gebhart/patrepeval huggingface dataset:
Fully Enzymatic Peptide Synthesis using <i>C</i>‐Terminal <i>tert</i>‐Butyl Ester Interconversion (2010)

Abstract Chemoenzymatic peptide synthesis is potentially the most cost‐efficient technology for the synthesis of short and medium‐sized peptides with some important advantages. For instance, stoichiometric amounts of expensive coupling reagents are not required and racemisation does not occur, thus rendering purification easier compared to chemical peptide synthesis. The economically most attractive synthesis runs in the N→C terminal direction wherein a cheap C‐ terminally protected amino acid is employed as the building block for elongation. However, C ‐terminal deprotection and activation after an elongation step – without cleavage of the side‐chain protective groups or the peptide bonds – was hitherto still a challenge. In this paper we describe a novel C ‐terminal ester interconversion catalysed by the serine endopeptidase Alcalase. C ‐Terminally protected peptide tert ‐butyl esters were enzymatically converted into primary alkyl esters in quantitative yield and used directly in the next enzymatic elongation step with another amino acid tert ‐butyl ester. This fully enzymatic N→C elongation strategy by C ‐terminal ester interconversion was applied toward the synthesis of biologically active peptides up to the pentamer level.
Structure−Activity Relationship of Heterobase-Modified 2‘-<i>C</i>-Methyl Ribonucleosides as Inhibitors of Hepatitis C Virus RNA Replication (2004)

Hepatitis C virus infection constitutes a significant health problem in need of more effective therapies. We have recently identified 2'-C-methyladenosine and 2'-C-methylguanosine as potent nucleoside inhibitors of HCV RNA replication in vitro. However, both of these compounds suffered from significant limitations. 2'-C-Methyladenosine was found to be susceptible to enzymatic conversions by adenosine deaminase and purine nucleoside phosphorylase, and it displayed limited oral bioavailability in the rat. 2'-C-Methylguanosine, on the other hand, was neither efficiently taken up in cells nor phosphorylated well. As part of an attempt to address these limitations, we now report upon the synthesis and evaluation of a series of heterobase-modified 2'-C-methyl ribonucleosides. The structure-activity relationship within this series of nucleosides reveals 4-amino-7-(2-C-methyl-beta-d-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine and 4-amino-5-fluoro-7-(2-C-methyl-beta-d-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine as potent and noncytotoxic inhibitors of HCV RNA replication. Both 4-amino-7-(2-C-methyl-beta-d-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine and 4-amino-5-fluoro-7-(2-C-methyl-beta-d-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine display improved enzymatic stability profiles as compared to that of 2'-C-methyladenosine. Consistent with these observations, the most potent compound, 4-amino-5-fluoro-7H-pyrrolo[2,3-d]pyrimidine ribonucleoside, is orally bioavailable in the rat. Together, the potency of the 2'-C-methyl-4-amino-pyrrolo[2,3-d]pyrimidine ribonucleosides and their improved pharmacokinetic properties relative to that of 2'-C-methyladenosine suggests that this class of compounds may have clinical utility.
Lift-Based Bidding in Ad Selection (2016)

Real-time bidding has become one of the largest online advertising markets in the world. Today the bid price per ad impression is typically decided by the expected value of how it can lead to a desired action event to the advertiser. However, this industry standard approach to decide the bid price does not consider the actual effect of the ad shown to the user, which should be measured based on the performance lift among users who have been or have not been exposed to a certain treatment of ads. In this paper, we propose a new bidding strategy and prove that if the bid price is decided based on the performance lift rather than absolute performance value, advertisers can actually gain more action events. We describe the modeling methodology to predict the performance lift and demonstrate the actual performance gain through blind A/B test with real ad campaigns. We also show that to move the demand-side platforms to bid based on performance lift, they should be rewarded based on the relative performance lift they contribute.
Multiple description coding for video using motion compensated prediction (2003)

We propose multiple description (MD) video coders which use motion compensated predictions. Our MD video coders utilize MD transform coding and three separate prediction paths at the encoder, to mimic the three possible scenarios at the decoder: both descriptions received or either of the single descriptions received. We provide three different algorithms to control the mismatch between the prediction loops at the encoder and decoder. The results show that when the main prediction loop is the central loop, it is important to have side prediction loops and transmit some redundancy information to control mismatch.
A controllable nanomechanical memory element (2005)

We report the realization of a completely controllable high-speed nanomechanical memory element fabricated from single-crystal silicon wafers. This element consists of a doubly-clamped suspended nanomechanical beam structure, which can be made to switch controllably between two stable and distinct states at a single frequency in the megahertz range. Because of their sub-micron size and high normal-mode frequencies, these nanomechanical memory elements offer the potential to rival the current state-of-the-art electronic data storage and processing.
Precious Metal Recovery from Fuel Cell MEA's (2004)

In 2003, Engelhard Corporation received a DOE award to develop a cost-effective, environmentally friendly approach to recover Pt from fuel cell membrane electrode assemblies (MEA’s). The most important precious metal used in fuel cells is platinum, but ruthenium is also added to the anode electrocatalyst if CO is present in the hydrogen stream. As part of the project, a large number of measurements of Pt and Ru need to be made. A low-cost approach to measuring Pt is using the industry standard spectrophotometric measurement of Pt complexed with stannous chloride. The interference of Ru can be eliminated by reading the Pt absorbance at 450 nm. Spectrophotometric methods for measuring Ru, while reported in the literature, are not as robust. These slides will discuss the options for measuring Pt and Ru using the method of UV-VIS spectrophotometry
Chiral fiber optical isolator (2009)

We propose an in-fiber chiral optical isolator based on chiral fiber polarizer technology and calculate its performance by incorporating the magnetic field into the scattering matrix. The design will be implemented in a special preform, which is passed through a miniature heat zone as it is drawn and twisted. The birefringence of the fiber is controlled by adjusted the diameter of a dual-core optical fiber. By adjusting the twist, the fiber can convert linear to circular polarization and reject one component of circular polarization. In the novel central portion of the isolator, the fiber diameter is large. The effective birefringence of the circular central core with high Verdet constant embedded in an outer core of slightly smaller index of refraction is small. The central potion is a non-reciprocal polarization converter which passes forward traveling left circularly polarized (LCP) light as LCP, while converting backward propagating LCP to right circularly polarized (RCP) light. Both polarizations of light traveling backwards are scattered out of the isolator. Since it is an all-glass structure, we anticipate that the isolator will be able to handle several watts of power and will be environmentally robust.
Kinetic studies examining the inhibitory potential of compounds selected using a computationally derived active site model of glutamate racemase from <i>S. Pneumoniae</i> (2015)

Antibiotic resistance is continually developing and diminishing the efficacy of current antibiotics and exploring novel targets is essential. Glutamate racemase, the enzyme responsible for the inter‐conversion between D‐ and L‐glutamate in bacteria, is a potential target. Glutamate racemase is essential for viability of several pathogens, making it an ideal target for developing a new class of antibiotics. Comparative modeling was employed to develop a three‐dimensional structure for the S. Pneumoniae glutamate racemase using Prime®. Several inhibitors were docked into the model's active site to investigate their binding modes. Our results indicate that inhibitor binding induces active site structural changles and that two active site water molecules are important for proper orientation. Our lab has synthesized and expressed the gene MurI, which encodes glutamate racemase. We have explored the inhibition potential of several compounds and present here the kinetic analysis. Inhibitor and substrate was reacted with glutamate racemase, followed by heat inactivation and subsequent reaction of L‐glutamate product with glutamate dehydrogenase. We were able to determine the inhibitory potential of the most promising compounds and compare them to the results obtained in whole cell assays.
Optoacoustic measurements of human placenta and umbilical blood oxygenation (2016)

Adequate oxygenation is essential for normal embryogenesis and fetal growth. Perturbations in the intrauterine oxidative environment during pregnancy are associated with several pathophysiological disorders such as pregnancy loss, preeclampsia, and intrauterine growth restriction. We proposed to use optoacoustic technology for monitoring placental and fetal umbilical blood oxygenation. In this work, we studied optoacoustic monitoring of oxygenation in placenta and umbilical cord blood ex vivo using technique of placenta perfusion. We used a medical grade, nearinfrared, tunable, optoacoustic system developed and built for oxygenation monitoring in blood vessels and in tissues. First, we calibrated the system for cord blood oxygenation measurements by using a CO-Oximeter (gold standard). Then we performed validation in cord blood circulating through the catheters localized on the fetal side of an isolated placental lobule. Finally, the oxygenation measurements were performed in the perfused placental tissue. To increase or decrease blood oxygenation, we used infusion of a gas mixture of 95% O<sub>2</sub> + 5% CO<sub>2</sub> and 95% N<sub>2</sub> + 5% CO<sub>2</sub>, respectively. In placental tissue, up to four cycles of changes in oxygenation were performed. The optoacoustically measured oxygenation in circulating cord blood and in placental lobule closely correlated with the actual oxygenation data measured by CO-Oximeter. We plan to further test the placental and cord blood oxygenation monitoring with optoacoustics in animal and clinical studies.
Antigenic and functional analysis of a neutralization site of HSV-1 glycoprotein D (1990)

Herpes simplex virus glycoprotein D is a component of the virion envelope and appears to be involved in attachment, penetration, and cell fusion. Monoclonal antibodies (MAbs) against this protein can be arranged in groups, on the basis of a number of biological and biochemical properties. Group I antibodies are type-common, have high complement-independent neutralization titers, recognize discontinuous (conformational) epitopes, and block each other in a binding assay. The sum of their epitopes constitutes antigenic site I of gD. Using a panel of neutralization-resistant mutants, we previously found that group I MAbs can be divided into two subgroups, Ia and Ib, such that mutations selected with Ia antibodies have little or no effect on binding and neutralization by Ib antibodies, and vice versa. Antigenic site I therefore consists of two parts, Ia and Ib. We have now identified the point mutations which prevent neutralization. Two Ib MAbs (DL11 and 4S) selected a Ser to Asn change at residue 140; this alteration creates a new N-linked glycosylation site, which is used. A third Ib MAb (D2) selected a Gln to Leu change at 132. The mutation selected by the Ia MAb HD1 (Ser to Asn at residue 216) is identical to that selected by MAb LP2, another Ia antibody. By using oligonucleotide-directed mutagenesis, we have produced gD genes with combinations of the above mutations. Attempts to recombine these genes into the virus genome were unsuccessful, suggesting that the combinations are lethal. This was confirmed by a complementation assay which measures the ability of gD transiently expressed in transfected Vero cells to rescue the production of infectious virus by the gD-minus mutant F-gD beta.
Single nucleotide polymorphisms in miRNA binding sites and miRNA genes as breast/ovarian cancer risk modifiers in Jewish high‐risk women (2009)

We hypothesized that aberrant gene silencing by miRNA may affect mutant BRCA penetrance. To test this notion, frequency of single nucleotide polymorphisms (SNPs; n = 42) within predicted miRNA binding sites or miRNA precursors were determined and compared in 363 BRCA1 mutation carriers: asymptomatic (n = 160), breast cancer (n = 140) and ovarian cancer (n = 63) patients, and in 125 BRCA2 mutation carriers: asymptomatic (n = 48), breast cancer (n = 58) and ovarian cancer (n = 19) patients. Overall, 16 of 42 SNPs were polymorphic, 11 had a minor allele frequency greater than 5% and 9 of them maintained the Hardy-Weinberg Equilibrium. Based on Cox regression and Kaplan-Meier analyses, statistically significant differences were noted in BRCA2 mutation carriers by health status in 3 SNPs: CC homozygosity at rs6505162 increased ovarian cancer risk (RR 2.77; p = 0.028; 95% CI, 1.11-6.9); heterozygote SNP carriers of rs11169571 had an approximately 2 fold increased risk for developing breast/ovarian cancer, whereas heterozygotes of the rs895819 SNP had an approximately 50% reduced risk for developing breast/ovarian cancer. This study provides preliminary evidence for another regulatory level of penetrance of deleterious mutations in cancer predisposition genes.
A novel biosensor using electrochemical surface plasmon resonance measurements (2000)

Surface plasmon resonance measurements have been conducted to construct a unique electrochemical enzyme sensor which detected the reversible change in the refractive index of a redox film containing an enzyme.
An analysis of the partial randomization dynamic element matching technique (1998)

Partial randomization dynamic element matching (DEM) was recently introduced as a promising DEM technique for low harmonic distortion digital-to-analog conversion. The DEM technique is well suited to applications such as direct digital synthesis in wireless communication systems for which low hardware complexity is essential in addition to low harmonic distortion. Previously reported simulation results demonstrate that partial randomization DEM greatly attenuates harmonic distortion resulting from static errors in the analog output levels of the DAC, while offering considerable savings in hardware compared to other DEM techniques. This paper presents the first quantitative performance analysis of partial randomization DEM. As a main result, the minimum spurious-free dynamic range provided by the digital-to-analog converter has been quantified as a function of its hardware complexity and the analog output level errors.
Re-designing Interleukin-12 to enhance its safety and potential as an anti-tumor immunotherapeutic agent (2017)

Interleukin-12 (IL-12) has emerged as one of the most potent agents for anti-tumor immunotherapy. However, potentially lethal toxicity associated with systemic administration of IL-12 precludes its clinical application. Here we redesign the molecule in such a way that its anti-tumor efficacy is not compromised, but toxic effects are eliminated. Deletion of the N-terminal signal peptide of IL-12 can effect such a change by preventing IL-12 secretion from cells. We use a newly designed tumor-targeted oncolytic adenovirus (Ad-TD) to deliver non-secreting (ns) IL-12 to tumor cells and examine the therapeutic and toxic effects in Syrian hamster models of pancreatic cancer (PaCa). Strikingly, intraperitoneal delivery of Ad-TD-nsIL-12 significantly enhanced survival of animals with orthotopic PaCa and cured peritoneally disseminated PaCa with no toxic side effects, in contrast to the treatment with Ad-TD expressing unmodified IL-12. These findings offer renewed hope for development of IL-12-based treatments for cancer.
Identifying counterfeit smart grid devices: A lightweight system level framework (2017)

The use of counterfeit smart grid devices throughout the smart grid communication infrastructure represents a real problem. Hence, monitoring and early detection of counterfeit smart grid devices is critical for protecting smart grid's components and data. To address these concerns, in this paper, we introduce a novel system level approach to identify counterfeit smart grid devices. Specifically, our approach is a configurable framework that combines system and function call tracing techniques and statistical analysis to detect counterfeit smart grid devices based on their behavioural characteristics. Moreover, we measure the efficacy of our framework with a realistic testbed that includes both resource-limited and resource-rich counterfeit devices. In total, we analyze six different counterfeit devices in our testbed. The devices communicate via an open source version of the IEC61850 protocol suite (i.e., libiec61850). Experimental results reveal an excellent rate on the detection of smart grid counterfeit devices. Finally, the performance analysis demonstrates that the use of the proposed framework has minimal overhead on the smart grid devices' computing resources.
The HMGB1-MD-2 axis as a novel therapeutic target in inflammatory diseases (CCR5P.210) (2015)

Abstract Innate immune cells express receptors for pathogen-associated molecular patterns (PAMP e.g. LPS) as well as damage-associated molecular patterns (DAMP e.g. HMGB1), and orchestrate inflammatory responses to both infection and sterile injury. Secreted by activated immune cells or passively released by damaged cells, HMGB1 is subjected to redox modulation that distinctly influences its extracellular functions. Previously, it was unknown how the TLR4 signalosome distinguishes between HMGB1 isoforms. Here we demonstrate that the TLR4 adaptor molecule, myeloid differentiation factor 2 (MD-2), binds specifically to the cytokine-inducing disulfide HMGB1 isoform, to the exclusion of other isoforms. Screening of HMGB1 peptide libraries identified a tetramer (FSSE, designated as P5779) as a specific MD-2-antagonist preventing MD-2/HMGB1 interaction and subsequent TLR4 signaling mediating cytokine and chemokine release. Moreover, P5779 does not interfere with LPS-induced cytokine production, thereby preserving PAMP-mediated TLR4-MD2 responses. P5779 conferred protection in animal models of hepatic ischemia/reperfusion injury, chemical toxicity and sepsis. Taken together, these findings reveal a novel mechanism by which innate systems selectively recognize specific HMGB1 isoforms and suggest strategies to attenuate DAMP-mediated inflammatory responses while preserving anti-microbial immune responsiveness.
Volume Holographic Storage and Retrieval of Digital Information (1995)

We discuss the experimental performance of a digital holographic data storage device and architectural and materials issues related to achieving large capacity and low bit error rates.
A novel methodology (Low Temperature Laminated Organics) for 3D integration using multilayer organics (2008)

This paper presents for the first time a new paradigm in the construction of multilayer RF, digital and mixed signal circuits using conventional low-loss organic laminates. The new process termed low temperature laminated organics, LTLOtrade [1], is a multilayer parallel process where individual layers are circuitized, tested and co-laminated at temperatures below 280degC to form a multilayer structure. Both stacked and staggered via structures have been realized with LTLO, thereby allowing for the realization of any layer, and any via interconnection schemes. The LTLO technology also facilitates the introduction of embedded active and passive components allowing for true 3D package integration. To date up to 24 metal layers have been demonstrated using LTLO.
A productivity centered application performance tuning framework (2007)

In response to the productivity challenge of the U.S. DARPA HPCS initiative, we have developed a methodology that provides an extremely simple and pain-free interface through which scientists can collect rich performance data from selected parts of an execution, digest the data at a very high level, and plan for improvements. This process can be easily repeated, each time refining the selection of parts of the application and revising the granularity of data collected, until complete insight is gained about bottlenecks. A distinct feature of our approach is that the framework is independent of the features being examined. Recognizing that the features to be examined change with systems/applications and also with depth at which an aspect is being examined, our framework provides an easy interface to continually add new features for examination. Furthermore, many different features can be collected simultaneously and examined in a non-interfering manner. Finally, all this is accomplished without changing the source code in any manner. We believe that this is an ideal platform for building knowledge-based repositories for automatic performance tuning, which is the subject of our future study.In this paper, we describe our productivity centered framework for application performance tuning. It comprises of three features: an unique source code and binary instrumentation feature, a versatile user-interface that brings all the sophisticated capabilities of the binary instrumentation to the user at a higher level of abstraction, and the functionality to collect different dimensions of performance data. The results of execution are all in terms of source level names and at no point does the scientist needs to worry about low-level details of instrumentation. We believe that it is this ability, of deciphering performance impacts at source level, that leads to high productivity of scientists to understand, direct and tune the behavior of the computing system.
The Three Members of the Arabidopsis Glycosyltransferase Family 92 are Functional β-1,4-Galactan Synthases (2018)

Pectin is a major component of primary cell walls and performs a plethora of functions crucial for plant growth, development and plant-defense responses. Despite the importance of pectic polysaccharides their biosynthesis is poorly understood. Several genes have been implicated in pectin biosynthesis by mutant analysis, but biochemical activity has been shown for very few. We used reverse genetics and biochemical analysis to study members of Glycosyltransferase Family 92 (GT92) in Arabidopsis thaliana. Biochemical analysis gave detailed insight into the properties of GALS1 (Galactan synthase 1) and showed galactan synthase activity of GALS2 and GALS3. All proteins are responsible for adding galactose onto existing galactose residues attached to the rhamnogalacturonan-I (RG-I) backbone. Significant GALS activity was observed with galactopentaose as acceptor but longer acceptors are favored. Overexpression of the GALS proteins in Arabidopsis resulted in accumulation of unbranched β-1, 4-galactan. Plants in which all three genes were inactivated had no detectable β-1, 4-galactan, and surprisingly these plants exhibited no obvious developmental phenotypes under standard growth conditions. RG-I in the triple mutants retained branching indicating that the initial Gal substitutions on the RG-I backbone are added by enzymes different from GALS.