gebhart/patrepeval huggingface dataset:
Improvement of Influenza A/Fujian/411/02 (H3N2) Virus Growth in Embryonated Chicken Eggs by Balancing the Hemagglutinin and Neuraminidase Activities, Using Reverse Genetics (2005)

The H3N2 influenza A/Fujian/411/02-like virus strains that circulated during the 2003-2004 influenza season caused influenza epidemics. Most of the A/Fujian/411/02 virus lineages did not replicate well in embryonated chicken eggs and had to be isolated originally by cell culture. The molecular basis for the poor replication of A/Fujian/411/02 virus was examined in this study by the reverse genetics technology. Two antigenically related strains that replicated well in embryonated chicken eggs, A/Sendai-H/F4962/02 and A/Wyoming/03/03, were compared with the prototype A/Fujian/411/02 virus. A/Sendai differed from A/Fujian by three amino acids in the neuraminidase (NA), whereas A/Wyoming differed from A/Fujian by five amino acids in the hemagglutinin (HA). The HA and NA segments of these three viruses were reassorted with cold-adapted A/Ann Arbor/6/60, the master donor virus for the live attenuated type A influenza vaccines (FluMist). The HA and NA residues differed between these three H3N2 viruses evaluated for their impact on virus replication in MDCK cells and in embryonated chicken eggs. It was determined that replication of A/Fujian/411/02 in eggs could be improved by either changing minimum of two HA residues (G186V and V226I) to increase the HA receptor-binding ability or by changing a minimum of two NA residues (E119Q and Q136K) to lower the NA enzymatic activity. Alternatively, recombinant A/Fujian/411/02 virus could be adapted to grow in eggs by two amino acid substitutions in the HA molecule (H183L and V226A), which also resulted in the increased HA receptor-binding activity. Thus, the balance between the HA and NA activities is critical for influenza virus replication in a different host system. The HA or NA changes that increased A/Fujian/411/02 virus replication in embryonated chicken eggs were found to have no significant impact on antigenicity of these recombinant viruses. This study demonstrated that the reverse genetics technology could be used to improve the manufacture of the influenza vaccines.
Structure Sensitivity of Acrolein Hydrogenation by Platinum Nanoparticles on BaxSr1−xTiO3 Nanocuboids (2017)

Abstract The structure sensitivity of Pt nanoparticles (Pt N ) for gas‐phase acrolein (AC) hydrogenation was probed for Pt N on Ba x Sr 1− x TiO 3 nanocuboid supports with (0 0 1) facets in a combined theoretical and experimental study. The in situ selectivity for allyl alcohol increased with the increase of the Sr concentration in the support, which corresponds to modifications in the stable Winterbottom shape and lattice strain of the Pt nanoparticles as a result of the interfacial energy between Pt and the Ba x Sr 1− x TiO 3 supports. “Local model” nanofacets of the Pt surface, edge, and corner morphologies were developed as compact representations of adsorption and reaction sites. DFT was used as the primary modeling tool for the equilibrium adsorption states. We argue that adsorption on edge sites is critically important for the overall allyl alcohol selectivity of Pt N catalysts. A simple model was developed to represent Pt N strain effects caused by its interaction with the substrate. Bader topological atom, spherical volume averaging charge, and modified bond valence sum analyses were used to understand the bonding structure. Density of states analysis was performed for the structures of Pt N , adsorbed AC, and intermediate products to examine adsorbate–particle interactions. The simulated hydrogenation of AC on Pt N nanofacets was compared to the in situ hydrogenation of AC by Pt N on Ba x Sr 1− x TiO 3 to examine the effects of facet, edge, and corner sites on the overall selectivity.
High-Resolution Mapping of Crossovers Reveals Extensive Variation in Fine-Scale Recombination Patterns Among Humans (2008)

Recombination plays a crucial role in meiosis, ensuring the proper segregation of chromosomes. Recent linkage disequilibrium (LD) and sperm-typing studies suggest that recombination rates vary tremendously across the human genome, with most events occurring in narrow "hotspots." To examine variation in fine-scale recombination patterns among individuals, we used dense, genome-wide single-nucleotide polymorphism data collected in nuclear families to localize crossovers with high spatial resolution. This analysis revealed that overall recombination hotspot usage is similar in males and females, with individual hotspots often active in both sexes. Across the genome, roughly 60% of crossovers occurred in hotspots inferred from LD studies. Notably, however, we found extensive and heritable variation among both males and females in the proportion of crossovers occurring in these hotspots.
RITUAL: a performance driven placement algorithm (1992)

An algorithm for obtaining a placement of large scale cell-based ICs subject to performance constraints is described. The problem is formulated as a constrained programming problem and is solved in two phases: continuous and discrete. Constraints are placed on total path delays including cell and interconnect delays, and the behavior of all the paths is captured. Mathematical techniques and heuristics based on Lagrangian relaxation are used to find an approximate solution to the constrained problem. The algorithm yields good results, as shown on a set of real examples. On the average, between 8% and 30% improvement in the interconnect delay of these examples is obtained with little or no impact on chip area after routing by modifying the placement alone.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
In situ detection of the hypermethylation-induced inactivation of the p16 gene as an early event in oncogenesis (1999)

We have developed a technique, methylation-specific PCR in situ hybridization (MSP-ISH), which allows for the methylation status of specific DNA sequences to be visualized in individual cells. We use MSP-ISH to monitor the timing and consequences of aberrant hypermethylation of the p16 tumor suppresser gene during the progression of cancers of the lung and cervix. Hypermethylation of p16 was localized only to the neoplastic cells in both in situ lesions and invasive cancers, and was associated with loss of p16 protein expression. MSP-ISH allowed us to dissect the surprising finding that p16 hypermethylation occurs in cervical carcinoma. This tumor is associated with infection of the oncogenic human papillomavirus, which expresses a protein, E7, that inactivates the retinoblastoma (Rb) protein. Thus, simultaneous Rb and p16 inactivation would not be needed to abrogate the critical cyclin D-Rb pathway. MSP-ISH reveals that p16 hypermethylation occurs heterogeneously within early cervical tumor cell populations that are separate from those expressing viral E7 transcripts. In advanced cervical cancers, the majority of cells have a hypermethylated p16, lack p16 protein, but no longer express E7. These data suggest that p16 inactivation is selected as the most effective mechanism of blocking the cyclin D-Rb pathway during the evolution of an invasive cancer from precursor lesions. These studies demonstrate that MSP-ISH is a powerful approach for studying the dynamics of aberrant methylation of critical tumor suppressor genes during tumor evolution.
실내 CO₂농도가 재실자의 수면의 질에 미치는 영향 (2012)

This study investigated the influence of the indoor CO2concentration level on sleep quality by polysomnography(PSG). One healthy female subject was selected among several subjects based on RI(Risk Indicator) value and BMI(Body Mass Index) value to evaluate judging the risk level of obstructive sleep apnea hypopnea. To get the impact of the indoor carbon dioxide concentration to sleep quality, both CO2concentration levels were set up using ventilating form with 700~800 ppm and 2000~3000 ppm. Other environments were controlled in the comfortable sleep scope by previous researches. To measure the sleep quality, measurements have carried on polysomnography(PSG). In conclusion, it have shown that high carbon dioxide concentration leads arousal effect about central nervous system and to sustaining dreams and excited condition by bring about REM sleep split phenomenon.
Expression of the EWS/FLI-1 Oncogene in Murine Primary Bone-Derived Cells Results in EWS/FLI-1–Dependent, Ewing Sarcoma–Like Tumors (2005)

Ewing sarcoma is the second most common malignant pediatric bone tumor. Over 80% of Ewing sarcoma contain the oncogene EWS/FLI-1, which encodes the EWS/FLI-1 oncoprotein, a hybrid transcription factor comprised of NH2-terminal sequences from the RNA-binding protein EWS and the DNA-binding and COOH-terminal regions of the Ets transcription factor FLI-1. Although numerous genes are dysregulated by EWS/FLI-1, advances in Ewing sarcoma cancer biology have been hindered by the lack of an animal model because of EWS/FLI-1-mediated cytotoxicity. In this study, we have developed conditions for the isolation and propagation of murine primary bone-derived cells (mPBDC) that stably express EWS/FLI-1. Early-passage EWS/FLI-1 mPBDCs were immortalized in culture but inefficient at tumor induction, whereas later-passage cells formed sarcomatous tumors in immunocompetent syngeneic mice. Murine EWS/FLI-1 tumors contained morphologically primitive cells that lacked definitive lineage markers. Molecular characterization of murine EWS/FLI-1 tumors revealed that some but not all had acquired a novel, clonal in-frame p53 mutation associated with a constitutive loss of p21 expression. Despite indications that secondary events facilitated EWS/FLI-1 mPBDC tumorigenesis, cells remained highly dependent on EWS/FLI-1 for efficient transformation in clonogenic assays. This Ewing sarcoma animal model will be a useful tool for dissecting the molecular pathogenesis of Ewing sarcoma and provides rationale for the broader use of organ-specific progenitor cell populations for the study of human sarcoma.
Protein Transduction Domains: Applications for Molecular Medicine (2012)

Protein transduction domains (PTD) or cell penetrating peptides (CTPs) are small peptides able to carry proteins, peptides, nucleic acid, and nanoparticles, including viral particles, across the cellular membranes into cells. In general, PTDs can be classified into 3 types: cationic peptides of 6-12 amino acids in length, comprised predominantly of arginine, ornithine and/or lysine residues; hydrophobic peptides such as leader sequences of secreted growth factors and cytokines; and cell-type specific peptides, identified by screening of peptide phage display libraries. These three types of transduction peptides have many different applications including delivery of therapeutic proteins and drugs, delivery of fluorescent or radioactive compounds for imaging, and improving uptake of DNA, RNA and even viral particles. Here we review the potential applications of protein transduction domains.
Plasma lipoproteins and progression of coronary artery disease evaluated by angiography and clinical events. (1993)

In patients with established coronary heart disease, increased levels of remnants of triglyceride-rich lipoproteins and decreased levels of high-density lipoproteins appear to promote progression of coronary artery atherosclerosis, which in turn may lead to an untoward clinical event. No such relation could be shown for the level of components of low-density lipoproteins. These and other observations call for reevaluation of relations between particular species of lipoproteins containing apolipoprotein B and the pathogenesis of coronary artery atherosclerosis and coronary heart disease.
Purification and characterization of the T4 bacteriophage uvsX protein. (1986)

Gene uvsX of bacteriophage T4 encodes a 40,000-dalton protein that plays a key role in the major pathway for genetic recombination in T4-infected cells. Mutations at the uvsX locus lead to increased sensitivity to various DNA-damaging agents, reduced phage bursts, decreased genetic recombination, and early arrest of DNA synthesis. Like the Escherichia coli recA protein, the purified uvsX protein is a DNA-dependent ATPase that catalyzes pairing between homologous single- and double-stranded DNA molecules in vitro (Yonesaki, T., Ryo, Y., Minagawa, T., and Takahashi, H., (1985) Eur. J. Biochem. 148, 127-134). At physiological salt concentrations, the uvsX protein binds tightly and cooperatively to single-stranded DNA, covering about five nucleotides per protein monomer; at lower salt concentrations, a similar type of binding to double-stranded DNA is detected (Griffith, J., and Formosa, T., (1985) J. Biol. Chem. 260, 4484-4491). We show here that the ATPase activity of this protein is unusual in producing both ADP plus Pi and AMP plus PPi as products. Generating the fully active form of the ATPase is a cooperative process, apparently requiring that a protein monomer be bound to single-stranded DNA while surrounded by other ATP-bound monomers. The catalysis of homologous pairing by the uvsX protein is shown to be greatly stimulated by the presence of the T4 gene 32 protein, a helix-destablizing protein previously studied in this laboratory, and it requires continued ATP hydrolysis. We present a method that allows the purification of the uvsX protein to essential homogeneity. We also describe the complete purification of two proteins that bind to the uvsX protein: the T4 uvsY protein (16,000 daltons) and an E. coli host protein of 32,000 daltons whose gene is unknown. The host protein is likely to play a role in DNA metabolism, because it also binds to the T4 gene 32 protein and to DNA; the sequence of its amino-terminal 29 amino acids has been determined.
The ERBB network facilitates KRAS-driven lung tumorigenesis (2018)

KRAS is the most frequently mutated driver oncogene in human adenocarcinoma of the lung. There are presently no clinically proven strategies for treatment of KRAS-driven lung cancer. Activating mutations in KRAS are thought to confer independence from upstream signaling; however, recent data suggest that this independence may not be absolute. We show that initiation and progression of KRAS-driven lung tumors require input from ERBB family receptor tyrosine kinases (RTKs): Multiple ERBB RTKs are expressed and active from the earliest stages of KRAS-driven lung tumor development, and treatment with a multi-ERBB inhibitor suppresses formation of KRAS<sup>G12D</sup>-driven lung tumors. We present evidence that ERBB activity amplifies signaling through the core RAS pathway, supporting proliferation of KRAS-mutant tumor cells in culture and progression to invasive disease in vivo. Brief pharmacological inhibition of the ERBB network enhances the therapeutic benefit of MEK (mitogen-activated protein kinase kinase) inhibition in an autochthonous tumor setting. Our data suggest that lung cancer patients with KRAS-driven disease may benefit from inclusion of multi-ERBB inhibitors in rationally designed treatment strategies.
Improving Protein Pharmacokinetics by Genetic Fusion to Simple Amino Acid Sequences (2004)

The role of primary amino acid sequences in protein pharmacokinetics, an issue of relevance in both basic knowledge and biotechnology, was addressed here using as a starting point two repetitive antigens from the hemoflagellate Trypanosoma cruzi that are known to stabilize their associated proteins in the bloodstream. A major drawback to their pharmacological application is that these repetitive sequences are highly immunogenic, being therefore the deletion of this characteristic desirable. Based on sequence homology and epitope mapping analyses, an artificial repetitive sequence (PSTAD) was engineered. This motif was tested by genetic fusion to the C terminus of both the trypanosomal trans-sialidase and the rat tyrosine aminotransferase and found to produce a 4.5-6-fold increase in the half-life of the associated proteins in blood while displaying significantly lower immunogenicity. Residues involved in the stabilizing properties of the novel peptide were mapped by a site-directed mutagenesis approach, allowing us to successfully identify another two motifs. Searching databases for sequences displaying some homology, embedded in proline frameworks and associated to shed virulence factors from unrelated microorganisms, resulted in the identification of four other protein extensions. Remarkably, three of them (from Streptococcus pneumoniae, Actinomyces viscosus, and Escherichia coli) revealed similar pharmacokinetic features, suggesting therefore an analogous evolutionarily acquired mechanism to ensure the biodistribution of their corresponding proteins. Our findings indicate that the insertion of defined motifs into a proline-rich framework constitutes a suitable alternative to construct a chimeric protein with extended half-life in blood.
Concurrent Cetuximab and Bevacizumab Therapy in a Murine Orthotopic Model of Anaplastic Thyroid Carcinoma (2007)

Cetuximab and bevacizumab alone and in combination inhibit tumor growth and angiogenesis in an in vivo model of ATC. Also, this therapy was superior to doxorubicin therapy.
Tissue specific changes in acyl-CoA: cholesterol acyltransferase (ACAT) mRNA levels in rabbits. (1995)

A human cDNA clone (K1) was recently isolated that encodes functional acyl-CoA:cholesterol acyltransferase (ACAT) protein (Chang et al. J. Biol. Chem. 1993. 268: 20747-20755). We used the K1 clone to screen a rabbit liver cDNA library and isolated a 919 base pair partial rabbit cDNA (ACAT14b) that was greater than 90% homologous with the human nucleotide sequence. Northern blotting using the rabbit ACAT cDNA14b revealed the existence of at least six related mRNA species (ranging from 6.2 to 1.7 kb) in various rabbit tissues. Using an RNAse protection assay, ACAT mRNA14b was detected in twelve separate rabbit organs. Adrenal gland contained the highest concentrations of ACAT mRNA14b (per microgram of total RNA) being 20-, 30-, and 50-fold higher than small intestine, aorta, and liver, respectively. Additional studies with isolated liver cell populations revealed that rabbit hepatic nonparenchymal cells contained 30-fold more ACAT mRNA14b (per microgram of total RNA) than parenchymal cells. To determine whether ACAT mRNA14b levels are regulated in vivo, rabbits were fed for 4 weeks a high fat/high cholesterol diet (HFHC; 0.5% cholesterol, 3% coconut oil, 3% peanut oil) at which point they were either kept for an additional 4 weeks on the HFHC-diet or switched to the HFHC-diet plus CI-976 (50 mg/kg), a potent and specific ACAT inhibitor; another group of rabbits was fed a chow diet for the entire 8 weeks. The HFHC-diet caused a 2- and 3-fold increase in hepatic and aortic ACAT mRNA14b levels, respectively, in comparison to chow-fed animals; there was no change in adrenal or small intestine levels. CI-976 treatment lowered ACAT mRNA14b levels by 60% and 40% in liver and aorta, respectively, in comparison to the HFHC controls; again there was no change in adrenal or small intestine levels. These data indicate that ACAT mRNA14b levels increase in a tissue specific manner in response to dietary fat and cholesterol.
DoReFa-Net: Training Low Bitwidth Convolutional Neural Networks with Low Bitwidth Gradients (2016)

We propose DoReFa-Net, a method to train convolutional neural networks that have low bitwidth weights and activations using low bitwidth parameter gradients. In particular, during backward pass, parameter gradients are stochastically quantized to low bitwidth numbers before being propagated to convolutional layers. As convolutions during forward/backward passes can now operate on low bitwidth weights and activations/gradients respectively, DoReFa-Net can use bit convolution kernels to accelerate both training and inference. Moreover, as bit convolutions can be efficiently implemented on CPU, FPGA, ASIC and GPU, DoReFa-Net opens the way to accelerate training of low bitwidth neural network on these hardware. Our experiments on SVHN and ImageNet datasets prove that DoReFa-Net can achieve comparable prediction accuracy as 32-bit counterparts. For example, a DoReFa-Net derived from AlexNet that has 1-bit weights, 2-bit activations, can be trained from scratch using 6-bit gradients to get 46.1\% top-1 accuracy on ImageNet validation set. The DoReFa-Net AlexNet model is released publicly.
The Carboxyl Terminus of B Class Ephrins Constitutes a PDZ Domain Binding Motif (1999)

Ephrin B proteins function as ligands for B class Eph receptor tyrosine kinases and are postulated to possess an intrinsic signaling function. The sequence at the carboxyl terminus of B-type ephrins contains a putative PDZ binding site, providing a possible mechanism through which transmembrane ephrins might interact with cytoplasmic proteins. To test this notion, a day 10.5 mouse embryonic expression library was screened with a biotinylated peptide corresponding to the carboxyl terminus of ephrin B3. Three of the positive cDNAs encoded polypeptides with multiple PDZ domains, representing fragments of the molecule GRIP, the protein syntenin, and PHIP, a novel PDZ domain-containing protein related to Caenorhabditis elegans PAR-3. In addition, the binding specificities of PDZ domains previously predicted by an oriented library approach (Songyang, Z., Fanning, A. S., Fu, C., Xu, J., Marfatia, S. M., Chishti, A. H., Crompton, A., Chan, A. C., Anderson, J. M., and Cantley, L. C. (1997) Science 275, 73-77) identified the tyrosine phosphatase FAP-1 as a potential binding partner for B ephrins. In vitro studies demonstrated that the fifth PDZ domain of FAP-1 and full-length syntenin bound ephrin B1 via the carboxyl-terminal motif. Lastly, syntenin and ephrin B1 could be co-immunoprecipitated from transfected COS-1 cells, suggesting that PDZ domain binding of B ephrins can occur in cells. These results indicate that the carboxyl-terminal motif of B ephrins provides a binding site for specific PDZ domain-containing proteins, which might localize the transmembrane ligands for interactions with Eph receptors or participate in signaling within ephrin B-expressing cells.
Glucagon and regulation of glucose metabolism (2003)

As a counterregulatory hormone for insulin, glucagon plays a critical role in maintaining glucose homeostasis in vivo in both animals and humans. To increase blood glucose, glucagon promotes hepatic glucose output by increasing glycogenolysis and gluconeogenesis and by decreasing glycogenesis and glycolysis in a concerted fashion via multiple mechanisms. Compared with healthy subjects, diabetic patients and animals have abnormal secretion of not only insulin but also glucagon. Hyperglucagonemia and altered insulin-to-glucagon ratios play important roles in initiating and maintaining pathological hyperglycemic states. Not surprisingly, glucagon and glucagon receptor have been pursued extensively in recent years as potential targets for the therapeutic treatment of diabetes.