Risk mitigation decisions for it security

Enterprises must manage their information risk as part of their larger operational risk management program. Managers must choose how to control for such information risk. This article defines the flow risk reduction problem and presents a formal model using a workflow framework. Three different control placement methods are introduced to solve the problem, and a comparative analysis is presented using a robust test set of 162 simulations. One year of simulated attacks is used to validate the quality of the solutions. We find that the math programming control placement method yields substantial improvements in terms of risk reduction and risk reduction on investment when compared to heuristics that would typically be used by managers to solve the problem. The contribution of this research is to provide managers with methods to substantially reduce information and security risks, while obtaining significantly better returns on their security investments. By using a workflow approach to control placement, which guides the manager to examine the entire infrastructure in a holistic manner, this research is unique in that it enables information risk to be examined strategically. © 2014 ACM

Dictionary Learning and Sparse Coding-based Denoising for High-Resolution Task Functional Connectivity MRI Analysis

We propose a novel denoising framework for task functional Magnetic Resonance Imaging (tfMRI) data to delineate the high-resolution spatial pattern of the brain functional connectivity via dictionary learning and sparse coding (DLSC). In order to address the limitations of the unsupervised DLSC-based fMRI studies, we utilize the prior knowledge of task paradigm in the learning step to train a data-driven dictionary and to model the sparse representation. We apply the proposed DLSC-based method to Human Connectome Project (HCP) motor tfMRI dataset. Studies on the functional connectivity of cerebrocerebellar circuits in somatomotor networks show that the DLSC-based denoising framework can significantly improve the prominent connectivity patterns, in comparison to the temporal non-local means (tNLM)-based denoising method as well as the case without denoising, which is consistent and neuroscientifically meaningful within motor area. The promising results show that the proposed method can provide an important foundation for the high-resolution functional connectivity analysis, and provide a better approach for fMRI preprocessing.Comment: 8 pages, 3 figures, MLMI201

Guidelines for the labelling of leucocytes with 111In-oxine

We describe here a protocol for labelling autologous white blood cells with 111In-oxine based on previously published consensus papers and guidelines. This protocol includes quality control and safety procedures and is in accordance with current European Union regulations and International Atomic Energy Agency recommendations

Treatment regimen determines whether an HIF-1 inhibitor enhances or inhibits the effect of radiation therapy

Hypoxia-inducible factor-1 (HIF-1) has been reported to promote tumour radioresistance; therefore, it is recognised as an excellent target during radiation therapy. However, the inhibition of HIF-1 in unsuitable timing can suppress rather than enhance the effect of radiation therapy because its anti-angiogenic effect increases the radioresistant hypoxic fraction. In this study, we imaged changes of HIF-1 activity after treatment with radiation and/or an HIF-1 inhibitor, YC-1, and optimised their combination. Hypoxic tumour cells were reoxygenated 6 h postirradiation, leading to von Hippel-Lindau (VHL)-dependent proteolysis of HIF-1α and a resultant decrease in HIF-1 activity. The activity then increased as HIF-1α accumulated in the reoxygenated regions 24 h postirradiation. Meanwhile, YC-1 temporarily but significantly suppressed HIF-1 activity, leading to a decrease in microvessel density and an increase in tumour hypoxia. On treatment with YC-1 and then radiation, the YC-1-mediated increase in tumour hypoxia suppressed the effect of radiation therapy, whereas on treatment in the reverse order, YC-1 suppressed the postirradiation upregulation of HIF-1 activity and consequently delayed tumour growth. These results indicate that treatment regimen determines whether an HIF-1 inhibitor enhances or inhibits the therapeutic effect of radiation, and the suppression of the postirradiation upregulation of HIF-1 activity is important for the best therapeutic benefit

Serum CA19-9 response as a surrogate for clinical outcome in patients receiving fixed-dose rate gemcitabine for advanced pancreatic cancer

The use of serial serum measurements of the carbohydrate antigen 19-9 (CA19-9) to guide treatment decisions and serve as a surrogate end point in clinical trial design requires further validation. We investigated whether CA19-9 decline represents an accurate surrogate for survival and time to treatment failure (TTF) in a cohort of 76 patients with advanced pancreatic cancer receiving fixed-dose rate gemcitabine in three separate studies. Statistically significant correlations between percentage CA19-9 decline and both overall survival and TTF were found, with median survival ranging from 12.0 months for patients with the greatest degree of biomarker decline (>75%) compared with 4.3 months in those whose CA19-9 did not decline during therapy (P<0.001). Using specific thresholds, patients with ⩾25% decline in CA19-9 during treatment had significantly better outcomes than those who did not (median survival and TTF of 9.6 and 4.6 months vs 4.4 and 1.5 months; P<0.001). Similar results were seen using both 50 and 75% as cutoff points. We conclude that serial CA19-9 measurements correlate well with clinical outcomes in this patient population, and that decline in this biomarker should be entertained for possible use as a surrogate end point in clinical trials for the selection of new treatments in this disease

Best practices in data analysis and sharing in neuroimaging using MRI

Given concerns about the reproducibility of scientific findings, neuroimaging must define best practices for data analysis, results reporting, and algorithm and data sharing to promote transparency, reliability and collaboration. We describe insights from developing a set of recommendations on behalf of the Organization for Human Brain Mapping, and identify barriers that impede these practices, including how the discipline must change to fully exploit the potential of the world’s neuroimaging data

The Germ Cell Nuclear Proteins hnRNP G-T and RBMY Activate a Testis-Specific Exon

The human testis has almost as high a frequency of alternative splicing events as brain. While not as extensively studied as brain, a few candidate testis-specific splicing regulator proteins have been identified, including the nuclear RNA binding proteins RBMY and hnRNP G-T, which are germ cell-specific versions of the somatically expressed hnRNP G protein and are highly conserved in mammals. The splicing activator protein Tra2β is also highly expressed in the testis and physically interacts with these hnRNP G family proteins. In this study, we identified a novel testis-specific cassette exon TLE4-T within intron 6 of the human transducing-like enhancer of split 4 (TLE4) gene which makes a more transcriptionally repressive TLE4 protein isoform. TLE4-T splicing is normally repressed in somatic cells because of a weak 5′ splice site and surrounding splicing-repressive intronic regions. TLE4-T RNA pulls down Tra2β and hnRNP G proteins which activate its inclusion. The germ cell-specific RBMY and hnRNP G-T proteins were more efficient in stimulating TLE4-T incorporation than somatically expressed hnRNP G protein. Tra2b bound moderately to TLE4-T RNA, but more strongly to upstream sites to potently activate an alternative 3′ splice site normally weakly selected in the testis. Co-expression of Tra2β with either hnRNP G-T or RBMY re-established the normal testis physiological splicing pattern of this exon. Although they can directly bind pre-mRNA sequences around the TLE4-T exon, RBMY and hnRNP G-T function as efficient germ cell-specific splicing co-activators of TLE4-T. Our study indicates a delicate balance between the activity of positive and negative splicing regulators combinatorially controls physiological splicing inclusion of exon TLE4-T and leads to modulation of signalling pathways in the testis. In addition, we identified a high-affinity binding site for hnRNP G-T protein, showing it is also a sequence-specific RNA binding protein