gebhart/patrepeval huggingface dataset:
Analysis of the epidermal growth factor receptor specific transcriptome: Effect of receptor expression level and an activating mutation (2005)

Overexpression or expression of activating mutations of the epidermal growth factor receptor (EGFR) is common in cancer and correlates with neoplastic progression. The present study employed Affymetrix oligonucleotide arrays to profile genes induced by ligand-activated EGFR with the receptor either moderately expressed or overexpressed at an in-itself transforming level. These changes were compared to those induced by the naturally occurring constitutively active variant EGFRvIII. This study provides novel insight on the activities and mechanisms of EGFRvIII and EGFR mediated transformation, as genes encoding proteins with functions in promoting cell proliferation, invasion, antiapoptosis, and angiogenesis featured prominently in the EGFRvIII- and EGFR-expressing cells. Surprisingly, it was found that ligand-activated EGFR induced the expression of a large group of genes known to be inducible by interferons. Expression of this module was absent in the EGFRvIII-expressing cell line and the parental cell line. Treatment with the specific EGFR inhibitor AG1478 indicated that the regulations were primary, receptor-mediated events. Furthermore, activation of this module correlated with activation of STAT1 and STAT3. The results thus demonstrate that ligand-activated EGFR at different expression levels results in different kinetics of signaling and induction of gene expression. In addition, the constitutively active variant EGFRvIII seems to activate only a subset of signal pathways and induce a subset of genes as compared to the ligand-activated EGFR.
Mitotic chromatin condensation in vitro using somatic cell extracts and nuclei with variable levels of endogenous topoisomerase II. (1990)

We report the development of a new method for producing mitotic extracts from tissue culture cells. These extracts reproducibly promote the condensation of chromatin in vitro when incubated with purified interphase nuclei. This condensation reaction is not species specific, since nuclei from chicken, human, and hamster cell lines all undergo chromatin condensation upon incubation with the extract. We have used this extract to investigate the role of DNA topoisomerase II (topo II) in the chromosome condensation process. Chromatin condensation does not require the presence of soluble topo II in the mitotic extract. However, the extent of formation of discrete chromosome-like structures correlates with the level of endogenous topo II present in the interphase nuclei. Our results further suggest that chromatin condensation in this extract may involve two processes: chromatin compaction and resolution into discrete chromosomes.
Endoplasmic Reticulum Vacuolization and Valosin-Containing Protein Relocalization Result from Simultaneous Hsp90 Inhibition by Geldanamycin and Proteasome Inhibition by Velcade (2006)

Geldanamycin and Velcade, new anticancer drugs with novel mechanisms of action, are currently undergoing extensive clinical trials. Geldanamycin interrupts Hsp90 chaperone activity and causes down-regulation of its many client proteins by the ubiquitin-proteasome pathway; Velcade is a specific proteasome inhibitor. Misfolded Hsp90 clients within the endoplasmic reticulum (ER) lumen are cleared by ER--associated protein degradation, a sequential process requiring valosin-containing protein (VCP)-dependent retrotranslocation followed by ubiquitination and proteasomal proteolysis. Cotreatment of cells with geldanamycin and Velcade prevents destruction of destabilized, ubiquitinated Hsp90 client proteins, causing them to accumulate. Here, we report that misfolded protein accumulation within the ER resulting from geldanamycin and Velcade exposure overwhelms the ability of the VCP--centered machine to maintain the ER secretory pathway, causing the ER to distend into conspicuous vacuoles. Overexpression of dominant-negative VCP or the "small VCP--interacting protein" exactly recapitulated the vacuolated phenotype provoked by the drugs, associating loss of VCP function with ER vacuolization. In cells transfected with a VCP--enhanced yellow fluorescent protein fluorescent construct, geldanamycin plus Velcade treatment redistributed VCP--enhanced yellow fluorescent protein from the cytoplasm and ER into perinuclear aggresomes. In further support of the view that compromise of VCP function is responsible for ER vacuolization, small interfering RNA interference of VCP expression induced ER vacuolization that was markedly increased by Velcade. VCP knockdown by small interfering RNA eventually deconstructed both the ER and Golgi and interdicted protein trafficking through the secretory pathway to the plasma membrane. Thus, simultaneous geldanamycin and Velcade treatment has far-reaching secondary cytotoxic consequences that likely contribute to the cytotoxic activity of this anticancer drug combination.
Tetrafunctional Photoaffinity Labels Based on Nakanishi'sm-Nitroalkoxy-Substituted Phenyltrifluoromethyldiazirine (2002)

Two generally applicable reagents for photoaffinity probes have been developed. They contain an m-nitrophenyl ether function with a trifluoromethyldiazirine side chain (photophore group), as well as a biotin tag for the identification of labeled proteins or peptides and either a free hydroxy or a squaramide group for the attachment of any suitably functionalized ligand which directs the reagent to the binding site of the target molecule (see picture). Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2002/z18343_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Human uncoupling protein gene: Structure, comparison with rat gene, and assignment to the long arm of chromosome 4 (1990)

The uncoupling protein (UCP) gene encodes a unique mammalian mitochondrial proton carrier that induces heat production in brown adipocytes. Human UCP gene was isolated and its organization analyzed. A comparison was made with rat UCP gene. Human UCP gene spans 13 Kb and contains a transcribed region that covers 9 Kb of the human genome. All of the exons were also sequenced except the extreme end of the 3' untranslated region. Two Kb DNA upstream the TATA box were also sequenced. This region contains several fragments that are highly homologous to the gene of rat UCP. Neither CCAAT sequence nor Sp 1 binding motif were detected. Human UCP gene is split into six exons. The complete amino acid sequence of the protein was determined. Human UCP has 305 amino acids and a molecular weight of 32,786. It has no N-terminal targeting sequence. It is 79% homologous to rat UCP both at nucleotidic and amino acid levels. The primary structure of UCP is significantly homologous to the primary structure of the human T1 ADP/ATP carrier, particularly in the C-terminal extremity, which is supposed to contain a nucleotide-binding site in both proteins. Human UCP gene is single type, as it is in rodents. Two genomic fragments were used to detect a 1.9 Kb mRNA in human perirenal brown adipose tissue. Using in situ hybridization, UCP gene was assigned in humans to chromosome 4 in q31. Interestingly, the T1 gene encoding the heart-skeletal muscle ADP/ATP carrier has recently been shown to be on the same chromosome (Li et al. Biol Chem 264:13998, 1989).
Expansion and Molecular Evolution of the Interferon-Induced 2′–5′ Oligoadenylate Synthetase Gene Family (2000)

The mammalian 2'-5' oligoadenylate synthetases (2'-5'OASs) are enzymes that are crucial in the interferon-induced antiviral response. They catalyze the polymerization of ATP into 2'-5'-linked oligoadenylates which activate a constitutively expressed latent endonuclease, RNaseL, to block viral replication at the level of mRNA degradation. A molecular evolutionary analysis of available OAS sequences suggests that the vertebrate genes are members of a multigene family with its roots in the early history of tetrapods. The modern mammalian 2'-5'OAS genes underwent successive gene duplication events resulting in three size classes of enzymes, containing one, two, or three homologous domains. Expansion of the OAS gene family occurred by whole-gene duplications to increase gene content and by domain couplings to produce the multidomain genes. Evolutionary analyses show that the 2'-5'OAS genes in rodents underwent gene duplications as recently as 11 MYA and predict the existence of additional undiscovered OAS genes in mammals.
Late Lumen Loss After Coronary Angioplasty Is Associated With the Activation Status of Circulating Phagocytes Before Treatment (1995)

The results of the present study indicate that activated blood granulocytes prevent luminal renarrowing after PTCA, while activated blood monocytes promote late lumen loss. To validate this new finding, further study in an independent patient group is required.
Vitiligo: new and emerging treatments (2008)

Vitiligo is a cosmetically disfiguring condition, and, although there is no therapeutic full solution yet, some treatment may induce good results in most patients. The disease can be successfully treated with various medical options. Both nonfocused or focused narrowband ultraviolet B phototherapy represents the current treatment of choice, to minimize side effects and reach optimal clinical results. Topical novel approaches are also considered. Surgical methods, consisting of autologous transplantation methods, is generally recommended for focal/stable vitiligo, after medical therapy has failed. Finally, for patients with extensive vitiligo, depigmentation of the residual melanin should be taken into account.
Synthesis of a chiral nonracemic segmented screwlike oligomer. An unusual form of molecular chirality (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of a chiral nonracemic segmented screwlike oligomer. An unusual form of molecular chiralityPeter V. Bedworth and James M. TourCite this: Macromolecules 1994, 27, 2, 622–624Publication Date (Print):January 1, 1994Publication History Published online1 May 2002Published inissue 1 January 1994https://pubs.acs.org/doi/10.1021/ma00080a047https://doi.org/10.1021/ma00080a047research-articleACS PublicationsRequest reuse permissionsArticle Views115Altmetric-Citations26LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Using novel fluorescent polymers as sensory materials for above-ground sensing of chemical signature compounds emanating from buried landmines (2001)

Chemical vapors originating from the explosive charge within landmines and unexploded ordnance (UXO) form a chemical "signature" unique to these devices. The fact that canines can detect this signature was a primary motivation for the Defense Advanced Research Projects Agency's (DARPA) Dog's Nose Program. One goal of this program was to develop electronic chemical sensors that mimic the canine's ability to detect landmines. The sensor described here, developed under this program, utilizes novel fluorescent polymers to detect landmine signature vapors in air at ultratrace concentration levels (parts-per-trillion or less). Thin films of the polymers are highly emissive but undergo a dramatic reduction in emission intensity when molecules of target analytes bind to the polymer. Binding of a single explosive molecule can quench the fluorescence from hundreds of polymer repeat units, resulting in an amplification of the quenching response. The polymer structure contains receptor sites designed to interact specifically with nitroaromatic explosives, enhancing the selectivity of the polymers for target analytes. A man-portable sensor prototype, similar in size and configuration to metal detectors currently used for mine detection, has demonstrated performance comparable to that of canines during field tests monitored by DARPA at Fort Leonard Wood, MO.
Effect of alcohol compounds found in hemicellulose hydrolysate on the growth and fermentation of ethanologenicEscherichia coli (2000)

Lignocellulose can be readily hydrolyzed into a mixture of sugars using dilute mineral acids. During hydrolysis, a variety of inhibitors are also produced which include aromatic alcohols from lignin and furfuryl alcohol from pentose destruction. Seven compounds were investigated individually and in binary combinations (catechol, coniferyl alcohol, furfuryl alcohol, guaiacol, hydroquinone, methylcatechol, and vanillyl alcohol). Aromatic alcohols and furfuryl alcohol inhibited ethanol production from xylose in batch fermentations primarily by inhibiting the growth of Escherichia coli LY01, the biocatalyst. The toxicities of these compounds were directly related to their hydrophobicity. Methylcatechol was the most toxic compound tested (MIC = 1.5 g/L). In binary combination, the extent of growth inhibition was roughly additive for most compounds tested. However, combinations with furfuryl alcohol and furfural (furaldehyde) appear synergistic in toxicity. When compared individually, alcohol components which are formed during hemicellulose hydrolysis are less toxic for growth than the aldehydes and organic acids either on a weight basis or a molar basis.
Vertical cavity lasers for telecom applications (1997)

The authors review the development of long-wavelength vertical cavity lasers (VCLs) for telecommunications applications. Long-wavelength VCLs provide an attractive choice for inexpensive fiber optic communication. The different designs of such lasers are presented, along with the advantages and disadvantages of each. System requirements and experiments are also presented at 2.5 Gb/s over 200 km of optical fiber.
A Phase II trial of the oral mTOR inhibitor everolimus in relapsed Hodgkin lymphoma (2010)

Everolimus is an oral antineoplastic agent that targets the raptor mammalian target of rapamycin (mTORC1). The phosphatidylinositol 3-kinase/mTOR signal transduction pathway has been demonstrated to be activated in tumor samples from patients with Hodgkin lymphoma (HL). The goal of this trial was to learn the antitumor activity and toxicity of everolimus in patients with relapsed/refractory HL. Patients were eligible if they had measurable disease, a platelet count >75,000, and an absolute neutrophil count >1,000. Patients received everolimus 10 mg PO daily. Dose reductions were allowed. Response was assessed after two and six cycles and then every three cycles until progression. Patients could remain on drug until progression or toxicity. Nineteen patients were enrolled. Median age was 37 years (range, 27-68). Patients had received a median of six prior therapies (range, 3-14) and 84% had undergone prior autologous stem cell transplant. The ORR was 47% (95% CI: 24-71%) with eight patients achieving a PR and one patient achieving a CR. The median TTP was 7.2 months. Four responders remained progression free at 12 months. Patients received a median of seven cycles of therapy. Of the 19 patients, one remains on therapy at 36 months; the others went off study because of progressive disease (16), toxicity (1), and death from infection (1). Four patients experienced a Grade 3 or higher pulmonary toxicity. Everolimus has single-agent activity in relapsed/refractory HL and provides proof-of-concept that targeting the mTOR pathway in HL is clinically relevant.
Quantum Inspired Training for Boltzmann Machines (2015)

We present an efficient classical algorithm for training deep Boltzmann machines (DBMs) that uses rejection sampling in concert with variational approximations to estimate the gradients of the training objective function. Our algorithm is inspired by a recent quantum algorithm for training DBMs. We obtain rigorous bounds on the errors in the approximate gradients; in turn, we find that choosing the instrumental distribution to minimize the alpha=2 divergence with the Gibbs state minimizes the asymptotic algorithmic complexity. Our rejection sampling approach can yield more accurate gradients than low-order contrastive divergence training and the costs incurred in finding increasingly accurate gradients can be easily parallelized. Finally our algorithm can train full Boltzmann machines and scales more favorably with the number of layers in a DBM than greedy contrastive divergence training.
Analysis of the Individual Contributions of Igα (CD79a)- and Igβ (CD79b)-Mediated Tonic Signaling for Bone Marrow B Cell Development and Peripheral B Cell Maturation (2006)

The individual contribution of Igalpha and Igbeta for BCR-triggered fates is unclear. Prior evidence supports conflicting ideas concerning unique as well as redundant functions for these proteins in the context of BCR/pre-BCR signaling. Part of this ambiguity may reflect the recent appreciation that Igalpha and Igbeta participate in both Ag-independent (tonic) and Ag-dependent signaling. The present study undertook defining the individual requirement for Igalpha and Igbeta under conditions where only ligand-independent tonic signaling was operative. In this regard, we have constructed chimeric proteins containing one or two copies of the cytoplasmic domains of either Igalpha or Igbeta and Igalpha/Igbeta heterodimers with targeted Tyr-->Phe modifications. The ability of these proteins to act as surrogate receptors and trigger early bone marrow and peripheral B cell maturation was tested in RAG2(-/-) primary pro-B cell lines and in gene transfer experiments in the muMT mouse model. We considered that the threshold for a functional activity mediated by the pre-BCR/BCR might only be reached when two functional copies of the Igalpha/Igbeta ITAM domain are expressed together, and therefore the specificity conferred by these proteins can only be observed in these conditions. We found that the ligand-independent tonic signal is sufficient to drive development into mature follicular B cells and both Igalpha and Igbeta chains supported formation of this population. In contrast, neither marginal zone nor B1 mature B cell subsets develop from bone marrow precursors under conditions where only tonic signals are generated.
P1–332: Evaluation of the relationship between TTP488 plasma concentrations and changes in ADAS‐cog relative to placebo (2013)

TTP488 is an orally active, centrally acting antagonist of RAGE-RAGE ligand interaction. Previous reports describe a decreased decline in ADAS-cog (Δ=3.1, p=0.008 at 18 months, ANCOVA with multiple imputation), relative to placebo, following a 5mg/day dose of TTP488. Acute, reversible cognitive worsening was seen with a 20 mg/day dose. The objective of this study was to evaluate the relationship between TTP488 plasma concentration and ADAS-cog scores. 399 patients with mild-to-moderate AD were randomized to one of two oral TTP488 doses (60 mg for 6 days followed by 20 mg/day; 15 mg for 6 days followed by 5 mg/day) or placebo for 18 months. The ADAS-cog was administered prior to dosing and at 3, 6, 9, 12, 15 and 18 months. Blood samples for TTP488 concentrations were collected serially at similar time points as the ADAS-cog. Analyses related TTP concentrations to ADAS-cog values and changes. Trough concentrations were analyzed for each subject by taking the maximum trough and also by taking the median trough for each subject over time. Subjects were classified into groups according to cutpoints (tertile, quartile, quintile and decile) in the distribution of concentration. Each subject was classified to a single category. Results were generally consistent across various cutpoints evaluated. 5 mg/day and 20 mg/day were associated with mean (95% CI) trough concentrations of 13 (11.7, 14.3) ng/mL and 68.6 (63.5, 73.7) ng/mL, respectively. TTP488 concentrations of 7.6–16.8 ng/mL showed a decreased decline in ADAS-cog over time compared to placebo. Concentrations of 46.8–167.0 ng/mL showed a numerical worsening in ADAS-cog relative to placebo.
Effect of l-ornithine l-aspartate against thioacetamide-induced hepatic damage in rats (2010)

Ornithine aspartate exhibited significant hepatoprotective activity against TAA-induced hepatic damage in rats.
Kinetic Analysis of Smad Nucleocytoplasmic Shuttling Reveals a Mechanism for Transforming Growth Factor β-Dependent Nuclear Accumulation of Smads (2005)

Upon transforming growth factor beta (TGF-beta) stimulation, Smads accumulate in the nucleus, where they regulate gene expression. Using fluorescence perturbation experiments on Smad2 and Smad4 fused to either enhanced green fluorescent protein or photoactivatable green fluorescent protein, we have studied the kinetics of Smad nucleocytoplasmic shuttling in a quantitative manner in vivo. We have obtained rate constants for import and export of Smad2 and show that the cytoplasmic localization of Smad2 in uninduced cells reflects its nuclear export being more rapid than import. We find that TGF-beta-induced nuclear accumulation of Smad2 is caused by a pronounced drop in the export rate of Smad2 from the nucleus, which is associated with a strong decrease in nuclear mobility of Smad2 and Smad4. TGF-beta-induced nuclear accumulation involves neither a release from cytoplasmic retention nor an increase in Smad2 import rate. Hence, TGF-beta-dependent nuclear accumulation of Smad2 is caused exclusively by selective nuclear trapping of phosphorylated, complexed Smad2. The proposed mechanism reconciles signal-dependent nuclear accumulation of Smad2 with its continuous nucleocytoplasmic cycling properties.
Dynamic assembly of TRPC1-STIM1-Orai1 ternary complex is involved in store-operated calcium influx. (2007)

PAGE 9105: The middle initial for Dr. Gill was inadvertently omitted. The correct author list is now shown above.
Analytical models of Doppler data signatures (1995)

A primary indicator of the accuracy of orbit determination based on Doppler tracking is the graph of residuals vs time. Parameter errors in the orbit determination model produce characteristic signatures in the residuals plot. A systematic method of modeling the signature due to a parameter error by means of first and second partial derivative approximations is presented. Signatures due to errors in station location, solar pressure, relativistic clock, and the Earth's troposphere are compared with residual plots from a spacecraft mission, corresponding to the introduction of the same parametric error into orbit determination software. A comparison of postfit residuals with and without the introduction of known modeling errors demonstrates that some errors can be masked by apparent convergence, resulting in erroneous estimates.