Termination Of Programs Research Articles

Smoking Cessation Ameliorates Microalbuminuria With Reduction of Blood Pressure and Pulse Rate in Patients With Already Diagnosed Diabetes Mellitus

BackgroundSmoking cessation in newly diagnosed type 2 diabetes patients is reported to be associated with amelioration of metabolic parameters and blood pressure (BP), and the reduction of microalbuminuria. The aim of this study is to demonstrate changes in BP, pulse rate (PR), and microalbuminuria in already diagnosed diabetes patients who quit smoking.MethodsWe retrospectively evaluated diabetes outpatients who were habitual smokers, and who visited to our smoking cessation clinic. Patients were divided into two groups based on their smoking status at the termination of a 3-month smoking cessation program (smoking cessation group and smoking group), and analyzed systolic and diastolic BPs, PR, HbA1c, and body weight at the start date, and at 1, 3, 6, and 12 months thereafter. The urinary albumin-to-creatinine ratio was also measured at the start date and at 12 months.ResultsThirty-five patients met our criteria. Mean diabetes duration was 12 years. Eighteen patients (52%) quit smoking. Success or failure of smoking cessation depended on nicotine dependence rather than good or bad glycemic control. Both BP and PR decreased significantly after 1 month or later in the smoking cessation group without worsening HbA1c, while both parameters did not show any changes in the smoking group. Microalbuminuria was also ameliorated significantly at 12 months compared with that at the start date in the smoking cessation group (95.8 ± 92.9 mg/gCr vs. 75.5 ± 96.3 mg/gCr, P = 0.0059), while it did not show a significant change in the smoking group. (61.9 ± 43.5 mg/gCr vs. 97.7 ± 90.4 mg/gCr, P = 0.1039).ConclusionsSmoking cessation might cause a reduction in chronic kidney disease progression through ameliorating microalbuminuria without metabolic adverse effects in patients already diagnosed with diabetes mellitus.

Lexicographic ranking supermartingales: an efficient approach to termination of probabilistic programs

Probabilistic programs extend classical imperative programs with real-valued random variables and random branching. The most basic liveness property for such programs is the termination property. The qualitative (aka almost-sure) termination problem asks whether a given program program terminates with probability 1. While ranking functions provide a sound and complete method for non-probabilistic programs, the extension of them to probabilistic programs is achieved via ranking supermartingales (RSMs). Although deep theoretical results have been established about RSMs, their application to probabilistic programs with nondeterminism has been limited only to programs of restricted control-flow structure. For non-probabilistic programs, lexicographic ranking functions provide a compositional and practical approach for termination analysis of real-world programs. In this work we introduce lexicographic RSMs and show that they present a sound method for almost-sure termination of probabilistic programs with nondeterminism. We show that lexicographic RSMs provide a tool for compositional reasoning about almost-sure termination, and for probabilistic programs with linear arithmetic they can be synthesized efficiently (in polynomial time). We also show that with additional restrictions even asymptotic bounds on expected termination time can be obtained through lexicographic RSMs. Finally, we present experimental results on benchmarks adapted from previous work to demonstrate the effectiveness of our approach.

Algorithmic analysis of termination problems for quantum programs

We introduce the notion of linear ranking super-martingale (LRSM) for quantum programs (with nondeterministic choices, namely angelic and demonic choices). Several termination theorems are established showing that the existence of the LRSMs of a quantum program implies its termination. Thus, the termination problems of quantum programs is reduced to realisability and synthesis of LRSMs. We further show that the realisability and synthesis problem of LRSMs for quantum programs can be reduced to an SDP (Semi-Definite Programming) problem, which can be settled with the existing SDP solvers. The techniques developed in this paper are used to analyse the termination of several example quantum programs, including quantum random walks and quantum Bernoulli factory for random number generation. This work is essentially a generalisation of constraint-based approach to the corresponding problems for probabilistic programs developed in the recent literature by adding two novel ideas: (1) employing the fundamental Gleason's theorem in quantum mechanics to guide the choices of templates; and (2) a generalised Farkas' lemma in terms of observables (Hermitian operators) in quantum physics.

A new proof rule for almost-sure termination

We present a new proof rule for proving almost-sure termination of probabilistic programs, including those that contain demonic non-determinism. An important question for a probabilistic program is whether the probability mass of all its diverging runs is zero, that is that it terminates "almost surely". Proving that can be hard, and this paper presents a new method for doing so. It applies directly to the program's source code, even if the program contains demonic choice. Like others, we use variant functions (a.k.a. "super-martingales") that are real-valued and decrease randomly on each loop iteration; but our key innovation is that the amount as well as the probability of the decrease are parametric. We prove the soundness of the new rule, indicate where its applicability goes beyond existing rules, and explain its connection to classical results on denumerable (non-demonic) Markov chains.

External signals regulate germinal center fate-determining transcription factors in the A20 lymphoma cell line

Due to the apoptosis-prone nature of primary germinal center B (GCB) cells, it remains a huge challenge to dissect signals that guide their differentiation towards memory B cells and plasma cells in vitro. Here we show that the murine lymphoma cell line A20 resembles primary GCB cells in expression of GC-specific surface markers and the master transcription factor BCL6 and may serve as a useful system to model certain GCB cell behaviors in vitro. Using these cells, we found that both CD40 and B cell receptor (BCR) signaling are able to drive BCL6 downregulation, which is a prerequisite of post-GC B-cell differentiation. Under the steady state, BCL6 is constantly and rapidly degraded in A20 cells by the proteasome in a strictly FBXO11-dependent manner. This process can be further enhanced by signals downstream of the BCR. Both CD40 and BCR stimulation can upregulate IRF4, a transcription factor that suppresses BCL6 expression. However, only BCR signaling downregulate PAX5 and BACH2, two transcription factors that help maintain the GCB identity. Together, these results validate the A20 cell line as an experimental system suitable for studying regulation of BCL6 and potentially other transcription factors relevant to post-GC fate determination, and they support that combined signaling from BCR and CD40 receptors would drive termination of the GC program.

Criminal Deterrence When There are Offsetting Risks: Traffic Cameras, Vehicular Accidents, and Public Safety

Numerous cities have enacted electronic monitoring programs at traffic intersections in an effort to reduce the high number of vehicle accidents. The rationale is that the higher expected fines for running a red light will induce drivers to stop and lead to fewer cross-road collisions. However, the cameras also incentivize drivers to accept a greater accident risk from stopping. We evaluate the termination of a monitoring program via a voter referendum using 12 years of geo-coded police accident data. We find that the cameras changed the composition of accidents, but no evidence of a reduction in total accidents or injuries.

FPA-FL: Incorporating static fault-proneness analysis into statistical fault localization

Despite the proven applicability of the statistical methods in automatic fault localization, these approaches are biased by data collected from different executions of the program. This biasness could result in unstable statistical models which may vary dependent on test data provided for trial executions of the program. To resolve the difficulty, in this article a new fault-proneness-aware statistical approach based on Elastic-Net regression, namely FPA-FL is proposed. The main idea behind FPA-FL is to consider the static structure and the fault-proneness of the program statements in addition to their dynamic correlations with the program termination state. The grouping effect of FPA-FL is helpful for finding multiple faults and supporting scalability. To provide the context of failure, cause-effect chains of program faults are discovered. FPA-FL is evaluated from different viewpoints on well-known test suites. The results reveal high fault localization performance of our approach, compared with similar techniques in the literature.

The WNT target SP5 negatively regulates WNT transcriptional programs in human pluripotent stem cells

The WNT/β-catenin signaling pathway is a prominent player in many developmental processes, including gastrulation, anterior–posterior axis specification, organ and tissue development, and homeostasis. Here, we use human pluripotent stem cells (hPSCs) to study the dynamics of the transcriptional response to exogenous activation of the WNT pathway. We describe a mechanism involving the WNT target gene SP5 that leads to termination of the transcriptional program initiated by WNT signaling. Integration of gene expression profiles of wild-type and SP5 mutant cells with genome-wide SP5 binding events reveals that SP5 acts to diminish expression of genes previously activated by the WNT pathway. Furthermore, we show that activation of SP5 by WNT signaling is most robust in cells with developmental potential, such as stem cells. These findings indicate a mechanism by which the developmental WNT signaling pathway reins in expression of transcriptional programs.

Dancing with the pygmy elephant: The Canadian space program, future directions amid challenges

Since the inception of the space age, Canada has pursued a partnership with the U.S. through NASA including participation from the Apollo era forward to the International Space Station. Canada joined the European Space Agency as a participating state since 1979. While these cooperative activities continued over the years, Canada also carved out areas of technology that both created economic returns but were valuable in terms of the joint projects. In a change that impacts Canada, NASA began restructuring its mission profile while it grappled with the shuttle program's termination and a downturn in the national economy. For Canada, finding a way forward for its space program is essential given the economic benefits and the international cache that accrues to a middle sized state that operates an independent space program. Finding its way forward is not easy given the costs associated with such endeavors. This paper examines Canada's current program development and its direction given the U.S. decline relative to other space powers. It also places Canada's program in the context of the debate over space technology utilization for economic development and competitiveness.

Productive corecursion in logic programming

AbstractLogic Programming is a Turing complete language. As a consequence, designing algorithms that decide termination and non-termination of programs or decide inductive/coinductive soundness of formulae is a challenging task. For example, the existing state-of-the-art algorithms can only semi-decide coinductive soundness of queries in logic programming for regular formulae. Another, less famous, but equally fundamental and important undecidable property is productivity. If a derivation is infinite and coinductively sound, we may ask whether the computed answer it determines actually computes an infinite formula. If it does, the infinite computation is productive. This intuition was first expressed under the name of computations at infinity in the 80s. In modern days of the Internet and stream processing, its importance lies in connection to infinite data structure processing. Recently, an algorithm was presented that semi-decides a weaker property – of productivity of logic programs. A logic program is productive if it can give rise to productive derivations. In this paper, we strengthen these recent results. We propose a method that semi-decides productivity of individual derivations for regular formulae. Thus, we at last give an algorithmic counterpart to the notion of productivity of derivations in logic programming. This is the first algorithmic solution to the problem since it was raised more than 30 years ago. We also present an implementation of this algorithm.

Design of the DREPAGREFFE trial: A prospective controlled multicenter study evaluating the benefit of genoidentical hematopoietic stem cell transplantation over chronic transfusion in sickle cell anemia children detected to be at risk of stroke by transcranial Doppler (NCT 01340404)

BackgroundChildren with sickle cell anemia (SCA) have an 11% risk of stroke by the age of 18. Chronic transfusion applied in patients detected to be at risk by transcranial Doppler allows a significant reduction of stroke risk. However, chronic transfusion exposes to several adverse events, including alloimmunization and iron overload, and is not curative. Hematopoietic stem cell transplantation allows termination of the transfusion program, but its benefit has not been demonstrated. DesignDREPAGREFFE (NCT01340404) is a multicenter, prospective trial enrolling SCA children younger than 15years receiving chronic transfusion due to a history of abnormal transcranial Doppler (velocities ≥200cm/s). Only those with at least one non-SCA sibling and parents accepting HLA-typing and transplantation with a genoidentical donor were eligible. Chronic transfusion was pursued in patients with no available donor, whereas others were transplanted. Comparison between the 2 arms (transfusion vs transplantation) was analyzed using both genetic randomization and propensity-score matching as a sensitivity analysis. The primary end-point was the velocity measure at 1year. Secondary endpoints were the incidence of stroke, silent cerebral infarcts and stenoses, cognitive performance in comparison with siblings, allo-immunization, iron-overload, phosphatidyl-serine, angiogenesis/hypoxia, brain injury-related factor expression, quality of life and cost. ObjectivesTo show that genoidentical transplantation decreases velocities significantly more than chronic transfusion in SCA children at risk of stroke. DiscussionDREPAGREFFE is the first prospective study to evaluate transplantation in SCA children. It compares the outcome of cerebral vasculopathy following genoidentical transplantation versus chronic transfusion using genetic randomization and causal inference methods.

Prévenir la violence associée à la schizophrénie avec la remédiation cognitive

ObjectivesThe association between schizophrenia and violence represents an important issue in psychiatry. Often highly publicized, violent acts raise the question of their detection, prevention, management and treatment. There is no single, direct and exclusive link between aggressiveness and the underlying psychiatric disorder. On the contrary, the processes underlying this violence are multiple and interlinked. In addition to static and dynamic risk factors, cognitive deficits play an important role in the genesis and maintenance of violent and aggressive behavior. MethodsUsing recent data from the international literature and the main databases, we first clarify the role played by cognitive deficits in the violence of patients with schizophrenia. We then evaluate the place of psychosocial interventions such as cognitive remediation and social cognitive training in managing the violent and aggressive behavior of these patients. ResultsExecutive functions and working memory are the most studied neurocognitive functions in the field of violence in schizophrenia. Impulsivity, lack of cognitive flexibility, lack of adaptation and inhibition of automatic motor responses, and altered anger regulation may explain this relationship. Three main components of social cognition are associated with violent behaviors in schizophrenia: (1) the recognition of facial emotions through the inoperability of systems of “emotional monitoring”, violent inhibition and recognition of informative facial zones; (2) the theory of the mind through the erroneous interpretation of the intentions of others; (3) the attributional style through the preferentially aggressive over interpretation of social situations and weak capacities of introspection. Overall, cognitive biases inhibit response in a socially acceptable manner and increase the risk of responding impulsively and aggressively to a stressful or provocative situation. In this context, we studied the place held by psychosocial interventions in the management of the violent and aggressive behaviors of these patients. Various cognitive remediation programs have shown their feasibility in people with schizophrenia and neurocognitive deficits with a history of violence as well as their effectiveness in reducing violence, mainly by reducing impulsivity. Similarly, specific programs dedicated to social cognitive training such as Social Cognition and Interaction Training (SCIT), Reasoning and Rehabilitation Mental Health Program (R&R2 MHP) and Metacognitive Training (MCT) have shown their positive impact on the control and reduction of global aggressive attitudes and on the numbers of physical and verbal aggressive incidents in schizophrenia. The improvement of social cognition would be achieved through the amendment of interpersonal relationships and social functioning. These interventions are effective at different stages of disease progression, in patients with varied profiles, on violent attitudes in general and on the number of verbal and physical attacks, whether for in-patients or out-patients. Beneficial effects can last up to 12months after termination of the study program. The interest of these interventions is preventive if the subject never entered in a violent register or curative in case of a personal history of violence. This type of care can be considered from a symptomatic point of view by limiting downstream the heavy consequences of such acts, but also etiologically by acting on one of the causes of violent behavior. Compliance with the eligibility criteria, carrying out a prior functional analysis and confirmation of the major impulsive part of the patient's violence are prerequisites for the use of these programs. Similarly, the early introduction of such therapies, their repetition over time and the integration of the patient into a comprehensive process of psychosocial rehabilitation will ensure the best chance of success. ConclusionsSome cognitive impairments appear to have their place in the genesis, progression and maintenance of violent acts of individuals with schizophrenia. Their management thus opens new therapeutic perspectives such as cognitive remediation, still rarely used in this aim, to complement the action of the traditional care tools. However, further therapeutic trials are needed before considering cognitive remediation and social cognitive training as central care modalities in the therapeutic control of violence in schizophrenia.

Modeling a Shallow Rock Tunnel Using Terrestrial Laser Scanning and Discrete Fracture Networks

Discontinuity mapping and analysis are extremely important for modeling shallow tunnels constructed in fractured rock masses. However, the limited exposure and variability of rock face orientation in tunnels must be taken into account. In this paper, an automatic method is proposed to generate discrete fracture networks (DFNs) using terrestrial laser scanner (TLS) geological mapping and to continuously calculate the volumetric intensities (P32) along a tunnel. The number of fractures intersecting rectangular sampling planes with different orientations, fitted in tunnel sections of finite lengths, is used as the program termination criteria to create multiple DFNs and to calculate the mean P32. All traces and orientations from three discontinuity sets of the Monte Seco tunnel (Vitoria Minas Railway) were mapped and the present method applied to obtain the continuous variation in P32 along the tunnel. A practical approach to creating single and continuous DFNs (for each discontinuity set), considering the P32 variations, is also presented, and the results are validated by comparing the trace intensities (P21) from the TLS mapping and DFNs generated. Three examples of 3DEC block models generated from different sections of the tunnel are shown, including the ground surface and the bedrock topographies. The results indicate that the proposed method is a practical and powerful tool for modeling fractured rock masses of uncovered tunnels. It is also promising for application during tunnel construction when TLS mapping is a daily task (for as-built tunnel controls), and the complete geological mapping (traces and orientations) is available.

Efficacy of a multi-component psychosocial intervention program for caregivers of persons living with neurocognitive disorders, Alexandria, Egypt: A randomized controlled trial.

Background:Unlike other chronic diseases, dementia caregiving is associated with enormous psychological burden, which stresses the need for caregivers-directed psychosocial interventions. Aim: This randomized controlled trial (RCT) was conducted to evaluate the short-term efficacy of a multi-component psychosocial intervention program for informal caregivers of persons with neurocognitive disorders in Alexandria, Egypt.Methods:Informal caregivers (120) were randomly assigned into intervention and control groups. The intervention group (60) participated in a multi-component program of 8 sessions, including psycho-education, group cognitive-behavioral therapy, and group social support. Program primary outcomes were assessed after program termination (post-1), and three months later (post-2). Measured outcomes included caregivers' knowledge, depression and anxiety symptoms, and perceived burden.Results:Caregivers' depression, anxiety, and perceived burden demonstrated significant drop at post-1, and post-2 compared to the control group (P< 0.001). The intervention group showed significant negative absolute change on depression, anxiety, and perceived burden measures, while on the dementia-related knowledge measure, a significant positive absolute change was found at post-1, and post-2 (P< 0.001), in comparison to controls. All outcome measures recorded a large effect size; the highest was for knowledge (partial eta2 = 0.98), and the least was for perceived burden (partial eta2 = 0.71).Conclusion:A multi-component psychosocial intervention for caregivers of persons with neurocognitive disorders demonstrated a short-term efficacy in reducing their burden, depression, and anxiety, as well as improving caregivers' knowledge. However, further research is needed to investigate long-term efficacy of the intervention.

Пронаталистская демографическая политика глазами населения: десять лет спустя

Pronatalist demographic policy in Russia has started in 2007 and now, 10 years after, there is an acute discussion about its further development. The aim of this article is the analysis of the attitude to the pronatalist policy in Russia in general and also to the definite demographic measures. Another goal of the study is to trace the changes in this attitude since 2011 up to the year 2017. The research is based on the data of the survey “Person, Family, Society”-2017. The survey includes in-depth interviews, the results of which are also included in the study. In order to make temporal comparative analysis authors use data of the survey “Parents and children, men and women”-2011, which is part of the international Generations & Gender Programme. The results of both surveys demonstrate high support of the pronatalist measures in Russia. Two thirds of respondents vote for prolongation of the maternal capital program in the unaltered way, others would like to change it into benefits to poor families with children. The second option is more favorable for people with low level of income and education, and residents of rural areas. The study also reveals the dissatisfaction with the health system of parents with small children. Respondents with more than 2 children evaluate the impact of the maternal capital program on their reproductive intentions higher than respondents with fewer children. The positive attitude of the population to the measures of the current pronatalist policy and especially maternal capital as well as the current socio-economic and demographic situation are unfavorable for the termination of the maternal capital program.

"Don't Teach These Plays!": Latina/o Theatre and the Termination of the Tucson Unified School District's Mexican American Studies Program

"Don't Teach These Plays!":Latina/o Theatre and the Termination of the Tucson Unified School District's Mexican American Studies Program Jimmy A. Noriega (bio) The second decade of the twenty-first century began with a series of milestones that signaled a major turning point for Latina/o theatre. In April 2010 Luis Valdez's classic Zoot Suit opened at the Compañía Nacional de Teatro in Mexico City, and the Association of Theatre Journalists honored it as the Best Mexican Musical of the year, making it the first time a non-Mexican play was given the award. John Leguizamo performed his one-man show Ghetto Klown at the Lyceum Theatre on Broadway from March to July 2011; it received Drama Desk and Outer Critics Circle awards and was eventually filmed for television. In 2012 Quiara Alegría Hudes became the first Latina to receive the Pulitzer Prize for Drama for her play Water by the Spoonful, which went on to become one of the most produced plays of the 2013–14 season. And in May 2012 eight theatre practitioners met in Washington, D.C., to set in motion the process that would lead to the founding of the Latina/o Theatre Commons, which in fall 2013 would hold its historic National Convening in Boston. It was during this period of noteworthy progress and acclaim that a number of Latina/o playwrights were thrust into the national spotlight in a way they did not anticipate. In January 2012 several books were removed from the classrooms of Tucson, Arizona, as a result of Arizona House Bill 2281. This legislation, passed in May 2010, targeted ethnic studies in the schools and led to the dismantling of the Tucson Unified School District's (TUSD) Mexican American Studies (MAS) program. The elimination led to what many called a "banning" of the books that were previously part of the curriculum and classrooms of the district. Among the many such titles, three books were collections of Latina/o theatrical texts: Zoot Suit and Other Plays (1992); Culture Clash: Life, Death, and Revolutionary Comedy (1998); and Puro Teatro: A Latina Anthology (2000). Puro Teatro, edited by Alberto Sandoval-Sánchez and Nancy Saporta Sternbach, consists of five full-length plays, three one-acts, four texts for performance pieces, and a series of testimonios by an array of Latinas working in the theatre. In their introduction to the collection, the editors assert that "[a]ccessibility to these plays and circulation of them in a variety of different venues will benefit communities, students at all levels of their education and their teachers, actors and actresses looking for material, and theaters at the community, regional, and national level" (xiv). Despite its well-intended aims, the anthology—created for social, cultural, and artistic empowerment—was deemed unsuitable and outlawed in Tucson classrooms. The legislation not only prevented accessibility and circulation of these works in the schools, but also emphasized the precarity of Latina cultural expression in the US today. Although perhaps it was not intentional, more Latina-written plays were censored than those by Latino men. This ban on Latina theatrical texts is even more egregious, given the lack of production opportunities for female playwrights in general (Evans). In many ways the banning of these plays in the Tucson schools became an extension of the erasure that Latinas face in season calendars and production budgets in theatres across the nation. [End Page 37] With this in mind, this essay aims to explore the ways in which HB 2281 further marginalized Latina/o theatrical texts in the US educational landscape. In the first part I will briefly outline the history and debate surrounding the legislation, focusing on the methods used to target Latina/o theory, pedagogy, and cultural production. The remainder of the essay discusses two banned texts from the Puro Teatro anthology as case studies by which to teach and understand the events: Silviana Wood's And Where Was Pancho Villa When You Really Needed Him? (2000), and Elaine Romero's The Fat-Free Chicana and the Snow Cap Queen (1995). Although both plays predate the events of HB 2281, they speak to a history of racist pedagogy and acts...

How Sustainable are Benefits from Extension for Smallholder Farmers? Evidence from a Randomized Phase-Out of the BRAC Program in Uganda

Many development programs are based on short-term interventions, either because of external funding constraints or because it is assumed that impacts persist post program termination (sustainability). Using a novel randomized phase-out research method, we provide experimental tests of the effects of program phase-out in the context of a large-scale agricultural input subsidy and extension program operated by the NGO BRAC to increase the use of improved seed varieties and basic farming practices among women smallholders in Uganda. We find that while supply of improved seeds through local, BRAC trained women declined, demand does not diminish, and farmers shift purchases from BRAC to market sources, indicating a persistent learning effect. We also find no evidence of declines in the practice of improved and less costly cultivation techniques taught by the program. These results have implications for both efficient program design and for models of technology adoption.

Recent developments in the science of proarrhythmic cardiac safety of new drugs.

Following marketing withdrawals of several drugs due to proarrhythmic safety concerns, the ICH Guidelines S7B and E14 were released in 2005 and have guided pre-approval cardiac safety assessments in multiple regulatory jurisdictions. While this S7B-E14 paradigm has successfully prevented drugs with unanticipated potential for inducing Torsades de Pointes entering the market, it has unintentionally resulted in the termination of development programs for potentially important compounds that could have exhibited a favourable benefit-risk balance. The Comprehensive In vitro Proarrhythmia Assay paradigm is currently attracting considerable attention as a solution to this problem. While much evaluative work in this new paradigm will be conducted in the non-clinical domain, human electrocardiographic assessments will remain an important component of the overall investigational strategy, possibly being conducted in Phase I trials employing exposure-response modelling. This article reviews recent developments in proarrhythmic cardiac safety assessments of new drugs, their rationales, and current limitations.

Rely-Guarantee Termination and Cost Analyses of Loops with Concurrent Interleavings

By following a rely-guarantee style of reasoning, we present novel termination and cost analyses for concurrent programs that, in order to prove termination or infer the cost of a considered loop: (1) infer the termination/cost of each loop as if it were a sequential one, imposing assertions on how shared-data is modified concurrently; and then (2) prove that these assertions cannot be violated infinitely many times and, for cost analysis, infer how many times they are violated. At the core of the analysis, we use a may-happen-in-parallel analysis to restrict the set of program points whose execution can interleave. Interestingly, the same kind of reasoning can be applied to prove termination and infer upper bounds on the number of iterations of loops with concurrent interleavings. To the best of our knowledge, this is the first method to automatically bound the cost of such kind of loops. We have implemented our analysis for an actor-based language, and showed its accuracy and efficiency by applying it on several typical applications for concurrent programs and on an industrial case study.

Distal Limb Patterning Requires Modulation of cis-Regulatory Activities by HOX13

SUMMARYThe combinatorial expression of Hox genes along the body axes is a major determinant of cell fate and plays a pivotal role in generating the animal body plan. Loss of HOXA13 and HOXD13 transcription factors (HOX13) leads to digit agenesis in mice, but how HOX13 proteins regulate transcriptional outcomes and confer identity to the distal-most limb cells has remained elusive. Here, we report on the genome-wide profiling of HOXA13 and HOXD13 in vivo binding and changes of the transcriptome and chromatin state in the transition from the early to the late-distal limb developmental program, as well as in Hoxa13−/−; Hoxd13−/−limbs. Our results show that proper termination of the early limb transcriptional program and activation of the late-distal limb program are coordinated by the dual action of HOX13 on cis-regulatory modules.