gebhart/patrepeval huggingface dataset:
Synthesis of bicyclic diones and thiones. Facile methylation of the enolates of bicyclo[2.2.1]heptane-2,5-dione and bicyclo[2.2.2]octane-2,5-dione. An AM1 computational study of bicyclic enolates (1992)

A group of bicyclic ketones and thiones have been synthesized for homenolization studies. Bicyclo[2.2.1]heptane-2,5-dione (6) undergoes unusually rapid tetramethylation giving 3,3,6,6-tetramethylbicyclo[2.2.1]heptane-2,5-dione (1) in good yield. Treatment of 1 with P 2 S 5 in xylene gave 3,3,6,6-tetramethylbicyclo[2.2.1]heptane-2,5-dithione (2) and 3,3,6,6-tetramethyl 15-oxo-bicyclo[2.2.1]heptane-2-thione (3), which was converted into 4 with Raney nickel. Bicyclo[2,2,2]octane-2,5-dione (7), prepared via a Diels–Alder reaction between 2-trimethylsilyloxy-1,3-cyclohexadiene and and α-acetoxyacrylonitrile followed by a one-step desilylation/hydrolysis, also undergoes facile tetramethylation giving 3,3,6,6-tetramethylbicyclo[2.2.2]octane-2,5-dione (5) in good yield. AM1 calculations were carried out on the α-enolates of bicyclo[2.2.1]heptan-2-one, 6, 5-methylidenebicyclo[2.2.1]heptan-2-one, and 4-acetylbicyclo[2.2.1]-heptan-2-one in an attempt to gain information on the source of the enhanced acidity of the C-3 hydrogens of 6 and 7. Keywords: bicyclic ketones, thiones, synthesis.
MiRTDL: A Deep Learning Approach for miRNA Target Prediction (2015)

MicroRNAs (miRNAs) regulate genes that are associated with various diseases. To better understand miRNAs, the miRNA regulatory mechanism needs to be investigated and the real targets identified. Here, we present miRTDL, a new miRNA target prediction algorithm based on convolutional neural network (CNN). The CNN automatically extracts essential information from the input data rather than completely relying on the input dataset generated artificially when the precise miRNA target mechanisms are poorly known. In this work, the constraint relaxing method is first used to construct a balanced training dataset to avoid inaccurate predictions caused by the existing unbalanced dataset. The miRTDL is then applied to 1,606 experimentally validated miRNA target pairs. Finally, the results show that our miRTDL outperforms the existing target prediction algorithms and achieves significantly higher sensitivity, specificity and accuracy of 88.43, 96.44, and 89.98 percent, respectively. We also investigate the miRNA target mechanism, and the results show that the complementation features are more important than the others.
Na<sup>+</sup>/K<sup>+</sup>‐ATPase as a signal transducer (2002)

Na(+)/K(+)-ATPase as an energy transducing ion pump has been studied extensively since its discovery in 1957. Although early findings suggested a role for Na(+)/K(+)-ATPase in regulation of cell growth and expression of various genes, only in recent years the mechanisms through which this plasma membrane enzyme communicates with the nucleus have been studied. This research, carried out mostly on cardiac myocytes, shows that in addition to pumping ions, Na(+)/K+-ATPase interacts with neighboring membrane proteins and organized cytosolic cascades of signaling proteins to send messages to the intracellular organelles. The signaling pathways that are rapidly elicited by the interaction of ouabain with Na(+)/K(+)-ATPase, and are independent of changes in intracellular Na(+) and K(+) concentrations, include activation of Src kinase, transactivation of the epidermal growth factor receptor by Src, activation of Ras and p42/44 mitogen-activated protein kinases, and increased generation of reactive oxygen species by mitochondria. In cardiac myocytes, the resulting downstream events include the induction of some early response proto-oncogenes, activation of the transcription factors, activator protein-1 and nuclear factor kappa-B, regulation of a number of cardiac growth-related genes, and stimulation of protein synthesis and myocyte hypertrophy. For these downstream events, the induced reactive oxygen species and rise in intracellular Ca(2+) are essential second messengers. In cells other than cardiac myocytes, the proximal pathways linked to Na(+)/K(+)-ATPase through protein-protein interactions are similar to those reported in myocytes, but the downstream events and consequences may be significantly different. The likely extracellular physiological stimuli for the signal transducing function of Na+/K+-ATPase are the endogenous ouabain-like hormones, and changes in extracellular K+ concentration.
Molecular Modeling of Carbonaceous Compounds Formed Inside the Pores of FER Zeolite during Skeletal Isomerization of <i>n</i>-Butene (2000)

Molecular mechanics calculations of isobutene, its dimer (2,4,4-trimethyl-2-pentene), its trimer (2,4,4,6,6-pentamethyl-2-heptene), and seven families of coke molecules formed during n-butene isomerization were carried out within the ferrierite pore system. Monte Carlo docking showed that most of these molecules are well solvated by the zeolite framework and are preferentially sited within one or two intersections along the 10-membered ring channel. The locations of most of the larger coke molecules in two adjacent intersections account for the significant influence of dehydrogenative coupling in the formation of coke molecules in FER-structured zeolites. The stability of the butene dimer is close to that of molecules of carbonaceous compounds, which are known to be trapped inside the zeolite pores, whereas the stability of a trimer intermediate is much lower. This is consistent with the bimolecular isomerization mechanism and autocatalytic process proposed previously. Of the coke molecules investigated, only fluoranthene is unstable in the FER pores. This suggests that fluoranthene is not completely located in the zeolite pores, and it is proposed that this molecule is formed at the pore mouth. The results of simulated diffusion calculations confirmed the minimum energy locations of biphenyl and naphthalene found by docking and were consistent with experimental data regarding the mobility of these two species in ferrierite.
B109 Vacc-4x and Vacc-C5 (2013)

Immune-based interventions for HIV-1 infection need to achieve both the induction of effective anti-viral responses as well as a reduction in HIV-associated hyperactivation of the immune system. Vacc-4x is a peptide-based therapeutic vaccine designed to induce cytotoxic T-cell-based killing of HIV-infected cells. Vacc-4x has recently completed a large phase II study in Europe and the USA enrolling 135 subjects (www.clinicaltrials.gov identifier NCT00659789). Vacc-4x Subjects that achieved a 6 month ART-free period showed a statistically significant reduction in viral load set point (64%) compared to placebo subjects that were similarly ART-free for 6 months (p=0.04). Immunological data suggest that in contrast to placebo, the quality of immune responses in subjects that received Vacc-4x influenced viral load in a manner that was independent of human leukocyte antigen (HLA) status. Vacc-C5 is a peptide-based therapeutic vaccine candidate designed to induce non-neutralizing antibodies to the 5th constant domain (C5) on the HIV-1 envelope glycoprotein gp120. This product is currently being evaluated in a phase I clinical study (www.clinicaltrials.gov identifier NCT01627678). Recent results from analysis of serum samples from a number of different cohorts of treatment naïve subjects in Norway and the United States support previous observations that the presence of anti-C5 antibodies is associated with low/moderate viral load in natural viral suppressor subjects whereas anti-C5 antibody levels are significantly reduced in subjects with elevated viral load that show disease progression. Vacc-4x and Vacc-C5 are being considered for use in combination as a therapeutic vaccine and ultimately as a preventive vaccine.
在 interleukin 之间的关系 18 多型性和危险性到长期的肝炎 B 病毒感染 (2012)

AIM:To identify the relationship between the tagging single nucleotide polymorphism sites(tagSNPs)of the Interleukin-18(IL-18)gene and genetic susceptibility to chronic hepatitis B virus infection in Chinese patients.METHODS:Five hundred and one cases of chronic hep-atitis B virus(HBV)infection and 301 HBV natural clearance controls were studied.Two tagSNPs in the IL-18 gene(rs1946518A/C and rs574424C/G)were genotyped by the Multiplex Snapshot technique.The genotype and allele frequencies were calculated and analyzed.RESULTS:In the genotypes of rs1946518,the AA type was present at a higher frequency in the patients compared to those in the controls.Odds ratio(OR)of theAA genotype for the comparison with that of the AC and the CC genotype was 1.537(95%confidence intervals(CI):1.116-2.218,P=0.009<0.025).In pheno-types,the allele C at rs1946518 was of a significantly lower frequency in the patients with chronic hepatitis B than that in the controls(P=0.017<0.025).OR of the allele A for the comparison with that of the allele C was 1.279(95%CI:1.045-1.567).As for the rs574424 genotypes,no significant difference in this genotype distribution or in this allele frequency between the patients and the control subjects was observed.No significant difference in the haplotype frequencies between the patients with chronic hepatitis B and HBV natural clearance individuals was displayed.CONCLUSION:The data suggest that genotype AA and the allele A of the IL-18 at position rs1946518 are closely associated with the resistance to chronic hepatitis B and may be the dangerous gene.However,no statistical association was found between polymorphisms of rs574424 for IL-18 and hepatitis B.
Value-at-Risk — Eine anwendungsorientierte Darstellung zentraler Methoden und Techniken des modernen Risikomanagements (2001)

Der Beitrag liefert einen Überblick über Ausgestaltungsformen des Value-at-Risk-Ansatzes zur Quantifizierung finanzieller Marktrisiken. Einleitend wird der Value-at-Risk (VaR) definiert und sein Aussagegehalt an einem einfachen Zahlenbeispiel veranschaulicht. Nach einer kurzen Beschreibung der wichtigsten Methoden der VaR-Ermittlung wird die zentrale Frage behandelt, wie Volatilitäten als Input für VaR-Modelle geschätzt werden können. Dabei zeigt sich, daß exponentiell gewichtete gleitende Durchschnitte und GARCH-Modelle geeignet sind, über die Zeit veränderliche Varianzen und Kovarianzen zu erfassen. Im Anschluß wird ausführlich auf Mapping-Verfahren eingegangen, indem die Überführung der gängigen Finanztitel auf sogenannte Risiko-oder Standardmarktfaktoren erläutert wird. Neben klassischen Zinstiteln, Aktien und Devisenpositionen werden die grundlegenden Derivate wie Futures und Optionen betrachtet. Der Beitrag schließt mit einer kurzen Beurteilung des VaR-Ansatzes und einem Ausblick auf Weiterentwicklungen.
Assessing the Risks of Insuring Reputation Risk (2015)

Abstract Reputation risk is becoming increasingly important, especially with the rapidly growing influence of social media, heightened scrutiny on reputation risk by banking and insurance regulators, and reputation's impact on organizational value. Insurers have responded to this development only recently by offering new reputation risk insurance solutions. The aim of this article is to present the first detailed academic analysis of these new insurance policies, including examination of the risks insurers face in offering such coverage. We also offer a conceptualization of reputation risk in an insurance and risk management context with focus on exposures, perils, and hazards. Our analysis indicates that loss identification and measurement generate the greatest challenges to insurers in providing reputation risk coverage. Lack of experience as well as the complexity of the chain of reputation risk events related to reputation insurance coverage present insurers with significant challenges in making this a viable line of business.
Clinical effects of recombinant human granulocyte colony-stimulating factor in leukemia patients: a phase I/II study. (1989)

A phase I/II study of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in 24 leukemia patients was conducted at our institute. Recombinant human G-CSF (50-200 micrograms/m2/day) was administered i.v. In seven allogeneic bone marrow transplantation (BMT) recipients, treatment with rhG-CSF was started 5 days after BMT. Neutrophils began to increase within 3 days after the start of rhG-CSF administration in five of seven patients. The mean duration necessary for recovery of neutrophils to greater than 500/microliters was 11.3 days after BMT with rhG-CSF; 26.8 days is the figure for recovery without rhG-CSF from Japanese historical data. In seven out of eight patients who received rhG-CSF administration after the first remission-induction chemotherapy, the neutrophil counts increased from less than 300/microliters to greater than 4000/microliters within 10 days. Blasts did not increase in all patients including four acute nonlymphocytic leukemia (ANLL) patients. Severe infections such as septicemia and pneumonia, which were unable to be controlled by antibiotics only, were successfully treated with rhG-CSF and antibiotics. rhG-CSF either stimulated or inhibited myeloid leukemic cells in some refractory cases. Mild bone pain occurred in one patient while receiving rhG-CSF i.v. rhG-CSF seems to have the ability to shorten the period of neutropenia, prevent infections after allogeneic BMT and remission-induction chemotherapy for acute leukemia, and support therapy for infections.
Virtual Knowledge Graphs: An Overview of Systems and Use Cases (2019)

In this paper, we present the virtual knowledge graph (VKG) paradigm for data integration and access, also known in the literature as Ontology-based Data Access. Instead of structuring the integration layer as a collection of relational tables, the VKG paradigm replaces the rigid structure of tables with the flexibility of graphs that are kept virtual and embed domain knowledge. We explain the main notions of this paradigm, its tooling ecosystem and significant use cases in a wide range of applications. Finally, we discuss future research directions.
Information systems in demand side management (2002)

The paper presents an idea of information system for demand side management (DSM). The problem of monitoring and load control is also discussed. The paper presents the solution of information and technical problem of energy demand. An OPC interface standard is used, based upon the functional requirements of OLE/COM and DCOM technology, that fosters greater interoperability between automation control applications, field systems-devices, and business-office applications.
Incorporating New Technologies Into Toxicity Testing and Risk Assessment: Moving From 21st Century Vision to a Data-Driven Framework (2013)

Based on existing data and previous work, a series of studies is proposed as a basis toward a pragmatic early step in transforming toxicity testing. These studies were assembled into a data-driven framework that invokes successive tiers of testing with margin of exposure (MOE) as the primary metric. The first tier of the framework integrates data from high-throughput in vitro assays, in vitro-to-in vivo extrapolation (IVIVE) pharmacokinetic modeling, and exposure modeling. The in vitro assays are used to separate chemicals based on their relative selectivity in interacting with biological targets and identify the concentration at which these interactions occur. The IVIVE modeling converts in vitro concentrations into external dose for calculation of the point of departure (POD) and comparisons to human exposure estimates to yield a MOE. The second tier involves short-term in vivo studies, expanded pharmacokinetic evaluations, and refined human exposure estimates. The results from the second tier studies provide more accurate estimates of the POD and the MOE. The third tier contains the traditional animal studies currently used to assess chemical safety. In each tier, the POD for selective chemicals is based primarily on endpoints associated with a proposed mode of action, whereas the POD for nonselective chemicals is based on potential biological perturbation. Based on the MOE, a significant percentage of chemicals evaluated in the first 2 tiers could be eliminated from further testing. The framework provides a risk-based and animal-sparing approach to evaluate chemical safety, drawing broadly from previous experience but incorporating technological advances to increase efficiency.
High Fidelity Receivers with Expanding Selectors (1935)

A high fidelity receiver for general use requires means for continuously expanding or contracting the resultant band width of all the carrier selectors, in order that the best compromise between fidelity and selectivity may be chosen for any given operating conditions. The expanding selector ("XPS") arrangement may be adapted for either unsymmetrical or symmetrical expansion of the resonance curve. Arrangements are described and the relative merits are discussed for both kinds of expansion. A superheterodyne receiver is described, which has a preferred form of symmetrical expanding selector, as wvell as other advantageous features. A tuning and expanding mechanism is described, in which the expansion is adjustable by moving the tuning knob in the axial direction. The mechanism includes an interlock which permits the operator to tune the receiver only when the band width is contracted. The operator is thereby constrained to follow the correct procedure of first tuning with maximum selectivity, and second, expanding to improve the fidelity to the (extent permitted by noise or adjacent channel interference.
Development of micro immunoreaction-based cell sorter for regenerative medicine (2005)

Development of micro cell sorters for stem cell extraction is reported. The principle of cell sorting is based on immunoreaction for accurate recognition of target stem cells. A micro immunomagnetic cell sorter (∝-IMCS) consisting of a lamination micro mixer and a separation reservoir with external permanent magnet was fabricated with soft lithography. Experiments with human umbilical cord vein endothelial cells (HUVEC) and anti-human CD31 antibody show that ∝-IMCS is capable of trapping target cells within much shorter processing time compared to conventional IMCS. From cell separation experiments with HUVEC and human mesenchymal stem cells (hMSC), the accuracy of cell separation was comparable to conventional IMCS, and the potential use ∝-IMCS in real applications is certified. Following the performance examination of ∝-IMCS, a concept of single-step cell separation method utilizing the affinity of cell-surface antigen and its counterpart antibody is introduced. For this, microfabrication of a cell separation channel and antibody coating of the micro channel walls are made successfully.
Thermodynamic efficiency of an intermediate band photovoltaic cell with low threshold Auger generation (2005)

The detailed balance method is used to study the thermodynamic efficiency of an intermediate band photovoltaic cell with low threshold Auger generation. Hot electrons generated by high-energy photons pump electrons from the intermediate band to the conduction band. The intermediate band is filled up after absorption of low-energy photons. A thermodynamic efficiency of about 70% is obtained, which is higher than the maximal efficiency of 63.2% for an intermediate band solar cell without Auger generation. The optimum band gap is shifted towards the silicon band gap. This result gives silicon its place in the new generation of solar cell materials using generation mechanism absent in single-band-gap solar cells.
Design of Local Atomic Environments in Single‐Atom Electrocatalysts for Renewable Energy Conversions (2020)

Single-atom electrocatalysts (SAECs) have recently attracted tremendous research interest due to their often remarkable catalytic responses, unmatched by conventional catalysts. The electrocatalytic performance of SAECs is closely related to the specific metal species and their local atomic environments, including their coordination number, the determined structure of the coordination sites, and the chemical identity of nearest and second nearest neighboring atoms. The wide range of distinct chemical bonding configurations of a single-metal atom with its surrounding host atoms creates virtually limitless opportunities for the rational design and synthesis of SAECs with tunable local atomic environment for high-performance electrocatalysis. In this review, the authors first identify fundamental hurdles in electrochemical conversions and highlight the relevance of SAECs. They then critically examine the role of the local atomic structures, encompassing the first and second coordination spheres of the isolated metal atoms, on the design of high-performance SAECs. The relevance of single-atom dopants for host activation is also discussed. Insights into the correlation between local structures of SAECs and their catalytic response are analyzed and discussed. Finally, the authors summarize major challenges to be addressed in the field of SAECs and provide some perspectives in the rational construction of superior SAECs for a wide range of electrochemical conversions.
Molecular detection of persistent Borrelia burgdorferi in the urine of patients with active Lyme disease (1991)

Current diagnostic tests for Lyme disease (LD) are dependent upon the host serologic response and are insensitive early in infection and, possibly, following antibiotic therapy. We cloned a library of Borrelia burgdorferi 297 DNA and studied one clone, Ly-1, for its potential in diagnostic and pathogenic studies. Using pulsed-field electrophoresis, we demonstrated that Ly-1 is of chromosomal origin and estimated that the B. burgdorferi chromosome is approximately 1,100 kb in size. The 3.7-kb Ly-1 clone hybridizes with geographically diverse strains of B. burgdorferi. No cross hybridization occurs with DNA from human cells, Escherichia coli, Staphylococcus aureus, Clostridium difficile, or the closely related B. hermsii. We used a dot blot assay to detect 100 pg of B. burgdorferi DNA. We partially determined the nucleotide sequence of Ly-1 and used it to select and synthesize oligonucleotides for use in the polymerase chain reaction (PCR). Two different primer pairs were found to amplify DNA from nine geographically diverse isolates. We could detect 10 fg (less than 10 molecules) of B. burgdorferi or less than five spirochetes added to human urine. Finally, we were able to use the PCR to detect B. burgdorferi DNA in the urine of four of eight patients with suspected active LD (three with arthritis and one with neurologic manifestations), all of whom responded to antibiotic treatment. In contrast, those patients who were PCR negative either had inactive disease or had been appropriately treated and did not respond to additional antibiotics, and all four control urine specimens were PCR negative. We conclude that B. burgdorferi DNA can be sensitively detected by the PCR with the primers and methods we describe and that the urinary tract is a site of persistent infection in some cases of human LD, an observation of potential diagnostic and pathogenic importance.