Interactive Simplifier Tracing and Debugging in Isabelle

The Isabelle proof assistant comes equipped with a very powerful tactic for term simplification. While tremendously useful, the results of simplifying a term do not always match the user's expectation: sometimes, the resulting term is not in the form the user expected, or the simplifier fails to apply a rule. We describe a new, interactive tracing facility which offers insight into the hierarchical structure of the simplification with user-defined filtering, memoization and search. The new simplifier trace is integrated into the Isabelle/jEdit Prover IDE.Comment: Conferences on Intelligent Computer Mathematics, 201

Antibody-based detection of protein phosphorylation status to track the efficacy of novel therapies using nanogram protein quantities from stem cells and cell lines

This protocol describes a highly reproducible antibody-based method that provides protein level and phosphorylation status information from nanogram quantities of protein cell lysate. Nanocapillary isoelectric focusing (cIEF) combines with UV-activated linking chemistry to detect changes in phosphorylation status. As an example application, we describe how to detect changes in response to tyrosine kinase inhibitors (TKIs) in the phosphorylation status of the adaptor protein ​CrkL, a major substrate of the oncogenic tyrosine kinase ​BCR-​ABL in chronic myeloid leukemia (CML), using highly enriched CML stem cells and mature cell populations in vitro. This protocol provides a 2.5 pg/nl limit of protein detection (<0.2% of a stem cell sample containing <104 cells). Additional assays are described for phosphorylated tyrosine 207 (pTyr207)-​CrkL and the protein tyrosine phosphatase ​PTPRC/​CD45; these assays were developed using this protocol and applied to CML patient samples. This method is of high throughput, and it can act as a screen for in vitro cancer stem cell response to drugs and novel agents

Memory usage verification using Hip/Sleek.

Embedded systems often come with constrained memory footprints. It is therefore essential to ensure that software running on such platforms fulfils memory usage specifications at compile-time, to prevent memory-related software failure after deployment. Previous proposals on memory usage verification are not satisfactory as they usually can only handle restricted subsets of programs, especially when shared mutable data structures are involved. In this paper, we propose a simple but novel solution. We instrument programs with explicit memory operations so that memory usage verification can be done along with the verification of other properties, using an automated verification system Hip/Sleek developed recently by Chin et al.[10,19]. The instrumentation can be done automatically and is proven sound with respect to an underlying semantics. One immediate benefit is that we do not need to develop from scratch a specific system for memory usage verification. Another benefit is that we can verify more programs, especially those involving shared mutable data structures, which previous systems failed to handle, as evidenced by our experimental results

Expression of the androgen receptor and an androgen-responsive protein, apolipoprotein D, in human breast cancer.

Little is known regarding the activity and function of the androgen receptor (AR) in human breast cancer. In the present study AR was evaluated in untreated primary breast cancers using antisera to the amino- and carboxy-termini of the receptor and quantitated using colour video image analysis. A strong correlation between tissue concentration and percentage AR-positive cells was observed for each antiserum. However, comparison of percentage positive cells using the amino- and carboxy-terminal AR antisera in individual breast cancer specimens revealed a subset of tumours with discordantly increased staining for the carboxy terminus. These findings suggest the presence of amino-terminal-truncated AR in a proportion of breast cancer cells or presence of AR mutations or associated protein alterations that affect binding of the amino-terminal AR antiserum. Immunohistochemical expression of the androgen-regulated glycoprotein, apolipoprotein D (apo-D), was also evaluated in the breast cancer specimens. Focal positivity of apo-D staining, which did not always co-localise with AR-positive cells, was observed within breast tumours. Furthermore, no correlation was evident between percentage positive cells stained for AR and apo-D in breast cancer specimens. These findings indicate that, although apo-D expression is androgen regulated in human breast cancer cell lines in vitro, its expression in primary breast cancers may be regulated by other factors. The expression of AR in primary breast cancers also suggests that the receptor may be involved in tumour responsiveness or in abnormal responses to endocrine therapies

Interleukin 7 from Maternal Milk Crosses the Intestinal Barrier and Modulates T- Cell Development in Offspring

Background Breastfeeding protects against illnesses and death in hazardous environments, an effect partly mediated by improved immune function. One hypothesis suggests that factors within milk supplement the inadequate immune response of the offspring, but this has not been able to account for a series of observations showing that factors within maternally derived milk may supplement the development of the immune system through a direct effect on the primary lymphoid organs. In a previous human study we reported evidence suggesting a link between IL-7 in breast milk and the thymic output of infants. Here we report evidence in mice of direct action of maternally-derived IL-7 on T cell development in the offspring. Methods and Findings  We have used recombinant IL-7 labelled with a fluorescent dye to trace the movement in live mice of IL-7 from the stomach across the gut and into the lymphoid tissues. To validate the functional ability of maternally derived IL- 7 we cross fostered IL-7 knock-out mice onto normal wild type mothers. Subsets of thymocytes and populations of peripheral T cells were significantly higher than those found in knock-out mice receiving milk from IL-7 knock-out mothers. Conclusions/Significance Our study provides direct evidence that interleukin 7, a factor which is critical in the development of T lymphocytes, when maternally derived can transfer across the intestine of the offspring, increase T cell production in the thymus and support the survival of T cells in the peripheral secondary lymphoid tissue

Mobile Resource Guarantees and Policies

Abstract. This paper introduces notions of resource policy for mobile code to be run on smart devices, to integrate with the proof-carrying code architecture of the Mobile Resource Guarantees (MRG) project. Two forms of policy are used: guaranteed policies which come with proofs and target policies which describe limits of the device. A guaranteed policy is expressed as a function of a methods input sizes, which determines a bound on consumption of some resource. A target policy is defined by a constant bound and input constraints for a method. A recipient of mobile code chooses whether to run methods by comparing between a guaranteed policy and the target policy. Since delivered code may use methods implemented on the target machine, guaranteed policies may also be provided by the platform; they appear symbolically as assumptions in delivered proofs. Guaranteed policies entail proof obligations that must be established from the proof certificate. Before proof, a policy checker ensures that the guaranteed policy refines the target policy; our policy format ensures that this step is tractable and does not require proof. Delivering policies thus mediates between arbitrary target requirements and the desirability to package code and certificate only once.

COVID-19: how has a global pandemic changed manual therapy technique education in chiropractic programs around the world?

Background Manual therapy is a cornerstone of chiropractic education, whereby students work towards a level of skill and expertise that is regarded as competent to work within the field of chiropractic. Due to the COVID-19 pandemic, chiropractic programs in every region around the world had to make rapid changes to the delivery of manual therapy technique education, however what those changes looked like was unknown. Aims The aims of this study were to describe the immediate actions made by chiropractic programs to deliver education for manual therapy techniques and to summarise the experience of academics who teach manual therapy techniques during the initial outbreak of COVID-19 pandemic. Methods A qualitative descriptive approach was used to describe the immediate actions made by chiropractic programs to deliver manual therapy technique education during the COVID-19 pandemic. Chiropractic programs were identified from the webpages of the Councils on Chiropractic Education International and the Council on Chiropractic Education – USA. Between May and June 2020, a convenience sample of academics who lead or teach in manual therapy technique in those programs were invited via email to participate in an online survey with open-ended questions. Responses were entered into the NVivo software program and analysed using a reflexive thematic analysis by a qualitative researcher independent to the data collection. Results Data from 16 academics in 13 separate chiropractic programs revealed five, interconnected themes: Immediate response; Move to online delivery; Impact on learning and teaching; Additional challenges faced by educators; and Ongoing challenges post lockdown. Conclusion This study used a qualitative descriptive approach to describe how some chiropractic programs immediately responded to the initial outbreak of the COVID-19 pandemic in their teaching of manual therapy techniques. Chiropractic programs around the world provided their students with rapid, innovative learning strategies, in an attempt to maintain high standards of chiropractic education; however, challenges included maintaining student engagement in an online teaching environment, psychomotor skills acquisition and staff workload

What lies beneath: exploring links between asylum policy and hate crime in the UK

This paper explores the link between increasing incidents of hate crime and the asylum policy of successive British governments with its central emphasis on deterrence. The constant problematisation of asylum seekers in the media and political discourse ensures that 'anti-immigrant' prejudice becomes mainstr earned as a common-sense response. The victims are not only the asylum seekers hoping for a better life but democratic society itself with its inherent values of pluralism and tolerance debased and destabilised