Fast Orbit Feedback at BESSY II Performance and Operational Experiences

At the 3rd generation light source BESSY II the first phase of a fast orbit feedback system has been completed and put into operation in 2012. In this first phase the aim was to achieve noise suppression in the 1Hz to several 10Hz range, mostly avoiding expensive upgrades to existing hardware, such as beam position monitors and the CAN based setpoint transmission to the power supplies. Only the power supplies were replaced with newer, faster versions. This paper describes the capability of the phase I FOFB with respect to beam motion transient suppression, low frequency damping and high frequency noise generation as well as aspects of operational integration and stabilit

Control of inflammation by stromal Hedgehog pathway activation restrains colitis

Inflammation disrupts tissue architecture and function, thereby contributing to the pathogenesis of diverse diseases; the signals that promote or restrict tissue inflammation thus represent potential targets for therapeutic intervention. Here, we report that genetic or pharmacologic Hedgehog pathway inhibition intensifies colon inflammation (colitis) in mice. Conversely, genetic augmentation of Hedgehog response and systemic small-molecule Hedgehog pathway activation potently ameliorate colitis and restrain initiation and progression of colitis-induced adenocarcinoma. Within the colon, the Hedgehog protein signal does not act directly on the epithelium itself, but on underlying stromal cells to induce expression of IL-10, an immune-modulatory cytokine long known to suppress inflammatory intestinal damage. IL-10 function is required for the full protective effect of small-molecule Hedgehog pathway activation in colitis; this pharmacologic augmentation of Hedgehog pathway activity and stromal IL-10 expression are associated with increased presence of CD4(+) Foxp3(+) regulatory T cells. We thus identify stromal cells as cellular coordinators of colon inflammation and suggest their pharmacologic manipulation as a potential means to treat colitis.11138Ysciescopu

Localized bioconvection of Euglena caused by phototaxis in the lateral direction

Euglena, a swimming micro-organism, exhibited a characteristic bioconvection that was localized at the center of a sealed chamber under bright illumination to induce negative phototaxis. This localized pattern consisted of high-density spots, in which convection was found. These observations were reproduced by a mathematical model that was based on the phototaxis of individual cells in both the vertical and lateral directions. Our results indicate that this convection is maintained by upward swimming, as with general bioconvection, and the localization originates from lateral phototaxis

The Phenotypic Radiation Resistance of CD44+/CD24−or low Breast Cancer Cells Is Mediated through the Enhanced Activation of ATM Signaling

Cancer initiating cells (CIC) are stem-like cells. CIC may contribute not only to the initiation of cancer but also to cancer recurrence because of the resistance of CIC both to chemotherapy and radiation therapy. From the MCF-7 and MDA-MB231 breast cancer cell lines and primary culture of patient breast cancer cells, we isolated by flow cytometry a CIC subset of cells with the CD44+/CD24−or low phenotype. The CD44+/CD24−or low subset showed increased sphere formation and resistance to radiation compared to the non- CD44+/CD24−or low subset. The increased radiation resistance was not dependent on the result of altered non-homologous end joining (NHEJ) DNA repair activity as both NHEJ activity and expression of the various proteins involved in NHEJ were not significantly different between the CD44+/CD24−or low and non- CD44+/CD24−or low subsets. However, activation of ATM signaling was significantly increased in CD44+/CD24−or low cells compared to non- CD44+/CD24−or low cells in both from breast cancer cell lines and primary human breast cancer cells. Application of an ATM inhibitor effectively decreased the radiation resistance of CD44+/CD24−or low subset, suggesting that targeting ATM signaling may provide a new tool to eradicate stem-like CIC and abolish the radiation resistance of breast cancer

Clinical Implication of Targeting of Cancer Stem Cells

The existence of cancer stem cells (CSCs) is receiving increasing interest particularly due to its potential ability to enter clinical routine. Rapid advances in the CSC field have provided evidence for the development of more reliable anticancer therapies in the future. CSCs typically only constitute a small fraction of the total tumor burden; however, they harbor self-renewal capacity and appear to be relatively resistant to conventional therapies. Recent therapeutic approaches aim to eliminate or differentiate CSCs or to disrupt the niches in which they reside. Better understanding of the biological characteristics of CSCs as well as improved preclinical and clinical trials targeting CSCs may revolutionize the treatment of many cancers. Copyright (c) 2012 S. Karger AG, Base

Facet Joint Signal Change on MRI at Levels of Acute/Subacute Lumbar Compression Fractures

ABSTRACT BACKGROUND AND PURPOSE: The prevalence of facet joint signal change in acute/subacute lumbar vertebral body compression fractures is unknown. We hypothesized that facet joint signal change on MR imaging is more common in facet joints associated with an acute/subacute lumbar compression fracture than those associated with normal vertebral bodies or ones that have a chronic compression fracture

Prevalence of hyperdense paraspinal vein sign in patients with spontaneous intracranial hypotension without dural CSF leak on standard CT myelography

PURPOSE:A recently identified and treatable cause of spontaneous intracranial hypotension (SIH) is cerebrospinal fluid (CSF)-venous fistula, and a recently described computed tomography myelogram (CTM) finding highly compatible with but not diagnostic of this entity is the hyperdense paraspinal vein sign. We aimed to retrospectively measure the prevalence of the hyperdense paraspinal vein sign on CTMs in SIH patients without dural CSF leak, in comparison with control groups.METHODS:Three CTM groups were identified: 1) SIH study group, which included dural CSF leak-negative standard CTMs performed for SIH, with early and delayed imaging; 2) Early control CTMs, which were performed for indications other than SIH, with imaging shortly after intrathecal contrast administration; 3) Delayed control CTMs, which included delayed imaging. CTMs were retrospectively reviewed for the hyperdense paraspinal vein sign by experienced neuroradiologists, blinded to the group assignment. All CTMs deemed by a single reader to be positive for the hyperdense paraspinal vein sign were independently reviewed by two additional neuroradiologists; findings were considered positive only if consensus was present among all three readers. For positive cases, noncontrast CTs and prior CTMs, if available, were reviewed for the presence of the sign.RESULTS:Seven of 101 (7%) SIH patients had contrast in a spinal/paraspinal vein consistent with the hyperdense paraspinal vein sign; no patient in either control group (total n=54) demonstrated the hyperdense paraspinal vein sign (P = 0.0463). The finding occurred only at thoracic levels. Each patient had a single level of involvement. Six (86%) occurred on the right. Four occurred in female patients (57%). The sign was seen on early images in 3 of 7 cases (43%) and on both early and delayed images in 4 of 7 cases (57%). In 2 of 7 patients (29%), a noncontrast CT covering the relevant location was available and negative for the sign. A prior CTM was available in 2 of 7 patients (29%), and in both cases the hyperdense paraspinal vein sign was also evident.CONCLUSION:The prevalence of the hyperdense paraspinal vein sign in SIH patients with dural CSF leak-negative standard CTM was 7%. As the sign was not seen in control groups, this sign is highly compatible with the presence of CSF-venous fistula. Since the CTMs were not specifically dedicated to identifying hyperdense paraspinal veins (i.e., they were not dynamic and were not preceded by digital subtraction myelography), the true prevalence of the sign may be higher. Radiologists should scrutinize conventional CTMs for this sign, especially in patients in whom a traditional dural CSF leak is not identified

GeneTools – application for functional annotation and statistical hypothesis testing

BACKGROUND: Modern biology has shifted from "one gene" approaches to methods for genomic-scale analysis like microarray technology, which allow simultaneous measurement of thousands of genes. This has created a need for tools facilitating interpretation of biological data in "batch" mode. However, such tools often leave the investigator with large volumes of apparently unorganized information. To meet this interpretation challenge, gene-set, or cluster testing has become a popular analytical tool. Many gene-set testing methods and software packages are now available, most of which use a variety of statistical tests to assess the genes in a set for biological information. However, the field is still evolving, and there is a great need for "integrated" solutions. RESULTS: GeneTools is a web-service providing access to a database that brings together information from a broad range of resources. The annotation data are updated weekly, guaranteeing that users get data most recently available. Data submitted by the user are stored in the database, where it can easily be updated, shared between users and exported in various formats. GeneTools provides three different tools: i) NMC Annotation Tool, which offers annotations from several databases like UniGene, Entrez Gene, SwissProt and GeneOntology, in both single- and batch search mode. ii) GO Annotator Tool, where users can add new gene ontology (GO) annotations to genes of interest. These user defined GO annotations can be used in further analysis or exported for public distribution. iii) eGOn, a tool for visualization and statistical hypothesis testing of GO category representation. As the first GO tool, eGOn supports hypothesis testing for three different situations (master-target situation, mutually exclusive target-target situation and intersecting target-target situation). An important additional function is an evidence-code filter that allows users, to select the GO annotations for the analysis. CONCLUSION: GeneTools is the first "all in one" annotation tool, providing users with a rapid extraction of highly relevant gene annotation data for e.g. thousands of genes or clones at once. It allows a user to define and archive new GO annotations and it supports hypothesis testing related to GO category representations. GeneTools is freely available through www.genetools.n

HDAC inhibitor confers radiosensitivity to prostate stem-like cells

Background: Radiotherapy can be an effective treatment for prostate cancer, but radiorecurrent tumours do develop. Considering prostate cancer heterogeneity, we hypothesised that primitive stem-like cells may constitute the radiation-resistant fraction. Methods: Primary cultures were derived from patients undergoing resection for prostate cancer or benign prostatic hyperplasia. After short-term culture, three populations of cells were sorted, reflecting the prostate epithelial hierarchy, namely stem-like cells (SCs, α2β1integrinhi/CD133+), transit-amplifying (TA, α2β1integrinhi/CD133−) and committed basal (CB, α2β1integrinlo) cells. Radiosensitivity was measured by colony-forming efficiency (CFE) and DNA damage by comet assay and DNA damage foci quantification. Immunofluorescence and flow cytometry were used to measure heterochromatin. The HDAC (histone deacetylase) inhibitor Trichostatin A was used as a radiosensitiser. Results: Stem-like cells had increased CFE post irradiation compared with the more differentiated cells (TA and CB). The SC population sustained fewer lethal double-strand breaks than either TA or CB cells, which correlated with SCs being less proliferative and having increased levels of heterochromatin. Finally, treatment with an HDAC inhibitor sensitised the SCs to radiation. Interpretation: Prostate SCs are more radioresistant than more differentiated cell populations. We suggest that the primitive cells survive radiation therapy and that pre-treatment with HDAC inhibitors may sensitise this resistant fraction