A new modelling approach of evaluating preventive and reactive strategies for mitigating supply chain risks

Supply chains are becoming more complex and vulnerable due to globalization and interdependency between different risks. Existing studies have focused on identifying different preventive and reactive strategies for mitigating supply chain risks and advocating the need for adopting specific strategy under a particular situation. However, current research has not addressed the issue of evaluating an optimal mix of preventive and reactive strategies taking into account their relative costs and benefits within the supply network setting of interconnected firms and organizations. We propose a new modelling approach of evaluating different combinations of such strategies using Bayesian belief networks. This technique helps in determining an optimal solution on the basis of maximum improvement in the network expected loss. We have demonstrated our approach through a simulation study and discussed practical and managerial implications

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Circulating Pneumolysin Is a Potent Inducer of Cardiac Injury during Pneumococcal Infection

Streptococcus pneumoniae accounts for more deaths worldwide than any other single pathogen through diverse disease manifestations including pneumonia, sepsis and meningitis. Life-threatening acute cardiac complications are more common in pneumococcal infection compared to other bacterial infections. Distinctively, these arise despite effective antibiotic therapy. Here, we describe a novel mechanism of myocardial injury, which is triggered and sustained by circulating pneumolysin (PLY). Using a mouse model of invasive pneumococcal disease (IPD), we demonstrate that wild type PLY-expressing pneumococci but not PLY-deficient mutants induced elevation of circulating cardiac troponins (cTns), well-recognized biomarkers of cardiac injury. Furthermore, elevated cTn levels linearly correlated with pneumococcal blood counts (r=0.688, p=0.001) and levels were significantly higher in non-surviving than in surviving mice. These cTn levels were significantly reduced by administration of PLY-sequestering liposomes. Intravenous injection of purified PLY, but not a non-pore forming mutant (PdB), induced substantial increase in cardiac troponins to suggest that the pore-forming activity of circulating PLY is essential for myocardial injury in vivo. Purified PLY and PLY-expressing pneumococci also caused myocardial inflammatory changes but apoptosis was not detected. Exposure of cultured cardiomyocytes to PLY-expressing pneumococci caused dose-dependent cardiomyocyte contractile dysfunction and death, which was exacerbated by further PLY release following antibiotic treatment. We found that high PLY doses induced extensive cardiomyocyte lysis, but more interestingly, sub-lytic PLY concentrations triggered profound calcium influx and overload with subsequent membrane depolarization and progressive reduction in intracellular calcium transient amplitude, a key determinant of contractile force. This was coupled to activation of signalling pathways commonly associated with cardiac dysfunction in clinical and experimental sepsis and ultimately resulted in depressed cardiomyocyte contractile performance along with rhythm disturbance. Our study proposes a detailed molecular mechanism of pneumococcal toxin-induced cardiac injury and highlights the major translational potential of targeting circulating PLY to protect against cardiac complications during pneumococcal infections

E3 Ligase Activity of XIAP RING Domain Is Required for XIAP-Mediated Cancer Cell Migration, but Not for Its RhoGDI Binding Activity

Although an increased expression level of XIAP is associated with cancer cell metastasis, the underlying molecular mechanisms remain largely unexplored. To verify the specific structural basis of XIAP for regulation of cancer cell migration, we introduced different XIAP domains into XIAP−/− HCT116 cells, and found that reconstitutive expression of full length HA-XIAP and HA-XIAP ΔBIR, both of which have intact RING domain, restored β-Actin expression, actin polymerization and cancer cell motility. Whereas introduction of HA-XIAP ΔRING or H467A mutant, which abolished its E3 ligase function, did not show obvious restoration, demonstrating that E3 ligase activity of XIAP RING domain played a crucial role of XIAP in regulation of cancer cell motility. Moreover, RING domain rather than BIR domain was required for interaction with RhoGDI independent on its E3 ligase activity. To sum up, our present studies found that role of XIAP in regulating cellular motility was uncoupled from its caspase-inhibitory properties, but related to physical interaction between RhoGDI and its RING domain. Although E3 ligase activity of RING domain contributed to cell migration, it was not involved in RhoGDI binding nor its ubiquitinational modification

Process Mining for Six Sigma

Process mining offers a set of techniques for gaining data-based insights into business processes from event logs. The literature acknowledges the potential benefits of using process mining techniques in Six Sigma-based process improvement initiatives. However, a guideline that is explicitly dedicated on how process mining can be systematically used in Six Sigma initiatives is lacking. To address this gap, the Process Mining for Six Sigma (PMSS) guideline has been developed to support organizations in systematically using process mining techniques aligned with the DMAIC (Define-Measure-Analyze-Improve-Control) model of Six Sigma. Following a design science research methodology, PMSS and its tool support have been developed iteratively in close collaboration with experts in Six Sigma and process mining, and evaluated by means of focus groups, demonstrations and interviews with industry experts. The results of the evaluations indicate that PMSS is useful as a guideline to support Six Sigma-based process improvement activities. It offers a structured guideline for practitioners by extending the DMAIC-based standard operating procedure. PMSS can help increasing the efficiency and effectiveness of Six Sigma-based process improving efforts. This work extends the body of knowledge in the fields of process mining and Six Sigma, and helps closing the gap between them. Hence, it contributes to the broad field of quality management

Radiografia torácica e bacteriologia na fase inicial de tratamento de 800 pacientes masculinos com tuberculose pulmonar

OBJETIVO: Avaliar radiografias de tórax de pacientes com tuberculose pulmonar e determinar se a extensão das lesões radiográficas correlaciona-se com os parâmetros bacteriológicos. MÉTODOS: Neste estudo descritivo e retrospectivo; foram avaliadas radiografias de tórax, baciloscopias para BAAR e culturas de escarro para Mycobacterium tuberculosis no momento basal e durante os dois primeiros meses de tratamento. A amostra foi composta por 800 pacientes masculinos internados entre 1995 até o presente em um hospital com 250 leitos no noroeste da Turquia. RESULTADOS: A VHS média inicial foi de 58 ± 37 mm/h. Inicialmente, a baciloscopia e as culturas de escarro tiveram resultado positivo em 83,8% e em 89,5% dos pacientes, respectivamente. Após o primeiro mês do tratamento, a proporção de culturas positivas foi maior nos pacientes com doença cavitária do que naqueles sem doença cavitária (53,7% vs. 37,7%; p 0.05 para todos), mas houve correlação positiva com VHS (r = 0,23, p OBJECTIVE: To evaluate chest X-rays of patients with pulmonary tuberculosis and to determine whether the extent of radiographic lesions correlates with bacteriological parameters. METHODS: In this retrospective, descriptive study, we evaluated chest X-rays, as well as AFB detection by smear microscopy and culture for Mycobacterium tuberculosis, initially and during the first two months of treatment, in 800 male patients hospitalized between 1995 and the present at a 250-bed hospital in northwestern Turkey. RESULTS: The initial mean ESR was 58 ± 37 mm/h. Initial sputum smears and cultures were positive in 83.8% and 89.5% of the patients, respectively. After the first month of treatment, the proportion of patients with positive sputum culture was higher among those with cavitary tuberculosis than among those with non-cavitary tuberculosis (53.7% vs. 37.7%, p 0.05 for all) but was positively correlated with the ESR (r = 0.23, p < 0.001). During the first and second months of treatment, conversion to smear-negative status was less common in patients with bilateral involvement than in those with unilateral involvement (p < 0.001 and p = 0.002 for months 1 and 2, respectively). Disease extent did not correlate with age, symptom duration, contact with an active tuberculosis patient, or concomitant diabetes but did correlate with delayed bacteriological recovery. CONCLUSIONS: Chest X-ray and bacteriology are valuable tools for the evaluation of pulmonary tuberculosi

GM-CSF-Producing Th Cells in Rats Sensitive and Resistant to Experimental Autoimmune Encephalomyelitis

Given that granulocyte macrophage colony-stimulating factor (GM-CSF) is identified as the key factor to endow auto-reactive Th cells with the potential to induce neuroinflammation in experimental autoimmune encephalomyelitis (EAE) models, the frequency and phenotype of GM-CSF-producing (GM-CSF+) Th cells in draining lymph nodes (dLNs) and spinal cord (SC) of Albino Oxford (AO) and Dark Agouti (DA) rats immunized for EAE were examined. The generation of neuroantigen-specific GM-CSF+ Th lymphocytes was impaired in dLNs of AO rats (relatively resistant to EAE induction) compared with their DA counterparts (susceptible to EAE) reflecting impaired CD4+ lymphocyte proliferation and less supportive of GM-CSF+ Th cell differentiation dLN cytokine microenvironment. Immunophenotyping of GM-CSF+ Th cells showed their phenotypic heterogeneity in both strains and revealed lower frequency of IL-17+ IFN-gamma+, IL-17+ IFN-gamma-, and IL-17-IFN-gamma+ cells accompanied by higher frequency of IL-17-IFN-gamma- cells among them in AO than in DA rats. Compared with DA, in AO rats was also found (i) slightly lower surface density of CCR2 (drives accumulation of highly pathogenic GM-CSF+ IFN-gamma+ Th17 cells in SC) on GM-CSF+ IFN-gamma+ Th17 lymphocytes from dLNs, and (ii) diminished CCL2 mRNA expression in SC tissue, suggesting their impaired migration into the SC. Moreover, dLN and SC cytokine environments in AO rats were shown to be less supportive of GM-CSF+ IFN-gamma+ Th17 cell differentiation (judging by lower expression of mRNAs for IL-1 beta, IL-6 and IL-23/p19). In accordance with the (i) lower frequency of GM-CSF+ Th cells in dLNs and SC of AO rats and their lower GM-CSF production, and (ii) impaired CCL2 expression in the SC tissue, the proportion of proinflammatory monocytes among peripheral blood cells and their progeny (CD45(hi) cells) among the SC CD11b+ cells were reduced in AO compared with DA rats. Collectively, the results indicate that the strain specificities in efficacy of several mechanisms controlling (auto) reactive CD4+ lymphocyte expansion/differentiation into the cells with pathogenic phenotype and migration of the latter to the SC contribute to AO rat resistance to EAE

Pubertal high fat diet: effects on mammary cancer development

INTRODUCTION: Epidemiological studies linking dietary fat intake and obesity to breast cancer risk have produced inconsistent results. This may be due to the difficulty of dissociating fat intake from obesity, and/or the lack of defined periods of exposure in these studies. The pubertal mammary gland is highly sensitive to cancer-causing agents. We assessed how high fat diet (HFD) affects inflammation, proliferative, and developmental events in the pubertal gland, since dysregulation of these can promote mammary tumorigenesis. To test the effect of HFD initiated during puberty on tumorigenesis, we utilized BALB/c mice, for which HFD neither induces obesity nor metabolic syndrome, allowing dissociation of HFD effects from other conditions associated with HFD. METHODS: Pubertal BALB/c mice were fed a low fat diet (12% kcal fat) or a HFD (60% kcal fat), and subjected to carcinogen 7,12-dimethylbenz[a]anthracene (DMBA)-induced tumorigenesis. RESULTS: HFD elevated mammary gland expression of inflammatory and growth factor genes at 3 and 4 weeks of diet. Receptor activator of nuclear factor kappa-B ligand (RANKL), robustly induced at 4 weeks, has direct mitogenic activity in mammary epithelial cells and, as a potent inducer of NF-κB activity, may induce inflammatory genes. Three weeks of HFD induced a transient influx of eosinophils into the mammary gland, consistent with elevated inflammatory factors. At 10 weeks, prior to the appearance of palpable tumors, there were increased numbers of abnormal mammary epithelial lesions, enhanced cellular proliferation, increased growth factors, chemokines associated with immune-suppressive regulatory T cells, increased vascularization, and elevated M2 macrophages. HFD dramatically reduced tumor latency. Early developing tumors were more proliferative and were associated with increased levels of tumor-related growth factors, including increased plasma levels of HGF in tumor-bearing animals. Early HFD tumors also had increased vascularization, and more intra-tumor and stromal M2 macrophages. CONCLUSIONS: Taken together in this non-obesogenic context, HFD promotion of inflammatory processes, as well as local and systemically increased growth factor expression, are likely responsible for the enhanced tumorigenesis. It is noteworthy that although DMBA mutagenesis is virtually random in its targeting of genes in tumorigenesis, the short latency tumors arising in animals on HFD showed a unique gene expression profile, highlighting the potent overarching influence of HFD