On-stack replacement, distilled

On-stack replacement (OSR) is essential technology for adaptive optimization, allowing changes to code actively executing in a managed runtime. The engineering aspects of OSR are well-known among VM architects, with several implementations available to date. However, OSR is yet to be explored as a general means to transfer execution between related program versions, which can pave the road to unprecedented applications that stretch beyond VMs. We aim at filling this gap with a constructive and provably correct OSR framework, allowing a class of general-purpose transformation functions to yield a special-purpose replacement. We describe and evaluate an implementation of our technique in LLVM. As a novel application of OSR, we present a feasibility study on debugging of optimized code, showing how our techniques can be used to fix variables holding incorrect values at breakpoints due to optimizations

Confirmation that somatic mutations of beta-2 microglobulin correlate with a lack of recurrence in a subset of stage II mismatch repair deficient colorectal cancers from the QUASAR trial

Aims: Beta2‐Microglobulin (B2M) forms part of the HLA class I complex and plays a role in metastatic biology. B2M mutations occur frequently in mismatch repair‐deficient colorectal cancer (dMMR CRC) with limited data suggesting they may protect against recurrence. Our experimental study tested this hypothesis by investigating B2M mutation status and B2M protein expression and recurrence in patients in the stage II QUASAR clinical trial. Methods: Sanger sequencing was performed for the three coding exons of B2M on 121 dMMR and a subsample of 108 pMMR tumours; 52 with recurrence and 56 without. B2M protein expression was assessed by immunohistochemistry. Mutation status and protein expression were correlated with recurrence and compared to proficient mismatch repair (pMMR) CRCs. Results: Deleterious B2M mutations were detected in 39/121 (32%) dMMR tumours. Five contained missense B2M‐variants of unknown significance, so were excluded from further analyses. With median follow‐up 7.4 years, none of the 39 B2M‐mutant tumours recurred, compared with 14/77 (18%) B2M‐wildtype tumours (p=0.005); six at local and eight at distant sites. Sensitivity and specificity of IHC in detecting B2M mutations was 87% and 71% respectively. Significantly (p<0.0001) fewer 3/104 (2.9%) of the 108 pMMR CRCs demonstrated deleterious B2M mutations. One pMMR tumour, containing a frameshift mutation, later recurred. Conclusion: B2M mutations were detected in nearly one third of dMMR cancers, none of which recurred. B2M mutation status has potential clinical utility as a prognostic biomarker in stage II dMMR CRC. The mechanism of protection against recurrence and whether this protection extends to stage III disease remains unclear

Long-Baseline Neutrino Facility (LBNF) and Deep Underground Neutrino Experiment (DUNE) Conceptual Design Report Volume 2: The Physics Program for DUNE at LBNF

The Physics Program for the Deep Underground Neutrino Experiment (DUNE) at the Fermilab Long-Baseline Neutrino Facility (LBNF) is described

Motor-Skill Learning in Alzheimer’s Disease: A Review with an Eye to the Clinical Practice

Since elderly people suffering from dementia want to go on living independently for as long as possible, they need to be able to maintain familiar and learn new practical skills. Although explicit or declarative learning methods are mostly used to train new skills, it is hypothesized that implicit or procedural techniques may be more effective in this population. The present review discusses 23 experimental studies on implicit motor-skill learning in patients with Alzheimer’s disease (AD). All studies found intact implicit motor-learning capacities. Subsequently, it is elaborated how these intact learning abilities can be exploited in the patients’ rehabilitation with respect to the variables ‘practice’ and ‘feedback.’ Recommendations for future research are provided, and it is concluded that if training programs are adjusted to specific needs and abilities, older people with AD are well able to (re)learn practical motor skills, which may enhance their autonomy

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

A measurement of the energy loss spectrum of 150 GeV muons in iron

The energy loss spectrum of 150 GeV muons has been measured with a prototype of the ATLAS hadron calorimeter in the H8 beam of the CERN SPS.\\ The differential probability $dP/dv$ per radiation length of a fractional energy loss $v = \Delta E_{\mu} / E_{\mu}$ has been measured in the range $v = 0.01 \div 0.95$; it is then compared with the theoretical predictions for energy losses due to bremsstrahlung and production of electron-positron pairs or of energetic knock-on electrons.\\ The integrated probability $\int_{0.01}^{0.95} (dP/dv) dv$ is $(1.610\pm0.015_{stat.}\pm0.105_{syst.})\cdot10^{-3}$ in agreement with the theoretical predictions of $1.556\cdot10^{-3}$ and $1.619\cdot10^{-3}$. %7.8.96 - start Agreement with theory is also found in two intervals of $v$ where production of electron-positron pairs and knock-on electrons dominates. In the region of bremsstrahlung dominance ($v = 0.12\div0.95$) the measured integrated probability $(1.160\pm0.040_{stat}\pm0.075_{syst})\cdot 10^{-4}$ is in agreement with the theoretical value of $1.185 \cdot 10^{-4}$, obtained using Petrukhin and Shestakov's \cite{PS} description of the bremsstrahlung process. The same result is about 3.6 standard deviations (defined as the quadratic sum of statistical and systematic errors) lower than the theoretical prediction of $1.472\cdot 10^{-4}$, obtained using Tsai's \cite{TS} description of bremsstrahlung

Use of SMS texts for facilitating access to online alcohol interventions: a feasibility study

A41 Use of SMS texts for facilitating access to online alcohol interventions: a feasibility study In: Addiction Science & Clinical Practice 2017, 12(Suppl 1): A4