The Cost of Monitoring Alone

We compare the succinctness of two monitoring systems for properties of infinite traces, namely parallel and regular monitors. Although a parallel monitor can be turned into an equivalent regular monitor, the cost of this transformation is a double-exponential blowup in the syntactic size of the monitors, and a triple-exponential blowup when the goal is a deterministic monitor. We show that these bounds are tight and that they also hold for translations between corresponding fragments of Hennessy-Milner logic with recursion over infinite traces.Comment: 22 page

Handling polymorphic algebraic effects

Algebraic effects and handlers are a powerful abstraction mechanism to represent and implement control effects. In this work, we study their extension with parametric polymorphism that allows abstracting not only expressions but also effects and handlers. Although polymorphism makes it possible to reuse and reason about effect implementations more effectively, it has long been known that a naive combination of polymorphic effects and let-polymorphism breaks type safety. Although type safety can often be gained by restricting let-bound expressions---e.g., by adopting value restriction or weak polymorphism---we propose a complementary approach that restricts handlers instead of let-bound expressions. Our key observation is that, informally speaking, a handler is safe if resumptions from the handler do not interfere with each other. To formalize our idea, we define a call-by-value lambda calculus that supports let-polymorphism and polymorphic algebraic effects and handlers, design a type system that rejects interfering handlers, and prove type safety of our calculus.Comment: Added the errata for the ESOP'19 paper (page 28

Supersymmetric contributions to Bˉs→ϕπ0\bar{B}_s \to \phi \pi^0 and Bˉs→ϕρ0\bar{B}_s \to \phi \rho^0 decays in SCET

We study the decay modes $\bar{B}_s\to \phi \pi^0$ and $\bar{B}_s\to \phi \rho^0$ using Soft Collinear Effective Theory. Within Standard Model and including the error due to the SU(3) breaking effect in the SCET parameters we find that BR $\bar{B}_s\to \phi \pi^0 =7_{-1-2}^{+1+2}\times 10^{-8}$ and BR $\bar{B}_s\to \phi \pi^0=9_{-1-4}^{+1+3}\times 10^{-8}$ corresponding to solution 1 and solution 2 of the SCET parameters respectively.For the decay mode $\bar{B}_s\to \phi \rho^0$, we find that BR $\bar{B}_s\to \phi \rho^0 = 20.2^{+1+9}_{-1-12}\times 10^{-8}$ and BR $\bar{B}_s\to \phi \rho^0 = 34.0^{+1.5 + 15}_{-1.5-22}\times 10^{-8}$ corresponding to solution 1 and solution 2 of the SCET parameters respectively. We extend our study to include supersymmetric models with non-universal A-terms where the dominant contributions arise from diagrams mediated by gluino and chargino exchanges. We show that gluino contributions can not lead to an enhancement of the branching ratios of $\bar{B}_s\to \phi \pi^0$ and $\bar{B}_s\to \phi \rho^0$. In addition, we show that SUSY contributions mediated by chargino exchange can enhance the branching ratio of $\bar{B}_s\to \phi \pi^0$ by about 14% with respect to the SM prediction. For the branching ratio of $\bar{B}_s\to \phi \rho^0$, we find that SUSY contributions can enhance its value by about 1% with respect to the SM prediction.Comment: 25 pages,5 figures, version accepted for publicatio

Protective Role of Interleukin-10 in Ozone-Induced Pulmonary Inflammation

BackgroundThe mechanisms underlying ozone (O3)-induced pulmonary inflammation remain unclear. Interleukin-10 (IL-10) is an anti-inflammatory cytokine that is known to inhibit inflammatory mediators.ObjectivesWe investigated the molecular mechanisms underlying interleuken-10 (IL-10)–mediated attenuation of O3-induced pulmonary inflammation in mice.MethodsIl10-deficient (Il10−/−) and wild-type (Il10+/+) mice were exposed to 0.3 ppm O3 or filtered air for 24, 48, or 72 hr. Immediately after exposure, differential cell counts and total protein (a marker of lung permeability) were assessed from bronchoalveolar lavage fluid (BALF). mRNA and protein levels of cellular mediators were determined from lung homogenates. We also used global mRNA expression analyses of lung tissue with Ingenuity Pathway Analysis to identify patterns of gene expression through which IL-10 modifies O3-induced inflammation.ResultsMean numbers of BALF polymorphonuclear leukocytes (PMNs) were significantly greater in Il10−/− mice than in Il10+/+ mice after exposure to O3 at all time points tested. O3-enhanced nuclear NF-κB translocation was elevated in the lungs of Il10−/− compared with Il10+/+ mice. Gene expression analyses revealed several IL-10–dependent and O3-dependent mediators, including macrophage inflammatory protein 2, cathepsin E, and serum amyloid A3.ConclusionsResults indicate that IL-10 protects against O3-induced pulmonary neutrophilic inflammation and cell proliferation. Moreover, gene expression analyses identified three response pathways and several genetic targets through which IL-10 may modulate the innate and adaptive immune response. These novel mechanisms of protection against the pathogenesis of O3-induced pulmonary inflammation may also provide potential therapeutic targets to protect susceptible individuals

Preliminary Limits on the WIMP-Nucleon Cross Section from the Cryogenic Dark Matter Search (CDMS)

We are conducting an experiment to search for WIMPs, or weakly-interacting massive particles, in the galactic halo using terrestrial detectors. This generic class of hypothetical particles, whose properties are similar to those predicted by extensions of the standard model of particle physics, could comprise the cold component of non-baryonic dark matter. We describe our experiment, which is based on cooled germanium and silicon detectors in a shielded low-background cryostat. The detectors achieve a high degree of background rejection through the simultaneous measurement of the energy in phonons and ionization. Using exposures on the order of one kilogram-day from initial runs of our experiment, we have achieved (preliminary) upper limits on the WIMP-nucleon cross section that are comparable to much longer runs of other experiments.Comment: 5 LaTex pages, 5 eps figs, epsf.sty, espcrc2dsa2.sty. Proceedings of TAUP97, Gran Sasso, Italy, 7-11 Sep 1997, Nucl. Phys. Suppl., A. Bottino, A. di Credico and P. Monacelli (eds.). See also http://cfpa.berkeley.ed

Enhanced cartilage regeneration in MIA/CD-RAP deficient mice

Melanoma inhibitory activity/cartilage-derived retinoic acid-sensitive protein (MIA/CD-RAP) is a small soluble protein secreted from chondrocytes. It was identified as the prototype of a family of extracellular proteins adopting an SH3 domain-like fold. In order to study the consequences of MIA/CD-RAP deficiency in detail we used mice with a targeted gene disruption of MIA/CD-RAP (MIA−/−) and analyzed cartilage organisation and differentiation in in vivo and in vitro models. Cartilage formation and regeneration was determined in models for osteoarthritis and fracture healing in vivo, in addition to in vitro studies using mesenchymal stem cells of MIA−/− mice. Interestingly, our data suggest enhanced chondrocytic regeneration in the MIA−/− mice, modulated by enhanced proliferation and delayed differentiation. Expression analysis of cartilage tissue derived from MIA−/− mice revealed strong downregulation of nuclear RNA-binding protein 54-kDa (p54nrb), a recently described modulator of Sox9 activity. In this study, we present p54nrb as a mediator of MIA/CD-RAP to promote chondrogenesis. Taken together, our data indicate that MIA/CD-RAP is required for differentiation in cartilage potentially by regulating signaling processes during differentiation

Exploring New Physics in the C7-C7' plane

The Wilson coefficient C7 governing the radiative electromagnetic decays of B meson has been calculated to a very high accuracy in the Standard Model, but experimental bounds on either the magnitude or the sign of C7 are often model-dependent. In the present paper, we attempt at constraining both the magnitude and sign of C7 using a systematic approach. We consider already measured observables like the branching ratios of B \rightarrow Xs mu+ mu- and B \rightarrow Xs gamma, the isospin and CP asymmetries in B \rightarrow K* gamma, as well as AFB and FL in B \rightarrow K*l+l-. We also discuss the transverse observable AT2 which, once measured, may help to disentangle some of the scenarios considered. We explore the constraints on C7, C9, C10 as well as their chirality-flipped counterparts. Within our framework, we find that we need to extend the constraints up to 1.6 sigma to allow for the "flipped-sign solution" of C7. The SM solution for C7 exhibits a very mild tension if New Physics is allowed in dipole operators only. We provide semi-numerical expressions for all these observables as functions of the relevant Wilson coefficients at the low scale.Comment: 54 pages, 16 figures, 15 tables. Normalization factor introduced for the integrated AFB and FL in Sec.2.5 (Eq.2.35-2.38). Conclusions unchanged. Not updated in JHE

Examining a staging model for anorexia nervosa: empirical exploration of a four stage model of severity.

Background: An illness staging model for anorexia nervosa (AN) has received increasing attention, but assessing the merits of this concept is dependent on empirically examining a model in clinical samples. Building on preliminary findings regarding the reliability and validity of the Clinician Administered Staging Instrument for Anorexia Nervosa (CASIAN), the current study explores operationalising CASIAN severity scores into stages and assesses their relationship with other clinical features. Method: In women with DSM-IV-R AN and sub-threshold AN (all met AN criteria using DSM 5), receiver operating curve (ROC) analysis (n = 67) assessed the relationship between the sensitivity and specificity of each stage of the CASIAN. Thereafter chi-square and post-hoc adjusted residual analysis provided a preliminary assessment of the validity of the stages comparing the relationship between stage and treatment intensity and AN sub-types, and explored movement between stages after six months (Time 3) in a larger cohort (n = 171). Results: The CASIAN significantly distinguished between milder stages of illness (Stage 1 and 2) versus more severe stages of illness (Stages 3 and 4), and approached statistical significance in distinguishing each of the four stages from one other. CASIAN Stages were significantly associated with treatment modality and primary diagnosis, and CASIAN Stage at Time 1 was significantly associated with Stage at 6 month follow-up. Conclusions: Provisional support is provided for a staging model in AN. Larger studies with longer follow-up of cases are now needed to replicate and extend these findings and evaluate the overall utility of staging as well as optimal staging models

Adding a treatment arm to an ongoing clinical trial: a review of methodology and practice

Incorporating an emerging therapy as a new randomisation arm in a clinical trial that is open to recruitment would be desirable to researchers, regulators and patients to ensure that the trial remains current, new treatments are evaluated as quickly as possible, and the time and cost for determining optimal therapies is minimised. It may take many years to run a clinical trial from concept to reporting within a rapidly changing drug development environment; hence, in order for trials to be most useful to inform policy and practice, it is advantageous for them to be able to adapt to emerging therapeutic developments. This paper reports a comprehensive literature review on methodologies for, and practical examples of, amending an ongoing clinical trial by adding a new treatment arm. Relevant methodological literature describing statistical considerations required when making this specific type of amendment is identified, and the key statistical concepts when planning the addition of a new treatment arm are extracted, assessed and summarised. For completeness, this includes an assessment of statistical recommendations within general adaptive design guidance documents. Examples of confirmatory ongoing trials designed within the frequentist framework that have added an arm in practice are reported; and the details of the amendment are reviewed. An assessment is made as to how well the relevant statistical considerations were addressed in practice, and the related implications. The literature review confirmed that there is currently no clear methodological guidance on this topic, but that guidance would be advantageous to help this efficient design amendment to be used more frequently and appropriately in practice. Eight confirmatory trials were identified to have added a treatment arm, suggesting that trials can benefit from this amendment and that it can be practically feasible; however, the trials were not always able to address the key statistical considerations, often leading to uninterpretable or invalid outcomes. If the statistical concepts identified within this review are considered and addressed during the design of a trial amendment, it is possible to effectively assess a new treatment arm within an ongoing trial without compromising the original trial outcomes

Radiostereometry and new prostheses

Optimising joint reconstruction management in arthritis and bone tumour patient