gebhart/patrepeval huggingface dataset:
Efficient discovery of DNA polymorphisms in natural populations by Ecotilling (2004)

We have adapted the mutation detection technology used in Targeting Induced Local Lesions in Genomes (TILLING) to the discovery of polymorphisms in natural populations. The genomic DNA of a queried individual is mixed with a reference DNA and used to amplify a target 1-kbp region of DNA with asymmetrically labeled fluorescent primers. After heating and annealing, heteroduplexes are nicked at mismatched sites by the endonuclease CEL I and cut strands are visualized using Li-cor gel analyzers. Putative polymorphisms detected in one fluorescence channel can be verified by appearance of the opposite cut strand in the other channel. We demonstrated the efficiency of this technology, called Ecotilling, by the discovery in 150+ individuals of 55 haplotypes in five genes, ranging from sequences differing by a single nucleotide polymorphism to those representing complex haplotypes. The discovered polymorphisms were confirmed by sequencing and included base-pair changes, small insertions and deletions, and variation in microsatellite repeat number. Ecotilling allows the rapid detection of variation in many individuals and is cost effective because only one individual for each haplotype needs to be sequenced. The technology is applicable to any organism including those that are heterozygous and polyploid.
OX40 Is a Potent Immune-Stimulating Target in Late-Stage Cancer Patients (2013)

OX40 is a potent costimulatory receptor that can potentiate T-cell receptor signaling on the surface of T lymphocytes, leading to their activation by a specifically recognized antigen. In particular, OX40 engagement by ligands present on dendritic cells dramatically increases the proliferation, effector function, and survival of T cells. Preclinical studies have shown that OX40 agonists increase antitumor immunity and improve tumor-free survival. In this study, we performed a phase I clinical trial using a mouse monoclonal antibody (mAb) that agonizes human OX40 signaling in patients with advanced cancer. Patients treated with one course of the anti-OX40 mAb showed an acceptable toxicity profile and regression of at least one metastatic lesion in 12 of 30 patients. Mechanistically, this treatment increased T and B cell responses to reporter antigen immunizations, led to preferential upregulation of OX40 on CD4(+) FoxP3(+) regulatory T cells in tumor-infiltrating lymphocytes, and increased the antitumor reactivity of T and B cells in patients with melanoma. Our findings clinically validate OX40 as a potent immune-stimulating target for treatment in patients with cancer, providing a generalizable tool to favorably influence the antitumor properties of circulating T cells, B cells, and intratumoral regulatory T cells.
Messenger RNA-based vaccines (2004)

RNA is the only molecule known to recapitulate all biochemical functions of life: definition, control and transmission of genetic information, creation of defined three-dimensional structures, enzymatic activities and storage of energy. Because of its versatility and thanks to several recent scientific breakthroughs, RNA became the focus of intense research in molecular medicine at the beginning of the millennium. In particular, mRNA can be seen as a safe and efficient alternative to protein-, recombinant virus- or DNA-based therapies in the field of vaccination. This review summarises the most remarkable advances in this area and presents the advantages and limits of the five different mRNA-based vaccination methods. The paper will present the official, industrial and financial aspects of mRNA-based vaccination that are paving the way for therapeutic and prophylactic drugs with mRNA as the active component.
Glycerol Accelerates Recovery of Barrier Function In Vivo (1999)

Two studies were performed to evaluate the influence of glycerol on the recovery of damaged stratum corneum barrier function. Measurements of transepidermal water loss and capacitance were conducted in a 3-day follow-up after tape stripping (study 1) and a 7-day follow-up after a barrier damage due to a repeated washing with sodium lauryl sulphate. In study 1 a faster barrier repair (transepidermal water loss) was monitored in glycerol-treated sites. Significant differences between glycerol open vs. untreated and glycerol occluded vs. untreated were observed at day 3. Stratum corneum hydration showed significantly higher values in the sites treated with glycerol+occlusion, compared with all other sites. In study 2 a faster barrier repair was seen in glycerol-treated sites, with significant differences against untreated and base-treated sites 7 days after the end of the treatment. Stratum corneum hydration showed highest values in the glycerol treated sites after 3 days of treatment. Glycerol creates a stimulus for barrier repair and improves the stratum corneum hydration; stratum corneum hydration is not strictly related to barrier homeostasis and can be optimized by different mechanisms and pathways. The observed effects were based on the modulation of barrier repair and were not biased by the humectant effect of glycerol. As the glycerol-induced recovery of barrier function and stratum corneum hydration were observed even 7 days after the end of treatment, glycerol can be regarded as a barrier stabilizing and moisturizing compound.
Human Cdk2 is a functional homolog of budding yeast Ime2, the meiosis-specific Cdk-like kinase (2009)

Progression through the cell cycle depends on sequential activation of Cyclin-Dependent Kinase(s). In this report we use budding-yeast meiosis as a tool to elucidate the specific functions of mammalian Cdks. Yeast meiosis is regulated by both Cdc28 (yCdk1) and Ime2 (a meiosis-specific Cdk-like kinase). We show that human Cdk2 is a functional homolog for most of Ime2 functions. It promotes efficient and timely entry into premeiotic DNA replication and the first nuclear division, as well as the regulated transcription of IME1 and the early meiosis-specific genes. We show that this effect is specific, and that neither mice Cdk1, nor mice Cdk4 can suppress ime2. We show that Cdk1 is a functional homolog of Cdc28 that also suppresses one of its meiotic functions, namely inhibiting the transcription of IME1. Cdk2, on the other hand, show dominant negative effects on entry into the cell cycle, most probably by inhibiting the function of Cdc28. Finally, we show that in the meiotic pathway Cdk4 functions as a transcriptional activator.
Über eine einfache Synthese der Yohimbinalkaloide (1976)

Abstract Das zur Synthese D/E‐ trans ‐und D/E‐ cis ‐verknüpfter Yohimbinalkaloide geeignete Zwischenprodukt 2a wird aus 1a durch Dieckmann ‐Kondensation mit 63% Ausbeute erhalten. Anschließende Hydrierung des Enonsystems ergibt Yohimbin ( 8a ) und β‐Yohimbin ( 8b ). Mit Basen wird 2a zu 3a umgewandelt, aus dem über 6a und 7a Alloyohimbin, α‐Yohimbin, 3‐Epi‐α‐yohimbin und die in der Natur nicht vorkommenden Isomeren 8e , g , h und i mit D/E‐ cis ‐Verknüpfung als Racemate erhalten werden.
High efficiency transformation of Schizosaccharomyces pombe pretreated with thiol compounds by electroporation (2001)

A highly efficient method for transformation of the fission yeast Schizosaccharomyces pombe by electroporation has been developed. Significantly higher transformation efficiency was obtained when intact cells grown in SD medium (0.67% Bacto yeast nitrogen base without amino acids, 2% glucose) were pretreated with thiol compounds before an electric pulse was applied to the cells. Among the thiol compounds tested, dithiothreitol (DTT) was the most effective for pretreatment. A high transformation efficiency was obtained when the cells were pretreated with 25 mM DTT at 30°C for 15 min in an osmotically adjusted buffer, since the cells were sensitive to osmotic pressure. It was important to exclude glucose from the DTT pretreatment buffer, as it caused a drastic decrease in efficiency. The optimal cell concentration and amount of DNA during the electric pulse were 1×109 cells/ml and 10 ng, respectively. The maximum transformation efficiency, 1.2×107 transformants/µg plasmid DNA, was obtained when an electric pulse of 11.0 kV/cm was applied for 5 ms. Furthermore, the high competency of cells pretreated with DTT was maintained by freezing them in a non-permeating cryoprotectant such as sorbitol. Copyright © 2001 John Wiley & Sons, Ltd.
Peptide Nucleic Acids: Analogs and Derivatives (2000)

Peptide Nucleic Acids (PNA) invented ten years ago are emerging rapidly as useful molecules in DNA hybridization and antisense techniques. Although therapeutic drugs based on PNA are still not in sight, applications in diagnostics, in particular in situ hybridization and PCR based systems, are making rapid strides. The simple structure of PNA in combination with impressive DNA mimicking properties has already provided inspiration to many synthetic organic chemists for designing and preparing several derivatives and analogs towards improving their physico-chemical and biological properties. This review which is not intended to be exhaustive, is aimed at highlighting the current progress in the areas of PNA chemistry, structure, hybridization, and applications. The various chemical backbone modifications of PNA reported till date are summarized in the context of DNA hybridization properties
Inhibition of the Complement Cascade by the Major Secretory Protein of Vaccinia Virus (1990)

The complement system contributes to host defenses against invasion by infectious agents. A 35-kilodalton protein, encoded by vaccinia virus and secreted from infected cells, has sequence similarities to members of a gene family that includes complement control proteins. Biochemical and genetic studies showed that the viral protein binds to derivatives of the fourth component of complement and inhibits the classical complement cascade, suggesting that it serves as a defense molecule to help the virus evade the consequences of complement activation.
STUDIES ON PLATELETS (1947)

Abstract 1. Washed isolated platelets added to physiologic saline produce fall in surface tension. 2. Higher concentrations of platelets in saline cause a greater fall in surface tension than lower concentrations. 3. After centrifugation of platelets suspended in saline, the supernatant may show a fall in surface tension as compared to saline in which no platelets have been suspended. In the higher concentrations of platelets, the fall is much greater than in the lower concentrations. 4. When platelets are suspended in heparinized plasma, they exhibit either no change or a higher surface tension than do either their supernatants following centrifugation or the heparinized plasma alone. 5. No full explanation for the observed phenomena can be given.
Activity and Transcriptional Regulation of Bacterial Protein-Like Glycerol-3-Phosphate Dehydrogenase of the Haloarchaea in Haloferax volcanii (2011)

Glycerol is a primary energy source for heterotrophic haloarchaea and a major component of "salty" biodiesel waste. Glycerol is catabolized solely by glycerol kinase (encoded by glpK) to glycerol-3-phosphate (G3P) in Haloferax volcanii. Here we characterized the next critical step of this metabolic pathway: the conversion of G3P to dihydroxyacetone phosphate by G3P dehydrogenase (G3PDH). H. volcanii harbors two putative G3PDH operons: (i) glpA1B1C1, located on the chromosome within the neighborhood of glpK, and (ii) glpA2B2C2, on megaplasmid pHV4. Analysis of knockout strains revealed that glpA1(and not glpA2) is required for growth on glycerol. However, both glpA1 and glpA2 could complement a glpA1 knockout strain (when expressed from a strong promoter in trans) and were required for the total G3PDH activity of cell lysates. The glpA1B1C1, glpK, glpF(encoding a putative glycerol facilitator), and ptsH2(encoding a homolog of the bacterial phosphotransferase system protein Hpr) genes were transcriptionally linked and appeared to be under the control of a strong, G3P-inducible promoter upstream of glpA1. Overall, this study provides fundamental insights into glycerol metabolism in H. volcanii and enhances our understanding of central metabolic pathways of haloarchaea.
Cognitive mission planning and system orchestration (2017)

We present an approach to increase likelihood that an automated reasoning system will make the best decisions for a system and sensor resource manager (SSRM) with limited resources. The introduction of automated game theory to mission planning allows for a modular architecture and scalable approach across a range of platforms and facilitates rapid integration of new modes and technology. Game theory enhances a multi-objective management system, enabling it to intelligently coordinate and optimally achieve disparate mission objectives of a converged system. Our solution may also save money by offering a Pareto efficient process for mission plan validation, which reduces time needed to validate scenarios. An area of significant contribution in our work is our new genetic linear optimization, which is an innovative, developmental extension of our efforts comparing genetic algorithms with linear programming. We show results in receiver-operating characteristic (ROC) curves and compare the performance. We also quantify the performance improvement across all combinations of decisions or players in a linear program. We further enhance decision making by combining the best parts of multiple solutions. Our design provides insight into the most important or optimal weights for degrees of freedom and can be used to efficiently tune those weights. We also discuss tradeoffs for improving processing time with a sensitivity analysis.
Discovery and structure-function analysis of alpha-melanocyte-stimulating hormone antagonists. (1994)

Structure-function relationships of alpha-melanocyte-stimulating hormone (alpha-MSH, alpha-melanotropin) were investigated and novel alpha-MSH receptor antagonists were identified. Based on the alpha-MSH-[5-13] peptide sequence, a multi-use peptide library consisting of 31,360 structurally different candidates was generated, and approximately 40% of the peptides were individually screened for their ability to block receptor function. This led to the identification of antagonists with a range of potencies and revealed structural requirements necessary for receptor inactivation. The most potent antagonist Met-Pro-D-Phe-Arg-D-Trp-Phe-Lys-Pro-Val-NH2 has an IC50 value of 11 +/- 7 nM. Analysis revealed that D-Trp5 and Phe6 were crucial to its antagonistic properties which could be potentiated by D-Phe3. This study demonstrates that residues in positions 5-6, 7-9, and 10 of the alpha-MSH sequence constitute crucial determinants for potent antagonist activity.
Imaging of gene expression in living cells and tissues (2005)

It is possible to observe gene expression within single cells using a tetracycline inducible promoter for activation. Transcription can be observed by using a fluorescent fusion protein to bind nascent RNA. Ultimately, it is desirable to activate a reporter gene within a single cell with only photons. This is achieved by preparing a chemically altered transcription factor that is functionally unable to activate a reporter gene until it is exposed to photon excitation. We apply two-photon imaging to visualize tumor cells expressing a transgene and ultimately this approach will provide the means to activate a specific gene within a single cell within any tissue to ultimately observe its functional significance in situ.
Ultrawide‐Bandgap Semiconductors: Research Opportunities and Challenges (2017)

Abstract Ultrawide‐bandgap (UWBG) semiconductors, with bandgaps significantly wider than the 3.4 eV of GaN, represent an exciting and challenging new area of research in semiconductor materials, physics, devices, and applications. Because many figures‐of‐merit for device performance scale nonlinearly with bandgap, these semiconductors have long been known to have compelling potential advantages over their narrower‐bandgap cousins in high‐power and RF electronics, as well as in deep‐UV optoelectronics, quantum information, and extreme‐environment applications. Only recently, however, have the UWBG semiconductor materials, such as high Al‐content AlGaN, diamond and Ga 2 O 3 , advanced in maturity to the point where realizing some of their tantalizing advantages is a relatively near‐term possibility. In this article, the materials, physics, device and application research opportunities and challenges for advancing their state of the art are surveyed.
The Coronary Vasodilatory and Hypotensive Effects of 3, 3', 4, 5'-Tetrahydroxystilbene and Its Derivatives (1984)

3, 3', 4, 5'-Tetrahydroxystilbene (1) isolated from the heartwood of Cassia garrettiana CRAIB showed strong coronary vasodilatory effects on guinea-pigs and hypotensive effects on rats. On the other hand, the coronary vasodilatory effects of derivatives of 1, i.e., 1-tetraacetate (2), 1-tetramethyl ether (3) and 3, 3', 4, 5'-tetrahydroxybibenzyl (4) were lower than that of 1. The hypotensive effect of 4 which was most weak in the coronary effect was far lower than that of 1. It is clear that for coronary vasodilatory effect, both the hydroxyl groups attached to benzene rings and trans-olefin structure are necessary while for hypotensive effect trans-olefin structure is necessary.
Directed Evolution Generates a Novel Oncolytic Virus for the Treatment of Colon Cancer (2008)

Using the "Directed Evolution" methodology, we have generated ColoAd1, a novel chimeric oncolytic virus. In vitro, this virus demonstrated a >2 log increase in both potency and selectivity when compared to ONYX-015 on colon cancer cells. These results were further supported by in vivo and ex vivo studies. Furthermore, these results have validated this methodology as a new general approach for deriving clinically-relevant, highly potent anti-cancer virotherapies.
Enhancement of mucosal IgA responses by interleukins 5 and 6 encoded in recombinant vaccine vectors (1994)

The expression of the genes for murine interleukin-5 (IL-5) or IL-6 in recombinant vaccinia virus vectors markedly increased IgA reactivity to co-expressed heterologous antigen in the lungs of mice inoculated intranasally with the viruses. These elevated local IgA responses reached a peak four times higher than those elicited by control viruses 14 days after infection and these peak levels were maintained for at least four weeks. Elevated IgA responses, reaching a peak 3-4 weeks after immunization, were also observed in the lungs of mice inoculated with IL-6 expressed by another vector, fowlpox virus. The results indicate that these factors enhance the development of mucosal IgA reactivity in vivo and suggest that their expression in mucosal vaccine vectors may stimulate local immune responses. The approach described in this study may be useful in stimulating mucosal immunity to a wide range of vector-encoded antigens, not only for vaccination against disease but also for immunocontraception by the co-expression of antigens involved in reproduction.
Peak-to-Average Power Ratio Analysis for NC-OFDM Transmissions (2007)

In this paper, we present a statistical analysis of the peak-to-average power ratio (PAPR) for non-contiguous orthogonal frequency division multiplexing (NC-OFDM) signals. When studying contiguous OFDM signals, most PAPR analysis techniques assume the symbols to be identically and independently distributed (i.i.d.). However, in an NC-OFDM transmission, where a large number of subcarriers could be deactivated, this assumption is no longer valid. The proposed PAPR analysis is derived specifically for the NC-OFDM transmission scenario. Results show that NC-OFDM signal exhibit higher PAPR values relative to contiguous OFDM transmission at the same information rate.
Sendai Virus Y Proteins Are Initiated by a Ribosomal Shunt (1998)

The Sendai virus P/C mRNA expresses eight primary translation products by using a combination of ribosomal choice and cotranscriptional mRNA editing. The longest open reading frame (ORF) of the mRNA starts at AUG104 (the second initiation site) and encodes the 568-amino-acid P protein, an essential subunit of the viral polymerase. The first (ACG81), third (ATG114), fourth (ATG183), and fifth (ATG201) initiation sites are used to express a C-terminal nested set of polypeptides (collectively named the C proteins) in the +1 ORF relative to P, namely, C', C, Y1, and Y2, respectively. Leaky scanning accounts for translational initiation at the first three start sites (a non-ATG followed by ATGs in progressively stronger contexts). Consistent with this, changing ACG81/C' to ATG (GCCATG81G) abrogates expression from the downstream ATG104/P and ATG114/C initiation codons. However, expression of the Y1 and Y2 proteins remains normal in this background. We now have evidence that initiation from ATG183/Y1 and ATG201/Y2 takes place via a ribosomal shunt or discontinuous scanning. Scanning complexes appear to assemble at the 5' cap and then scan ca. 50 nucleotides (nt) of the 5' untranslated region before being translocated to an acceptor site at or close to the Y initiation codons. No specific donor site sequences are required, and translation of the Y proteins continues even when their start codons are changed to ACG. Curiously, ATG codons (in good contexts) in the P ORF, placed either 16 nt upstream of Y1, 29 nt downstream of Y2, or between the Y1 and Y2 codons, are not expressed even in the ACGY1/ACGY2 background. This indicates that ATG183/Y1 and ATG201/Y2 are privileged start sites within the acceptor site. Our observations suggest that the shunt delivers the scanning complex directly to the Y start codons.
Frequency–wavenumber domain filtering for improved damage visualization (2007)

This paper presents a technique for the analysis of full wavefield data in the wavenumber/frequency domain as an effective tool for damage detection, visualization and characterization. Full wavefield data contain a wealth of information regarding the space and time variation of propagating waves in damaged structural components. Such information can be used to evaluate the response spectrum in the frequency/wavenumber domain, which effectively separates incident waves from reflections caused by discontinuities encountered along the wave paths. This allows removing the injected wave from the overall response through simple filtering strategies, thus highlighting the presence of reflections associated with damage. The concept is first illustrated on analytical and numerically simulated data, and then tested on experimental results. In the experiments, full wavefield measurements are conveniently obtained using a scanning laser Doppler vibrometer, which allows the detection of displacements and/or velocities over a user-defined grid, and it is able to provide the required spatial and time information in a timely manner. Tests performed on a simple aluminum plate with artificially seeded slits simulating longitudinal cracks, and on a disbonded tongue and groove joint, show the effectiveness of the technique and its potentials for the inspection of a variety of structural components.