The Kuramoto model in complex networks

181 pages, 48 figures. In Press, Accepted Manuscript, Physics Reports 2015 Acknowledgments We are indebted with B. Sonnenschein, E. R. dos Santos, P. Schultz, C. Grabow, M. Ha and C. Choi for insightful and helpful discussions. T.P. acknowledges FAPESP (No. 2012/22160-7 and No. 2015/02486-3) and IRTG 1740. P.J. thanks founding from the China Scholarship Council (CSC). F.A.R. acknowledges CNPq (Grant No. 305940/2010-4) and FAPESP (Grants No. 2011/50761-2 and No. 2013/26416-9) for financial support. J.K. would like to acknowledge IRTG 1740 (DFG and FAPESP).Peer reviewedPreprin

VapC Toxins from Mycobacterium tuberculosis Are Ribonucleases that Differentially Inhibit Growth and Are Neutralized by Cognate VapB Antitoxins

The chromosome of Mycobacterium tuberculosis (Mtb) encodes forty seven toxin-antitoxin modules belonging to the VapBC family. The role of these modules in the physiology of Mtb and the function(s) served by their expansion are unknown. We investigated ten vapBC modules from Mtb and the single vapBC from M. smegmatis. Of the Mtb vapCs assessed, only Rv0549c, Rv0595c, Rv2549c and Rv2829c were toxic when expressed from a tetracycline-regulated promoter in M. smegmatis. The same genes displayed toxicity when conditionally expressed in Mtb. Toxicity of Rv2549c in M. smegmatis correlated with the level of protein expressed, suggesting that the VapC level must exceed a threshold for toxicity to be observed. In addition, the level of Rv2456 protein induced in M. smegmatis was markedly lower than Rv2549c, which may account for the lack of toxicity of this and other VapCs scored as ‘non-toxic’. The growth inhibitory effects of toxic VapCs were neutralized by expression of the cognate VapB as part of a vapBC operon or from a different chromosomal locus, while that of non-cognate antitoxins did not. These results demonstrated a specificity of interaction between VapCs and their cognate VapBs, a finding corroborated by yeast two-hybrid analyses. Deletion of selected vapC or vapBC genes did not affect mycobacterial growth in vitro, but rendered the organisms more susceptible to growth inhibition following toxic VapC expression. However, toxicity of ‘non-toxic’ VapCs was not unveiled in deletion mutant strains, even when the mutation eliminated the corresponding cognate VapB, presumably due to insufficient levels of VapC protein. Together with the ribonuclease (RNase) activity demonstrated for Rv0065 and Rv0617 – VapC proteins with similarity to Rv0549c and Rv3320c, respectively – these results suggest that the VapBC family potentially provides an abundant source of RNase activity in Mtb, which may profoundly impact the physiology of the organism

36-month clinical outcomes of patients with venous thromboembolism:GARFIELD-VTE

Background: Venous thromboembolism (VTE), encompassing both deep vein thrombosis (DVT) and pulmonary embolism (PE), is a leading cause of morbidity and mortality worldwide. Methods: GARFIELD-VTE is a prospective, non-interventional observational study of real-world treatment practices. We aimed to capture the 36-month clinical outcomes of 10,679 patients with objectively confirmed VTE enrolled between May 2014 and January 2017 from 415 sites in 28 countries. Findings: A total of 6582 (61.6 %) patients had DVT alone, 4097 (38.4 %) had PE ± DVT. At baseline, 98.1 % of patients received anticoagulation (AC) with or without other modalities of therapy. The proportion of patients on AC therapy decreased over time: 87.6 % at 3 months, 73.0 % at 6 months, 54.2 % at 12 months and 42.0 % at 36 months. At 12-months follow-up, the incidences (95 % confidence interval [CI]) of all-cause mortality, recurrent VTE and major bleeding were 6.5 (7.0–8.1), 5.4 (4.9–5.9) and 2.7 (2.4–3.0) per 100 person-years, respectively. At 36-months, these decreased to 4.4 (4.2–4.7), 3.5 (3.2–2.7) and 1.4 (1.3–1.6) per 100 person-years, respectively. Over 36-months, the rate of all-cause mortality and major bleeds were highest in patients treated with parenteral therapy (PAR) versus oral anti-coagulants (OAC) and no OAC, and the rate of recurrent VTE was highest in patients on no OAC versus those on PAR and OAC. The most frequent cause of death after 36-month follow-up was cancer (n = 565, 48.6 %), followed by cardiac (n = 94, 8.1 %), and VTE (n = 38, 3.2 %). Most recurrent VTE events were DVT alone (n = 564, 63.3 %), with the remainder PE, (n = 236, 27.3 %), or PE in combination with DVT (n = 63, 7.3 %). Interpretation: GARFIELD-VTE provides a global perspective of anticoagulation patterns and highlights the accumulation of events within the first 12 months after diagnosis. These findings may help identify treatment gaps for subsequent interventions to improve patient outcomes in this patient population.</p

Opicapone as adjunct to levodopa in treated Parkinson\u27s disease without motor complications: A randomized clinical trial

\ua9 2024 The Author(s). European Journal of Neurology published by John Wiley &amp; Sons Ltd on behalf of European Academy of Neurology.Background: Catechol-O-methyl transferase (COMT) inhibitors are routinely used to manage motor fluctuations in Parkinson\u27s disease (PD). We assessed the effect of opicapone on motor symptom severity in levodopa-treated patients without motor complications. Methods: This was a randomized, double-blind, 24-week, placebo-controlled study of opicapone 50 mg as adjunct to levodopa (NCT04978597). Levodopa-treated patients without motor complications were randomized to 24 weeks of double-blind treatment with adjunct opicapone 50 mg or matching placebo. The primary efficacy endpoint was the mean change from baseline to week 24 in Movement Disorder Society-Unified Parkinson\u27s Disease Rating Scale Part III (MDS-UPDRS-III) total score. Results: A total of 355 patients were randomized (opicapone 50 mg n = 177, placebo n = 178) and 322 (91%) completed the double-blind period. The adjusted mean [95% CI] change from baseline to week 24 in MDS-UPDRS-III subscore was −6.5 [−7.9, −5.2] in the opicapone group versus −4.3 [−5.7, 3.0] in the placebo group resulting in a significant difference of −2.2 [−3.9, −0.5] favoring opicapone (p = 0.010). There was no difference in the incidence of patients who developed motor complications (5.5% with opicapone vs. 9.8% with placebo) and the incidence of adverse events considered related to study medication was similar between groups (opicapone 10.2% vs. placebo 13.5%). Conclusions: Treatment with once-daily adjunct opicapone was well tolerated, improved motor severity, and did not induce the development of motor complications. These results support the clinical usefulness of opicapone in the management of PD patients without motor complications

Potential of a geothermal doublet on the Wiśniowa structure (outer Carpathians, Poland), based on dynamic modelling

Wynikiem naftowych prac poszukiwawczych w obszarze depresji strzyżowskiej (płaszczowina skolska) było odwiercenie w 1991 roku otworu Wiśniowa-1. Na głębokości 3793 m uzyskano przypływ wody o mineralizacji 15,15 g/dm3, wydajności 180 m3/h i temperaturze 85°C. Poziom zbiornikowy stanowią zeszczelinowane piaskowce warstw spaskich (kreda dolna) z anormalnie wysokim ciśnieniem złożowym. Skonstruowany trójwymiarowy model porowatości efektywnej, przepuszczalności szczelinowej i temperatury, poddano symulacjom z użyciem symulatora Eclipse (Schlumberger). W modelowaniach wykorzystano istniejące otwory wiertnicze:Wiśniowa-1, Szufnarowa-1 i Nawsie-1, oraz zaprojektowany otwór zrzutowy (INJ1), oddalony o 1km na NW od otworu produkcyjnego. Przeprowadzone modelowania dynamiczne pozwoliły na wyliczenie optymalnej pracy dubletu geotermalnego, gdzie wielkość produkcji otworem Wioeniowa-1 przy jednoczesnym zrzucie tej samej objętości otworem zatłaczającym (INJ1) wyliczono na poziomie 640 m3/dobę. Dla modelu wyjściowego zapewnia ona ciągłość eksploatacji jedynie przy kilku stopniach spadku temperatury produkowanej wody przez okres niemal 50 lat. Wykonano analizę czułości systemu ze względu na różne scenariusze modelu parametrycznego (model pesymistyczny, model wyjściowy i model optymistyczny).Well Wiśniowa-1 was drilled in 1991 in the Strzyżów Depression (Skole Nappe) for petroleum exploration. At a depth of 3793 m, low-mineralized water was encountered. The water exhibits temperature of 85°C and inflow rate of 180 m3/h. Water reservoir consists of fractured sandstones belonging to the Spas Beds (Lower Cretaceous) and displays anomalously high pressures. A three-dimensional model of effective porosity, fracture permeability and temperature was constructed and subjected to dynamic simulations using Eclipse simulator (Schlumberger). In modelling process, three existing wells (Wiśniowa-1, Szufnarowa-1, Nawsie-1) and the new designed well (INJ1), located about 1 km to the NWof the production well, were used. The modelling results have shown that at the level of 640 m3/day of water production and injection the geothermal doublet will work most efficiently. For the base case model, this would ensure a continuous operation with only a few degree drop in the temperature of the produced water over a period of almost 50 years. We have also made sensitivity analysis of the system for various scenarios of the parametric model (low case, base case and high case)

The Analysis of Trajectory of 122 mm Rotary Missile under the Influence of Interferences

W artykule przedstawiono analizę wpływu zakłóceń na tor lotu 122 mm niekierowanego wirującego pocisku rakietowego. Efektem działania zakłóceń na torze lotu niekierowanego pocisku rakietowego jest jego rozrzut w postaci uchylenia w donośności i uchylenia bocznego. Wpływ gazodynamicznego mimośrodu ciągu i wiatru na tor lotu wirującego pocisku rakietowego przeanalizowano przy wykorzystaniu symulacji komputerowej. Wyniki analiz i badań przedstawiono w postaci wykresów i tabel.In this paper the analysis of influence on trajectory of 122 mm unguided rotary missile has been presented. Results of interferences that act during the flight of unguided missile are his dispersion in the form of range and lateral deflections. The influence of deviation of thrust has been researched by means of computer simulation. Results of analysis and research work have been presented in the form of graphs and charts

Experimental studies of pulsed rocket engine for gas-dynamic steering of flying objects

Idea gazodynamicznego sterowania lub korygowania trajektorii lotu obiektów kosmicznych znalazła zastosowanie również w pociskach rakietowych [1]. Zasada gazodynamicznej korekcji toru lotu polega na krótkotrwałym przyłożeniu siły określonej wartości, wywołanej ukierunkowanym strumieniem gazów, w odpowiedni punkt na powierzchni korygowanego obiektu. Do wytworzenia takiej siły może być użyty małogabarytowy silnik rakietowy na paliwo stałe. W artykule przedstawiono wyniki wyznaczonych doświadczalnie charakterystyk balistycznych rakietowego silnika korekcyjnego. Przedstawiono także wyniki badań wpływu oddziaływania takiego silnika na dynamikę makiety pocisku, uzyskane na stanowisku badawczym opracowanym i wykonanym specjalnie do realizacji tego zagadnienia.Gas-dynamic steering or correcting of flight trajectory of cosmic objects founds application in the rocket missiles as well. The principle of gas-dynamic correction of flight path consists on a short duration application of a defined force, created by a gas stream of an appropriate directed on a defined point of the corrected object. The force can be produced by a rocket engine of small overall dimension operating on a solid fuel. The results of the experimentally determined ballistic characteristics of the rocket correcting engine are presented. The results of studies on the impact of the interaction of this kind of engine on the dynamics of the missile dummy are also presented. The stand has been elaborated and realized in order to perform the mentioned studies

Rapidity and transverse momentum structure in Pi+ and K+ collisions with Al and Au nuclei at 250 GeV/c

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