Concurrent constraint programming with process mobility

We propose an extension of concurrent constraint programming with primitives for process migration within a hierarchical network, and we study its semantics. To this purpose, we first investigate a "pure " paradigm for process migration, namely a paradigm where the only actions are those dealing with transmissions of processes. Our goal is to give a structural definition of the semantics of migration; namely, we want to describe the behaviour of the system, during the transmission of a process, in terms of the behaviour of the components. We achieve this goal by using a labeled transition system where the effects of sending a process, and requesting a process, are modeled by symmetric rules (similar to handshaking-rules for synchronous communication) between the two partner nodes in the network. Next, we extend our paradigm with the primitives of concurrent constraint programming, and we show how to enrich the semantics to cope with the notions of environment and constraint store. Finally, we show how the operational semantics can be used to define an interpreter for the basic calculus.

Results of ASERTAA, a randomized prospective crossover pharmacogenetic study of immediate-release versus extended-release tacrolimus in African American kidney transplant recipients

BACKGROUND: Differences in tacrolimus dosing across ancestries is partly attributable to polymorphisms in CYP3A5 genes that encode tacrolimus-metabolizing cytochrome P450 3A5 enzymes. The CYP3A5*1 allele, preponderant in African Americans, is associated with rapid metabolism, subtherapeutic concentrations, and higher dose requirements for tacrolimus, all contributing to worse outcomes. Little is known about the relationship between CYP3A5 genotype and the tacrolimus pharmacokinetic area under the curve (AUC) profile in African Americans or whether pharmacogenetic differences exist between conventional twice-daily, rapidly absorbed, immediate-release tacrolimus (IR-Tac) and once-daily extended-release tacrolimus (LifeCycle Pharma Tac [LCPT]) with a delayed absorption profile. STUDY DESIGN: Randomized prospective crossover study. SETTING & PARTICIPANTS: 50 African American maintenance kidney recipients on stable IR-Tac dosing. INTERVENTION: Recipients were randomly assigned to continue IR-Tac on days 1 to 7 and then switch to LCPT on day 8 or receive LCPT on days 1 to 7 and then switch to IR-Tac on day 8. The LCPT dose was 85% of the IR-Tac total daily dose. OUTCOMES: Tacrolimus 24-hour AUC (AUC MEASUREMENTS: CYP3A5 genotype, 24-hour tacrolimus pharmacokinetic profiles. RESULTS: ∼80% of participants carried the CYP3A5*1 allele (CYP3A5 expressers). There were no significant differences in AUC LIMITATIONS: This was primarily a pharmacogenetic study rather than an efficacy study; the follow-up period was too short to capture clinical outcomes. CONCLUSIONS: Achieving therapeutic tacrolimus trough concentrations with IR-Tac in most African Americans results in significantly higher peak concentrations, potentially magnifying the risk for toxicity and adverse outcomes. This pharmacogenetic effect is attenuated by delayed tacrolimus absorption with LCPT. TRIAL REGISTRATION: Registered at ClinicalTrials.gov, with study number NCT01962922

Evaluating the Reliability of Human Brain White Matter Tractometry

Published Nov 17, 2021The validity of research results depends on the reliability of analysis methods. In recent years, there have been concerns about the validity of research that uses diffusion-weighted MRI (dMRI) to understand human brain white matter connections in vivo, in part based on the reliability of analysis methods used in this field. We defined and assessed three dimensions of reliability in dMRI-based tractometry, an analysis technique that assesses the physical properties of white matter pathways: (1) reproducibility, (2) test-retest reliability, and (3) robustness. To facilitate reproducibility, we provide software that automates tractometry (https://yeatmanlab.github.io/pyAFQ). In measurements from the Human Connectome Project, as well as clinical-grade measurements, we find that tractometry has high test-retest reliability that is comparable to most standardized clinical assessment tools. We find that tractometry is also robust: showing high reliability with different choices of analysis algorithms. Taken together, our results suggest that tractometry is a reliable approach to analysis of white matter connections. The overall approach taken here both demonstrates the specific trustworthiness of tractometry analysis and outlines what researchers can do to establish the reliability of computational analysis pipelines in neuroimaging.This work was supported through grant 1RF1MH121868- 01 from the National Institute of Mental Health/the BRAIN Initiative, through grant 5R01EB027585-02 to Eleftherios Garyfallidis (Indiana University) from the National Institute of Biomedical Imaging and Bioengineering, through Azure Cloud Computing Credits for Research & Teaching provided through the University of Washington’s Research Computing unit and the University of Washington eScience Institute, and NICHD R21HD092771 to Jason D. Yeatma

Assessment of viral and non-viral gene transfer into adult rat brains using HSV-1, calcium phosphate and PEI-based methods

CNS gene transfer could provide new approaches to the modelling of neurodegenerative diseases and devising potential therapies. One such disorder is Parkinson’s disease (PD), in which dysfunction of several different metabolic processes has been implicated. Here we review the literature on gene transfer systems based on herpes simplex virus type 1 (HSV-1) and non-viral polyethyleneimine (PEI) and calcium phosphate nanoparticle methods. We also assess the usefulness of various CNS gene delivery methods and present some of our own data to exemplify such usefulness. Our data result from vectors stereotaxically introduced to the substantia nigra (SN) of adult rats and evaluated 1 week and/or 1 month post injection using histochemical methods to assess recombinant ß-galactosidase enzyme activity. Gene transfer using PEI or calcium phosphate-mediated transfections was observed for both methods and PEI was comparable to that of HSV-1 amplicon. Our data show that the amplicon delivery was markedly increased when packaged with a helper virus and was similar to the expression profile achieved with a full-size replication-defective HSV-1 recombinant (8117/43). We also examine whether PEI or HSV-1 amplicon-mediated gene transfer could facilitate assessment of the biological effects induced by a dominant negative FGF receptor-1 mutant to model the reduced FGF signalling thought to occur in Parkinson’s disease

The complex light-curve of the afterglow of GRB071010A

We present and discuss the results of an extensive observational campaign devoted to GRB071010A, a long-duration gamma-ray burst detected by the Swift satellite. This event was followed for almost a month in the optical/near-infrared (NIR) with various telescopes starting from about 2min after the high-energy event. Swift-XRT observations started only later at about 0.4d. The light-curve evolution allows us to single out an initial rising phase with a maximum at about 7min, possibly the afterglow onset in the context of the standard fireball model, which is then followed by a smooth decay interrupted by a sharp rebrightening at about 0.6d. The rebrightening was visible in both the optical/NIR and X-rays and can be interpreted as an episode of discrete energy injection, although various alternatives are possible. A steepening of the afterglow light curve is recorded at about 1d. The entire evolution of the optical/NIR afterglow is consistent with being achromatic. This could be one of the few identified GRB afterglows with an achromatic break in the X-ray through the optical/NIR bands. Polarimetry was also obtained at about 1d, just after the rebrightening and almost coincident with the steepening. This provided a fairly tight upper limit of 0.9% for the polarized-flux fraction.Comment: 11 pages, 3 figures, MNRAS, in pres

Mortality and Cardiovascular Disease among Older Live Kidney Donors

Over the past two decades, live kidney donation by older individuals (≥55 years) has become more common. Given the strong associations of older age with cardiovascular disease (CVD), nephrectomy could make older donors vulnerable to death and cardiovascular events. We performed a cohort study among older live kidney donors who were matched to healthy older individuals in the Health and Retirement Study. The primary outcome was mortality ascertained through national death registries. Secondary outcomes ascertained among pairs with Medicare coverage included death or CVD ascertained through Medicare claims data. During the period from 1996 to 2006, there were 5717 older donors in the United States. We matched 3368 donors 1:1 to older healthy nondonors. Among donors and matched pairs, the mean age was 59 years; 41% were male and 7% were black race. In median follow-up of 7.8 years, mortality was not different between donors and matched pairs (p = 0.21). Among donors with Medicare, the combined outcome of death/CVD (p = 0.70) was also not different between donors and nondonors. In summary, carefully selected older kidney donors do not face a higher risk of death or CVD. These findings should be provided to older individuals considering live kidney donation

The complex light-curve of the afterglow of GRB071010A

We present and discuss the results of an extensive observational campaign devoted to GRB071010A, a long-duration gamma-ray burst detected by the Swift satellite. This event was followed for almost a month in the optical/near-infrared (NIR) with various telescopes starting from about 2min after the high-energy event. Swift-XRT observations started only later at about 0.4d. The light-curve evolution allows us to single out an initial rising phase with a maximum at about 7min, possibly the afterglow onset in the context of the standard fireball model, which is then followed by a smooth decay interrupted by a sharp rebrightening at about 0.6d. The rebrightening was visible in both the optical/NIR and X-rays and can be interpreted as an episode of discrete energy injection, although various alternatives are possible. A steepening of the afterglow light curve is recorded at about 1d. The entire evolution of the optical/NIR afterglow is consistent with being achromatic. This could be one of the few identified GRB afterglows with an achromatic break in the X-ray through the optical/NIR bands. Polarimetry was also obtained at about 1d, just after the rebrightening and almost coincident with the steepening. This provided a fairly tight upper limit of 0.9% for the polarized-flux fraction.Comment: 11 pages, 3 figures, MNRAS, in pres

Search for the Decay τ−→4pi−3π+(π0)ντ\tau^{-}\to 4pi^{-}3\pi^{+}(\pi^{0})\nu_{\tau}

We have searched for the decay of the tau lepton into seven charged particles and zero or one pi0. The data used in the search were collected with the CLEO II detector at the Cornell Electron Storage Ring (CESR) and correspond to an integrated luminosity of 4.61 fb^(-1). No evidence for a signal is found. Assuming all the charged particles are pions, we set an upper limit on the branching fraction, B(tau- -> 4pi- 3pi+ (pi0) nu_tau) < 2.4 x 10^(-6) at the 90% confidence level. This limit represents a significant improvement over the previous limit.Comment: 9 page postscript file, postscript file also available through http://w4.lns.cornell.edu/public/CLN