The Meaning of Memory Safety

We give a rigorous characterization of what it means for a programming language to be memory safe, capturing the intuition that memory safety supports local reasoning about state. We formalize this principle in two ways. First, we show how a small memory-safe language validates a noninterference property: a program can neither affect nor be affected by unreachable parts of the state. Second, we extend separation logic, a proof system for heap-manipulating programs, with a memory-safe variant of its frame rule. The new rule is stronger because it applies even when parts of the program are buggy or malicious, but also weaker because it demands a stricter form of separation between parts of the program state. We also consider a number of pragmatically motivated variations on memory safety and the reasoning principles they support. As an application of our characterization, we evaluate the security of a previously proposed dynamic monitor for memory safety of heap-allocated data.Comment: POST'18 final versio

Tumoricidal efficacy coincides with CD11c up-regulation in antigen-specific CD8+ T cells during vaccine immunotherapy

Background: Dendritic cells (DCs) mount tumor-associated antigens (TAAs), and the double-stranded RNA adjuvant Poly(I:C) stimulates Toll-like receptor 3 (TLR3) signal in DC, which in turn induces type I interferon (IFN) and interleukin-12 (IL-12), then cross-primes cytotoxic T lymphocytes (CTLs). Proliferation of CTLs correlates with tumor regression. How these potent cells expand with high quality is crucial to the outcome of CTL therapy. However, good markers reflecting the efficacy of DC-target immunotherapy have not been addressed. Methods: Using an EG7 (ovalbumin, OVA-positive) tumor-implant mouse model, we examined what is a good marker for active CTL induction in treatment with Poly(I:C)/OVA. Results: Simultaneous administration of Poly(I:C) and antigen (Ag) OVA significantly increased a minor population of CD8+ T cells, that express CD11c in lymphoid and tumor sites. The numbers of the CD11c+ CD8+ T cells correlated with those of induced Ag-specific CD8+ T cells and tumor regression. The CD11c+ CD8+ T cell moiety was characterized by its high killing activity and IFN-γ-producing ability, which represent an active phenotype of the effector CTLs. Not only a TLR3-specific (TICAM-1-dependent) signal but also TLR2 (MyD88) signal in DC triggered the expansion of CD11c+ CD8+ T cells in tumor-bearing mice. Notably, human CD11c+ CD8+ T cells also proliferated in peripheral blood mononuclear cells (PBMC) stimulated with cytomegalovirus (CMV) Ag. Conclusions: CD11c expression in CD8+ T cells reflects anti-tumor CTL activity and would be a marker for immunotherapeutic efficacy in mouse models and probably cancer patients as well

The stigma of obesity in the general public and its implications for public health - a systematic review

<p>Abstract</p> <p>Background</p> <p>Up to this date, prevalence rates of obesity are still rising. Aside from co-morbid diseases, perceived discrimination and stigmatization leads to worsen outcomes in obese individuals. Higher stigmatizing attitudes towards obese individuals may also result in less support of preventive and interventive measures. In light of the immense burden of obesity on health care systems and also on the individuals' quality of life, accepted and subsidized preventive measures are needed. Policy support might be determined by views of the lay public on causes of obesity and resulting weight stigma. This study seeks to answer how representative samples of the lay public perceive people with obesity or overweight status (stigmatizing attitudes); what these samples attribute obesity to (causal attribution) and what types of interventions are supported by the lay public and which factors determine that support (prevention support).</p> <p>Methods</p> <p>A systematic literature search was conducted. All studies of representative samples reporting results on (a) stigmatizing attitudes towards overweight and obese individuals, (b) causal beliefs and (c) prevention support were included.</p> <p>Results</p> <p>Only 7 articles were found. One study reported prevalence rates of stigmatizing attitudes. About a quarter of the population in Germany displayed definite stigmatizing attitudes. Other studies reported causal attributions. While external influences on weight are considered as well, it seems that internal factors are rated to be of higher importance. Across the studies found, regulative prevention is supported by about half of the population, while childhood prevention has highest approval rates. Results on sociodemographic determinants differ substantially.</p> <p>Conclusions</p> <p>Further research on public attitudes toward and perception of overweight and obesity is urgently needed to depict the prevailing degree of stigmatization. Introducing a multidimensional concept of the etiology of obesity to the lay public might be a starting point in stigma reduction.</p

The potential impact of climate change on Australia's soil organic carbon resources

BACKGROUND: Soil organic carbon (SOC) represents a significant pool of carbon within the biosphere. Climatic shifts in temperature and precipitation have a major influence on the decomposition and amount of SOC stored within an ecosystem and that released into the atmosphere. We have linked net primary production (NPP) algorithms, which include the impact of enhanced atmospheric CO(2 )on plant growth, to the SOCRATES terrestrial carbon model to estimate changes in SOC for the Australia continent between the years 1990 and 2100 in response to climate changes generated by the CSIRO Mark 2 Global Circulation Model (GCM). RESULTS: We estimate organic carbon storage in the topsoil (0–10 cm) of the Australian continent in 1990 to be 8.1 Gt. This equates to 19 and 34 Gt in the top 30 and 100 cm of soil, respectively. By the year 2100, under a low emissions scenario, topsoil organic carbon stores of the continent will have increased by 0.6% (49 Mt C). Under a high emissions scenario, the Australian continent becomes a source of CO(2 )with a net reduction of 6.4% (518 Mt) in topsoil carbon, when compared to no climate change. This is partially offset by the predicted increase in NPP of 20.3% CONCLUSION: Climate change impacts must be studied holistically, requiring integration of climate, plant, ecosystem and soil sciences. The SOCRATES terrestrial carbon cycling model provides realistic estimates of changes in SOC storage in response to climate change over the next century, and confirms the need for greater consideration of soils in assessing the full impact of climate change and the development of quantifiable mitigation strategies

Molecular subtypes of breast cancer are associated with characteristic DNA methylation patterns

Introduction: Five different molecular subtypes of breast cancer have been identified through gene expression profiling. Each subtype has a characteristic expression pattern suggested to partly depend on cellular origin. We aimed to investigate whether the molecular subtypes also display distinct methylation profiles. Methods: We analysed methylation status of 807 cancer-related genes in 189 fresh frozen primary breast tumours and four normal breast tissue samples using an array-based methylation assay. Results: Unsupervised analysis revealed three groups of breast cancer with characteristic methylation patterns. The three groups were associated with the luminal A, luminal B and basal-like molecular subtypes of breast cancer, respectively, whereas cancers of the HER2-enriched and normal-like subtypes were distributed among the three groups. The methylation frequencies were significantly different between subtypes, with luminal B and basal-like tumours being most and least frequently methylated, respectively. Moreover, targets of the polycomb repressor complex in breast cancer and embryonic stem cells were more methylated in luminal B tumours than in other tumours. BRCA2-mutated tumours had a particularly high degree of methylation. Finally, by utilizing gene expression data, we observed that a large fraction of genes reported as having subtype-specific expression patterns might be regulated through methylation. Conclusions: We have found that breast cancers of the basal-like, luminal A and luminal B molecular subtypes harbour specific methylation profiles. Our results suggest that methylation may play an important role in the development of breast cancers

Mechanisms of leukocyte lipid body formation and function in inflammation

An area of increasingly interest for the understanding of cell signaling are the spatio-temporal aspects of the different enzymes involved in lipid mediator generation (eicosanoid-forming enzymes, phospholipases and their regulatory kinases and phosphatases) and pools of lipid precursors. The compartmentalization of signaling components within discrete and dynamic sites in the cell is critical for specificity and efficiency of enzymatic reactions of phosphorilation, enzyme activation and function. We hypothesized that lipid bodies - inducible non-membrane bound cytoplasmic lipid domains - function as specialized intracellular sites of compartmentalization of signaling with major roles in lipid mediator formation within leukocytes engaged in inflammatory process. Over the past years substantial progresses have been made demonstrating that all enzymes involved in eicosanoid synthesis localize at lipid bodies and lipid bodies are distinct sites for eicosanoid generation. Here we will review our current knowledge on the mechanisms of formation and functions of lipid bodies pertinent to inflammation

Comparative Performance Information Plays No Role in the Referral Behaviour of GPs

Comparative performance information (CPI) about the quality of hospital care is information used to identify high-quality hospitals and providers. As the gatekeeper to secondary care, the general practitioner (GP) can use CPI to reflect on the pros and cons of the available options with the patient and choose a provider best fitted to the patient’s needs. We investigated how GPs view their role in using CPI to choose providers and support patients. Method: We used a mixed-method, sequential, exploratory design to conduct explorative interviews with 15 GPs about their referral routines, methods of referral consideration, patient involvement, and the role of CPI. Then we quantified the qualitative results by sending a survey questionnaire to 81 GPs affiliated with a representative national research network. Results: Seventy GPs (86% response rate) filled out the questionnaire. Most GPs did not know where to find CPI (87%) and had never searched for it (94%). The GPs reported that they were not motivated to use CPI due to doubts about its role as support information, uncertainty about the effect of using CPI, lack of faith in better outcomes, and uncertainty about CPI content and validity. Nonetheless, most GPs believed that patients would like to be informed about quality-of- care differences (62%), and about half the GPs discussed quality-of-care differences with their patients (46%), though these discussions were not based on CPI. Conclusion: Decisions about referrals to hospital care are not based on CPI exchanges during GP consultations. As a gatekeeper, the GP is in a good position to guide patients through the enormous amount of quality information that is available. Nevertheless, it is unclear how and whether the GP’s role in using information about quality of care in the referral process can grow, as patients hardly ever initiate a discussion based on CPI, though they seem to be increasingly more critical about differences in quality of care. Future research should address the conditions needed to support GPs’ ability and willingness to use CPI to guide their patients in the referral process