Diffraction microstrain in nanocrystalline solids under load - heterogeneous medium approach

This is an account of the computation of X-ray microstrain in a polycrystal with anisotropic elasticity under uniaxial external load. The results have been published in the article "Microstrain in nanocrystalline solids under load by virtual diffraction", at Europhysics Letters 89, 66002 (2010). The present information was submitted to Europhysics Letters as part of the manuscript package, and was available to the reviewers who recommended the paper for publication.Comment: Supporting online material for J. Markmann, D. Bachurin, L.-H. Shao, P. Gumbsch, J. Weissm\"uller, Microstrain in nanocrystalline solids under load by virtual diffraction, Europhys. Lett. 89, 66002 (2010

Analysis of the Copenhagen Accord pledges and its global climatic impacts‚ a snapshot of dissonant ambitions

This analysis of the Copenhagen Accord evaluates emission reduction pledges by individual countries against the Accord's climate-related objectives. Probabilistic estimates of the climatic consequences for a set of resulting multi-gas scenarios over the 21st century are calculated with a reduced complexity climate model, yielding global temperature increase and atmospheric CO2 and CO2-equivalent concentrations. Provisions for banked surplus emission allowances and credits from land use, land-use change and forestry are assessed and are shown to have the potential to lead to significant deterioration of the ambition levels implied by the pledges in 2020. This analysis demonstrates that the Copenhagen Accord and the pledges made under it represent a set of dissonant ambitions. The ambition level of the current pledges for 2020 and the lack of commonly agreed goals for 2050 place in peril the Accord's own ambition: to limit global warming to below 2 °C, and even more so for 1.5 °C, which is referenced in the Accord in association with potentially strengthening the long-term temperature goal in 2015. Due to the limited level of ambition by 2020, the ability to limit emissions afterwards to pathways consistent with either the 2 or 1.5 °C goal is likely to become less feasibl

Visualizing polymeric components that define distinct root barriers across plant lineages

Hydrophobic cell wall depositions in roots play a key role in plant development and interaction with the soil environment, as they generate barriers that regulate bidirectional nutrient flux. Techniques to label the respective polymers are emerging, but are efficient only in thin roots or sections. Moreover, simultaneous imaging of the barrier constituents lignin and suberin remains problematic owing to their similar chemical compositions. Here, we describe a staining method compatible with single- and multiphoton confocal microscopy that allows for concurrent visualization of primary cell walls and distinct secondary depositions in one workflow. This protocol permits efficient separation of suberin- and lignin-specific signals with high resolution, enabling precise dissection of barrier constituents. Our approach is compatible with imaging of fluorescent proteins, and can thus complement genetic markers or aid the dissection of barriers in biotic root interactions. We further demonstrate applicability in deep root tissues of plant models and crops across phylogenetic lineages. Our optimized toolset will significantly advance our understanding of root barrier dynamics and function, and of their role in plant interactions with the rhizospheric environment

Transfection of Sertoli cells with androgen receptor alters gene expression without androgen stimulation

Background: Androgens play an important role for the development of male fertility and gained interest as growth and survival factors for certain types of cancer. Androgens act via the androgen receptor (AR/Ar), which is involved in various cell biological processes such as sex differentiation. To study the functional mechanisms of androgen action, cell culture systems and AR-transfected cell lines are needed. Transfection of AR into cell lines and subsequent gene expression analysis after androgen treatment is well established to investigate the molecular biology of target cells. However, it remains unclear how the transfection with AR itself can modulate the gene expression even without androgen stimulation. Therefore, we transfected Ar-deficient rat Sertoli cells 93RS2 by electroporation using a full length human AR. Results: Transfection success was confirmed by Western Blotting, immunofluorescence and RT-PCR. AR transfection-related gene expression alterations were detected with microarray-based genome-wide expression profiling of transfected and non-transfected 93RS2 cells without androgen stimulation. Microarray analysis revealed 672 differentially regulated genes with 200 up- and 472 down-regulated genes. These genes could be assigned to four major biological categories (development, hormone response, immune response and metabolism). Microarray results were confirmed by quantitative RT-PCR analysis for 22 candidate genes. Conclusion: We conclude from our data, that the transfection of Ar-deficient Sertoli cells with AR has a measurable effect on gene expression even without androgen stimulation and cause Sertoli cell damage. Studies using AR-transfected cells, subsequently stimulated, should consider alterations in AR-dependent gene expression as off-target effects of the AR transfection itself

Live Donor Partial Hepatectomy for Liver Transplantation: Is There a Learning Curve?

Background: Donor safety is the first priority in living donor liver transplantation (LDLT). Objective: To determine the characteristics and outcome of live liver donors who underwent donor hepatectomy from January, 1997 to May, 2007 at Massachusetts General Hospital. Methods: 30 patients underwent LDLT between January, 1997 and May, 2007 at our institution. Results: The type of graft was the right lobe (segments 5-8) in 14, left lobe (segments 2-4) in 4, and left lateral sector (segments 2 and 3) in 12 patients. The mean donor age was 36 (range: 26-57) years. The mean follow-up was 48 (range: 18-120) months. No deaths occurred. Overall, 8 (26.6%) patients experienced a total of 14 post-operative complications. Donor complications based on graft type were as follows: left lateral sector (16.7%), left lobe (25%), and right lobe (35.7%). The experience was divided into two periods 1997-2001 (n=15) and 2002-2007 (n=15). Overall complications during 2 periods were 40% and 13.3%, respectively (p<0.001). The incidence of grade III complication also significantly decreased; 66.7% vs 33.3% (p<0.01). Conclusion: Partial hepatectomy in living donors has a learning curve which appears to be approximately 15 cases. This learning curve is not restricted to the surgeons performing the procedure but involves all aspects of patient care

Heat Stroke as a Cause of Liver Failure and Evaluation of Liver Transplant

Heat stroke is a multiple organ dysfunction syndrome of poorly understood pathogenesis. Exertional heat stroke with acute liver failure is a rarely reported condition. Liver transplant has been recommended as treatment in cases of severe liver dysfunction; however, there are only 5 described cases of long-term survival after this procedure in patients with heat stroke. Here, we present 2 cases of young athletes who developed heat stroke. Both patients developed acute liver failure and were listed for liver transplant. Liver function tests of one patient improved, and he was discharged on postoperative day 13. The other patient showed no signs of improvement and liver biopsy showed massive necrosis. The patient underwent combined kidney-liver transplant and was discharged on postoperative day 17. After a follow-up of longer than 6 years, both patients are doing well with normal liver function and no neurologic sequelae. We also reviewed all published cases of hepatic failure associated with heat stroke and found 9 published cases of liver transplant for heat stroke in the English literature. Conservative management appears to be justified in heat stroke-associated liver failure, even in the presence of accepted criteria for emergency liver transplant

Heat Stroke as a Cause of Liver Failure and Evaluation of Liver Transplant

Heat stroke is a multiple organ dysfunction syndrome of poorly understood pathogenesis. Exertional heat stroke with acute liver failure is a rarely reported condition. Liver transplant has been recommended as treatment in cases of severe liver dysfunction; however, there are only 5 described cases of long-term survival after this procedure in patients with heat stroke. Here, we present 2 cases of young athletes who developed heat stroke. Both patients developed acute liver failure and were listed for liver transplant. Liver function tests of one patient improved, and he was discharged on postoperative day 13. The other patient showed no signs of improvement and liver biopsy showed massive necrosis. The patient underwent combined kidney-liver transplant and was discharged on postoperative day 17. After a follow-up of longer than 6 years, both patients are doing well with normal liver function and no neurologic sequelae. We also reviewed all published cases of hepatic failure associated with heat stroke and found 9 published cases of liver transplant for heat stroke in the English literature. Conservative management appears to be justified in heat stroke-associated liver failure, even in the presence of accepted criteria for emergency liver transplant

Induction with Rabbit Antithymocyte Globulin following Orthotopic Liver Transplantation for Hepatitis C

Background: Hepatitis C (HCV) is the most common indication for liver transplantation in the US. Objective: Since steroids are the major stimulus of viral replication, we postulated that steroid-free immunosuppression might be a safer approach. Methods: From January 1995 to October 2002, we used steroid plus calcineurin inhibitor (CNI) immunosuppression after liver transplantation for HCV (steroid group, n=81). From October 2002 to June 2007, rabbit antithymocyte globulin (RATG) induction, followed by CNI and azathioprine (RATG group, n=73) was utilized. Results: There were no differences in 1- and 3-year patient/allograft survival rates. The incidence of acute rejection rate (19% vs. 28%), of biopsy-proven HCV recurrence (70% vs. 75%), and chronic rejection (6% vs. 9%) were comparable. The mean time to develop recurrent HCV was significantly longer in the RATG group (16.2 vs. 9.2 months, p=0.008). The incidence of severe portal fibrosis appears to be lower in RATG group compared to the steroid group; 14% vs. 4% (p=0.07). Conclusions: RATG induction is safe and effective after liver transplantation for HCV, but has no impact on the incidence of HCV recurrence and patient/allograft survival. However, a significant delay in time to HCV recurrence and a trend toward less rejection and portal fibrosis was observed

Bifunctional Small Molecules Enhance Neutrophil Activities Against Aspergillus fumigatus in vivo and in vitro

Aspergillosis is difficult to treat and carries a high mortality rate in immunocompromised patients. Neutrophils play a critical role in control of infection but may be diminished in number and function during immunosuppressive therapies. Here, we measure the effect of three bifunctional small molecules that target Aspergillus fumigatus and prime neutrophils to generate a more effective response against the pathogen. The molecules combine two moieties joined by a chemical linker: a targeting moiety (TM) that binds to the surface of the microbial target, and an effector moiety (EM) that interacts with chemoattractant receptors on human neutrophils. We report that the bifunctional compounds enhance the interactions between primary human neutrophils and A. fumigatus in vitro, using three microfluidic assay platforms. The bifunctional compounds significantly enhance the recruitment of neutrophils, increase hyphae killing by neutrophils in a uniform concentration of drug, and decrease hyphal tip growth velocity in the presence of neutrophils compared to the antifungal targeting moiety alone. We validated that the bifunctional compounds are also effective in vivo, using a zebrafish infection model with neutrophils expressing the appropriate EM receptor. We measured significantly increased phagocytosis of A. fumigatus conidia by neutrophils expressing the EM receptor in the presence of the compounds compared to receptor-negative cells. Finally, we demonstrate that treatment with our lead compound significantly improved the antifungal activity of neutrophils from immunosuppressed patients ex vivo. This type of bifunctional compounds strategy may be utilized to redirect the immune system to destroy fungal, bacterial, and viral pathogens

Convalescent Plasma Therapy in Four Critically Ill Pediatric Patients With Coronavirus Disease 2019: A Case Series

Background: Coronavirus disease 2019 is a pandemic with no specific therapeutic agents or vaccination. Small published case series on critically ill adults suggest improvements in clinical status with minimal adverse events when patients receive coronavirus disease 2019 convalescent plasma, but data on critically ill pediatric patients are lacking. We report a series of four critically ill pediatric patients with acute respiratory failure who received coronavirus disease 2019 convalescent plasma as a treatment strategy for severe disease. Case Summary:  Patients ranged in age from 5 to 16 years old. All patients received coronavirus disease 2019 convalescent plasma within the first 26 hours of hospitalization. Additional disease modifying agents were also used. All patients made a full recovery and were discharged home off of oxygen support. No adverse events occurred from the coronavirus disease 2019 convalescent plasma transfusions. Conclusion: Coronavirus disease 2019 convalescent plasma is a feasible therapy for critically ill pediatric patients infected with severe acute respiratory syndrome coronavirus 2. Well-designed clinical trials are necessary to determine overall safety and efficacy of coronavirus disease 2019 convalescent plasma and additional treatment modalities in pediatric patients