient management of network resources.
Impact of a Spacer–Drain Overlap on the Characteristics of a Silicon Tunnel Field-Effect Transistor Based on Vertical Tunneling (2013)

A tunnel field-effect transistor (FET) (TFET), in which the dominant carrier tunneling occurs in a direction that is in line with the gate electric field, shows great promise for sub-0.6-V operation. A detailed investigation, with the help of extensive device simulations, of the effects of a spacer-drain overlap on the device characteristics of such silicon TFET is reported in this paper. It is demonstrated that a supersteep subthreshold swing and a significantly reduced off-state current <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">I</i> <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">OFF</sub> can be achieved by appropriate designing of the spacer-drain overlap. An investigation of the influence of the drain potential on the device characteristics reveals that the absence of a tunnel-resistance limited region results in long-channel metal-oxide-semiconductor FET-like output characteristics for such a structure. Short-channel effects, such as drain-induced barrier lowering, are also greatly suppressed in it. Results of the investigation on the scaling properties of such devices are also reported.
Effect of Data Center Layout on Rack Inlet Air Temperatures (2005)

The heat dissipated by large servers and switching equipment is reaching levels that make it very difficult to cool these systems in data centers or telecommunications rooms. Some of the highest powered systems are dissipating upwards of 4000 watts/ft2(43,000 watts/m2) based on the equipment footprint. When systems dissipate this amount of heat and then are clustered together within a data center significant cooling challenges can result. This paper describes the thermal profile of 3 data center layouts (2 are of the same data center but different points in time with a different layout). Detailed measurements of all three were taken: electronic equipment power usage; perforated floor tile airflow; cable cutout airflow; computer room air conditioning (CRAC) airflow, temperatures and power usage; electronic equipment inlet air temperatures. Although the detailed measurements were recorded this paper will focus at the macro level results of the data center to see if some patterns present themselves that might be helpful for future guidelines of data center layout for optimized cooling. Specifically, areas of the data center where racks have similar inlet air temperatures are examined relative to the rack and CRAC unit layout.
Immunoassay for detection of feline immunodeficiency virus core antigen (1990)

The feline immunodeficiency virus (FIV) is a recently identified feline lentivirus that has been found at significant levels in domestic cat populations worldwide. A microdilution plate format, monoclonal antibody-based enzyme-linked immunosorbent assay was developed for the detection of the FIV group-associated antigen (gag) designated p24. Assays of serially diluted samples containing disrupted virus showed that the assay had a sensitivity limit of approximately 0.2 ng/ml for FIV p24. The assay was approximately eightfold more sensitive than the assay for viral reverse transcriptase activity when it was tested with diluted tissue culture samples. A qualitative confirmation assay by standard antibody inhibition techniques was coupled to the screening test methodology. The test was used to detect and confirm the presence of virus in cultured feline lymphocytes from infected animals.
Current status of pig heart xenotransplantation (2015)

Significant progress in understanding and overcoming cardiac xenograft rejection using a clinically relevant large animal pig-to-baboon model has accelerated in recent years. This advancement is based on improved immune suppression, which attained more effective regulation of B lymphocytes and possibly newer donor genetics. These improvements have enhanced heterotopic cardiac xenograft survival from a few weeks to over 2 years, achieved intrathoracic heterotopic cardiac xenograft survival of 50 days and orthotopic survival of 57 days. This encouraging progress has rekindled interest in xenotransplantation research and refocused efforts on preclinical orthotopic cardiac xenotransplantation.
Method of deposition of silicon carbide layers on substrates (1982)

A method for direct chemical vapor deposition of silicon carbide to substrates, especially nuclear waste particles, is provided by the thermal decomposition of methylsilane at 800 to 1050/sup 0/C when the substrates have been confined within a suitable coating environment.
Density Functional Theory Study of Oxygen Adsorption on Polymer Surfaces for Atomic-Layer Etching: Implications for Semiconductor Device Fabrication (2020)

Atomic-layer etching (ALE) is a technique that removes thin layers of material using sequential self-limiting reactions and is considered to be one of the most promising techniques for achieving the low-process variability necessary in the imminent atomic-scale era of semiconductor device fabrication. Here, a theoretical investigation of the ALE of organic polymer surfaces using oxygen pulses has been performed, by means of density functional theory calculations. Experimental evidence shows that ion bombardment of polymer surfaces results in carbon-abundant layers, which are formed as a competition between two opposite effects, the breaking of C–H and C–C bonds, which leads to either structural evolution or sputtering of the polymer surface. Cognizant of that, we develop appropriate polymer surface models, first, to investigate whether the adsorption of oxygen on organic surfaces can be rendered self-limiting, as required in ALE and, second, to establish the conditions for obtaining controlled, self-limiting etching of surface carbon atoms. Our results show that, indeed, for large oxygen flux densities, atomically controlled etching can be obtained in the form of desorption of different carbonate species. We quantify the etching process through both the oxygen flux density and the initial kinetic energy of the impacting oxygen atoms. On the basis of a saturated carbon surface model, the theoretical maximum etch rate was estimated to be 0.51 ± 0.05 Å/cycle (4.94 ± 0.1 ng/cm2·cycle), which matches the range of maximum experimental values.
Estimation of clock drift in underwater acoustic instruments using propagation channel analysis (2017)

All underwater acoustic sensors require accurate on-board clocks for subsequent data analysis and interpretation. Unfortunately, most clocks suffer from a phenomenon called “clock drift” (loss of accuracy), which occurs due to environmental changes, aging, and other factors. Typically, the clock drift is accounted for by calibrating the clock in the instrument before and after the deployment, and applying a correction during data post-processing. This method, however, does not allow accurate estimation of clock errors during a particular experimental event. In this presentation a small subset of data collected on the last day of the Bottom Seismometer Augmentation in the North Pacific (OBSANP) Experiment in June-July 2013 is analyzed. It is shown that advanced signal processing techniques can be used to accurately reconstruct the motion of the ship-suspended acoustic source, which, in turn, can improve the accuracy of the acoustic receivers deployed on the seafloor in the deep ocean. [Work supported by the MITRE Innovation Program and ONR.]