537 research outputs found
Exploring passenger assessments of bus service quality using Bayesian networks
Studies on public transit have emphasized the role of passenger satisfaction with service quality in travel choice decisions and indicated that satisfaction depends on various service attributes. Few studies have, however, systematically examined the underlying relationships among service attributes to assess their influence on passenger overall satisfaction. Therefore, to contribute to this rapidly-emerging literature, this paper applies Bayesian networks to quantify the influence of each service aspect on passenger overall satisfaction with regular bus service quality. This analysis involved 609 passengers who participated in a 2013 regular bus service survey in Nanjing, China. The derived Bayesian network shows the relationships among service attributes and passenger overall satisfaction graphically. In particular, service aspects such as running on schedule, acceptable waiting time, available seats, clean onboard environment, pleasant environment at stations, convenient design for transfers, and air-conditioning were the key determinants of overall satisfaction with bus service
Utilizing Coiled tube rig for mineral exploration application
Mineral exploration is in a race to employ drilling technology that can perform the exploration and drilling investigation in a fast and inexpensive manner. After an extensive study of the available drilling technologies in the market, coiled tubing was chosen as a tool to be employed for mineral exploration due to its flexible mobility and ease of operation with minimum number of personnel. Since coiled tubing technology is primarily used in oil and gas industry, it was important to re-design the coiled tube rig to drill hard rocks in a fast and feasible manner. The main requirements were to drill the smallest feasible hole diameter and go as deep in the ground as possible, in the shortest reasonable time. The drilled rock particles, cuttings, are to be collected and analysed at the surface for their metal mineral contents. The process also needs to be repeated multiple times at different locations for mapping, without the need to change the tube on the rig due to failure or potential failure. The focus of the new designed coiled tube, for drilling and mineral exploration, is three fold. First is to increase the rate of penetration (ROP) in drilling by designing a small high speed turbo motor. Second is to determine the controlling parameters of cuttings transport to effectively lift the cuttings to the surface for analysis and third is to minimize the overall weight of the rig for manoeuvring and to prolong the life span of the coiled tube string. In this paper, a small downhole turbo motor, 5cm outer diameter, is designed to achieve a rotation speed of up to 10,000 rpm to fit on a small bit, coiled tube drilling assembly. The motor design utilised multiple finite volume and finite element analysis software for fluid flow study and fluid structural interaction analysis.The paper is also introducing the concept of flow slurry loop that is designed to lift the cutting particles to the surface for mineralisation analysis. The controlling parameters of the cuttings transportation are the particles physical properties such as size, density, concentration and shape, as well as the rheological properties of the carrying fluid, drilled hole angle, as well as the fluid flow rate and flow dynamics within the annulus gap between the coiled tube and drilled hole. Such parameters are addressed via experimental work as well as numerical analysis. The paper is also presenting the selection and testing procedure of the material type for the coiled tube string. The tube needs to be light in weight for rig transportation and to drill few dozens of drill investigations holes before failing due to fatigue. A fatigue bending machine is designed to test the endurance limit of candidate materials for coiled tube string and performance index methodology is followed for material selection of the optimum material. The coiled tube rig is designed to be light in weight for transportation and relocation. It is also required to speed the drilling operation with the minimum foot print and will reclaim the drilled rock particles for mineral composition analysis at the surface
NUP98 oncofusions in myeloid malignancies:An update on molecular mechanisms and therapeutic opportunities
Acute myeloid leukemia (AML) is an aggressive hematological malignancy with a heterogeneous molecular landscape. In the pediatric context, the NUP98 gene is a frequent target of chromosomal rearrangements that are linked to poor prognosis and unfavorable treatment outcomes in different AML subtypes. The translocations fuse NUP98 to a diverse array of partner genes, resulting in fusion proteins with novel functions. NUP98 fusion oncoproteins induce aberrant biomolecular condensation, abnormal gene expression programs, and re-wired protein interactions which ultimately cause alterations in the cell cycle and changes in cellular structures, all of which contribute to leukemia development. The extent of these effects is steered by the functional domains of the fusion partners and the influence of concomitant somatic mutations. In this review, we discuss the complex characteristics of NUP98 fusion proteins and potential novel therapeutic approaches for NUP98 fusion-driven AML.</p
Quantum mechanics and geodesic deviation in the brane world
We investigate the induced geodesic deviation equations in the brane world
models, in which all the matter forces except gravity are confined on the
3-brane. Also, the Newtonian limit of induced geodesic deviation equation is
studied. We show that in the first Randall-Sundrum model the Bohr-Sommerfeld
quantization rule is as a result of consistency between the geodesic and
geodesic deviation equations. This indicates that the path of test particle is
made up of integral multiples of a fundamental Compton-type unit of length
.Comment: 5 pages, no figure
Runaway electron energy measurement using hard x-ray spectroscopy in "Damavand" tokamak
Set of experiments has been developed to study existing runaway electrons in "Damavand" tokamak plasma upon characteristics of hard x-ray emissions produced by collision of the runaway electrons with the plasma particles and limiters. As a first step, spatial distribution of hard x-ray emissions on the equatorial plane of the torus was considered. Obtained spectra of hard x-ray emissions for different alignments of shielded detector indicate isotropic emissivity in the equatorial plane. This is in agreement with wide angle cone of bremsstrahlung radiations, deduced from the mean value of energy of the runaway electrons. The mean energy was calculated from the slope of the energy spectrum of hard x-ray photons. In the second stage in order to investigate time evolution of energy of the runaway electrons, similar technique were applied to obtain hard x-ray energy in every 3 ms intervals, from the beginning to the end of plasma. The mean energy of the runaway electrons increases during the ramp up phase and reaches its maximum between 3 and 9 ms after plasma formation. Also considering the time dependence of the counted photons in each energy range shows that energetic photons are emitted during the ramp up phase of the plasma current in Damavand tokamak
Genetic Risk Factors for Type 2 Diabetes: A Trans-Regulatory Genetic Architecture?
To date, 68 loci have been associated with type 2 diabetes (T2D) or glucose homeostasis traits. We report here the results of experiments aimed at functionally characterizing the SNPs replicated for T2D and glucose traits. We sought to determine whether these loci were associated with transcript levels in adipose, muscle, liver, lymphocytes, and pancreatic β-cells. We found an excess of trans, rather than cis, associations among these SNPs in comparison to what was expected in adipose and muscle. Among transcripts differentially expressed (FDR \u3c 0.05) between muscle or adipose cells of insulin-sensitive individuals and those of insulin-resistant individuals (matched on BMI), trans-regulated transcripts, in contrast to the cis-regulated ones, were enriched. The paucity of cis associations with transcripts was confirmed in a study of liver transcriptome and was further supported by an analysis of the most detailed transcriptome map of pancreatic β-cells. Relative to location- and allele-frequency-matched random SNPs, both the 68 loci and top T2D-associated SNPs from two large-scale genome-wide studies were enriched for trans eQTLs in adipose and muscle but not in lymphocytes. Our study suggests that T2D SNPs have broad-reaching and tissue-specific effects that often extend beyond local transcripts and raises the question of whether patterns of cis or trans transcript regulation are a key feature of the architecture of complex traits
Global Gene Expression Profiles of Subcutaneous Adipose and Muscle from Glucose-Tolerant, Insulin-Sensitive, and Insulin-Resistant Individuals Matched for BMI
OBJECTIVE - To determine altered gene expression profiles in subcutaneous adipose and skeletal muscle from nondiabetic, insulin-resistant individuals compared with insulin-sensitive individuals matched for BMI.
RESEARCH DESIGN AND METHODS - A total of 62 nondiabetic individuals were chosen for extremes of insulin sensitivity (31 insulin-resistant and 31 insulin-sensitive subjects; 40 were European American and 22 were African American) and matched for age and obesity measures. Global gene expression profiles were determined and compared between ethnic groups and between insulin-resistant and insulin-sensitive participants individually and using gene-set enrichment analysis.
RESULTS - African American and European American subjects differed in 58 muscle and 140 adipose genes, including many inflammatory and metabolically important genes. Peroxisome proliferator-activated receptor γ cofactor 1A (PPARGC1A) was 1.75-fold reduced with insulin resistance in muscle, and fatty acid and lipid metabolism and oxidoreductase activity also were down-regulated. Unexpected categories included ubiquitination, citrullination, and protein degradation. In adipose, highly represented categories included lipid and fatty acid metabolism, insulin action, and cell-cycle regulation. Inflammatory genes were increased in European American subjects and were among the top Kyoto Encyclopedia of Genes and Genomes pathways on gene-set enrichment analysis. FADS1, VEGFA, PTPN3, KLF15, PER3, STEAP4, and AGTR1 were among genes expressed differentially in both adipose and muscle.
CONCLUSIONS - Adipose tissue gene expression showed more differences between insulin-resistant versus insulin-sensitive groups than the expression of genes in muscle. We confirm the role of PPARGC1A in muscle and show some support for inflammation in adipose from European American subjects but find prominent roles for lipid metabolism in insulin sensitivity independent of obesity in both tissues. Diabetes 60:1019–1029, 201
A population biological model with a singular nonlinearity
summary:We consider the existence of positive solutions of the singular nonlinear semipositone problem of the form where is a bounded smooth domain of with , , , , and , , and are positive parameters. Here is a continuous function. This model arises in the studies of population biology of one species with representing the concentration of the species. We discuss the existence of a positive solution when satisfies certain additional conditions. We use the method of sub-supersolutions to establish our results
Prevalence of musculoskeletal disorders and postural analysis of beekeepers
Work-related musculoskeletal disorders (WRMSDs) lead to fatigue and decreased productivity in workers, resulting in the need for many affected individuals to seek medical treatment annually. Beekeepers, like other agricultural workers, are susceptible to WRMSDs due to the continuous demands of their work and the repetitive movements involved. Thus, the objective of this study is to determine the prevalence of WRMSDs and assess the level of risk associated with different postures among beekeepers to improve their musculoskeletal health. To achieve this, a cross-sectional study was conducted involving 33 beekeepers, consisting of two stages. Firstly, the Nordic Questionnaire was utilized to assess the prevalence of WRMSDs. Subsequently, the Ovako Working Posture Analysis System (OWAS) was employed to analyze and categorize the riskiest postures into four levels of corrective measures. The findings indicate that the most commonly affected areas were the back (51.5%) and waist (45.4%). The occurrence of WRMSDs in various body regions was significantly associated with the beekeepers’ years of experience and weekly working hours. Additionally, the prevalence of neck and back pain was significantly related to their body mass index (BMI). The OWAS postural analysis revealed that the back (36.75%) and arm (21.08%) regions required corrective measures as soon as possible (level III), while the back (26.47%) and legs (14.70%) fell under the category of corrective measures needed in the near future (level II). Combining the postural analysis results, 28.43% were classified as Action Levels (AL) II, 37.73% as level III, and 0.98% as level IV. This study demonstrates that WRMSDs are relatively common among beekeepers, primarily due to their extensive work experience and the adoption of awkward postures during their tasks. As a result, recommendations regarding ergonomics and physiotherapy are provided to alleviate pain and reduce the strain on critical posture
Therapeutic targeting in pediatric acute myeloid leukemia with aberrant HOX/MEIS1 expression
Despite advances in the clinical management of childhood acute myeloid leukemia (AML) during the last decades, outcome remains fatal in approximately one third of patients. Primary chemoresistance, relapse and acute and long-term toxicities to conventional myelosuppressive therapies still constitute significant challenges and emphasize the unmet need for effective targeted therapies. Years of scientific efforts have translated into extensive insights on the heterogeneous spectrum of genetics and oncogenic signaling pathways of AML and identified a subset of patients characterized by upregulation of HOXA and HOXB homeobox genes and myeloid ecotropic virus insertion site 1 (MEIS1). Aberrant HOXA/MEIS1 expression is associated with genotypes such as rearrangements in Histone-lysine N-methyltransferase 2A (KMT2A-r), nucleoporin 98 (NUP98-r) and mutated nucleophosmin (NPM1c) that are found in approximately one third of children with AML. AML with upregulated HOXA/MEIS1 shares a number of molecular vulnerabilities amenable to recently developed molecules targeting the assembly of protein complexes or transcriptional regulators. The interaction between the nuclear scaffold protein menin and KMT2A has gained particular interest and constitutes a molecular dependency for maintenance of the HOXA/MEIS1 transcription program. Menin inhibitors disrupt the menin-KMT2A complex in preclinical models of KMT2A-r, NUP98-r and NPM1c acute leukemias and its occupancy at target genes leading to leukemic cell differentiation and apoptosis. Early-phase clinical trials are either ongoing or in development and preliminary data suggests tolerable toxicities and encouraging efficacy of menin inhibitors in adults with relapsed or refractory KMT2A-r and NPM1c AML. The Pediatric Acute Leukemia/European Pediatric Acute Leukemia (PedAL/EUPAL) project is focused to advance and coordinate informative clinical trials with new agents and constitute an ideal framework for testing of menin inhibitors in pediatric study populations. Menin inhibitors in combination with standard chemotherapy or other targeting agents may enhance anti-leukemic effects and constitute rational treatment strategies for select genotypes of childhood AML, and provide enhanced safety to avoid differentiation syndrome. In this review, we discuss the pathophysiological mechanisms in KMT2A-r, NUP98-r and NPM1c AML, emerging molecules targeting the HOXA/MEIS1 transcription program with menin inhibitors as the most prominent examples and future therapeutic implications of these agents in childhood AML.</p
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