A paleoepidemiological approach to the osteological paradox : Investigating stress, frailty and resilience through cribra orbitalia

Open Access via the Jisc Wiley Agreement Funder: British Academy (GrantNumber(s): GP2\190224)Peer reviewedPublisher PD

Tsetse Salivary Gland Hypertrophy Virus: Hope or Hindrance for Tsetse Control?

Many species of tsetse flies (Diptera: Glossinidae) are infected with a virus that causes salivary gland hypertrophy (SGH), and flies with SGH symptoms have a reduced fecundity and fertility. The prevalence of SGH in wild tsetse populations is usually very low (0.2%–5%), but higher prevalence rates (15.2%) have been observed occasionally. The successful eradication of a Glossina austeni population from Unguja Island (Zanzibar) using an area-wide integrated pest management approach with a sterile insect technique (SIT) component (1994–1997) encouraged several African countries, including Ethiopia, to incorporate the SIT in their national tsetse control programs. A large facility to produce tsetse flies for SIT application in Ethiopia was inaugurated in 2007. To support this project, a Glossina pallidipes colony originating from Ethiopia was successfully established in 1996, but later up to 85% of adult flies displayed symptoms of SGH. As a result, the colony declined and became extinct by 2002. The difficulties experienced with the rearing of G. pallidipes, epitomized by the collapse of the G. pallidipes colony originating from Ethiopia, prompted the urgent need to develop management strategies for the salivary gland hypertrophy virus (SGHV) for this species. As a first step to identify suitable management strategies, the virus isolated from G. pallidipes (GpSGHV) was recently sequenced and research was initiated on virus transmission and pathology. Different approaches to prevent virus replication and its horizontal transmission during blood feeding have been proposed. These include the use of antiviral drugs such as acyclovir and valacyclovir added to the blood for feeding or the use of antibodies against SGHV virion proteins. In addition, preliminary attempts to silence the expression of an essential viral protein using RNA interference will be discussed

Fast Leakage Assessment

We describe a fast technique for performing the computationally heavy part of leakage assessment, in any statistical moment (or other property) of the leakage samples distributions. The proposed technique outperforms by orders of magnitude the approach presented at CHES 2015 by Schneider and Moradi. We can carry out evaluations that before took 90 CPU-days in 4 CPU-hours (about a 500-fold speed-up). As a bonus, we can work with exact arithmetic, we can apply kernel-based density estimation methods, we can employ arbitrary pre-processing functions such as absolute value to power traces, and we can perform information-theoretic leakage assessment. Our trick is simple and elegant, and lends itself to an easy and compact implementation. We fit a prototype implementation in about 130 lines of C code

From Improved Leakage Detection to the Detection of Points of Interests in Leakage Traces

Leakage detection usually refers to the task of identifying data-dependent information in side-channel measurements, independent of whether this information can be exploited. Detecting Points-Of-Interest (POIs) in leakage traces is a complementary task that is a necessary first step in most side-channel attacks, where the adversary wants to turn this information into (e.g.) a key recovery. In this paper, we discuss the differences between these tasks, by investigating a popular solution to leakage detection based on a t-test, and an alternative method exploiting Pearson\u27s correlation coefficient. We first show that the simpler t-test has better sampling complexity, and that its gain over the correlation-based test can be predicted by looking at the Signal-to-Noise Ratio (SNR) of the leakage partitions used in these tests. This implies that the sampling complexity of both tests relates more to their implicit leakage assumptions than to the actual statistics exploited. We also put forward that this gain comes at the cost of some intuition loss regarding the localization of the exploitable leakage samples in the traces, and their informativeness. Next, and more importantly, we highlight that our reasoning based on the SNR allows defining an improved t-test with significantly faster detection speed (with approximately 5 times less measurements in our experiments), which is therefore highly relevant for evaluation laboratories. We finally conclude that whereas t-tests are the method of choice for leakage detection only, correlation-based tests exploiting larger partitions are preferable for detecting POIs. We confirm this intuition by improving automated tools for the detection of POIs in the leakage measurements of a masked implementation, in a black box manner and without key knowledge, thanks to a correlation-based leakage detection test

White matter changes in microstructure associated with a maladaptive response to stress in rats

In today's society, every individual is subjected to stressful stimuli with different intensities and duration. This exposure can be a key trigger in several mental illnesses greatly affecting one's quality of life. Yet not all subjects respond equally to the same stimulus and some are able to better adapt to them delaying the onset of its negative consequences. The neural specificities of this adaptation can be essential to understand the true dynamics of stress as well as to design new approaches to reduce its consequences. In the current work, we employed ex vivo high field diffusion magnetic resonance imaging (MRI) to uncover the differences in white matter properties in the entire brain between Fisher 344 (F344) and Sprague-Dawley (SD) rats, known to present different responses to stress, and to examine the effects of a 2-week repeated inescapable stress paradigm. We applied a tract-based spatial statistics (TBSS) analysis approach to a total of 25 animals. After exposure to stress, SD rats were found to have lower values of corticosterone when compared with F344 rats. Overall, stress was found to lead to an overall increase in fractional anisotropy (FA), on top of a reduction in mean and radial diffusivity (MD and RD) in several white matter bundles of the brain. No effect of strain on the white matter diffusion properties was observed. The strain-by-stress interaction revealed an effect on SD rats in MD, RD and axial diffusivity (AD), with lower diffusion metric levels on stressed animals. These effects were localized on the left side of the brain on the external capsule, corpus callosum, deep cerebral white matter, anterior commissure, endopiriform nucleus, dorsal hippocampus and amygdala fibers. The results possibly reveal an adaptation of the SD strain to the stressful stimuli through synaptic and structural plasticity processes, possibly reflecting learning processes.We thank Neurospin (high field MRI center CEA Saclay) for providing its support for MRI acquisition. JB was supported by grants from Fondation pour la Recherche Médicale (FRM) and Groupe Pasteur Mutualité (GPM). This work was supported by a grant from ANR (SIGMA). This work was performed on a platform of France Life Imaging (FLI) network partly funded by the grant ANR-11-INBS-0006. This work and RM were supported by a fellowship of the project FCT-ANR/NEU-OSD/0258/2012 founded by FCT/MEC (www.fct.pt) and by Fundo Europeu de Desenvolvimento Regional (FEDER). AC was supported by a grant from the Fondation NRJ.info:eu-repo/semantics/publishedVersio

Making Masking Security Proofs Concrete - Or How to Evaluate the Security of any Leaking Device

We investigate the relationships between theoretical studies of leaking cryptographic devices and concrete security evaluations with standard side-channel attacks. Our contributions are in four parts. First, we connect the formal analysis of the masking countermeasure proposed by Duc et al. (Eurocrypt 2014) with the Eurocrypt 2009 evaluation framework for side-channel key recovery attacks. In particular, we re-state their main proof for the masking countermeasure based on a mutual information metric, which is frequently used in concrete physical security evaluations. Second, we discuss the tightness of the Eurocrypt 2014 bounds based on experimental case studies. This allows us to conjecture a simplified link between the mutual information metric and the success rate of a side-channel adversary, ignoring technical parameters and proof artifacts. Third, we introduce heuristic (yet well-motivated) tools for the evaluation of the masking countermeasure when its independent leakage assumption is not perfectly fulfilled, as it is frequently encountered in practice. Thanks to these tools, we argue that masking with non-independent leakages may provide improved security levels in certain scenarios. Eventually, we consider the tradeoff between measurement complexity and key enumeration in divide-and-conquer side-channel attacks, and show that it can be predicted based on the mutual information metric, by solving a non-linear integer programming problem for which efficient solutions exist. The combination of these observations enables significant reductions of the evaluation costs for certification bodies

Lipophilic aroylhydrazone chelator HNTMB and its multiple effects on ovarian cancer cells

<p>Abstract</p> <p>Background</p> <p>Metal chelators have gained much attention as potential anti-cancer agents. However, the effects of chelators are often linked solely to their capacity to bind iron while the potential complexation of other trace metals has not been fully investigated. In present study, we evaluated the effects of various lipophilic aroylhydrazone chelators (AHC), including novel compound HNTMB, on various ovarian cancer cell lines (SKOV-3, OVCAR-3, NUTU-19).</p> <p>Methods</p> <p>Cell viability was analyzed via MTS cytotoxicity assays and NCI60 cancer cell growth screens. Apoptotic events were monitored via Western Blot analysis, fluorescence microscopy and TUNEL assay. FACS analysis was carried out to study Cell Cycle regulation and detection of intracellular Reactive Oxygen Species (ROS)</p> <p>Results</p> <p>HNTMB displayed high cytotoxicity (IC50 200-400 nM) compared to previously developed AHC (oVtBBH, HNtBBH, StBBH/206, HNTh2H/315, HNI/311; IC50 0.8-6 μM) or cancer drug Deferoxamine, a hexadentate iron-chelator (IC50 12-25 μM). In a NCI60 cancer cell line screen HNTMB exhibited growth inhibitory effects with remarkable differences in specificity depending on the cell line studied (GI50 10 nM-2.4 μM). In SKOV-3 ovarian cancer cells HNTMB treatment led to chromatin fragmentation and activation of the extrinsic and intrinsic pathways of apoptosis with specific down-regulation of Bcl-2. HNTMB caused delayed cell cycle progression of SKOV-3 through G2/M phase arrest. HNTMB can chelate iron and copper of different oxidation states. Complexation with copper lead to high cytotoxicity via generation of reactive oxygen species (ROS) while treatment with iron complexes of the drug caused neither cytotoxicity nor increased ROS levels.</p> <p>Conclusions</p> <p>The present report suggests that both, non-complexed HNTMB as a chelator of intracellular trace-metals as well as a cytotoxic HNTMB/copper complex may be developed as potential therapeutic drugs in the treatment of ovarian and other solid tumors.</p

The Glasgow Outcome Scale -- 40 years of application and refinement

The Glasgow Outcome Scale (GOS) was first published in 1975 by Bryan Jennett and Michael Bond. With over 4,000 citations to the original paper, it is the most highly cited outcome measure in studies of brain injury and the second most-cited paper in clinical neurosurgery. The original GOS and the subsequently developed extended GOS (GOSE) are recommended by several national bodies as the outcome measure for major trauma and for head injury. The enduring appeal of the GOS is linked to its simplicity, short administration time, reliability and validity, stability, flexibility of administration (face-to-face, over the telephone and by post), cost-free availability and ease of access. These benefits apply to other derivatives of the scale, including the Glasgow Outcome at Discharge Scale (GODS) and the GOS paediatric revision. The GOS was devised to provide an overview of outcome and to focus on social recovery. Since the initial development of the GOS, there has been an increasing focus on the multidimensional nature of outcome after head injury. This Review charts the development of the GOS, its refinement and usage over the past 40 years, and considers its current and future roles in developing an understanding of brain injury

The Salivary Secretome of the Tsetse Fly Glossina pallidipes (Diptera: Glossinidae) Infected by Salivary Gland Hypertrophy Virus

Tsetse fly (Diptera; Glossinidae) transmits two devastating diseases to farmers (human African Trypanosomiasis; HAT) and their livestock (Animal African Trypanosomiasis; AAT) in 37 sub-Saharan African countries. During the rainy seasons, vast areas of fertile, arable land remain uncultivated as farmers flee their homes due to the presence of tsetse. Available drugs against trypanosomiasis are ineffective and difficult to administer. Control of the tsetse vector by Sterile Insect Technique (SIT) has been effective. This method involves repeated release of sterilized males into wild tsetse populations, which compete with wild type males for females. Upon mating, there is no offspring, leading to reduction in tsetse populations and thus relief from trypanosomiasis. The SIT method requires large-scale tsetse rearing to produce sterile males. However, tsetse colony productivity is hampered by infections with the salivary gland hypertrophy virus, which is transmitted via saliva as flies take blood meals during membrane feeding and often leads to colony collapse. Here, we investigated the salivary gland secretome proteins of virus-infected tsetse to broaden our understanding of virus infection, transmission and pathology. By this approach, we obtain insight in tsetse-hytrosavirus interactions and identified potential candidate proteins as targets for developing biotechnological strategies to control viral infections in tsetse colonies