83 research outputs found

    Indexed Labels for Loop Iteration Dependent Costs

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    We present an extension to the labelling approach, a technique for lifting resource consumption information from compiled to source code. This approach, which is at the core of the annotating compiler from a large fragment of C to 8051 assembly of the CerCo project, looses preciseness when differences arise as to the cost of the same portion of code, whether due to code transformation such as loop optimisations or advanced architecture features (e.g. cache). We propose to address this weakness by formally indexing cost labels with the iterations of the containing loops they occur in. These indexes can be transformed during the compilation, and when lifted back to source code they produce dependent costs. The proposed changes have been implemented in CerCo's untrusted prototype compiler from a large fragment of C to 8051 assembly.Comment: In Proceedings QAPL 2013, arXiv:1306.241

    Strong Normalization of MLF via a Calculus of Coercions

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    MLF is a type system extending ML with first-class polymorphism as in system F. The main goal of the present paper is to show that MLF enjoys strong normalization, i.e. it has no infinite reduction paths. The proof of this result is achieved in several steps. We first focus on xMLF, the Church-style version of MLF, and show that it can be translated into a calculus of coercions: terms are mapped into terms and instantiations into coercions. This coercion calculus can be seen as a decorated version of system F, so that the simulation results entails strong normalization of xMLF through the same property of system F. We then transfer the result to all other versions of MLF using the fact that they can be compiled into xMLF and showing there is a bisimulation between the two. We conclude by discussing what results and issues are encountered when using the candidates of reducibility approach to the same problem

    Percutaneous treatment of the spinal metastases

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    Background: The spinal column is the most frequent site of bone metastases, and between 30% and 70% of patients with cancer will have evidence of spinal metastasis at autopsy. The majority of metastasis occurs in the thoracic spine (70%) followed by the lumbar (20%) and cervical region (10%). The surgical treatment of the vertebral metastases remains a real challenge in spine surgeons. Recent advancements in surgical techniques allow a less aggressive approach of the patient with better results in terms of decreasing pain, improvement of the quality of life. We must avoid the overtreatment of terminally ill patients; some patients may survive for several years and benefit from surgery. Materials and methods: The surgical techniques that we used from August 2006 to October 2011 were the coablation associated with vertebroplasty and percutaneous osteosynthesis. Very important were the operating room set up and the surgical technique. In our clinic, in the last 5 years, were treated 115 patients. With vertebroplasty and ablation 76 patients (94 vertebrae). We used the percutaneous osteosynthesis in 39 patients aged between 42 and 88 years (mean 65 years). Results: In both types of treatment, the postoperative elapsed were regular with early mobilization and regression of pain. Conclusion: The diagnosis and treatment of spinal metastases require multidisciplinary review. The optimal treatment depends from a balance between the morbidity of the surgical procedure, the estimated survival time, and the overall quality of life. We believe that these minimally invasive techniques are certainly a viable alternative to “open’’ traditional spine surgery and can help in order to reduce the pain and to restore the stability.</br

    HLA-DRB1-DQB1 Haplotypes Confer Susceptibility and Resistance to Multiple Sclerosis in Sardinia

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    Introduction: Genetic predisposition to multiple sclerosis (MS) in Sardinia (Italy) has been associated with five DRB1*-DQB1* haplotypes of the human leukocyte antigen (HLA). Given the complexity of these associations, an in-depth re-analysis was performed with the specific aims of confirming the haplotype associations; establishing the independence of the associated haplotypes; and assessing patients ’ genotypic risk of developing MS. Methods and Results: A transmission disequilibrium test (TDT) of the DRB1*-DQB1 * haplotypes in 943 trio families

    Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

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    To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

    Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis

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    Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.Objective: To identify the genetic variants associated with juvenile ALS.Design, Setting, and Participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism.Main Outcomes and Measures: De novo variants present only in the index case and not in unaffected family members.Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway.Conclusions and Relevance: These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.</p

    Termination of Threads with Shared Memory via Infinitary Choice

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    We present a static type discipline on an extension of lambda-calculus with threads and shared memory ensuring termination. This discipline is based on a type and effects system, and is a condition forced on regions. It generalizes and clarifies the stratification discipline previously proposed in the literature with the same objective, and is directly inspired by positive recursive types. The proof is carried out by translating the calculus with memory reference into an extension of lambda-calculus with a non-deterministic infinitary choice, whose strong normalization is in turn proved by a standard reducibility method

    Translating Types and Effects with State Monads and Linear Logic

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    Abstract—We study a lambda-calculus with references and a types and effects system. In the first part of the paper, we translate it into the ordinary lambda-calculus with products, implementing an interacting family of state monads localized at sets of regions. In general the target language must be endowed with recursive types. However we prove that the stratification condition on regions, already used in type and effect systems to assure termination, is equivalent to completely avoid the use of recursion in the types used in the translation. We thus obtain a logical characterization of stratification, and by simulation we also provide a new proof that it yields termination. In the second part of the paper we extend the call-by-value translation of ordinary lambda-terms in linear logic proof nets to the calculus with references. This allows for a parallel evaluation of the calculus that preserves its sequential semantics. I

    Termination of Threads with Shared Memory via Infinitary Choice

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    Abstract. We present a static type discipline on an extension of λ-calculus with threads and shared memory ensuring termination. This discipline is based on a type and effects system, and is a condition forced on regions. It generalizes and clarifies the stratification discipline previously proposed in the literature with the same objective, and is directly inspired by positive recursive types. The proof is carried out by translating the calculus with memory reference into an extension of lambda-calculus with a non-deterministic infinitary choice, whose strong normalization is in turn proved by a standard reducibility method.
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