Supply chain security certification and operational performance:The role of upstream complexity

Supply chain security (SCS) incidents increasingly cause financial losses to manufacturing facilities and logistics service providers. Thus, supply chain security certification can have implications for production economics, particularly for importing firms who rely on a smooth logistics flow across country borders. However, it largely remains unknown regarding how such certification could influence a firm's operational performance. To this end, we empirically examine whether and how the adoption of Customs-Trade Partnership Against Terrorism (C-TPAT) certification, initiated by the U.S. Customs and Border Protection (CBP), could improve operational performance in adopter firms. This study draws upon signaling theory to empirically investigate the value of C-TPAT certification on U.S. publicly-traded importer firms' operational performance by analyzing the longitudinal data of properly-matched sample-control groups. The data come from multiple sources: public announcements of C-TPAT certification from the News Retrieval Service database, import data from lading records, and financial data from Standard & Poor's COMPUSTAT database. Employing a coarsened exact matching (CEM) method and a difference-in-difference (DID) analysis, we find that C-TPAT certified importers have better operational performance than that of non-certified importers. We also find that the level of upstream supply chain complexity (detail, dynamic, and spatial complexity) enhances the operational performance derived from C-TPAT certification. This study sheds light on the performance value of a management standard that is attributed to the non-process mechanism (not due to process improvements) enabled by the signaling effectiveness incorporating the upstream supply chain complexities. Our findings have important theoretical and practical implications for production economics and supply chain management studies

Resolved Molecular Gas in a Quasar Host Galaxy at Redshift z=6.42

We present high-resolution VLA observations of the molecular gas in the host galaxy of the highest redshift quasar currently known, SDSS J1148+5251 (z=6.42). Our VLA data of the CO(3-2) emission have a maximum resolution of 0.17'' x 0.13'' (~1 kpc), and enable us to resolve the molecular gas emission both spatially and in velocity. The molecular gas in J1148+5251 is extended to a radius of 2.5 kpc, and the central region shows 2 peaks, separated by 0.3'' (1.7 kpc). These peaks account for about half of the total emission, while the remainder is more extended. Each of these unresolved peaks contains a molecular gas mass of ~5 x 10^9 M_sun (similar to the total mass found in nearby ULIRGS) and has an intrinsic brightness temperature of ~35 K (averaged over the 1 kpc-sized beam), comparable to what is found in nearby starburst centers. Assuming that the molecular gas is gravitationally bound, we estimate a dynamical mass of ~4.5 x 10^10 M_sun within a radius of 2.5 kpc (~5.5 x 10^10 M_sun if corrected for a derived inclination of i~65 deg.). This dynamical mass estimate leaves little room for matter other than the detected molecular gas, and in particular the data are inconsistent with a ~10^12 M_sun stellar bulge which would be predicted based on the M_BH-sigma_bulge relation. This finding may indicate that black holes form prior to the assembly of the stellar bulges and that the dark matter halos are less massive than predicted based on the black hole/bulge mass relationship.Comment: ApJ letters, Nov 2004, accepte

Molecular Gas in the Host Galaxy of a Quasar at Redshift z=6.42

Observations of the molecular gas phase in quasar host galaxies provide fundamental constraints on galaxy evolution at the highest redshifts. Molecular gas is the material out of which stars form; it can be traced by spectral line emission of carbon--monoxide (CO). To date, CO emission has been detected in more than a dozen quasar host galaxies with redshifts (z) larger 2, the record holder being at z=4.69. At these distances the CO lines are shifted to longer wavelengths, enabling their observation with sensitive radio and millimetre interferometers. Here we present the discovery of CO emission toward the quasar SDSS J114816.64+525150.3 (hereafter J1148+5251) at a redshift of z=6.42, when the universe was only 1/16 of its present age. This is the first detection of molecular gas at the end of cosmic reionization. The presence of large amounts of molecular gas (M(H_2)=2.2e10 M_sun) in an object at this time demonstrates that heavy element enriched molecular gas can be generated rapidly in the earliest galaxies.Comment: 12 pages, 2 figures. To appear in Nature, July, 200

Follow-up analyses to the O3 LIGO-Virgo-KAGRA lensing searches

Along their path from source to observer, gravitational waves may be gravitationally lensed by massive objects. This results in distortions of the observed signal which can be used to extract new information about fundamental physics, astrophysics, and cosmology. Searches for these distortions amongst the observed signals from the current detector network have already been carried out, though there have as yet been no confident detections. However, predictions of the observation rate of lensing suggest detection in the future is a realistic possibility. Therefore, preparations need to be made to thoroughly investigate the candidate lensed signals. In this work, we present some of the follow-up analyses and strategies that could be applied to assess the significance of such events and ascertain what information may be extracted about the lens-source system from such candidate signals by applying them to a number of O3 candidate events, even if these signals did not yield a high significance for any of the lensing hypotheses. For strongly-lensed candidates, we verify their significance using a background of simulated unlensed events and statistics computed from lensing catalogs. We also look for potential electromagnetic counterparts. In addition, we analyse in detail a candidate for a strongly-lensed sub-threshold counterpart that is identified by a new method. For microlensing candidates, we perform model selection using a number of lens models to investigate our ability to determine the mass density profile of the lens and constrain the lens parameters. We also look for millilensing signatures in one of the lensed candidates. Applying these additional analyses does not lead to any additional evidence for lensing in the candidates that have been examined. However, it does provide important insight into potential avenues to deal with high-significance candidates in future observations.Comment: 34 pages, 27 figure

Proline-Rich Tyrosine Kinase 2 (Pyk2) Promotes Cell Motility of Hepatocellular Carcinoma through Induction of Epithelial to Mesenchymal Transition

Aims: Proline-rich tyrosine kinase 2 (Pyk2), a non-receptor tyrosine kinase of the focal adhesion kinase (FAK) family, is up-regulated in more than 60% of the tumors of hepatocellular carcinoma (HCC) patients. Forced overexpression of Pyk2 can promote the proliferation and invasion of HCC cells. In this study, we aimed to explore the underlying molecular mechanism of Pyk2-mediated cell migration of HCC cells. Methodology/Principal Findings: We demonstrated that Pyk2 transformed the epithelial HCC cell line Hep3B into a mesenchymal phenotype via the induction of epithelial to mesenchymal transition (EMT), signified by the up-regulation of membrane ruffle formation, activation of Rac/Rho GTPases, down-regulation of epithelial genes E-cadherin and cytokeratin as well as promotion of cell motility in presence of lysophosphatidic acid (LPA). Suppression of Pyk2 by overexpression of dominant negative PRNK domain in the metastatic HCC cell line MHCC97L transformed its fibroblastoid phenotype to an epithelial phenotype with up-regulation of epithelial genes, down-regulation of mesenchymal genes N-cadherin and STAT5b, and reduction of LPA-induced membrane ruffle formation and cell motility. Moreover, overexpression of Pyk2 in Hep3B cells promoted the phosphorylation and localization of mesenchymal gene Hic-5 onto cell membrane while suppression of Pyk2 in MHCC97L cells attenuated its phosphorylation and localization. Conclusion: These data provided new evidence of the underlying mechanism of Pyk2 in controlling cell motility of HCC cells through regulation of genes associated with EMT. © 2011 Sun et al.published_or_final_versio

Artificial Polyploidy Improves Bacterial Single Cell Genome Recovery

BACKGROUND: Single cell genomics (SCG) is a combination of methods whose goal is to decipher the complete genomic sequence from a single cell and has been applied mostly to organisms with smaller genomes, such as bacteria and archaea. Prior single cell studies showed that a significant portion of a genome could be obtained. However, breakages of genomic DNA and amplification bias have made it very challenging to acquire a complete genome with single cells. We investigated an artificial method to induce polyploidy in Bacillus subtilis ATCC 6633 by blocking cell division and have shown that we can significantly improve the performance of genomic sequencing from a single cell. METHODOLOGY/PRINCIPAL FINDINGS: We inhibited the bacterial cytoskeleton protein FtsZ in B.subtilis with an FtsZ-inhibiting compound, PC190723, resulting in larger undivided single cells with multiple copies of its genome. qPCR assays of these larger, sorted cells showed higher DNA content, have less amplification bias, and greater genomic recovery than untreated cells. SIGNIFICANCE: The method presented here shows the potential to obtain a nearly complete genome sequence from a single bacterial cell. With millions of uncultured bacterial species in nature, this method holds tremendous promise to provide insight into the genomic novelty of yet-to-be discovered species, and given the temporary effects of artificial polyploidy coupled with the ability to sort and distinguish differences in cell size and genomic DNA content, may allow recovery of specific organisms in addition to their genomes

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Integrated motor drives: state of the art and future trends

With increased need for high power density, high efficiency and high temperature capabilities in Aerospace and Automotive applications, Integrated Motor Drives (IMD) offers a potential solution. However, close physical integration of the converter and the machine may also lead to an increase in components temperature. This requires careful mechanical, structural and thermal analysis; and design of the IMD system. This paper reviews existing IMD technologies and their thermal effects on the IMD system. The effects of the power electronics (PE) position on the IMD system and its respective thermal management concepts are also investigated. The challenges faced in designing and manufacturing of an IMD along with the mechanical and structural impacts of close physical integration is also discussed and potential solutions are provided. Potential converter topologies for an IMD like the Matrix converter, 2-level Bridge, 3-level NPC and Multiphase full bridge converters are also reviewed. Wide band gap devices like SiC and GaN and their packaging in power modules for IMDs are also discussed. Power modules components and packaging technologies are also presented

Discovery of four recessive developmental disorders using probabilistic genotype and phenotype matching among 4,125 families.

Discovery of most autosomal recessive disease-associated genes has involved analysis of large, often consanguineous multiplex families or small cohorts of unrelated individuals with a well-defined clinical condition. Discovery of new dominant causes of rare, genetically heterogeneous developmental disorders has been revolutionized by exome analysis of large cohorts of phenotypically diverse parent-offspring trios. Here we analyzed 4,125 families with diverse, rare and genetically heterogeneous developmental disorders and identified four new autosomal recessive disorders. These four disorders were identified by integrating Mendelian filtering (selecting probands with rare, biallelic and putatively damaging variants in the same gene) with statistical assessments of (i) the likelihood of sampling the observed genotypes from the general population and (ii) the phenotypic similarity of patients with recessive variants in the same candidate gene. This new paradigm promises to catalyze the discovery of novel recessive disorders, especially those with less consistent or nonspecific clinical presentations and those caused predominantly by compound heterozygous genotypes