On the Finiteness Problem for Automaton (Semi)groups

This paper addresses a decision problem highlighted by Grigorchuk, Nekrashevich, and Sushchanskii, namely the finiteness problem for automaton (semi)groups. For semigroups, we give an effective sufficient but not necessary condition for finiteness and, for groups, an effective necessary but not sufficient condition. The efficiency of the new criteria is demonstrated by testing all Mealy automata with small stateset and alphabet. Finally, for groups, we provide a necessary and sufficient condition that does not directly lead to a decision procedure

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

BET Bromodomain Inhibitors Which Permit Treg Function Enable a Combinatorial Strategy to Suppress GVHD in Pre-clinical Allogeneic HSCT

A recent approach for limiting production of pro-inflammatory cytokines has been to target bromodomain and extra-terminal (BET) proteins. These epigenetic readers of histone acetylation regulate transcription of genes involved in inflammation, cardiovascular disease, and cancer. Development of BET inhibitors (BETi) has generated enormous interest for their therapeutic potential. Because inflammatory signals and donor T cells promote graft-versus-host disease (GVHD), regulating both pathways could be effective to abrogate this disorder. The objective of the present study was to identify a BETi which did not interfere in vivo with CD4+FoxP3+ regulatory T cell (Treg) expansion and function to utilize together with Tregs following allogeneic hematopoietic stem cell transplantation (aHSCT) to ameliorate GVHD. We have reported that Tregs can be markedly expanded and selectively activated with increased functional capacity by targeting TNFRSF25 and CD25 with TL1A-Ig and low dose IL-2, respectively. Here, mice were treated over 7 days (TL1A-Ig + IL-2) together with BETi. We found that the BETi EP11313 did not decrease frequency/numbers or phenotype of expanded Tregs as well as effector molecules, such as IL-10 and TGF-β. However, BETi JQ1 interfered with Treg expansion and altered subset distribution and phenotype. Notably, in Treg expanded mice, EP11313 diminished tnfa and ifng but not il-2 RNA levels. Remarkably, Treg pSTAT5 expression was not affected by EP11313 supporting the notion that Treg IL-2 signaling remained intact. MHC-mismatched aHSCT (B6 → BALB/c) was performed using in vivo expanded donor Tregs with or without EP11313 short-term treatment in the recipient. Early post-transplant, improvement in the splenic and LN CD4/CD8 ratio along with fewer effector cells and high Treg levels in aHSCT recipients treated with expanded Tregs + EP11313 was detected. Interestingly, this group exhibited a significant diminution of GVHD clinical score with less skin and ocular involvement. Finally, using low numbers of highly purified expanded Tregs, improved clinical GVHD scores were observed in EP11313 treated recipients. In total, we conclude that use of this novel combinatorial strategy can suppress pre-clinical GVHD and posit, in vivo EP11313 treatment might be useful combined with Treg expansion therapy for treatment of diseases involving inflammatory responses

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Spatial interrelations in the placement of woody plants in the middle taiga virgin spruce forests of the upper reaches of the Pechora river

Investigation was carried out in virgin spruce forests in the upper reaches of the Pechora river in middle taiga condition. It was show that spruce forests of different types are characterized by common features of the structure of stands and undergrowth. There was a large variability of trees in volume of stem and undergrowth height. Investigated stands formed a cyclical-multi-age type of age structure. The calculated data obtained using spatial statistics and analyses of point processes were presented. It was found that in spruce forests is expressed regardless of forest types, the group distribution of young individuals of woody plants, which passes into random distribution at more late stages of generation. The spatial relationships between woody plants tested using the cross-correlation function gij(r) show that the undergrowth is attracted to each other at distances of up to 1 meter. There were no spatial interrelation between the undergrowth and the trees. Trees demonstrated independent from each other placement in the area. The density of trees in the area and their phytosocial status are determining the intensity of competitive relations between woody plants in the indigenous spruce communities of the upper reaches of the Pechora River

Biological productivity of the naturally developing and disturbed by windfall lichen pine forest (Komi Republic)

The evidence characterizing the changes in the structural organization and productivity of the post-windfall middle-taiga lichen pine forest growing in the Northern Ural region are presented. It is shown that the stand after the windfall changes from a relatively uneven age with demutative phases of the dynamics of the age structure type to a conditionally uneven age. Pine undergrowth in both the background and disturbed areas is characterized as «healthy». It has been established that with an increase in the height of undergrowth, the number of individuals of the oppressed categories decreases. It was revealed that in naturally developing lichen pine forests of the same age, the morphometric indicators of trees (diameter, height), the reserves of organic matter of phytocenoses are higher than in post-windfall pine stand. A comparative analysis is made of the accumulation of the deposition of plant organic matter of naturally developing and post-windfall pine forests. Ten years after the windfall in the lichen pine forest, 91.8 t ha–1 of phytomass is concentrated, which is 1.4 times less than in the background pine forest. Ten years after the windfall, the bulk of organic matter is concentrated in large tree residues, whereas in naturally growing cenosis in growing trees, the annual production of phytomass of disturbed pine trees is 1.9 times less than in the background, makes up 1019 kg ha–1. The accumulation of phytomass production in the post-windfall lichen pine forest is equivalent to the role of woody plants and plants of ground cover, whereas in the background pine forest the main role is played by woody plants. It was revealed that after windfall there was a decrease in the participation of lichens and an increase in the participation of shrubs and mosses in the formation of ground cover. Annually, the decomposition constants of large wood residues in the windfall were 0.02 year–1