gebhart/patrepeval huggingface dataset:
Broad host range DNA cloning system for gram-negative bacteria: construction of a gene bank of Rhizobium meliloti. (1980)

A broad host range cloning vehicle that can be mobilized at high frequency into Gram-negative bacteria has been constructed from the naturally occurring antibiotic resistance plasmid RK2. The vehicle is 20 kilobase pairs in size, encodes tetracycline resistance, and contains two single restriction enzyme sites suitable for cloning. Mobilization is effected by a helper plasmid consisting of the RK2 transfer genes linked to a ColE1 replicon. By use of this plasmid vehicle, a gene bank of the DNA from a wild-type strain of Rhizobium meliloti has been constructed and established in Escherichia coli. One of the hybrid plasmids in the bank contains a DNA insert of approximately 26 kilobase pairs which has homology to the nitrogenase structural gene region of Klebsiella pneumoniae.
Haptotactic Migration Induced by Midkine (2001)

Midkine, a heparin-binding growth factor, plays a critical role in cell migration causing suppression of neointima formation in midkine-deficient mice. Here we have determined the molecules essential for midkine-induced migration. Midkine induced haptotaxis of osteoblast-like cells, which was abrogated by the soluble form of midkine or pleiotrophin, a midkine-homologous protein. Chondroitin sulfate B, E, chondroitinase ABC, B, and orthovanadate, an inhibitor of protein-tyrosine phosphatase, suppressed the migration. Supporting these data, the cells examined expressed PTPzeta, a receptor-type protein-tyrosine phosphatase that exhibits high affinity to both midkine and pleiotrophin and harbors chondroitin sulfate chains. Furthermore, strong synergism between midkine and platelet-derived growth factor in migration was detected. The use of specific inhibitors demonstrated that mitogen-activated protein (MAP) kinase and protein-tyrosine phosphatase were involved in midkine-induced haptotaxis but not PDGF-induced chemotaxis, whereas phosphatidylinositol 3 (PI3)-kinase and protein kinase C were involved in both functions. Midkine activated both PI3-kinase and MAP kinases, the latter activation was blocked by a PI3-kinase inhibitor. Midkine further recruited PTPzeta and PI3-kinase. These results indicate that PTPzeta and concerted signaling involving PI3-kinase and MAP kinase are required for midkine-induced migration and demonstrate for the first time the synergism between midkine and platelet-derived growth factor in cell migration.
Efficacy of fluralaner administered either orally or topically for the treatment of naturally acquired Sarcoptes scabiei var. canis infestation in dogs (2016)

Fluralaner administered either orally or topically to naturally infested dogs eliminates Sarcoptes scabiei var. canis mites and improves clinical signs over a 4-week observation period.
Impact of Variation in the FTO Gene on Whole Body Fat Distribution, Ectopic Fat, and Weight Loss (2008)

Polymorphisms in the fat mass- and obesity-associated (FTO) gene have been identified to be associated with obesity and diabetes in large genome-wide association studies. We hypothesized that variation in the FTO gene has an impact on whole body fat distribution and insulin sensitivity, and influences weight change during lifestyle intervention. To test this hypothesis, we genotyped 1,466 German subjects, with increased risk for type 2 diabetes, for single-nucleotide polymorphism rs8050136 in the FTO gene and estimated glucose tolerance and insulin sensitivity from an oral glucose tolerance test (OGTT). Distribution of fat depots was quantified using whole body magnetic resonance (MR) imaging and spectroscopy in 298 subjects. Two-hundred and four subjects participated in a lifestyle intervention program and were examined after a follow-up of 9 months. In the cross-sectional analysis, the A allele of rs8050136 in FTO was associated with a higher BMI, body fat, and lean body mass (all P < 0.001). There was a significant effect of variation in the FTO gene on subcutaneous fat (P < or = 0.05) and a trend for liver fat content, nonvisceral adipose tissue, and visceral fat (all P < or = 0.1). However, the single-nucleotide polymorphism was not associated with insulin sensitivity or secretion independent of BMI (all P > 0.05). During lifestyle intervention, there was also no influence of the FTO polymorphism on changes in body weight or fat distribution. In conclusion, despite an association with BMI and whole body fat distribution, variation in the FTO locus has no effect on the success of a lifestyle intervention program.
Activation of protein tyrosine phosphorylation after retinal branch vein occlusion in cats. (1997)

The BVO increased overall protein tyrosine phosphorylation in the cat retina in association with increase of angiogenic growth factors (VEGF and bFGF) and activation of two signal proteins (PLC gamma and MAPK) in the tyrosine kinase pathways. These results suggest that the protein tyrosine phosphorylation may in part play an important role in mitogenesis of vascular endothelial cells and other retinal responses after BVO.
Exposure‐Response Analysis of Vamorolone (VBP15) in Boys With Duchenne Muscular Dystrophy (2020)

Exposure-response relationships of vamorolone, a novel dissociative steroidal anti-inflammatory drug, were investigated in clinical trials in boys with Duchenne muscular dystrophy. Variables were clinical outcome measures, Fridericia-corrected QT (QTcF) duration, and pharmacodynamic (PD) biomarkers. Exposure metrics were area under the plasma concentration time curve (AUC) and maximum plasma concentration (C<sub>max</sub> ), with a sigmoid E<sub>max</sub> model applied. Significant improvement in clinical efficacy outcomes was observed after 24 weeks of daily dosing. The primary outcome, time to stand from supine velocity, exhibited the highest sensitivity to vamorolone, with the lowest AUC value providing 50% of maximum effect (E<sub>50</sub> = 186 ng·h/mL), followed by time to climb 4 stairs (E<sub>50</sub> = 478 ng·h/mL), time to run/walk 10 m (E<sub>50</sub> = 1220 ng·h/mL), and 6-minute walk test (E<sub>50</sub> = 1770 ng·h/mL). Week 2 changes of proinflammatory PD biomarkers showed exposure-dependent decreases. The E<sub>50</sub> was 260 ng·h/mL for insulin-like growth factor-binding protein 2, 1200 ng·h/mL for matrix metalloproteinase 12, 1260 ng·h/mL for lymphotoxin α1/β2, 1340 ng·h/mL for CD23, 1420 ng·h/mL for interleukin-22-binding protein, and 1600 ng·h/mL for macrophage-derived chemokine/C-C motif chemokine 22. No relationship was found between QTcF interval changes from baseline and C<sub>max</sub> in week 2 or 24. This analysis showed that improvements in clinical efficacy end points in week 24 and PD biomarkers in week 2 were achieved at typical vamorolone exposure of 2 mg/kg daily dose with a median AUC dose of 6 mg/kg (3651 ng·h/mL), corresponding to approximately 95% of maximum effects for most response variables.
Control of the beat cycle of respiratory tract cilia by Ca2+ and cAMP (1992)

Beat frequency and the duration of the constituent recovery, effective, and rest phases of the beat cycle of respiratory tract cilia were measured photoelectronically before and after manipulation with ionomycin or isoproterenol. Both ionomycin, acting by increasing intracellular Ca2+, and isoproterenol, acting by elevating intracellular adenosine 3',5'-cyclic monophosphate (cAMP), increased beat frequency by reducing the duration of the three phases of the ciliary beat cycle in a similar manner. The addition of increasing concentrations of ATP to ciliated cells permeabilized by exposure to saponin caused a pattern of phase reduction indistinguishable from that observed in whole cells. The beat frequency of permeabilized cells was slower than that of whole cells and insensitive to changes in Ca2+ and cAMP. Ca2+ and cAMP may regulate ciliary beat frequency by acting at a common site within intact cells, possibly regulating the rate at which the axoneme can use ATP or the availability of ATP to the axoneme.
RF energy harvesting with multiple antennas in the same space (2005)

It is highly desirable to increase the amount of energy derived from a given space by an energy-harvesting device. In this paper, multiple energy-harvesting antennas in essentially one space or area are proposed and experimentally studied as a means to increase the energy or power/area ratio. Four cooperating antennas are proposed in a square area that is less than twice the area required for a single antenna. The results obtained suggest that this can be a very promising method for energy harvesting.
The Hiero machine translation system (2005)

Hierarchical organization is a well known property of language, and yet the notion of hierarchical structure has been largely absent from the best performing machine translation systems in recent community-wide evaluations. In this paper, we discuss a new hierarchical phrase-based statistical machine translation system (Chiang, 2005), presenting recent extensions to the original proposal, new evaluation results in a community-wide evaluation, and a novel technique for fine-grained comparative analysis of MT systems.
Probing Protein Ligand Interactions by Automated Hydrogen/Deuterium Exchange Mass Spectrometry (2006)

Amide hydrogen/deuterium exchange is a powerful biophysical technique for probing changes in protein dynamics induced by ligand interaction. The inherent low throughput of the technology has limited its impact on drug screening and lead optimization. Automation increases the throughput of H/D exchange to make it compatible with drug discovery efforts. Here we describe the first fully automated H/D exchange system that provides highly reproducible H/D exchange kinetics from 130 ms to 24 h. Throughput is maximized by parallel sample processing, and the system can run H/D exchange assays in triplicate without user intervention. We demonstrate the utility of this system to differentiate structural perturbations in the ligand-binding domain (LBD) of the nuclear receptor PPARgamma induced upon binding a full agonist and a partial agonist. PPARgamma is the target of glitazones, drugs used for treatment of insulin resistance associated with type II diabetes. Recently it has been shown that partial agonists of PPARgamma have insulin sensitization properties while lacking several adverse effects associated with full agonist drugs. To further examine the mechanism of partial agonist activation of PPARgamma, we extended our studies to the analysis of ligand interactions with the heterodimeric complex of PPARgamma/RXRalpha LBDs. To facilitate analysis of H/D exchange of large protein complexes, we performed the experiment with a 14.5-T Fourier transform ion cyclotron resonance mass spectrometer capable of measuring mass with accuracy in the ppb range.
Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer (2008)

Numerous studies have established a causal link between aberrant mammalian target of rapamycin (mTOR) activation and tumorigenesis, indicating that mTOR inhibition may have therapeutic potential. In this study, we show that rapamycin and its analogs activate the MAPK pathway in human cancer, in what represents a novel mTORC1-MAPK feedback loop. We found that tumor samples from patients with biopsy-accessible solid tumors of advanced disease treated with RAD001, a rapamycin derivative, showed an administration schedule-dependent increase in activation of the MAPK pathway. RAD001 treatment also led to MAPK activation in a mouse model of prostate cancer. We further show that rapamycin-induced MAPK activation occurs in both normal cells and cancer cells lines and that this feedback loop depends on an S6K-PI3K-Ras pathway. Significantly, pharmacological inhibition of the MAPK pathway enhanced the antitumoral effect of mTORC1 inhibition by rapamycin in cancer cells in vitro and in a xenograft mouse model. Taken together, our findings identify MAPK activation as a consequence of mTORC1 inhibition and underscore the potential of a combined therapeutic approach with mTORC1 and MAPK inhibitors, currently employed as single agents in the clinic, for the treatment of human cancers.
Randomized Phase II-III Trial of Combination Beta and Gamma Interferons and Etoposide and Cisplatin in Inoperable Non-Small Cell Cancer of the Lung (1989)

We observed major responses in two patients with adenocarcinoma of the lung who had received a combination of interferon (IFN)-beta and IFN-gamma, immediately followed by chemotherapy. To verify these observations, we initiated a prospective randomized phase II-III trial of etoposide and cisplatin, with or without IFN-beta and IFN-gamma, in patients with inoperable non-small cell lung cancer. Thirty-seven patients were randomized to receive either two cycles of chemotherapy or 6 weeks of IFN-beta plus IFN-gamma followed by two cycles of chemotherapy. Chemotherapy consisted of 60 mg of cisplatin/m2 on day 1 and 120 mg of etoposide/m2 on days 4, 6, and 8, repeated every 21 days. Patients who were randomized to the IFN plus chemotherapy arm received 200 micrograms of IFN-gamma and 30 x 10(6) U of IFN-beta three times per week for 6 weeks, followed by two cycles of chemotherapy. Three of 18 (17%) eligible patients in the chemotherapy arm and two of 18 (11%) patients in the combination arm had partial responses. All responses occurred while patients were receiving chemotherapy. Median survival was 190 days for the chemotherapy arm and 246 days in the combined modality arm, as estimated from Kaplan-Meier curves (P = .35). We observed no significant difference in subjective toxic effects between the two arms. We observed more hematologic toxicity during chemotherapy on the combined modality arm (P = .02). We conclude that pretreatment with IFN-beta and IFN-gamma does not enhance the efficacy of etoposide and cisplatin in this disease. Although the combined modality arm is relatively well tolerated, it does result in more chemotherapy-associated toxic effects. This study also exemplifies a hybrid phase II-III trial design, which is useful in allowing phase II results to be quickly incorporated into a phase III trial.
Some applications of holography in fluid mechanics (1966)

The methods of wavefront reconstruction or holography discovered by Gabor and developed by Leith and Upatnieks greatly increase the amount of information which may be recorded on a single photographic plate. Holography often requires the use of slow, high resolution plates and at first sight might seem unsuitable for use in aerodynamics, in which we are usually concerned with rapidly changing phase objects. The present paper shows, however, that for some purposes the spatial frequencies required are low enough to record on fast plates. A single hologram can be produced which can be viewed at leisure by all the normal visualization methods. Some experimental results are given.
New synthesis of 1,2,4-triazoles and 1,2,4-oxadiazoles (1979)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNew synthesis of 1,2,4-triazoles and 1,2,4-oxadiazolesYang-I. Lin, Stanley A. Lang Jr., Maurice F. Lovell, and Nancy A. PerkinsonCite this: J. Org. Chem. 1979, 44, 23, 4160–4164Publication Date (Print):November 1, 1979Publication History Published online1 May 2002Published inissue 1 November 1979https://pubs.acs.org/doi/10.1021/jo01337a031https://doi.org/10.1021/jo01337a031research-articleACS PublicationsRequest reuse permissionsArticle Views1956Altmetric-Citations74LEARN 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
Design and Synthesis of Pyrido[2,1-b][1,3,5]thiadiazine Library via Uncatalyzed Mannich-Type Reaction (2014)

This Research Article describes the synthesis of an over 700-member library of (8R/8S)-3-R-8-aryl-6-oxo-3,4,7,8-tetrahydro-2H,6H-pyrido[2,1-b][1,3,5]thiadiazin-9-carbonitriles by uncatalyzed Mannich-type reaction of N-methylmorpholinium (4R/4S)-4-aryl-3-cyano-6-oxo-1,4,5,6-tetrahydropyridin-2-thiolates with a set of primary amines and excessive HCHO. The scope and limitations of the reaction were studied. Starting thiolates were obtained in yields of 53-82% by multicomponent reaction of aromatic aldehydes, cyanothioacetamide, 2,2-dimethyl-1,3-dioxane-4,6-dione (Meldrum's acid), and N-methylmorpholine, followed by heterocyclization of the resulting Michael adducts.
Molecular Plasmonics with Tunable Exciton−Plasmon Coupling Strength in J-Aggregate Hybridized Au Nanorod Assemblies (2007)

Controlling coherent electromagnetic interactions in molecular systems is a problem of both fundamental interest and important applicative potential in the development of photonic and opto-electronic devices. The strength of these interactions determines both the absorption and emission properties of molecules coupled to nanostructures, effectively governing the optical properties of such a composite metamaterial. Here we report on the observation of strong coupling between a plasmon supported by an assembly of oriented gold nanorods (ANR) and a molecular exciton. We show that the coupling is easily engineered and is deterministic as both spatial and spectral overlap between the plasmonic structure and molecular aggregates are controlled. We think that these results in conjunction with the flexible geometry of the ANR are of potential significance to the development of plasmonic molecular devices.
A Microporous Metal–Organic Framework for Gas‐Chromatographic Separation of Alkanes (2006)

Filling the pores: A zinc-based metal–organic framework (MOF) can be transformed reversibly from an open (a) to a dense (b) configuration. The microporous solid is the first example of a MOF that is highly selective in the gas-chromatographic separation of alkanes.
Murine Low-Density Lipoprotein Receptor-Related Protein 1 (LRP) Is Required for Phagocytosis of Targets Bearing LRP Ligands but Is Not Required for C1q-Triggered Enhancement of Phagocytosis (2008)

C1q and members of the defense collagen family are pattern recognition molecules that bind to pathogens and apoptotic cells and trigger a rapid enhancement of phagocytic activity. Candidate phagocytic cell receptors responsible for the enhancement of phagocytosis by defense collagens have been proposed but not yet discerned. Engagement of phagocyte surface-associated calreticulin in complex with the large endocytic receptor, low-density lipoprotein receptor-related protein 1 (LRP/CD91), by defense collagens has been suggested as one mechanism governing enhanced ingestion of C1q-coated apoptotic cells. To investigate this possibility, macrophages were derived from transgenic mice genetically deficient in LRP resulting from tissue-specific loxP/Cre recombination. LRP-deficient macrophages were impaired in their ability to ingest beads coated with an LRP ligand when compared with LRP-expressing macrophages, confirming for the first time that LRP participates in phagocytosis. When LRP-deficient and -expressing macrophages were plated on C1q-coated slides, they demonstrated equivalently enhanced phagocytosis of sheep RBC suboptimally opsonized with IgG or complement, compared with cells plated on control protein. In addition, LRP-deficient and -expressing macrophages ingested equivalent numbers of apoptotic Jurkat cells in the presence and absence of serum. Both LRP-deficient and -expressing macrophages ingested fewer apoptotic cells when incubated in the presence of C1q-deficient serum compared with normal mouse serum, and the addition of purified C1q reconstituted uptake to control serum levels. These studies demonstrate a direct contribution of LRP to phagocytosis and indicate that LRP is not required for the C1q-triggered enhancement of phagocytosis, suggesting that other, still undefined, receptor(s) exist to mediate this important innate immune function.
Immune Activation and a 9-Year Ongoing Complete Remission Following CD40 Antibody Therapy and Metastasectomy in a Patient with Metastatic Melanoma (2014)

Direct immune activation via agonistic mAbs is a potentially complementary approach to therapeutic blockade of inhibitory immune receptors in cancer. Here, we provide genetic analysis of the immunologic consequences associated with the use of an agonistic CD40 mAb in a patient with metastatic melanoma who responded, underwent a single metastasectomy, and then achieved a complete remission ongoing for more than 9 years after starting therapy. Tumor microenvironment after immunotherapy was associated with proinflammatory modulations and emergence of a de novo T-cell repertoire as detected by next-generation sequencing of T-cell receptors (TCR) in the tumor and blood. The de novo T-cell repertoire identified in the posttreatment metastasectomy sample was also present-and in some cases expanded-in the circulation years after completion of therapy. Comprehensive study of this "exceptional responder" highlights the emerging potential of direct immune agonists in the next wave of cancer immunotherapies and a potential role for TCR deep sequencing in cancer immune assessment.
Multiple antibiotics produced by Pseudomonas fluorescens HV37a and their differential regulation by glucose (1986)

Pseudomonas fluorescens HV37a inhibited growth of the fungus Pythium ultimum on potato dextrose agar (PDA). An antibiotic activity produced under these conditions was fractionated and partially characterized. Extracts prepared from the PDA on which HV37a was grown revealed a single peak of antibiotic activity on thin-layer chromatograms. Similar extracts were prepared from mutants of HV37a. Their analysis indicated that the antibiotic observed in thin-layer chromatograms was responsible for fungal inhibition observed on PDA. The production of the PDA antibiotic required the presence of glucose, whereas two other antibiotic activities were produced only on potato agar without added glucose. Two mutants (denoted AfuIa and AfuIb) previously characterized as deficient in fungal inhibition on PDA showed altered regulation of the production of all three antibiotics in response to glucose. These mutants were also deficient in glucose dehydrogenase. Mutants isolated as deficient in glucose dehydrogenase were also deficient in fungal inhibition and were grouped into two classes on the basis of complementation analysis with an AfuI cosmid. Glucose regulation of antibiotic biosynthesis therefore involves at least two components and requires glucose dehydrogenase.
Epitaxial layer transfer by bond and etch back of porous Si (1994)

We demonstrate a novel method for bond and etch back silicon on insulator in which an epitaxial Si layer over porous Si is transferred onto a dissimilar substrate by bonding and etch back of porous Si. The highest etching selectivity (100 000:1) between the porous Si and the epitaxial layer is achieved by the alkali free solution of HF, H2O2, and H2O which is essential for this single etch-stop method to produce a submicron-thick active layer with superior thickness uniformity (473±14 nm) across a 5 in. silicon-on-insulator wafer.