gebhart/patrepeval huggingface dataset:
Signaling networks assembled by oncogenic EGFR and c-Met (2008)

A major question regarding the sensitivity of solid tumors to targeted kinase inhibitors is why some tumors respond and others do not. The observation that many tumors express EGF receptor (EGFR), yet only a small subset with EGFR-activating mutations respond clinically to EGFR inhibitors (EGFRIs), suggests that responsive tumors uniquely depend on EGFR signaling for their survival. The nature of this dependence is not understood. Here, we investigate dependence on EGFR signaling by comparing non-small-cell lung cancer cell lines driven by EGFR-activating mutations and genomic amplifications using a global proteomic analysis of phospho-tyrosine signaling. We identify an extensive receptor tyrosine kinase signaling network established in cells expressing mutated and activated EGFR or expressing amplified c-Met. We show that in drug sensitive cells the targeted tyrosine kinase drives other RTKs and an extensive network of downstream signaling that collapse with drug treatment. Comparison of the signaling networks in EGFR and c-Met-dependent cells identify a “core network” of ≈50 proteins that participate in pathways mediating drug response.
The yellow fever 17D virus as a platform for new live attenuated vaccines (2014)

The live-attenuated yellow fever 17D virus is one of the most outstanding human vaccines ever developed. It induces efficacious immune responses at a low production cost with a well-established manufacture process. These advantages make the YF17D virus attractive as a vector for the development of new vaccines. At the beginning of vector development studies, YF17D was genetically manipulated to express other flavivirus prM and E proteins, components of the viral envelope. While these 17D recombinants are based on the substitution of equivalent YF17D genes, other antigens from unrelated pathogens have also been successfully expressed and delivered by recombinant YF17D viruses employing alternative strategies for genetic manipulation of the YF17D genome. Herein, we discuss these strategies in terms of possibilities of single epitope or larger sequence expression and the main properties of these replication-competent viral platforms.
Electrical and luminescent characteristics of a-SiC:H p-i-n thin-film LED'S with graded-gap junctions (1997)

a-SiC:H p-i-n thin-film LED's (TFLED's) containing a single graded-gap p-i-n junction (SG) or double graded-gap p-i-n and i-n junctions (DG) have been postulated and fabricated successfully on indium-tin-oxide (ITO)-coated glass substrates, with a plasma-enhanced chemical vapor deposition (PECVD) system. Some important characteristics and related physics of these two types of TFLED's are presented and discussed. At an injection current density (J) of 600 mA/cm/sup 2/, the brightness (B) of the SG and DG TFLED's obtained were 30 and 207 cd/m/sup 2/, respectively. This significant improvement of brightness, as compared to those of the previously reported TFLED's with a highest brightness of 20 cd/m/sup 2/, could be ascribed to the reduced interface states with the graded-gap junctions, lower contact resistance between ITO and the p-layer due to plasma treatment of ITO prior to p-layer deposition, post metallization annealing of thermally evaporated Al on n-layer, and higher optical gaps (E/sub opt/'s) of the doped layers employed. The slopes of the nearly linear B-J relationships show a diode factor very close to unity for the fabricated SG and DG TFLED's. This implies that the electroluminescence (EL) mechanism of these TFLED's might be a tail-to-tail-state recombination. In addition, the conduction currents of these TFLED's are almost temperature dependent, and that of the DG TFLED might consist of an ohmic current and a space-charge-limited current (SCLC) within the lower and higher applied-bias regions, respectively.
Isolation of an Active Catalytic Core of Streptococcus downei MFe28 GTF-I Glucosyltransferase (1999)

Truncated variants of GTF-I from Streptococcus downei MFe28 were purified by means of a histidine tag. Sequential deletions showed that the C-terminal domain was not directly involved in the catalytic process but was required for primer activation. A fully active catalytic core of only 100 kDa was isolated.
Selective abolition of pancreatic RNase binding to its inhibitor protein (2003)

We have modified RNase inhibitor (RI) protein so that it no longer detectably binds pancreatic RNases but retains near-native affinity for human angiogenin (ANG). The K(i) value for RNase A is increased by a factor of >10(8), from 36 fM to >4 microM, and the selectivity factor for ANG is now >10(9). This dramatic change was achieved by remodeling the human RI loop segment Cys-408 -Leu-409 -Gly-410, which makes minor interactions with pancreatic RNase but does not contact ANG. The modifications selected were designed to sterically hinder docking of the undesired ligand. Three of the variants tested (C408W, G410W, and C408W/G410W) bind RNase A with almost the same avidity as WT RI. However, combination of the 408/410 double Trp replacement with deletion of the intervening residue, Leu-409, was sufficient to abolish inhibition of RNase A and human pancreatic RNase. The K(i) value for ANG with the deletion variant is 1.1 fM, only 2-fold higher than with WT RI. This variant may have potential utility both as an anticancer drug targeting ANG and as a tool for the investigation of the biological function of ANG. More generally, these findings demonstrate that a protein-protein interaction can be effectively and specifically disrupted by redesigning an interface region that makes no major energetic contribution to complex stability. This finding, in turn, may have implications for the development of small molecules that modulate protein-protein interactions.
Efficient Solid Phase Synthesis of Cleavable Oligodeoxynucleotides Based on a Novel Strategy for the Synthesis of 5′‐S‐(4,4′‐Dimethoxytrityl)‐2′‐deoxy‐5′‐thionucleoside Phosphoramidites (2004)

Abstract The incorporation of a specific cleavage site into an oligodeoxynucleotide can be achieved by utilizing the four 5′‐ S ‐(4,4′‐dimethoxytrityl)‐2′‐deoxy‐5′‐thionucleoside 3′‐(2‐cyanoethyl diisopropylphosphoramidites) 5 and 15a – c ( Fig. 1 ). Based on the silver ion assisted cleavage of PS and CS bonds, we synthesized oligodeoxynucleotides with an achiral 5′‐phosphorothioate linkage 3′–O–P–S–5′ by the solid‐phase phosphoramidite procedure. The efficient cleavage of these modified oligodeoxynucleotides can be detected by HPLC, PAGE, and surface plasmon resonance (SPR) spectrometry. The liberated 5′‐thiol moiety can be used directly for post‐reaction labeling with appropriately functionalized reporter groups.
Increased cancer risk of heterozygotes with NBS1 germline mutations in poland (2004)

It has been suggested based on familial data that Nijmegen breakage syndrome (NBS) heterozygotes have an increased risk of malignant tumors. We found 15 carriers of the 657del5 mutation and 8 carriers of the R215W molecular variant of the NBS1 gene among 1,289 consecutive patients from Central Poland with various cancers and only 10 and 4 such carriers, respectively, in 1,620 controls from this region. Most of the 657del5 mutation carriers were found among patients with melanoma (4/105), non-Hodgkin lymphoma (2/42) and breast cancer (4/224) and of the 234 patients with colorectal carcinoma 3 carried the 657del5 mutation and 3 others the R215W molecular variant. The frequencies of 657del5 mutation carriers among patients with melanoma and non-Hodgkin lymphoma and of R215W carriers in patients with colorectal cancer were significantly higher than in controls (p < 0.01, < 0.05 and < 0.05 respectively). The pooled frequencies of 657del5 and R215W mutations in all cancer patients were also significantly higher than in controls (p < 0.05). Two carriers of the 657del5 mutation had second primary tumors. Malignant tumors among parents and siblings of 657del5 mutation carriers (14/77) were twice more frequent than in population controls. Three carriers of this mutation (2 probands with melanoma) reported melanoma in relatives. These results suggest strongly that NBS1 heterozygosity may be associated with elevated risk of some cancers. Larger studies are needed to evaluate the impact of the high frequency of germline NBS1 mutations on the cancer burden in the Slav populations.
Synthetic approaches for the preparation of cyclic polymers (2009)

Despite decades of studies devoted to the unique physical properties and potential applications of cyclic polymer topologies, their exploration has remained limited because of synthetic inefficiencies and acyclic impurities. Many recently developed synthetic techniques offer efficient routes to well-defined cyclic macromolecules to answer this need. This tutorial review aims to provide a concise overview of the most significant synthetic contributions in this field, and highlight the relative advantages and disadvantages of each approach.
Management of Atopic Dermatitis in the Pediatric Population (2008)

Atopic dermatitis, one of the most common skin disorders in young children, has a prevalence of 10% to 20% in the first decade of life. It is a chronic illness that requires a multifaceted treatment strategy in the setting of limited therapeutic options. Balancing safety concerns with efficacious treatment is of particular importance in the pediatric population. Parents of patients with atopic dermatitis turn to their primary caregivers for guidance regarding this physically demanding and psychologically stressful condition. In addition to serving as a review of atopic dermatitis, this article delves into the state-of-the-art therapeutic options and includes a detailed review of the differences between topical corticosteroids and topical calcineurin inhibitors. We also discuss new treatment strategies that are being used by atopic dermatitis specialists, such as comprehensive "education-as-intervention" models, wet wraps, bleach baths, and systemic immunomodulatory therapies.
An untethered miniature origami robot that self-folds, walks, swims, and degrades (2015)

A miniature robotic device that can fold-up on the spot, accomplish tasks, and disappear by degradation into the environment promises a range of medical applications but has so far been a challenge in engineering. This work presents a sheet that can self-fold into a functional 3D robot, actuate immediately for untethered walking and swimming, and subsequently dissolve in liquid. The developed sheet weighs 0.31 g, spans 1.7 cm square in size, features a cubic neodymium magnet, and can be thermally activated to self-fold. Since the robot has asymmetric body balance along the sagittal axis, the robot can walk at a speed of 3.8 body-length/s being remotely controlled by an alternating external magnetic field. We further show that the robot is capable of conducting basic tasks and behaviors, including swimming, delivering/carrying blocks, climbing a slope, and digging. The developed models include an acetone-degradable version, which allows the entire robot's body to vanish in a liquid. We thus experimentally demonstrate the complete life cycle of our robot: self-folding, actuation, and degrading.
Antigen-Binding Properties of Monoclonal Antibodies Reactive with EBNA1 and Use in Immunoaffinity Chromatography (2009)

Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) was overexpressed and purified from Escherichia coli. Mouse monoclonal antibodies (mAbs) were prepared that react with EBNA1. Eleven high affinity mAbs were recovered. Nine mAbs are isotype IgG (all subisotype IgG(1)) and two mAbs are isotype IgM. All mAbs react strongly with EBNA1 in an ELISA assay while only one mAb (designated 1EB6) fails to react in a Western blot assay. The epitopes for these mAbs were mapped to seven different regions, providing good coverage of the entire EBNA1 protein. The mAbs had differing affinity for an EBNA1/DNA complex with four mAbs able to supershift the complex completely. All mAbs can immunoprecipitate EBNA1 from E. coli overexpressing EBNA1. A modified ELISA assay, termed ELISA-elution assay, was used to screen for mAbs that release EBNA1 in the presence of a low molecular weight polyhydroxylated compound (polyol) and a nonchaotropic salt. MAbs with this property, termed polyol-responsive (PR)-mAbs, allow gentle elution of labile proteins and protein complexes. Four mAbs are polyol-responsive with two showing usefulness in gentle immunoaffinity chromatography. Purification with these PR-mAbs may be useful in purifying EBNA1 complexes and elucidating EBNA1-associated proteins. This panel of anti-EBNA1 mAbs will advance the study of EBV by providing new tools to detect and purify EBNA1.
Serum-starvation-induced changes in protein synthesis and morphology of Borrelia burgdorferi (2000)

It has been demonstrated previously that motile Borrelia burgdorferi cells transform into non-motile cyst-forms when incubated for several weeks in BSKII (a complex medium) lacking rabbit serum. B. burgdorferi cells cannot synthesize fatty acids de novo and serum is thought to provide a source of fatty acids and lipids. When B. burgdorferi cells were serum-starved in defined RPMI medium, -90% of the cells formed spherical cysts within 48 h. Cyst formation was inhibited by tetracycline. Cyst opening and recovery of vegetative cells was rapidly induced by the addition of either BSKII or rabbit serum. The percentage of viable cells recovered from cysts ranged from 2.9% to 52-5%. Viability was inversely proportional to cyst age. Protein synthesis by B. burgdorferi during serum starvation was examined by labelling cells with Tran35S-Label and analysing the labelled proteins by two-dimensional gel electrophoresis and fluorography. The synthesis of over 20 proteins was induced during serum starvation. Western blots of proteins from vegetative cells and cysts probed with sera from either B. burgdorferi-infected humans or monkeys revealed that several cyst proteins were antigenic. These data suggest that cells of B. burgdorferi, although possessing a small genome and extremely limited biosynthetic capabilities, rapidly respond to conditions of serum starvation by inducing changes in protein synthesis and cell morphology. This study may help explain how cells of B. burgdorferi can survive periods of nutrient deprivation in different hosts and host tissues.
Measuring the Burden of Major Cancers due to Premature Death in Korea (2000)

Objective : To estimate the burden of diseases in Korea especially caused by major cancers using the YLL(years of life lost due to premature death) measurement. Methods : First, we determined the parameters: such as age-specific standard life expectancy, age on death, sex, cause of death by analyzing the national death certificate data and life table collected during 1996 provided by the National Statistical Office. Secondly, we estimated the age group-specific YLL by employing standard expected years of life lost(SEYLL). Thirdly, final burden of disease due to premature death was estimated by using YLLs measurement which developed by global burden of disease study group. Results : The burden of premature death by cancer for male was attributed mainly to liver cancer(514.5 person-year), stomach cancer(436.4 person-year), and lung cancer(367.7 person-year). Each of these cancers was responsible for the loss of over 100 person-year based on our YLL measurement. The burden of premature death by cancer for female was attributed mainly to liver cancer(135.1 person-year), stomach cancer(252.1 person-year), and lung cancer(121.8 person-year). Each of these cancers was responsible for the loss of over 100 person year based on our YLL measurement. Conclusion : We found the YLL method employed in this study was appropriate to quantify the burden of premature death. Thereby, it would provide a rational bases to plan a national health policy regarding premature death caused by cancer.
The effect of high fat diet and dehydroepiandrosterone (DHEA) administration in the rhesus monkey. (1996)

Dehydroepiandrosterone (DHEA) lowers serum cholesterol, particularly the low density lipoprotein (LDL) fraction, in rhesus monkeys on a commercial diet (12% calories from fat, 0.0083% cholesterol). We fed rhesus monkeys a diet of 30% calories from fat and 0.1% cholesterol for 12 weeks, then commercial chow for 7 weeks. Six monkeys each received DHEA or placebo, orally for 17 weeks. Food intake increased the first 6 weeks, but decreased thereafter. Monkeys had a 22% mean weight gain while on high fat diet. DHEA monkeys had higher T4 levels than placebo monkeys at weeks 8 and 16. After 12 weeks on high fat diet, all monkeys had elevated serum cholesterol concentrations, an increase in amount and percentage of intermediate density lipoprotein and LDL cholesterol, and an increase in amount, but a decrease in percentage of high density lipoprotein cholesterol. There were no significant differences in serum cholesterol or plasma lipoprotein concentrations between DHEA and placebo monkeys while on high fat diet (a trend toward lower levels was noted in the DHEA group). On commercial chow, plasma lipoprotein concentrations decreased for all monkeys, and DHEA monkeys had significantly lower total and LDL cholesterol than placebo monkeys. We conclude that a high fat diet (30% fat) masks any cholesterol-lowering effects of DHEA.
Fluoroscopic Surrogate for Pharyngeal Strength: The Pharyngeal Constriction Ratio (PCR) (2009)

The pharyngeal constriction ratio (PCR), derived directly from videofluoroscopy without the need for manometry, requires validation as a surrogate for pharyngeal strength. A correlation of -0.70 was previously identified between PCR and pharyngeal clearing pressures (PP) on separate fluoroscopic and manometric studies. As PP increases, PCR decreases. The objective of the current study was to evaluate the correlation between PCR and PP in 25 patients undergoing simultaneous fluoroscopy and pharyngeal manometry. The effect of the manometric catheter on PCR was also investigated. The correlation between the PCR and averaged pharyngeal clearing pressures was -0.72 (p<0.001). All patients with a PCR>0.25 had a P <60 mmHg. PCR did not differ significantly as a consequence of the manometric catheter. Results suggest the utility of an objective fluoroscopic measure in assessing pharyngeal strength when manometry may not be available or possible.
Analysis of Proteins and Peptides Directly from Biological Fluids by Immunoprecipitation/Mass Spectrometry (2003)

We have developed a simple and sensitive method for characterizing amyloid β-peptide (Aβ) and its variants in biological media and clinical specimens in Alzheimer’s disease research (1). This method, termed immunoprecipitation/mass spectrometry (IP/MS), utilizes anti-Aβ-specific monoclonal antibodies, 4G8 and 6E10 (2,3), to capture Aβ and its related peptides directly from complex biological fluids. The molecular masses of these captured Aβ peptides are measured by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) (4) and used to determine the identity of these peptides. The signal intensity of a given Aβ peptide relative to that of an internal standard is used, together with its standard quantitation curve, to determine the concentration of the peptide.
High-Performance SIFT Hardware Accelerator for Real-Time Image Feature Extraction (2011)

Feature extraction is an essential part in applications that require computer vision to recognize objects in an image processed. To extract the features robustly, feature extraction algorithms are often very demanding in computation so that the performance achieved by pure software is far from real-time. Among those feature extraction algorithms, scale-invariant feature transform (SIFT) has gained a lot of popularity recently. In this paper, we propose an all-hardware SIFT accelerator-the fastest of its kind to our knowledge. It consists of two interactive hardware components, one for key point identification, and the other for feature descriptor generation. We successfully developed a segment buffer scheme that could not only feed data to the computing modules in a data-streaming manner, but also reduce about 50% memory requirement than a previous work. With a parallel architecture incorporating a three-stage pipeline, the processing time of the key point identification is only 3.4 ms for one video graphics array (VGA) image. Taking also into account the feature descriptor generation part, the overall SIFT processing time for a VGA image can be kept within 33 ms (to support real-time operation) when the number of feature points to be extracted is fewer than 890.
A probabilistic method for identifying start codons in bacterial genomes (2001)

As the pace of genome sequencing has accelerated, the need for highly accurate gene prediction systems has grown. Computational systems for identifying genes in prokaryotic genomes have sensitivities of 98-99% or higher (Delcher et al., Nucleic Acids Res., 27, 4636-4641, 1999). These accuracy figures are calculated by comparing the locations of verified stop codons to the predictions. Determining the accuracy of start codon prediction is more problematic, however, due to the relatively small number of start sites that have been confirmed by independent, non-computational methods. Nonetheless, the accuracy of gene finders at predicting the exact gene boundaries at both the 5' and 3' ends of genes is of critical importance for microbial genome annotation, especially in light of the important signaling information that is sometimes found on the 5' end of a protein coding region. In this paper we propose a probabilistic method to improve the accuracy of gene identification systems at finding precise translation start sites. The new system, RBSfinder, is tested on a validated set of genes from Escherichia coli, for which it improves the accuracy of start site locations predicted by computational gene finding systems from the range 67-77% to 90% correct.
Molecular and Therapeutic Potential and Toxicity of Valproic Acid (2010)

Valproic acid (VPA), a branched short-chain fatty acid, is widely used as an antiepileptic drug and a mood stabilizer. Antiepileptic properties have been attributed to inhibition of Gamma Amino Butyrate (GABA) transaminobutyrate and of ion channels. VPA was recently classified among the Histone Deacetylase Inhibitors, acting directly at the level of gene transcription by inhibiting histone deacetylation and making transcription sites more accessible. VPA is a widely used drug, particularly for children suffering from epilepsy. Due to the increasing number of clinical trials involving VPA, and interesting results obtained, this molecule will be implicated in an increasing number of therapies. However side effects of VPA are substantially described in the literature whereas they are poorly discussed in articles focusing on its therapeutic use. This paper aims to give an overview of the different clinical-trials involving VPA and its side effects encountered during treatment as well as its molecular properties.