gebhart/patrepeval huggingface dataset:
Molecular variation at the vermilion locus in geographically diverse populations of Drosophila melanogaster and D. simulans. (1995)

We surveyed nucleotide variation at vermilion in population samples of Drosophila melanogaster from Africa, Asia and the Americas to test the hypothesis that the vermilion gene was a target of balancing selection and to improve our understanding of geographic differentiation. Patterns of polymorphism and divergence showed no evidence for non-neutral evolution. However, the frequency spectrum of polymorphic sites in some non-African samples departed from the neutral equilibrium expectation. Furthermore, there were high levels of linkage disequilibrium in non-African samples, despite apparently high rates of crossing over in the vermilion region. In the absence of comparable data from other loci in these same population samples, we cannot determine whether the unusual patterns of variation at vermilion reflect demographic as opposed to locus-specific events. We found surprisingly high levels of differentiation at vermilion between U.S. and Congo samples of D. simulans. In light of previously published allozyme and mtDNA data that provided no evidence for significant differentiation between African and non-African D. simulans populations, the vermilion data raise the possibility that both mtDNA and allozymes have been influenced by selection.
STUDIES OF CANINE RESPIRATORY VIRUSES. I. EXPERIMENTAL INFECTION OF DOGS WITH AN SV5-LIKE CANINE PARAINFLUENZA AGENT1 (1971)

Journal Article STUDIES OF CANINE RESPIRATORY VIRUSES. I. EXPERIMENTAL INFECTION OF DOGS WITH AN SV5-LIKE CANINE PARAINFLUENZA AGENT Get access FELIX J. ROSENBERG, FELIX J. ROSENBERG Search for other works by this author on: Oxford Academic PubMed Google Scholar FLORENCE S. LIEF, FLORENCE S. LIEF Reprint requests to Dr. Lief. Search for other works by this author on: Oxford Academic PubMed Google Scholar JUDSON D. TODD, JUDSON D. TODD Search for other works by this author on: Oxford Academic PubMed Google Scholar JOHN S. REIF JOHN S. REIF Search for other works by this author on: Oxford Academic PubMed Google Scholar American Journal of Epidemiology, Volume 94, Issue 2, August 1971, Pages 147–165, https://doi.org/10.1093/oxfordjournals.aje.a121307 Published: 01 August 1971 Article history Received: 16 December 1970 Published: 01 August 1971
Graph-to-Sequence Learning using Gated Graph Neural Networks (2018)

Many NLP applications can be framed as a graph-to-sequence learning problem. Previous work proposing neural architectures on this setting obtained promising results compared to grammar-based approaches but still rely on linearisation heuristics and/or standard recurrent networks to achieve the best performance. In this work, we propose a new model that encodes the full structural information contained in the graph. Our architecture couples the recently proposed Gated Graph Neural Networks with an input transformation that allows nodes and edges to have their own hidden representations, while tackling the parameter explosion problem present in previous work. Experimental results show that our model outperforms strong baselines in generation from AMR graphs and syntax-based neural machine translation.
Functional Expression of a Bacterial Xylose Isomerase in Saccharomyces cerevisiae (2009)

In industrial fermentation processes, the yeast Saccharomyces cerevisiae is commonly used for ethanol production. However, it lacks the ability to ferment pentose sugars like d-xylose and l-arabinose. Heterologous expression of a xylose isomerase (XI) would enable yeast cells to metabolize xylose. However, many attempts to express a prokaryotic XI with high activity in S. cerevisiae have failed so far. We have screened nucleic acid databases for sequences encoding putative XIs and finally were able to clone and successfully express a highly active new kind of XI from the anaerobic bacterium Clostridium phytofermentans in S. cerevisiae. Heterologous expression of this enzyme confers on the yeast cells the ability to metabolize d-xylose and to use it as the sole carbon and energy source. The new enzyme has low sequence similarities to the XIs from Piromyces sp. strain E2 and Thermus thermophilus, which were the only two XIs previously functionally expressed in S. cerevisiae. The activity and kinetic parameters of the new enzyme are comparable to those of the Piromyces XI. Importantly, the new enzyme is far less inhibited by xylitol, which accrues as a side product during xylose fermentation. Furthermore, expression of the gene could be improved by adapting its codon usage to that of the highly expressed glycolytic genes of S. cerevisiae. Expression of the bacterial XI in an industrially employed yeast strain enabled it to grow on xylose and to ferment xylose to ethanol. Thus, our findings provide an excellent starting point for further improvement of xylose fermentation in industrial yeast strains.
A simple "universal" DNA extraction procedure using SDS and proteinase K is compatible with direct PCR amplification. (1995)

Department of Medical Microbiology, University of Z/irich, 8028 Z/irich, Switzerland A large number of different protocols for the efficient isolation of highly purified DNA from eukaryotic and prokaryotic cells is extant. (1-4) These procedures usually include treatment with proteinase K in the presence of SDS, which efficiently lyses the cells and nuclei and liberates the DNA tightly bound in chromatin. (s) Proteins are then extracted with phenol and chloroform, and the nucleic acids are precipitated with ethanol. This procedure is tedious and time-consuming, and significant amounts of DNA may be lost, especially when working with small specimens (e.g., joint biopsies). Therefore, this approach is not appropriate for diagnostic tests. Direct amplification of digested samples without phenol/chloroform extraction and precipitation is not possible because SDS is inhibitory to Taq polymerase at concentrations as low as 0 . 0 1 % . (6) Alternative simple DNA extraction procedures have been used but have often resulted in incomplete lysis of the cells. These procedures typically have included detergents (e.g., Triton X-100), chaotropes (e.g., guanidium isothiocyanate or sodium iodide), proteases (e.g., proteinase K), substances that lyse erythrocytes and leukocytes (e.g., saponin), or heat denaturation. (7) Often nonionic detergents such as Tween 20 or Laureth 12 in combination with proteinase K are used, followed by heat inactivation of the enzyme prior to PCR amplification. (7-1°) In our laboratory we have aimed at establishing an efficient but simple DNA extraction procedure applicable to various types of clinical specimens, including tissue, sputum, liquid specimens, and bacterial cultures. The procedure would allow direct PCR amplification without purification or precipitation of the DNA. Here, we describe the application of the widely used SDS/proteinase K method made compatible with direct PCR amplification, and including the use of uracil N glycosylase (UNG) to prevent false positives caused by amplicon carryover.( ] 1)
Electrografting of Poly(ethylene glycol) Acrylate: A One‐Step Strategy for the Synthesis of Protein‐Repellent Surfaces (2005)

Hydrophilic adherent coatings: Electrografting of acrylate end-capped poly(ethylene glycol) (PEG) is an important technique for the one-step coating of electroconductive substrates by an adherent hydrophilic coating (see figure). This technique is very efficient for the production of new protein-repellent surfaces.
Index array flattening through program transformation (1995)

This paper presents techniques for compiling loops with complex, indirect array accesses into loops whose array references have at most one level of indirection. The transformation allows prefetching of array indices for more efficient structuring of communication on distributed-memory machines. It can also improve performance on other architectures by enabling prefetching of data between levels of the memory hierarchy or exploitation of hardware support for vectorized gather/scatter. Our techniques are implemented in a compiler for Fortran D and execution speed improvements are given for multiprocessor and vector machines.
Dual targeting of EGFR can overcome a major drug resistance mutation in mouse models of EGFR mutant lung cancer (2009)

EGFR is a major anticancer drug target in human epithelial tumors. One effective class of agents is the tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib. These drugs induce dramatic responses in individuals with lung adenocarcinomas characterized by mutations in exons encoding the EGFR tyrosine kinase domain, but disease progression invariably occurs. A major reason for such acquired resistance is the outgrowth of tumor cells with additional TKI-resistant EGFR mutations. Here we used relevant transgenic mouse lung tumor models to evaluate strategies to overcome the most common EGFR TKI resistance mutation, T790M. We treated mice bearing tumors harboring EGFR mutations with a variety of anticancer agents, including a new irreversible EGFR TKI that is under development (BIBW-2992) and the EGFR-specific antibody cetuximab. Surprisingly, we found that only the combination of both agents together induced dramatic shrinkage of erlotinib-resistant tumors harboring the T790M mutation, because together they efficiently depleted both phosphorylated and total EGFR. We suggest that these studies have immediate therapeutic implications for lung cancer patients, as dual targeting with cetuximab and a second-generation EGFR TKI may be an effective strategy to overcome T790M-mediated drug resistance. Moreover, this approach could serve as an important model for targeting other receptor tyrosine kinases activated in human cancers.
Intramuscular Injection of AAV8 in Mice and Macaques Is Associated with Substantial Hepatic Targeting and Transgene Expression (2014)

Intramuscular (IM) administration of adeno-associated viral (AAV) vectors has entered the early stages of clinical development with some success, including the first approved gene therapy product in the West called Glybera. In preparation for broader clinical development of IM AAV vector gene therapy, we conducted detailed pre-clinical studies in mice and macaques evaluating aspects of delivery that could affect performance. We found that following IM administration of AAV8 vectors in mice, a portion of the vector reached the liver and hepatic gene expression contributed significantly to total expression of secreted transgenes. The contribution from liver could be controlled by altering injection volume and by the use of traditional (promoter) and non-traditional (tissue-specific microRNA target sites) expression control elements. Hepatic distribution of vector following IM injection was also noted in rhesus macaques. These pre-clinical data on AAV delivery should inform safe and efficient development of future AAV products.
In situ hybridization in neurobiology : advances in methodology (1994)

1. Methodological considerations in the utilization of In situ hybridization 2. Combining non-isotopic In situ hybridization histochemistry with steroid autoradiography 3. Development of techniques to combine isotopic and non-isotopic In situ hybridization and immunocytochemistry for phenotypic characterization of individual neurons 4. Enzyme histochemical detection of neuronal mRNA 5. Characterization of the receptor complement of individual neurons using dual-label In situ hybridization histochemistry 6. Assessment of peptide secretion and gene expression within individual cells 7. Quantitative micro-In situ hybridation 8. Quantification of In situ hybridization histochemistry 9. Analysis of transcription levels using intervening sequence In situ hybridization 10. Analysis of alternatively-transcribed messages in brain by In situ hybridization using biotinylated oligonucleotide probes 11. In situ polymerase chain reaction: A powerful new methodology 12. In situ transcription: Methodology and multi-faceted applications
Structural features of the herpes simplex virus alpha gene 4, 0, and 27 promoter-regulatory sequences which confer alpha regulation on chimeric thymidine kinase genes (1982)

Previous studies have shown that herpes simplex virus genes form three groups, alpha, beta, and gamma, whose expression is coordinately regulated and sequentially ordered in a cascade fashion. Chimeric genes constructed by fusion of the coding and 5' nontranslated leader sequences of the thymidine kinase (TK) gene to the sequences upstream from the site of initiation of transcription of alpha genes 4 and 27 are regulated as alpha genes and are induced in cells converted to TK+ phenotype by infection with TK- virus. In alpha gene 4 (S. Mackem and B. Roizman, Proc. Natl. Acad. Sci. U.S.A. 79:4917-4921, 1982), both the promoter and the regulatory region are separable and movable. The promoter permits expression but not induction when fused to TK in the noncoding leader region of the gene. The regulator, when fused to the promoter of an expressible but noninducible portion of the natural beta TK, renders the gene inducible as an alpha gene; it consists of multiple regulatory units acting cumulatively. In this paper, we report on the precise site of initiation of transcription of alpha gene 0 within the inverted b sequences of the L component of viral DNA. We also report the following. (i) The chimeric gene consisting of the coding and 5' nontranslated leader regions of the TK gene fused to portions of the domain of alpha gene 0 extending largely upstream from the site of initiation of transcription of alpha gene 0 was regulated in the same fashion as the alpha 4- and alpha 27-TK chimeras. The regulatory region in the alpha gene 0 is largely upstream from nucleotide - 140. (ii) The promoter-regulatory regions of alpha genes 0, 4, and 27 share TATA sequences, A + T-rich (consensus) sequences occurring in regulating regions of alpha genes 0 and 4 in more than one copy, and multiple G + C-rich inverted repeats. The relation of these sequences to the function of the promoter-regulatory regions of the alpha genes is discussed.
Cloning, Expression and Characterization of 3-Hydroxyisobutyrate Dehydrogenase from Pseudomonas denitrificans ATCC 13867 (2013)

The gene encoding an NAD(+)-dependent, 3-hydroxyisobutyrate dehydrogenase (3HIBDH-IV) from Pseudomonas denitrificans ATCC 13867 was cloned and expressed in Escherichia coli BL 21 (DE3) and characterized to understand its physiological relevance in the degradation of 3-hydroxypropionic acid (3-HP). The deduced amino acid sequence showed high similarity to other 3-hydroxyisobutyrate dehydrogenase isozymes (3HIBDHs) of P. denitrificans ATCC 13867. A comparison of 3HIBDH-IV with its relevant enzymes along with molecular docking studies suggested that Lys171, Asn175 and Gly123 are important for its catalytic function on 3-hydroxyacids. The recombinant 3HIBDH-IV was purified to homogeneity utilizing a Ni-NTA-HP resin column in high yield. 3HIBDH-IV was very specific to (S)-3-hydroxyisobutyrate, but also catalyzed the oxidation of 3-HP to malonate semialdehyde. The specific activity and half-saturation constant (K m) for 3-HP at 30°C and pH 9.0 were determined to be 17 U/mg protein and 1.0 mM, respectively. Heavy metals, such as Ag(+) and Hg(2+), completely inhibited the 3HIBDH-IV activity, whereas dithiothreitol, 2-mercaptoethanol and ethylenediaminetetraacetic acid increased its activity 1.5-1.8-fold. This paper reports the characteristics of 3HIBDH-IV as well as its probable role in 3-HP degradation.
Six-month administration of 1% testosterone gel is able to restore erectile function in hypogonadal patients with erectile dysfunction. (2008)

Our study demonstrated that 1% hydroalcoholic testosterone gel is an effective and safe treatment option in subjects with ED.
Catalytic Antibody Route to the Naturally Occurring Epothilones: Total Synthesis of Epothilones A–F (2001)

Naturally occurring epothilones have been synthesized starting from enantiomerically pure aldol compounds 9–11, which were obtained by antibody catalysis. Aldolase antibody 38C2 catalyzed the resolution of (±)-9 by enantioselective retro-aldol reaction to afford 9 in 90 % ee at 50 % conversion. Compounds 10 and 11 were obtained in more than 99 % ee at 50 % conversion by resolution of their racemic mixtures using newly developed aldolase antibodies 84G3, 85H6 or 93F3. Compounds 9, 10 and 11 were resolved in multigram quantities and then converted to the epothilones by metathesis processes, which were catalyzed by Grubbs' catalysts.
Sphingosine-1-phosphate Signaling Promotes Critical Migratory Events in Vasculogenesis (2004)

Here we have investigated the role of sphingosine-1-phosphate (S1P) signaling in the process of vasculogenesis in the mouse embryo. At stages preceding the formation of blood vessels (7.5-8 dpc) in the embryo proper, yolk sac, and allantois, the S1P receptor S1P(2) is expressed in conjunction with S1P(1) and/or S1P(3). Additionally, sphingosine kinase-2 (SK2), an enzyme that catalyzes the formation of S1P, is expressed in these tissues throughout periods of vasculogenesis. Using the cultured mouse allantois explant model of blood vessel formation, we found that vasculogenesis was dependent on S1P signaling. We showed that S1P could replace the ability of serum to promote vasculogenesis in cultured allantois explants. Instead of small poorly reticulated clusters of rounded endothelial cells that formed under serum-free conditions, S1P promoted the formation of elongated endothelial cells that arranged into expansive branched networks of capillary-like vessels. These effects could not be reproduced by vascular endothelial growth factor or basic fibroblast growth factor administration. The ability of S1P to promote blood vessel formation was not due to effects on cell survival or on changes in numbers of endothelial cells (Flk1(+)/PECAM(+)), angioblasts (Flk1(+)/PECAM(-)), or undifferentiated mesodermal cells (Flk1(-)/PECAM(-)). The S1P effect on blood vessel formation was attributed to it promoting migratory activities of angioblasts and early endothelial cells required for the expansion of vascular networks. Together, our findings suggest that migratory events critical to the de novo formation of blood vessels are under the influence of S1P, possibly synthesized via the action of SK2, with signaling mediated by S1P receptors that include S1P(1), S1P(2), and S1P(3).
Upregulation of EphA3 Receptor after Spinal Cord Injury (2005)

Spinal cord injury (SCI) releases a cascade of events that leads to the onset of an inhibitory milieu for axonal regeneration. Some of these changes result from the presence of repulsive factors that may restrict axonal outgrowth after trauma. The Eph receptor tyrosine kinase (RTK) family has emerged as a key repellent cue known to be involved in neurite outgrowth, synapse formation, and axonal pathfinding during development. Given the nonpermissive environment for axonal regeneration after SCI, we questioned whether re-expression of one of these molecules occurs during regenerative failure. We examined the expression profile of EphA3 at the mRNA and protein levels after SCI, using the NYU contusion model. There is a differential distribution of this molecule in the adult spinal cord and EphA3 showed an increase in expression after several injury models like optic nerve and brain injury. Standardized semi-quantitative RT-PCR analysis demonstrated a time-dependent change in EphA3 mRNA levels, without alterations in beta-actin levels. The basal level of EphA3 mRNA in the adult spinal cord is low and its expression was induced 2 days after trauma (the earliest time point analyzed) and this upregulation persisted for 28 days post-injury (the latest time point examined). These results were corroborated at the protein level by immunohistochemical analysis and the cell phenotype identified by double labeling studies. In control animals, EphA3 immunoreactivity was observed in motor neurons of the ventral horn but not in lesioned animals. In addition, GFAP-positive cells were visualized in the ventral region of injured white matter. These results suggest that upregulation of EphA3 in reactive astrocytes may contribute to the repulsive environment for neurite outgrowth and may be involved in the pathophysiology generated after SCI.
On non-preemptive scheduling of period and sporadic tasks (2002)

A fundamental problem in the theory of real-time scheduling is examined: scheduling a set of periodic or sporadic tasks on a uniprocessor without preemption and without inserted idle time. The authors give a necessary and sufficient set of conditions C for a set of periodic or sporadic tasks to be schedulable for arbitrary release times of the tasks. They show that any set of periodic or sporadic tasks that satisfies C can be scheduled with an earliest-deadline-first (EDF) scheduling algorithm. The authors present the scheduling model, briefly review the literature in real-time scheduling, prove that the non-preemptive EDF algorithm is universal for sets of tasks, whether periodic or sporadic, and demonstrate the absence of a universal algorithm for periodic tasks with specified release times. It is proved that the problem of deciding schedulability of a set of concrete periodic tasks is intractable.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Testing of a CR5 Solar Thermochemical Heat Engine Prototype (2010)

Sandia National Laboratories (SNL) is investigating thermochemical approaches for reenergizing CO2 and H2O feed stocks for input to synthetic liquid hydrocarbon fuels production. Key to the approach is the Counter-Rotating-Ring Receiver/Reactor/Recuperator (CR5), a novel solar-driven thermochemical heat engine concept for high-temperature carbon dioxide and water splitting based on two-step, nonvolatile metal oxide thermochemical cycles. The CR5 integrates two reactors, recuperators, and solar receiver and intrinsically separates the product gases. The CR5 thermochemical heat engine concept and the underlying thermodynamics and kinetics have many uncertainties. While results from laboratory scale material tests are promising, they are different than what occurs in a CR5. To evaluate the potential of the CR5 we have designed and built a CR5 prototype. The overall objective of the SNL Sunshine to Petrol (S2P) project is to show a solar thermochemical pathway for the efficient production of liquid fuels from CO2 and H2O feed stocks. To achieve the overall long-term goal of 10% efficient conversion of sunlight to petroleum, the thermochemical solar conversion of sunlight to CO needs to be 20% efficient. The short-term goal for the CR5 prototype is to demonstrate a solar to chemical conversion efficiency of at least 2%. In this paper, we present initial test results for the CR5 prototype in the 16 kWt National Solar Thermal Test Facility (NSTTF) solar furnace in Albuquerque, NM. Lessons learned from the initial tests and approaches for improving performance to achieve our goals are also presented.
Identification of a Mobility-Limiting Scattering Mechanism in Modulation-Doped Si/SiGe Heterostructures (1994)

High electron mobilities in modulation-doped Si/SiGe in the range of (1.5-1.8) \ifmmode\times\else\texttimes\fi{} ${10}^{5}$ ${\mathrm{cm}}^{2}$/V s at 0.4-1.4 K have been achieved by several groups. Those numbers fall short of the expected theoretical value. We have examined how strain in the Si channel affects the low temperature electron mobility by systematically varying the Ge content in the relaxed buffer underneath, and by changing the Si channel thickness. A clear reduction in mobility is observed at a critical layer thickness, which is identified as the thickness at which remaining threading dislocations glide in the Si channel, resulting in misfit dislocations at the bottom interface. Understanding and control of this mechanism have led to the growth of samples with mobility values in the range of (3-4) \ifmmode\times\else\texttimes\fi{} ${10}^{5}$ ${\mathrm{cm}}^{2}$/V s.