Goal driven optimization of process parameters for maximum efficiency in laser bending of advanced high strength steels

Laser forming or bending is fast becoming an attractive option for the forming of advanced high strength steels (AHSS), due primarily to the reduced formability of AHSS when compared with conventional steels in traditional contact-based forming processes. An inherently iterative process, laser forming must be optimized for efficiency in order to compete with contact based forming processes; as such, a robust and accurate method of optimal process parameter prediction is required. In this paper, goal driven optimization is conducted, utilizing numerical simulations as the basis for the prediction of optimal process parameters for the laser bending of DP 1000 steel. A key consideration of the optimization process is the requirement for minimal microstructural transformation in automotive grade high strength steels such as DP 1000

Lymphotoxins and cytomegalovirus cooperatively induce interferon-beta, establishing host-virus détente

Tumor necrosis factor (TNF)-related cytokines regulate cell death and survival and provide strong selective pressures for viruses, such as cytomegalovirus (CMV), to evolve counterstrategies in order to persist in immune-competent hosts. Signaling by the lymphotoxin (LT)-β receptor or TNF receptor-1, but not Fas or TRAIL receptors, inhibits the cytopathicity and replication of human CMV by a nonapoptotic, reversible process that requires nuclear factor κB (NF-κB)-dependent induction of interferon-β (IFN-β). Efficient induction of IFN-β requires virus infection and LT signaling, demonstrating the need for both host and viral factors in the curtailment of viral replication without cellular elimination. LTα-deficient mice and LTβR-Fc transgenic mice were profoundly susceptible to murine CMV infection. Together, these results reveal an essential and conserved role for LTs in establishing host defense to CMV

Dimethyl sulfoxide blocks herpes simplex virus-1 productive infection in vitro acting at different stages with positive cooperativity. Application of micro-array analysis

BackgroundDimethyl sulfoxide (DMSO) is frequently used at a concentration of up to 95% in the formulation of antiherpetic agents because of its properties as a skin penetration enhancer. Here, we have analyzed the effect of DMSO on several parameters of Herpes Simplex Virus replication.MethodsProductive infection levels of HSV-1 were determined by plaque assay or by reporter gene activity, and its DNA replication was estimated by PCR. Transcript levels were evaluated with HSV-specific DNA micro-arrays.ResultsDMSO blocks productive infection in vitro in different cell types with a 50% inhibitory concentration (IC50) from 0.7 to 2% depending upon the multiplicity of infection. The concentration dependence exhibits a Hill coefficient greater than 1, indicating that DMSO blocks productive infection by acting at multiple different points (mechanisms of action) with positive cooperativity. Consistently, we identified at least three distinct temporal target mechanisms for inhibition of virus growth by DMSO. At late stages of infection, DMSO reduces virion infectivity, and markedly inhibits viral DNA replication. A third mode of action was revealed using an oligonucleotide-based DNA microarray system for HSV. These experiments showed that DMSO reduced the transcript levels of many HSV-1 genes; including several genes coding for proteins involved in forming and assembling the virion. Also, DMSO markedly inhibited some but not all early transcripts indicating a previously unknown mode for inhibiting the early phase of HSV transcription-replication cycle.ConclusionThese observations suggest that DMSO itself may have a role in the anti-herpetic activity of formulations utilizing it as a dispersant

Time-to-positivity in bloodstream infection is not a prognostic marker for mortality:analysis of a prospective multicentre randomized control trial

Objectives Time to positivity (TTP), calculated automatically in modern blood culture systems, is considered a proxy for microbial load and has been suggested as a potential prognostic marker in bloodstream infections. In this large, multicentre, prospectively collected cohort, our primary analysis aimed to quantify the relationship between the TTP of monomicrobial blood cultures and mortality. Methods Data from a multicentre randomized controlled trial (RAPIDO) in bloodstream infection were analysed. Bloodstream infections were classified into 13 groups/subgroups. The relationship between mortality and TTP was assessed by logistic regression, adjusted for site, organism, and clinical variables, and linear regression was applied to examine the association between clinical variables and TTP. Robustness was assessed by sensitivity analysis. Results In total 4468 participants were included in the RAPIDO. After exclusions, 3462 were analysed, with the most common organisms being coagulase-negative staphylococci (1072 patients) and Escherichia coli (861 patients); 785 patients (22.7%) died within 28 days. We found no relationship between TTP and mortality for any groups except for streptococci (odds ratio (OR) with each hour 0.98, 95%CI 0.96–1.00) and Candida (OR 1.03, 95%CI 1.00–1.05). There was large variability between organisms and sites in TTP. Fever (geometric mean ratio (GMR) 0.95, 95%CI 0.92–0.99), age (GMR per 10 years 1.01, 95%CI 1.00–1.02), and neutrophilia were associated with TTP (GMR 1.03, 95%CI 1.02–1.04). Conclusions Time to positivity is not associated with mortality, except in the case of Candida spp. (longer times associated with worse outcomes) and possibly streptococci (shorter times associated with worse outcomes). There was a large variation between median times across centres, limiting external validity

Utility of surveillance blood cultures in patients undergoing hematopoietic stem cell transplantation

Background Surveillance blood cultures are often obtained in hematopoietic stem cell transplant (HSCT) patients for detection of bloodstream infection. The major aims of this retrospective cohort study were to determine the utility of the practice of obtaining surveillance blood cultures from asymptomatic patients during the first 100 post-transplant days and to determine if obtaining more than one positive blood culture helps in the diagnosis of bloodstream infection. Methods We conducted a 17-month retrospective analysis of all blood cultures obtained for patients admitted to the hospital for HSCT from January 2010 to June 2011. Each patient’s clinical course, vital signs, diagnostic testing, treatment, and response to treatment were reviewed. The association between number of positive blood cultures and the final diagnosis was analyzed. Results Blood culture results for 205 patients were reviewed. Cultures obtained when symptoms of infection were present (clinical cultures) accounted for 1,033 culture sets, whereas 2,474 culture sets were classified as surveillance cultures (no symptoms of infection were present). The total number of positive blood cultures was 185 sets (5.3% of cultures obtained) and accounted for 84 positive culture episodes. Incidence of infection in autologous, related allogeneic and unrelated allogeneic transplants was 8.3%, 20.0%, and 28.6% respectively. Coagulase-negative staphylococci were the most common organisms isolated. Based on our application of predefined criteria there were 29 infections and 55 episodes of positive blood cultures that were not infections. None of the patients who developed infection were diagnosed by surveillance blood cultures. None of the uninfected patients with positive blood cultures showed any clinical changes after receiving antibiotics. There was a significant difference between the incidence of BSI in the first and second 50-day periods post-HSCT. There was no association between the number of positive blood cultures and the final diagnosis. Conclusion Surveillance blood cultures in patients who have undergone HSCT do not identify bloodstream infections. The number of positive blood cultures was not helpful in determining which patients had infection. Patients are at higher risk of infection in the first 50 days post-transplant period

Biochip sensors for the rapid and sensitive detection of viral disease

Recent advances in DNA and protein microarray methodology and the emerging technology of cell-based sensors have massively increased the speed and sensitivity with which we can detect viral infections. The advantages of the multi-parameter microarray technologies could be combined with the speed and sensitivity of cell-based systems to give 'cell-omic' sensors

Direct monitoring of calcium-triggered phase transitions in cubosomes using small-angle X-ray scattering combined with microfluidics

This article introduces a simple microfluidic device that can be combined with synchrotron small-angle X-ray scattering (SAXS) for monitoring dynamic structural transitions. The microfluidic device is a thiol-ene-based system equipped with 125 μm-thick polystyrene windows, which are suitable for X-ray experiments. The device was prepared by soft lithography using elastomeric molds followed by a simple UV-initiated curing step to polymerize the chip material and simultaneously seal the device with the polystyrene windows. The microfluidic device was successfully used to explore the dynamics of the structural transitions of phytantriol/dioleoylphosphatidylglycerol-based cubosomes on exposure to a buffer containing calcium ions. The resulting SAXS data were resolved in the time frame between 0.5 and 5.5 s, and a calcium-triggered structural transition from an internal inverted-type cubic phase of symmetry Im3m to an internal inverted-type cubic phase of symmetry Pn3m was detected. The combination of microfluidics with X-ray techniques opens the door to the investigation of early dynamic structural transitions, which is not possible with conventional techniques such as glass flow cells. The combination of microfluidics with X-ray techniques can be used for investigating protein unfolding, for monitoring the formation of nanoparticles in real time, and for other biomedical and pharmaceutical investigations. A combination of microfluidics with X-ray techniques has been used to perform dynamic structural studies on nanoparticulate formulations

Experiments using microarray technology: limitations and standard operating procedures

Microarrays are a powerful method for the global analysis of gene or protein content and expression, opening up new horizons in molecular and physiological systems. This review focuses on the critical aspects of acquiring meaningful data for analysis following fluorescence-based target hybridisation to arrays. Although microarray technology is adaptable to the analysis of a range of biomolecules (DNA, RNA, protein, carbohydrates and lipids), the scheme presented here is applicable primarily to customised DNA arrays fabricated using long oligomer or cDNA probes. Rather than provide a comprehensive review of microarray technology and analysis techniques, both of which are large and complex areas, the aim of this paper is to provide a restricted overview, highlighting salient features to provide initial guidance in terms of pitfalls in planning and executing array projects. We outline standard operating procedures, which help streamline the analysis of microarray data resulting from a diversity of array formats and biological systems. We hope that this overview will provide practical initial guidance for those embarking on microarray studies