An RNAi-based system for loss-of-function analysis identifies Raf1 as a crucial mediator of BCR-ABL - Driven leukemogenesis

Genetic loss-of-function studies in murine tumor models have been essential in the analysis of downstream mediators of oncogenic transformation. Unfortunately, these studies are frequently limited by the availability of genetically modified mouse strains. Here we describe a versatile method allowing the efficient expression of an oncogene and simultaneous knockdown of targets of interest (TOI) from a single retroviral vector. Both oncogene and TOI-specific miR30-based shRNA are under the control of the strong viral long terminal repeat promoter, resulting in a single shared RNA transcript. Using this vector in a murine syngeneic BM transplantation model for BCR-ABL - induced chronic myeloid leukemia, we find that oncogene expression andtargetknockdownin primary hematopoietic cells with this vector is efficient both in vitro and in vivo, and demonstrate that Raf1, but not BRAF, modulates BCR-ABL - dependent ERK activation and transformation of hematopoietic cells. This expression system could facilitate genetic loss-of-function studies and allow the rapid validation of potential drug targets in a broad range of oncogene-driven murine tumor models. © 2011 by The American Society of Hematology

Comparative study of the effect of long-term ageing on the behaviour of bitumen and mastics with mineral fillers

This paper is based on a part of the research project carried out at the request of the German Research Foundation (DFG), under research project No. WE 1642/1-2 and LE 3649/1-2 (FOR2089).This study aims to evaluate the effect of mineral fillers on bitumen ageing. Two different bitumens and four mastics were investigated in the unaged and long-term aged states, based on different properties (consistency, rheology, fatigue resistance and ductility). Mastics stiffened less due to ageing treatment than bitumens, especially with granite filler. However, the results of the performance tests were not definitive regarding the effect of the filler. Aged bitumen showed greater fatigue resistance and higher specific energy of ductile fracture than unaged bitumen, whereas the mastics showed minor variations in the specific energy of ductile fracture with ageing treatment, which is indicative of less ageing, but the fatigue resistance decreased significantly in mastics with one of the bitumens.authorsversionpublishe

Development of Cortical Lesion Volumes on Double Inversion Recovery MRI in Patients With Relapse-Onset Multiple Sclerosis

Background and Objective: In multiple sclerosis (MS) patients, Double Inversion Recovery (DIR) magnetic resonance imaging (MRI) can be used to detect cortical lesions (CL). While the quantity and distribution of CLs seems to be associated with patients' disease course, literature lacks frequent assessments of CL volumes (CL-V) in this context. We investigated the reliability of DIR for the longitudinal assessment of CL-V development with frequent follow-up MRIs and examined the course of CL-V progressions in relation to white-matter lesions (WML), contrast enhancing lesions (CEL) and clinical parameters in patients with Relapsing-Remitting Multiple Sclerosis (RRMS).Methods: In this post-hoc analysis, image- and clinical data of a subset of 24 subjects that were part of a phase IIa clinical trial on the “Safety, Tolerability and Mechanisms of Action of Boswellic Acids in Multiple Sclerosis (SABA)” (ClinicalTrials.gov, NCT01450124) were included. The study was divided in three phases (screening, treatment, study-end). All patients received 12 MRI follow-up-examinations (including DIR) during a 16-months period. CL-Vs were assessed for each patient on each follow-up MRI separately by two experienced neuroradiologists. Results of neurological screening tests, as well as other MRI parameters (WML number and volume and CELs) were included from the SABA investigation data.Results: Inter-rater agreement regarding CL-V assessment over time was good-to-excellent (κ = 0.89). Mean intraobserver variability was 1.1%. In all patients, a total number of 218 CLs was found. Total CL-Vs of all patients increased during the 4 months of baseline screening followed by a continuous and significant decrease from month 5 until study-end (p < 0.001, Kendall'W = 0.413). A positive association between WML volumes and CL-Vs was observed during baseline screening. Decreased CL-V were associated with lower EDSS and also with improvements of SDMT- and SCRIPPS scores.Conclusion: DIR MRI seems to be a reliable tool for the frequent assessment of CL-Vs. Overall CL-Vs decreased during the follow-up period and were associated with improvements of cognitive and disability status scores. Our results suggest the presence of short-term CL-V dynamics in RRMS patients and we presume that the laborious evaluation of lesion volumes may be worthwhile for future investigations.Clinical Trial Numbers:www.ClinicalTrials.gov, “The SABA trial”; number: NCT0145012

The Healthfulness of Entrées and Students\u27 Purchases in a University Campus Dining Environment

The purpose of this study is to determine the availability of more healthful (MH) versus less healthful (LH) entrée items in the campus dining and if students\u27 purchases are reflective of what is offered. This is an observational study in which purchases of the available entrée items in the campus dining at South Dakota State University in one academic year were collected and categorized as either MH or LH according to the American Heart Association guidelines. Chi-square tests were used to determine the differences between the proportion of purchased MH and LH versus those available. Odds ratio estimates with 95% confidence limits were used to determine the associations between the demographics and MH and LH purchases. Of the total entrée items available, 15.0% were MH and 85.0% were LH. In the fall, 8.0% of purchases were MH and 92.0% purchases were LH as compared to 8.9% MH and 91.1% LH in the spring. Whites were less likely than non-whites to purchase a MH entrée. Females were two times more likely to choose MH entrées than males. The campus dining offerings and students\u27 purchases of entrees were primarily LH. Work with campus dining providers to create profitable, yet healthful, dining entrees is needed to improve the healthfulness of offerings

The Healthfulness of Entrées and Students’ Purchases in a University Campus Dining Environment

The purpose of this study is to determine the availability of more healthful (MH) versus less healthful (LH) entrée items in the campus dining and if students\u27 purchases are reflective of what is offered. This is an observational study in which purchases of the available entrée items in the campus dining at South Dakota State University in one academic year were collected and categorized as either MH or LH according to the American Heart Association guidelines. Chi-square tests were used to determine the differences between the proportion of purchased MH and LH versus those available. Odds ratio estimates with 95% confidence limits were used to determine the associations between the demographics and MH and LH purchases. Of the total entrée items available, 15.0% were MH and 85.0% were LH. In the fall, 8.0% of purchases were MH and 92.0% purchases were LH as compared to 8.9% MH and 91.1% LH in the spring. Whites were less likely than non-whites to purchase a MH entrée. Females were two times more likely to choose MH entrées than males. The campus dining offerings and students\u27 purchases of entrees were primarily LH. Work with campus dining providers to create profitable, yet healthful, dining entrees is needed to improve the healthfulness of offerings

Influence of different fillers on mechanical properties of porous asphalt mixtures using microstructural finite-element analysis

202303 bcfcAccepted ManuscriptOthersNNSFC; German Research Foundation (DFG),German Academic Exchange Service (DAAD)Publishe