gebhart/patrepeval huggingface dataset:
The variable regions of hepatitis C virus glycoprotein E2 have an essential structural role in glycoprotein assembly and virion infectivity (2010)

The three variable regions of hepatitis C virus (HCV) glycoprotein E2 can be removed simultaneously from the E2 ectodomain (residues 384-661) without affecting folding or CD81 binding. In this study, we show that deletion of hypervariable region (HVR) 2 or the intergenotypic variable region (igVR) in the context of the E1E2 polyprotein eliminates formation of heterodimers, reduces CD81 binding and abolishes virus entry. The replication competence of genomic RNA transcribed from the JFH1 infectious HCV clone was not affected by the HVR1, HVR2 or igVR deletions in transfected Huh7.5 cells. However, infectivity of the resultant cell-culture-derived HCV (HCVcc) was abolished by HVR2 or igVR deletions, while deletion of HVR1 led to a 5- to 10-fold reduction in infectivity. Serial passage of cells transfected with genomes lacking HVR1 generated reverted viruses with wild-type levels of infectivity. Sequencing of viral cDNA obtained after full reversion revealed mutations in E1 (I262L) and E2 (N415D) that were present in 35 and 27 % of clones, respectively. Insertion of N415D into HVR1-deleted HCV genomes conferred wild-type levels of infectivity, while I262L increased infectivity by 2.5-fold. These results suggest that HVR2 and the igVR, but not HVR1, are essential for structural integrity and function of the HCV glycoprotein heterodimer.
High productivity continuous ethanol fermentations (1980)

In the current research program, continuous culture systems with cell recycle are being evaluated for ethanol production. The successful development of such a system could lead to a significant reduction in fermentation costs. Bacterial ethanol fermentations using strains of zymomonas mobilis have been found to offer many advantages over the traditional yeast fermentations. These include higher specific rates of sugar uptake and ethanol production and improved yields. In a continuous process with cell recycle ethanol productivities have been achieved with the bacterial cultures which are several times higher than those reported for yeasts (a).
Diagnostic Bioluminescent Phage for Detection of <i>Yersinia pestis</i> (2009)

Yersinia pestis is the etiological agent of the plague. Because of the disease's inherent communicability, rapid clinical course, and high mortality, it is critical that an outbreak, whether it is natural or deliberate, be detected and diagnosed quickly. The objective of this research was to generate a recombinant luxAB ("light")-tagged reporter phage that can detect Y. pestis by rapidly and specifically conferring a bioluminescent signal response to these cells. The bacterial luxAB reporter genes were integrated into a noncoding region of the CDC plague-diagnostic phage phiA1122 by homologous recombination. The identity and fitness of the recombinant phage were assessed through PCR analysis and lysis assays and functionally verified by the ability to transduce a bioluminescent signal to recipient cells. The reporter phage conferred a bioluminescent phenotype to Y. pestis within 12 min of infection at 28 degrees C. The signal response time and signal strength were dependent on the number of cells present. A positive signal was obtained from 10(2) cells within 60 min. A signal response was not detectable with Escherichia coli, although a weak signal (100-fold lower than that with Y. pestis) was obtained with 1 (of 10) Yersinia enterocolitica strains and 2 (of 10) Yersinia pseudotuberculosis strains at the restrictive temperature. Importantly, serum did not prevent the ability of the reporter phage to infect Y. pestis, nor did it significantly quench the resulting bioluminescent signal. Collectively, the results indicate that the reporter phage displays promise for the rapid and specific diagnostic detection of cultivated Y. pestis isolates or infected clinical specimens.
Adaptive Imaging Using the I-ImaS X-Ray Imaging System (2006)

The I-ImaS (intelligent imaging sensors) is an European Union project whose objective is to design and develop intelligent imaging sensors and evaluate their use within an adaptive imaging system. The system employs an in-line scanning technology approach and use of CMOS active pixel sensors developed specifically for high spatial resolution, efficient light collection and large dynamic range. This paper discusses the principle of the data acquisition (DAQ) system and the characterisation of the I-ImaS sensors, both optically and using mono-energetic X-rays.
Field Test Kit for Gun Residue Detection (2002)

One of the major needs of the law enforcement field is a product that quickly, accurately, and inexpensively identifies whether a person has recently fired a gun--even if the suspect has attempted to wash the traces of gunpowder off. The Field Test Kit for Gunshot Residue Identification based on Sandia National Laboratories technology works with a wide variety of handguns and other weaponry using gunpowder. There are several organic chemicals in small arms propellants such as nitrocellulose, nitroglycerine, dinitrotoluene, and nitrites left behind after the firing of a gun that result from the incomplete combustion of the gunpowder. Sandia has developed a colorimetric shooter identification kit for in situ detection of gunshot residue (GSR) from a suspect. The test kit is the first of its kind and is small, inexpensive, and easily transported by individual law enforcement personnel requiring minimal training for effective use. It will provide immediate information identifying gunshot residue.
Abstract 5434: Development and biological characterization of novel, potent and stable isoform-specific inhibitors of histone deacetylase-8 (HDAC8) (2010)

Abstract Histone deacetylase (HDAC) inhibitors have shown promise for the treatment of hematological and solid tumors. The current clinical candidates all inhibit multiple isoforms of the 11-member zinc-dependent HDAC family. With a view to increasing disease specificity and decreasing toxicity, we have developed potent and selective inhibitors of one isoform, HDAC8. We have previously described one such molecule, PCI-34051, which inhibited HDAC8 with a Ki of 10 nM and greater than 200-fold selectivity over other HDAC isoforms. However, this compound displayed poor metabolic stability and was not suitable for in vivo testing in animal models. We have therefore developed a series of analogs to increase metabolic stability while maintaining potency and isoform selectivity. These compounds, which are based on different pharmacophores, have similar potency and selectivity to PCI-34051 but have increased cellular potency, inhibiting cell growth and inducing apoptosis with EC50 of ∼1-2 μM in Jurkat and Hut78 lymphoma cells. These compounds also showed increased metabolic stability in an in-vitro rat liver microsomal assay. Since increased HDAC8 expression has recently been shown to be correlated with poor survival in neuroblastoma, the biological activities of these novel HDAC8 inhibitors were tested in neuroblastoma cell lines. Interestingly, these compounds were found to inhibit cell growth and induce differentiation in neuroblastoma cells. However, incubation with higher concentrations of these compounds did induce caspase activation and apoptosis in these cells. In keeping with the HDAC8 selectivity, no tubulin or histone acetylation was observed at upto 25μM. The best of these inhibitors is currently being tested in mouse xenograft models of T-cell lymphoma as well as neuroblastoma and the results will be presented. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5434.
Inhibition of collagen cross-linking: A new approach to ocular scarring (1981)

A method for the production of alkali-induced conjunctival scarring in rabbits with minimal corneal involvement is presented. The lathyritic agent Beta-aminopropionitrile (BAPN), an inhibitor of collagen cross-linking, was applied topically for a period of 21 days after induction of injury. There was a statistically significant (p less than .025) increase in both the interpalpebral fissure length and width of scarred treated animals compared with the scarred control group. BAPN did not affect the interpalpebral fissure measurements of unscarred rabbit eyes. No clinical adverse effects were observed after the treatment period. Histological evaluation of the treated scar tissue was consistent with lathyrism.
A novel process of etching EUV masks for future generation technology (2006)

Studies on pattern transfer of next generation lithographic (EUV) photomask were carried out. Based on current absorber layer material candidates, thermodynamic calculations were performed and plasma etch gas system and composition were investigated. The gas systems have the advantage of all etch products being in volatile condition. This is helpful to keep the etch process and etch chamber clean. For etch CD bias challenge in EUV photomask etch, self-mask concept was investigated, which makes anti-reflective (AR) sub-layer of the absorber layer function as a hard mask for the bulk absorber layer beneath. It significantly reduces etch CD bias and improves pattern transfer fidelity. For common candidates of EUV mask absorber layers such as TaBO/TaBN and TaSiON/TaSi, reactive gas systems were proposed according to thermodynamic calculations with all products volatile. AR sub-layers were etched in one gas composition with volatiles. Once the AR sub-layer is etched through, gas composition was changed so that the bulk absorber sub-layer beneath is etched selectively with volatile products. Excellent results in profiles, CD bias, CD uniformity, and underneath buffer/capping layer impact have been demonstrated.
Performance optimization for distributed intra-node-parallel streaming systems (2013)

The performance of intra-node parallel dataflow programs in the context of streaming systems depends mainly on two parameters: the degree of parallelism for each node of the dataflow program as well as the batching size for each node. In the state-of-the-art systems the user has to specify those values manually. Manual tuning of both parameters is necessary in order to get good performance. However, this process is difficult and time consuming-even for experts. In this paper we introduce and optimization algorithm that optimizes both parameters automatically. We define a novel cost model for intra-node parallel dataflow programs with user-defined functions. Furthermore, we introduce different batching schemes to reduce the number of output buffers, i. e., main memory consumption. We implemented our approach on top of the open source system Storm and ran experiments with different workloads. Our results show a throughput improvement of more than one order of magnitude while the optimization time is less than a second.
Multiscale deformation measurements using multispectral optical metrology (2018)

Remote measurements using images are particularly useful in structural health monitoring cases in which the installation of contact sensors is difficult. Some limitations, though, associated with photogrammetry-type optical metrology involve the application of speckle patterns, which become even more important with variable working distance or when the required resolution and sensitivity are not a priori known which are both very practical common issues. In this context, multispectral sensing can circumvent some of the challenges of acquiring data at different working distances. The objective of this investigation is therefore to use multispectral imaging combined with the method of digital image correlation to demonstrate an approach for remote sensing related to deformation measurements at the structural level. To demonstrate this novel approach, two speckle patterns were designed for measurements at specified working distances; one was set to work in the visible and the second in the ultraviolet spectrum. The results show that the spectral specific reflectivity of the speckle patterns can be used for spatial overlay without affecting imaging in either spectral range considered, which allows the extraction of multiscale deformation information.
Holey fiber amplifiers and lasers (2004)

We review our recent activities in the development of small-core, active holey fibers and describe a number of experiments that highlight the advantages of this technology within a range of both linear and nonlinear devices.
Expression of Anthocyanins and Proanthocyanidins after Transformation of Alfalfa with Maize <i>Lc</i>   (2003)

Three anthocyanin regulatory genes of maize (Zea mays; Lc, B-Peru, and C1) were introduced into alfalfa (Medicago sativa) in a strategy designed to stimulate the flavonoid pathway and alter the composition of flavonoids produced in forage. Lc constructs included a full-length gene and a gene with a shortened 5'-untranslated region. Lc RNA was strongly expressed in Lc transgenic alfalfa foliage, but accumulation of red-purple anthocyanin was observed only under conditions of high light intensity or low temperature. These stress conditions induced chalcone synthase and flavanone 3-hydroxylase expression in Lc transgenic alfalfa foliage compared with non-transformed plants. Genotypes containing the Lc transgene construct with a full-length 5'-untranslated region responded more quickly to stress conditions and with a more extreme phenotype. High-performance liquid chromatography analysis of field-grown tissue indicated that flavone content was reduced in forage of the Lc transgenic plants. Leucocyanidin reductase, the enzyme that controls entry of metabolites into the proanthocyanidin pathway, was activated both in foliage and in developing seeds of the Lc transgenic alfalfa genotypes. Proanthocyanidin polymer was accumulated in the forage, but (+)-catechin monomers were not detected. B-Peru transgenic and C1 transgenic populations displayed no visible phenotypic changes, although these transgenes were expressed at detectable levels. These results support the emerging picture of Lc transgene-specific patterns of expression in different recipient species. These results demonstrate that proanthocyanidin biosynthesis can be stimulated in alfalfa forage using an myc-like transgene, and they pave the way for the development of high quality, bloat-safe cultivars with ruminal protein bypass.
Silicon-on-ceramic coating process. Silicon sheet growth development for the Large-Area Silicon Sheet and Cell Development Tasks of the Low-Cost Silicon Solar Array Project. Quarterly report No. 8, December 28, 1977--March 28, 1977 (1978)

A research program to investigate the technical and economic feasibility of producing solar-cell-quality sheet silicon by coating inexpensive ceramic substrates with a thin layer of polycrystalline silicon is described. The coating methods to be developed are directed toward a minimum-cost process for producing solar cells with a terrestrial conversion efficiency of 12 percent or greater. By applying a graphite coating to one face of a ceramic substrate, molten silicon can be caused to wet only that graphite-coated face and produce uniform thin layers of large-grain polycrystalline silicon; thus, only a minimal quantity of silicon is consumed. A dip-coating method for putting silicon on ceramic (SOC) has been shown to produce solar-cell-quality sheet silicon. This method and a continuous coating process also being investigated have excellent scale-up potential which offers an outstanding cost-effective way to manufacture large-area solar cells. A variety of ceramic materials have been dip-coated with silicon. The investigation has shown that mullite substrates containing an excess of SiO/sub 2/ best match the thermal expansion coefficient of silicon and hence produce the best SOC layers. With such substrates, smooth and uniform silicon layers 25 cm/sup 2/ in area have been achieved with single-crystal grains as large as 4 mm in width and several cm in length. Solar cells with areas from 1 to 10 cm/sup 2/ have been fabricated from material withas-grown surface. Recently, an antireflection (AR) coating has been applied to SOC cells. Conversion efficiencies greater than 9% have been achieved without optimizing series resistance characteristics. Such cells typically have open-circuit voltages and short-circuit current densities of 0.51 V and 20 mA/cm/sup 2/, respectively.
The Structural and Functional Role of the B‐chain C‐terminal Arginine in the Relaxin‐3 Peptide Antagonist, R3(BΔ23‐27)R/I5 (2008)

Relaxin-3, a member of the insulin superfamily, is involved in regulating stress and feeding behavior. It is highly expressed in the brain and is the endogenous ligand for the receptor RXFP3. As relaxin-3 also interacts with the relaxin receptor RXFP1, selective agonists and antagonists are crucial for studying the physiological function(s) of the relaxin-3/RXFP3 pair. The analog R3(BDelta23-27)R/I5, in which a C-terminally truncated human relaxin-3 (H3) B-chain is combined with the INSL5 A-chain, is a potent selective RXFP3 antagonist and has an Arg residue remaining on the B-chain C-terminus as a consequence of the recombinant protein production process. To investigate the role of this residue in the RXFP3 receptor binding and activation, the analogs R3(BDelta23-27)R/I5 and R3(BDelta23-27)R containing the B-chain C-terminal Arg as well as R3(BDelta23-27)/I5 and R3(BDelta23-27), both lacking the Arg, were chemically assembled and their secondary structure and receptor activity assessed. The peptides generally had a similar conformation but those with the extra Arg residue displayed a significantly increased affinity for the RXFP3. Interestingly, in contrast to R3(BDelta23-27)R and R3(BDelta23-27)R/I5, the peptide R3(BDelta23-27) is a weak agonist. This suggests that the C-terminal Arg, although increasing the affinity, alters the manner in which the peptide binds to the receptor and thereby prevents activation, giving R3(BDelta23-27)R/I5 its potent antagonistic activity.
Computer Extracted Features from Initial H&E Tissue Biopsies Predict Disease Progression for Prostate Cancer Patients on Active Surveillance (2020)

In this work, we assessed the ability of computerized features of nuclear morphology from diagnostic biopsy images to predict prostate cancer (CaP) progression in active surveillance (AS) patients. Improved risk characterization of AS patients could reduce over-testing of low-risk patients while directing high-risk patients to therapy. A total of 191 (125 progressors, 66 non-progressors) AS patients from a single site were identified using The Johns Hopkins University's (JHU) AS-eligibility criteria. Progression was determined by pathologists at JHU. 30 progressors and 30 non-progressors were randomly selected to create the training cohort D<sub>1</sub> (<i>n</i> = 60). The remaining patients comprised the validation cohort D<sub>2</sub> (<i>n</i> = 131). Digitized Hematoxylin & Eosin (H&E) biopsies were annotated by a pathologist for CaP regions. Nuclei within the cancer regions were segmented using a watershed method and 216 nuclear features describing position, shape, orientation, and clustering were extracted. Six features associated with disease progression were identified using D<sub>1</sub> and then used to train a machine learning classifier. The classifier was validated on D<sub>2</sub>. The classifier was further compared on a subset of D<sub>2</sub> (<i>n</i> = 47) against pro-PSA, an isoform of prostate specific antigen (PSA) more linked with CaP, in predicting progression. Performance was evaluated with area under the curve (AUC). A combination of nuclear spatial arrangement, shape, and disorder features were associated with progression. The classifier using these features yielded an AUC of 0.75 in D<sub>2</sub>. On the 47 patient subset with pro-PSA measurements, the classifier yielded an AUC of 0.79 compared to an AUC of 0.42 for pro-PSA. Nuclear morphometric features from digitized H&E biopsies predicted progression in AS patients. This may be useful for identifying AS-eligible patients who could benefit from immediate curative therapy. However, additional multi-site validation is needed.
Rewired cellular signaling coordinates sugar and hypoxic responses for anaerobic xylose fermentation in yeast (2019)

Microbes can be metabolically engineered to produce biofuels and biochemicals, but rerouting metabolic flux toward products is a major hurdle without a systems-level understanding of how cellular flux is controlled. To understand flux rerouting, we investigated a panel of Saccharomyces cerevisiae strains with progressive improvements in anaerobic fermentation of xylose, a sugar abundant in sustainable plant biomass used for biofuel production. We combined comparative transcriptomics, proteomics, and phosphoproteomics with network analysis to understand the physiology of improved anaerobic xylose fermentation. Our results show that upstream regulatory changes produce a suite of physiological effects that collectively impact the phenotype. Evolved strains show an unusual co-activation of Protein Kinase A (PKA) and Snf1, thus combining responses seen during feast on glucose and famine on non-preferred sugars. Surprisingly, these regulatory changes were required to mount the hypoxic response when cells were grown on xylose, revealing a previously unknown connection between sugar source and anaerobic response. Network analysis identified several downstream transcription factors that play a significant, but on their own minor, role in anaerobic xylose fermentation, consistent with the combinatorial effects of small-impact changes. We also discovered that different routes of PKA activation produce distinct phenotypes: deletion of the RAS/PKA inhibitor IRA2 promotes xylose growth and metabolism, whereas deletion of PKA inhibitor BCY1 decouples growth from metabolism to enable robust fermentation without division. Comparing phosphoproteomic changes across ira2Δ and bcy1Δ strains implicated regulatory changes linked to xylose-dependent growth versus metabolism. Together, our results present a picture of the metabolic logic behind anaerobic xylose flux and suggest that widespread cellular remodeling, rather than individual metabolic changes, is an important goal for metabolic engineering.
Detection and identification of a water mixture of E. coli cells and B. subtilis spores with raman chemical imaging microscopy (2007)

Raman chemical imaging microscopy was used to visualize and discriminate between biological substances with Raman spectral database identification. Water suspensions were investigated for mixtures of different concentrations of E. coli and Bacillus subtilis spores.