Execution Integrity with In-Place Encryption

Instruction set randomization (ISR) was initially proposed with the main goal of countering code-injection attacks. However, ISR seems to have lost its appeal since code-injection attacks became less attractive because protection mechanisms such as data execution prevention (DEP) as well as code-reuse attacks became more prevalent. In this paper, we show that ISR can be extended to also protect against code-reuse attacks while at the same time offering security guarantees similar to those of software diversity, control-flow integrity, and information hiding. We present Scylla, a scheme that deploys a new technique for in-place code encryption to hide the code layout of a randomized binary, and restricts the control flow to a benign execution path. This allows us to i) implicitly restrict control-flow targets to basic block entries without requiring the extraction of a control-flow graph, ii) achieve execution integrity within legitimate basic blocks, and iii) hide the underlying code layout under malicious read access to the program. Our analysis demonstrates that Scylla is capable of preventing state-of-the-art attacks such as just-in-time return-oriented programming (JIT-ROP) and crash-resistant oriented programming (CROP). We extensively evaluate our prototype implementation of Scylla and show feasible performance overhead. We also provide details on how this overhead can be significantly reduced with dedicated hardware support

A new baenid turtle from the early Paleocene (Torrejonian) of New Mexico and a species-level phylogenetic analysis of Baenidae

New cranial and postcranial material of the baenid turtle Neurankylus from the Paleocene Nacimiento Formation (Torrejonian NALMA) of northwestern New Mexico represents a new species, Neurankylus torrejonensis. The material consists of a fragmented but mostly complete skull, a partial carapace and plastron, portions of both humeri, a partial pelvis, a complete right femur, and a distal phalanx. The small, undivided cervical scale, wide vertebrals, complete ring of marginals, and large size (carapace length 520 mm) diagnose the new taxon as belonging to Neurankylus. The narrow fifth vertebral scale and scalloped posterior shell margin reveal affinities with Neurankylus baueri Gilmore, 1916, which is known from Campanian sediments in New Mexico and Utah. The holotype of Neurankylus torrejonensis is the youngest known specimen of the Neurankylus lineage, which is known to reach at least back to the Late Cretaceous (Santonian). A nearly complete species-level analysis of baenids confirms the basal placement of Neurankylus outside of Baenodda and the split of Baenodda into two primary subclades, herein named Palatobaeninae and Eubaeninae

An overt chemical protective garment reduces thermal strain compared with a covert garment in warm-wet but not hot-dry environments

© 2017 The Authors. Published by Frontiers Media. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.3389/fphys.2017.00913© 2017 Maley, Costello, Borg, Bach, Hunt and Stewart. Objectives: A commercial chemical, biological, radiological and nuclear (CBRN) protective covert garment has recently been developed with the aim of reducing thermal strain. A covert CBRN protective layer can be worn under other clothing, with equipment added for full chemical protection when needed. However, it is unknown whether the covert garment offers any alleviation to thermal strain during work compared with a traditional overt ensemble. Therefore, the aim of this study was to compare thermal strain and work tolerance times during work in an overt and covert ensemble offering the same level of CBRN protection. Methods: Eleven male participants wore an overt (OVERT) or covert (COVERT) CBRN ensemble and walked (4 km·h-1, 1% grade) for a maximum of 120 min in either a wet bulb globe temperature [WBGT] of 21, 30, or 37°C (Neutral, WarmWet and HotDry, respectively). The trials were ceased if the participants' gastrointestinal temperature reached 39°C, heart rate reached 90% of maximum, walking time reached 120 min or due to self-termination. Results: All participants completed 120 min of walking in Neutral. Work tolerance time was greater in OVERT compared with COVERT in WarmWet (P 0.05). Conclusion: Those dressed in OVERT experienced lower thermal strain and longer work tolerance times compared with COVERT in a warm-wet environment. However, COVERT may be an optimal choice in a hot-dry environment. These findings have practical implications for those making decisions on the choice of CBRN ensemble to be used during work.This project is financially supported by the Australian Government, managed by the National Security Science and Technology Centre within the Defence Science and Technology Organization, and the US Government through the Technical Support Working Group within the Combating Terrorism Technical Support Office.Published versio

Environment Dictates Dependence on Mitochondrial Complex I for NAD+ and Aspartate Production and Determines Cancer Cell Sensitivity to Metformin

Metformin use is associated with reduced cancer mortality, but how metformin impacts cancer outcomes is controversial. Although metformin can act on cells autonomously to inhibit tumor growth, the doses of metformin that inhibit proliferation in tissue culture are much higher than what has been described in vivo. Here, we show that the environment drastically alters sensitivity to metformin and other complex I inhibitors. We find that complex I supports proliferation by regenerating nicotinamide adenine dinucleotide (NAD)+, and metformin's anti-proliferative effect is due to loss of NAD+/NADH homeostasis and inhibition of aspartate biosynthesis. However, complex I is only one of many inputs that determines the cellular NAD+/NADH ratio, and dependency on complex I is dictated by the activity of other pathways that affect NAD+ regeneration and aspartate levels. This suggests that cancer drug sensitivity and resistance are not intrinsic properties of cancer cells, and demonstrates that the environment can dictate sensitivity to therapies that impact cell metabolism. Keywords: cancer metabolism; metformin; biguanide; NAD+/NADH ratio; drug sensitivity; complex I; mitochondria; aspartateNational Institutes of Health (U.S.) (Grant P30CA1405141)National Institutes of Health (U.S.) (Grant GG006413)National Institutes of Health (U.S.) (Grant R01 CA168653)National Institutes of Health (U.S.) (Grant R01 CA201276

A reassuring presence: An evaluation of Bradford District Hospice at Home service

Within the United Kingdom, a developing role for primary care services in cancer and palliative care has resulted in an increase in palliative home care teams. The provision of professional care in the home setting seeks to provide necessary services and enhanced choice for patients whose preference is to die at home. A mismatch between patient preference for home death and the actual number of people who died at home was identified within Bradford, the locality of this study. In response to this mismatch, and reflecting the policy environment of wishing to enhance community service provision, the four Primary Care Trusts (PCTs) in the city sought to offer support to patients who wished to remain in their own homes through the final stages of a terminal illness. To offer this support they set up a dedicated hospice at home team. This would provide services and support for patients in achieving a dignified, symptom free and peaceful death, allowing families to maximise time spent together. The aim of the study was to evaluate the Bradford hospice at home service from the perspective of carers, nurses and General Practitioners. Postal questionnaires were sent to carers (n = 289), district nurses (n = 508) and GP's (n = 444) using Bradford's hospice at home service. Resulting quantitative data was analysed using the Statical Package for Social Sciences (SPSS) and qualitative data was analysed using grounded theory techniques. The data from carers, district nurses and GPs provide general support for the Bradford hospice at home service. Carers valued highly the opportunity to 'fulfil a promise' to the individual who wished to be cared for at home. District nurses and GPs cited the positive impact of access to specialist expertise. This was a 'reassuring presence' for primary healthcare teams and offered 'relief of carer anxiety' by providing prompt, accessible and sensitive care. Carers and health professionals welcomed the increased possibility of patients being cared for at home. The study identified the need to focus on improving skill levels of staff and on ensuring continuity of care

Enhancement of electroporation facilitated immunogene therapy via T-reg depletion

Regulatory T cells (T-regs) can negatively impact tumor antigen-specific immune responses after infiltration into tumor tissue. However, depletion of T-regs can facilitate enhanced anti-tumor responses, thus augmenting the potential for immunotherapies. Here we focus on treating a highly aggressive form of cancer using a murine melanoma model with a poor prognosis. We utilize a combination of T-reg depletion and immunotherapy plasmid DNA delivered into the B16F10 melanoma tumor model via electroporation. Plasmids encoding murine granulocyte macrophage colony-stimulating factor and human B71 were transfected with electroporation into the tumor and transient elimination of T-regs was achieved with CD25-depleting antibodies (PC61). The combinational treatment effectively depleted T-regs compared to the untreated tumor and significantly reduced lung metastases. The combination treatment was not effective in increasing the survival, but only effective in suppression of metastases. These results indicate the potential for combining T-reg depletion with immunotherapy-based gene electrotransfer to decrease systemic metastasis and potentially enhance survival

Annual assessment of the predation of Mnemiopsis leidyi in a new invaded environment, the Kiel Fjord (Western Baltic Sea): a matter of concern?

The sudden occurrence of the ctenophore Mnemiopsis leidyi has been reported recently from different regions of the Baltic Sea and it has been suggested that the species has invaded the whole basin. Here we provide the first set of quantitative data of seasonal diet composition and life history traits of M. leidyi and its predatory role in the pelagic ecosystem of the Western Baltic Sea. The size structure of the species appeared to be dominated by small size classes and only a few adults were as large as those reported in the native region of the species and in other invaded areas. We show that the species has a high preference for small-sized and slow swimming prey, mainly during the winter low temperature period. Barnacle nauplii appeared to be the main source of carbon for the over-wintering population of M. leidyi. A preference for copepods was only found during August when these prey contributed up to 20% of the gut composition. In summer, planula larvae of the jellyfish Aurelia aurita were the most abundant prey in the gut content (feeding rate of 621 ind. ctenophore−1day−1). We further found that at highest densities of the species, in summer, a significant predation on its larvae occurs, this being the major carbon source of adults. Overall, these results are discussed in the context of trade-offs M. leidyi faces in the new environment and adverse environmental conditions, which are likely forcing the species toward reduced sizes and also probably reducing its potential predatory impact in the Baltic Sea

Evolutionary biology and anthropology suggest biome reconstitution as a necessary approach toward dealing with immune disorders

Industrialized society currently faces a wide range of non-infectious, immune-related pandemics. These pandemics include a variety of autoimmune, inflammatory and allergic diseases that are often associated with common environmental triggers and with genetic predisposition, but that do not occur in developing societies. In this review, we briefly present the idea that these pandemics are due to a limited number of evolutionary mismatches, the most damaging being ‘biome depletion’. This particular mismatch involves the loss of species from the ecosystem of the human body, the human biome, many of which have traditionally been classified as parasites, although some may actually be commensal or even mutualistic. This view, evolved from the ‘hygiene hypothesis’, encompasses a broad ecological and evolutionary perspective that considers host-symbiont relations as plastic, changing through ecological space and evolutionary time. Fortunately, this perspective provides a blueprint, termed 'biome reconstitution', for disease treatment and especially for disease prevention. Biome reconstitution includes the controlled and population-wide reintroduction (i.e. domestication) of selected species that have been all but eradicated from the human biome in industrialized society and holds great promise for the elimination of pandemics of allergic, inflammatory and autoimmune diseases

Redox proteomics of the inflammatory secretome identifies a common set of redoxins and other glutathionylated proteins released in inflammation, influenza virus infection and oxidative stress

Protein cysteines can form transient disulfides with glutathione (GSH), resulting in the production of glutathionylated proteins, and this process is regarded as a mechanism by which the redox state of the cell can regulate protein function. Most studies on redox regulation of immunity have focused on intracellular proteins. In this study we have used redox proteomics to identify those proteins released in glutathionylated form by macrophages stimulated with lipopolysaccharide (LPS) after pre-loading the cells with biotinylated GSH. Of the several proteins identified in the redox secretome, we have selected a number for validation. Proteomic analysis indicated that LPS stimulated the release of peroxiredoxin (PRDX) 1, PRDX2, vimentin (VIM), profilin1 (PFN1) and thioredoxin 1 (TXN1). For PRDX1 and TXN1, we were able to confirm that the released protein is glutathionylated. PRDX1, PRDX2 and TXN1 were also released by the human pulmonary epithelial cell line, A549, infected with influenza virus. The release of the proteins identified was inhibited by the anti-inflammatory glucocorticoid, dexamethasone (DEX), which also inhibited tumor necrosis factor (TNF)-α release, and by thiol antioxidants (N-butanoyl GSH derivative, GSH-C4, and N-acetylcysteine (NAC), which did not affect TNF-α production. The proteins identified could be useful as biomarkers of oxidative stress associated with inflammation, and further studies will be required to investigate if the extracellular forms of these proteins has immunoregulatory functions

EGLN1 Inhibition and Rerouting of α-Ketoglutarate Suffice for Remote Ischemic Protection

Ischemic preconditioning is the phenomenon whereby brief periods of sublethal ischemia protect against a subsequent, more prolonged, ischemic insult. In remote ischemic preconditioning (RIPC), ischemia to one organ protects others organs at a distance. We created mouse models to ask if inhibition of the alpha-ketoglutarate (αKG)-dependent dioxygenase Egln1, which senses oxygen and regulates the hypoxia-inducible factor (HIF) transcription factor, could suffice to mediate local and remote ischemic preconditioning. Using somatic gene deletion and a pharmacological inhibitor, we found that inhibiting Egln1 systemically or in skeletal muscles protects mice against myocardial ischemia-reperfusion (I/R) injury. Parabiosis experiments confirmed that RIPC in this latter model was mediated by a secreted factor. Egln1 loss causes accumulation of circulating αKG, which drives hepatic production and secretion of kynurenic acid (KYNA) that is necessary and sufficient to mediate cardiac ischemic protection in this setting.Broad Institute of MIT and Harvard. SPARC ProgramBurroughs Wellcome Fun