The alternative Medicago truncatula defense proteome of ROS - defective transgenic roots during early microbial infection

ROP-type GTPases of plants function as molecular switches within elementary signal transduction pathways such as the regulation of ROS synthesis via activation of NADPH oxidases (RBOH-respiratory burst oxidase homolog in plants). Previously, we reported that silencing of the Medicago truncatula GTPase MtROP9 led to reduced ROS production and suppressed induction of ROS-related enzymes in transgenic roots (MtROP9i) infected with pathogenic (Aphanomyces euteiches) and symbiotic microorganisms (Glomus intraradices, Sinorhizobium meliloti). While fungal infections were enhanced, S. meliloti infection was drastically impaired. In this study, we investigate the temporal proteome response of M. truncatula MtROP9i transgenic roots during the same microbial interactions under conditions of deprived potential to synthesize ROS. In comparison with control roots (Mtvector), we present a comprehensive proteomic analysis using sensitive MS protein identification. For four early infection time-points (1, 3, 5, 24 hpi), 733 spots were found to be different in abundance: 213 spots comprising 984 proteins (607 unique) were identified after S. meliloti infection, 230 spots comprising 796 proteins (580 unique) after G. intraradices infection, and 290 spots comprising 1240 proteins (828 unique) after A. euteiches infection. Data evaluation by GelMap in combination with a heatmap tool allowed recognition of key proteome changes during microbial interactions under conditions of hampered ROS synthesis. Overall, the number of induced proteins in MtROP9i was low as compared with controls, indicating a dual function of ROS in defense signaling as well as alternative response patterns activated during microbial infection. Qualitative analysis of induced proteins showed that enzymes linked to ROS production and scavenging were highly induced in control roots, while in MtROP9i the majority of proteins were involved in alternative defense pathways such as cell wall and protein degradation

Preliminary SP-100/Stirling heat exchanger designs

Analytic modeling of several heat exchanger concepts to couple the SP-100 nuclear reactor primary lithium loop and the Space Stirling Power Convertor (SSPC) was performed. Four 25 kWe SSPC's are used to produce the required 100 kW of electrical power. This design work focused on the interface between a single SSPC and the primary lithium loop. Manifolding to separate and collect the four channel flow was not modeled. This work modeled two separate types of heat exchanger interfaces (conductive coupling and radiative coupling) to explore their relative advantages and disadvantages. The minimum mass design of the conductively coupled concepts was 18 kg or 0.73 kg/kWe for a single 25 kWe convertor. The minimum mass radiatively coupled concept was 41 kg or 1.64 kg/kWe. The direct conduction heat exchanger provides a lighter weight system because of its ability to operate the Stirling convertor evaporator at higher heat fluxes than those attainable by the radiatively coupled systems. Additionally the conductively coupled concepts had relatively small volumes and provide potentially simpler assembly. Their disadvantages were the tight tolerances and material joining problems associated with this refractory to superalloy interface. The advantages of the radiatively coupled designs were the minimal material interface problems

The barycenter in free nilpotent Lie groups and its application to iterated-integrals signatures

We establish well-definedness of the barycenter for every integrable measure on the free nilpotent Lie group of step $L$ (over $\mathbb{R}^d$). Our main motivation stems from measures induced by iterated-integrals signatures.Comment: 49 pages, 1 figur

Preliminary Design of a SP-100/Stirling Radiatively Coupled Heat Exchanger

Several methods for coupling the SP-100 space nuclear reactor to the NASA Lewis Research Center's Free Piston Stirling Power Convertor (FPSPC) are presented. A 25 kWe, dual opposed Stirling convertor configuration is used in these designs. The concepts use radiative coupling between the SP-100 lithium loop and the sodium heat pipe of the Stirling convertor to transfer the heat from the reactor to the convertor. Four separate configurations are presented. Masses for the four designs vary from 41 to 176 kgs. Each design's structure, heat transfer characteristics, and heat pipe performance are analytically modeled

Rituximab Maintenance for the Treatment of Patients With Follicular Lymphoma: Systematic Review and Meta-analysis of Randomized Trials

Background Follicular lymphoma is characterized by slow growth and an initially high rate of response to treatment, but patients typically relapse and experience progressive disease. Rituximab in combination with chemotherapy has been shown to improve overall survival in patients with follicular lymphoma compared with chemotherapy alone, but data from randomized clinical trials evaluating rituximab maintenance treatment in these patients are limited. We aimed to evaluate the effect of maintenance treatment with rituximab on the overall survival of patients with follicular lymphoma. Methods We performed a systematic review and meta-analysis of randomized controlled trials that compared rituximab maintenance therapy with observation or treatment at relapse (no maintenance therapy). We searched The Cochrane Library, PubMed, EMBASE, LILACS, conference proceedings, databases of ongoing trials, and references of published trials. Two reviewers independently assessed the quality of the trials and extracted data. Hazard ratios for time-to-event data were estimated and pooled. Results Five trials including 1143 adult patients were included in this meta-analysis. Data for 985 patients with follicular lymphoma were available for the meta-analysis of overall survival. Patients treated with maintenance rituximab had statistically significantly better overall survival than patients in the observation arm or patients treated at relapse (hazard ratio [HR] for death = 0.60, 95% confidence interval [CI] = 0.45 to 0.79). The rate of infection-related adverse events was higher with rituximab maintenance treatment (HR = 1.99, 95% CI = 1.21 to 3.27). Patients with refractory or relapsed (ie, previously treated) follicular lymphoma had a survival benefit with maintenance rituximab therapy (HR for death = 0.58, 95% CI = 0.42 to 0.79), whereas previously untreated patients did not (HR for death = 0.68, 95% CI = 0.37 to 1.25). Conclusions These results suggest that maintenance therapy with rituximab, either as four weekly infusions every 6 months or as a single infusion every 2-3 months, should be added to standard therapy for patients with relapsed or refractory (ie, previously treated) follicular lymphoma after successful induction therapy. The higher rate of infections with rituximab therapy should be taken into consideration when making treatment decision

Peculiar Type II Supernovae from Blue Supergiants

The vast majority of Type II supernovae (SNe) are produced by red supergiants (RSGs), but SN 1987A revealed that blue supergiants (BSGs) can produce members of this class as well, albeit with some peculiar properties. This best studied event revolutionized our understanding of SNe, and linking it to the bulk of Type II events is essential. We present here optical photometry and spectroscopy gathered for SN 2000cb, which is clearly not a standard Type II SN and yet is not a SN 1987A analog. The light curve of SN 2000cb is reminiscent of that of SN 1987A in shape, with a slow rise to a late optical peak, but on substantially different time scales. Spectroscopically, SN 2000cb resembles a normal SN II but with ejecta velocities that far exceed those measured for SN 1987A or normal SNe II, above 18000 km/s for H-alpha at early times. The red colours, high velocities, late photometric peak, and our modeling of this object all point toward a scenario involving the high-energy explosion of a small-radius star, most likely a BSG, producing 0.1 solar masses of Ni-56. Adding a similar object to the sample, SN 2005ci, we derive a rate of about 2% of the core-collapse rate for this loosely defined class of BSG explosions.Comment: Accepted to MNRAS on March 14, 201

West-Nile virus replicon particles infect 293T cells expressing DC-SIGNR

West-Nile virus (WNV) is an arbovirus usually transmitted to humans via a mosquito vector. Infections commonly result in febrile symptoms while rare severe neuroinvasive cases may result in encephalitis or meningitis. Studies have shown that WNV infection efficiency is enhanced by expression of DC-SIGNR on target cells, which normally do not express DC-SIGNR. To investigate WNV tropism, we established 293T kidney epithelial cell lines that stably express vector, DC-SIGNR and mutants of DC-SIGNR that lack the entire carbohydrate-recognition domain (CRD) or lack the C-terminal half of the CRD. We demonstrate successful surface expression of DC-SIGNR and its mutants from stablytransfected 293T cells, but not vector-transfected 293T cells. Further, we show that monoclonal antibody 120604 which binds specifically to the DC-SIGNR CRD binds to DCSIGNR expressing 293T cells, but not to vector nor any of the DC-SIGNR mutants expressing cells. Virus replicon particles (VRPs), replication-incompetent viral particles containing necessary structural proteins for infection and a viral plasmid including a GFP reporter are used to safely and conveniently study viral entry. Entry assays using WNV (NY99) VRPs as well as a variant of WNV (NY99) which contains the beta-lactamase enzyme show significant entry into DC-SIGNR expressing cell lines, but not in controls that do not express DC-SIGNR. Additionally, we show that WNV VRPs do not enter DC-SIGNR expressing cells that lack the CRD or the C-terminal half of the CRD suggesting that the Cterminal half of the CRD is required for successful entry of WNV via DC-SIGNR. Future experiments may be able to shed light on which amino acids are required for entryhttps://openriver.winona.edu/urc2018/1057/thumbnail.jp

A randomized controlled trial to investigate the influence of low dose radiotherapy on immune stimulatory effects in liver metastases of colorectal cancer

<p>Abstract</p> <p>Background</p> <p>Insufficient migration and activation of tumor specific effector T cells in the tumor is one of the main reasons for inadequate host anti-tumor immune response. External radiation seems to induce inflammation and activate the immune response. This phase I/II clinical trial aims to evaluate whether low dose single fraction radiotherapy can improve T cell associated antitumor immune response in patients with colorectal liver metastases.</p> <p>Methods/Design</p> <p>This is an investigator-initiated, prospective randomised, 4-armed, controlled Phase I/II trial. Patients undergoing elective hepatic resection due to colorectal cancer liver metastasis will be enrolled in the study. Patients will receive 0 Gy, 0.5 Gy, 2 Gy or 5 Gy radiation targeted to their liver metastasis. Radiation will be applied by external beam radiotherapy using a 6 MV linear accelerator (Linac) with intensity modulated radiotherapy (IMRT) technique two days prior to surgical resection. All patients admitted to the Department of General-, Visceral-, and Transplantion Surgery, University of Heidelberg for elective hepatic resection are consecutively screened for eligibility into this trial, and written informed consent is obtained before inclusion. The primary objective is to assess the effect of active local external beam radiation dose on, tumor infiltrating T cells as a surrogate parameter for antitumor activity. Secondary objectives include radiogenic treatment toxicity, postoperative morbidity and mortality, local tumor control and recurrence patterns, survival and quality of life. Furthermore, frequencies of systemic tumor reactive T cells in blood and bone marrow will be correlated with clinical outcome.</p> <p>Discussion</p> <p>This is a randomized controlled patient blinded trial to assess the safety and efficiency of low dose radiotherapy on metastasis infiltrating T cells and thus potentially enhance the antitumor immune response.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01191632">NCT01191632</a></p

Are We Ready to Treat Diffuse Large B-cell and High-Grade Lymphoma According to Major Genetic Subtypes?

Diffuse Large B-Cell Lymphoma (DLBCL) is a clinically and biologically heterogeneous disease. The revised Classification of Lymphoproliferative diseases published in 2016 (WHO, 2016) refined the previous DLBLC subtypes and identified four categories: DLBCL not otherwise specified (NOS), other lymphomas of large B cells, high grade B-cell lymphoma, and B-cell lymphoma unclassifiable. High grade B-cell lymphomas include the entities carrying MYC, BCL2 and/or BCL6 translocations or cases with blastoid morphology without DH translocations. This classification also acknowledges the cell of origin (COO) classification, that has only a limited impact on the choice of frontline treatment for DLBCL, as most patients still receive R-CHOP chemoimmunotherapy. Attempts to improve the outcomes of specific subgroups, especially COO groups, have so far had limited success. Newer analyses have further subdivided DLBCL into genomically distinct subsets, not yet incorporated in the WHO classification, which may facilitate targeted approaches to therapy. In this review, we discuss the subgroups that are recognized by the WHO 2016 classification, review the newer genomic data, and speculate on how this could alter the treatment landscape of DLBCL in the future. We also discuss novel approaches to salvage therapy in the broad context of the heterogeneity of DLBCL

Viewpoints on Factors for Successful Employment for Adults with Autism Spectrum Disorder

This article explores the key factors for successful employment from the viewpoints of adults with autism spectrum disorder (ASD) and employers. Two groups of individuals participated in this study, 40 adults with ASD and 35 employers. Q method was used to understand and contrast the viewpoints of the two groups. Data were analysed using by-person varimax rotation factor analysis. Results showed that although both groups appear committed to the employment process, the difference in their understanding regarding the type of workplace support required, job expectations and productivity requirements continues to hinder successful employment. These results highlight the need to facilitate communication between employees and employers to ensure a clear understanding of the needs of both groups are met. The use of an ASD-specific workplace tool may assist in facilitating the necessary communication between these two groups