Everything You Want to Know About Pointer-Based Checking

Lack of memory safety in C/C++ has resulted in numerous security vulnerabilities and serious bugs in large software systems. This paper highlights the challenges in enforcing memory safety for C/C++ programs and progress made as part of the SoftBoundCETS project. We have been exploring memory safety enforcement at various levels - in hardware, in the compiler, and as a hardware-compiler hybrid - in this project. Our research has identified that maintaining metadata with pointers in a disjoint metadata space and performing bounds and use-after-free checking can provide comprehensive memory safety. We describe the rationale behind the design decisions and its ramifications on various dimensions, our experience with the various variants that we explored in this project, and the lessons learned in the process. We also describe and analyze the forthcoming Intel Memory Protection Extensions (MPX) that provides hardware acceleration for disjoint metadata and pointer checking in mainstream hardware, which is expected to be available later this year

Syntax-guided synthesis

The classical formulation of the program-synthesis problem is to find a program that meets a correctness specification given as a logical formula. Recent work on program synthesis and program optimization illustrates many potential benefits of allowing the user to supplement the logical specification with a syntactic template that constrains the space of allowed implementations. Our goal is to identify the core computational problem common to these proposals in a logical framework. The input to the syntax-guided synthesis problem (SyGuS) consists of a background theory, a semantic correctness specification for the desired program given by a logical formula, and a syntactic set of candidate implementations given by a grammar. The computational problem then is to find an implementation from the set of candidate expressions so that it satisfies the specification in the given theory. We describe three different instantiations of the counter-example-guided-inductive-synthesis (CEGIS) strategy for solving the synthesis problem, report on prototype implementations, and present experimental results on an initial set of benchmarks.National Science Foundation (U.S.) (Expeditions in Computing Project ExCAPE Award CCF 1138996

Little-Parks effect and multiquanta vortices in a hybrid superconductor--ferromagnet system

Within the phenomenological Ginzburg-Landau theory we investigate the phase diagram of a thin superconducting film with ferromagnetic nanoparticles. We study the oscillatory dependence of the critical temperature on an external magnetic field similar to the Little-Parks effect and formation of multiquantum vortex structures. The structure of a superconducting state is studied both analytically and numerically.Comment: 7 pages, 1 figure. Submitted to J. Phys.: Condens. Mat

Regulation of neutrophil senescence by microRNAs

Neutrophils are rapidly recruited to sites of tissue injury or infection, where they protect against invading pathogens. Neutrophil functions are limited by a process of neutrophil senescence, which renders the cells unable to respond to chemoattractants, carry out respiratory burst, or degranulate. In parallel, aged neutrophils also undergo spontaneous apoptosis, which can be delayed by factors such as GMCSF. This is then followed by their subsequent removal by phagocytic cells such as macrophages, thereby preventing unwanted inflammation and tissue damage. Neutrophils translate mRNA to make new proteins that are important in maintaining functional longevity. We therefore hypothesised that neutrophil functions and lifespan might be regulated by microRNAs expressed within human neutrophils. Total RNA from highly purified neutrophils was prepared and subjected to microarray analysis using the Agilent human miRNA microarray V3. We found human neutrophils expressed a selected repertoire of 148 microRNAs and that 6 of these were significantly upregulated after a period of 4 hours in culture, at a time when the contribution of apoptosis is negligible. A list of predicted targets for these 6 microRNAs was generated from http://mirecords.biolead.org and compared to mRNA species downregulated over time, revealing 83 genes targeted by at least 2 out of the 6 regulated microRNAs. Pathway analysis of genes containing binding sites for these microRNAs identified the following pathways: chemokine and cytokine signalling, Ras pathway, and regulation of the actin cytoskeleton. Our data suggest that microRNAs may play a role in the regulation of neutrophil senescence and further suggest that manipulation of microRNAs might represent an area of future therapeutic interest for the treatment of inflammatory disease

Albumin and multiple sclerosis

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Leakage of the blood–brain barrier (BBB) is a common pathological feature in multiple sclerosis (MS). Following a breach of the BBB, albumin, the most abundant protein in plasma, gains access to CNS tissue where it is exposed to an inflammatory milieu and tissue damage, e.g., demyelination. Once in the CNS, albumin can participate in protective mechanisms. For example, due to its high concentration and molecular properties, albumin becomes a target for oxidation and nitration reactions. Furthermore, albumin binds metals and heme thereby limiting their ability to produce reactive oxygen and reactive nitrogen species. Albumin also has the potential to worsen disease. Similar to pathogenic processes that occur during epilepsy, extravasated albumin could induce the expression of proinflammatory cytokines and affect the ability of astrocytes to maintain potassium homeostasis thereby possibly making neurons more vulnerable to glutamate exicitotoxicity, which is thought to be a pathogenic mechanism in MS. The albumin quotient, albumin in cerebrospinal fluid (CSF)/albumin in serum, is used as a measure of blood-CSF barrier dysfunction in MS, but it may be inaccurate since albumin levels in the CSF can be influenced by multiple factors including: 1) albumin becomes proteolytically cleaved during disease, 2) extravasated albumin is taken up by macrophages, microglia, and astrocytes, and 3) the location of BBB damage affects the entry of extravasated albumin into ventricular CSF. A discussion of the roles that albumin performs during MS is put forth

The global retinoblastoma outcome study : a prospective, cluster-based analysis of 4064 patients from 149 countries

DATA SHARING : The study data will become available online once all analyses are complete.BACKGROUND : Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. METHODS : We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. FINDINGS : The cohort included 4064 children from 149 countries. The median age at diagnosis was 23·2 months (IQR 11·0–36·5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0·8%) of 636 children from high-income countries, 55 (5·4%) of 1027 children from upper-middle-income countries, 342 (19·7%) of 1738 children from lower-middle-income countries, and 196 (42·9%) of 457 children from low-income countries. Enucleation surgery was available for all children and intravenous chemotherapy was available for 4014 (98·8%) of 4064 children. The 3-year survival rate was 99·5% (95% CI 98·8–100·0) for children from high-income countries, 91·2% (89·5–93·0) for children from upper-middle-income countries, 80·3% (78·3–82·3) for children from lower-middle-income countries, and 57·3% (52·1-63·0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16·67; 95% CI 4·76–50·00), cT4 advanced tumour compared to cT1 (8·98; 4·44–18·18), and older age at diagnosis in children up to 3 years (1·38 per year; 1·23–1·56). For children aged 3–7 years, the mortality risk decreased slightly (p=0·0104 for the change in slope). INTERPRETATION : This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes.The Queen Elizabeth Diamond Jubilee Trust and the Wellcome Trust.https://www.thelancet.com/journals/langlo/homeam2023Paediatrics and Child Healt

Formal Verification and its Impact on the Snooping versus Directory Protocol Debate

This invited paper argues that to facilitate formal verification, multiprocessor systems should (1) decouple enforcing coherence from enforcing a memory consistency model and (2) decouple the interconnection network from the cache coherence protocol (by not relying on any specific interconnect ordering or synchronicity properties). Of the two dominant classes of cache coherence protocols—directory protocols and snooping protocols—these two desirable properties favor use of directory protocols over snooping protocols. Although the conceptual simplicity of snooping protocols is seductive, aggressive implementations of snooping protocols lack these decoupling properties, making them perhaps more difficult in practice to reason about, verify, and implement correctly. Conversely, directory protocols may seem more complicated, but they are more amenable to these decoupling properties, which simplify protocol design and verification. Finally, this paper describes the recently-proposed token coherence protocol’s adherence to these properties and discusses some of its implications for future multiprocessor systems