Sequential primed kinases create a damage-responsive phosphodegron on Eco1.

Sister-chromatid cohesion is established during S phase when Eco1 acetylates cohesin. In budding yeast, Eco1 activity falls after S phase due to Cdk1-dependent phosphorylation, which triggers ubiquitination by SCF(Cdc4). We show here that Eco1 degradation requires the sequential actions of Cdk1 and two additional kinases, Cdc7-Dbf4 and the GSK-3 homolog Mck1. These kinases recognize motifs primed by previous phosphorylation, resulting in an ordered sequence of three phosphorylation events on Eco1. Only the latter two phosphorylation sites are spaced correctly to bind Cdc4, resulting in strict discrimination between phosphates added by Cdk1 and by Cdc7. Inhibition of Cdc7 by the DNA damage response prevents Eco1 destruction, allowing establishment of cohesion after S phase. This elaborate regulatory system, involving three independent kinases and stringent substrate selection by a ubiquitin ligase, enables robust control of cohesion establishment during normal growth and after stress

Two types of bone necrosis in the middle triassic pistosaurus longaevus bones: The results of integrated studies

Avascular necrosis, diagnosed on the basis of either a specific pathological modification of the articular surfaces of bone or its radiologic appearance in vertebral centra, has been recognized in many Mesozoic marine reptiles as well as in present-day marine mammals. Its presence in the zoological and paleontologic record is usually associated with decompression syndrome, a disease that affects secondarily aquatic vertebrates that could dive. Bone necrosis can also be caused by infectious processes, but it differs in appearance from decompression syndrome-associated aseptic necrosis. Herein, we report evidence of septic necrosis in the proximal articular surface of the femur of a marine reptile, Pistosaurus longaevus, from the Middle Triassic of Poland and Germany. This is the oldest recognition of septic necrosis associated with septic arthritis in the fossil record so far, and the mineralogical composition of pathologically altered bone is described herein in detail. The occurrence of septic necrosis is contrasted with decompression syndrome-associated avascular necrosis, also described in Pistosaurus longaevus bone from Middle Triassic of Germany

The Effect of absorbing sites on the one-dimensional cellular automaton traffic flow with open boundaries

The effect of the absorbing sites with an absorbing rate $\beta_{0}$, in both one absorbing site (one way out) and two absorbing sites (two ways out) in a road, on the traffic flow phase transition is investigated using numerical simulations in the one-dimensional cellular automaton traffic flow model with open boundaries using parallel dynamics.In the case of one way out, there exist a critical position of the way out $i_{c1}$ below which the current is constant for $\beta_{0}$$<$$\beta_{0c2}$ and decreases when increasing $\beta_{0}$ for $\beta_{0}$$>$$\beta_{0c2}$. When the way out is located at a position greater than $i_{c2}$, the current increases with $\beta_{0}$ for $\beta_{0}$$<$$\beta_{0c1}$ and becomes constant for any value of $\beta_{0}$ greater than $\beta_{0c1}$. While, when the way out is located at any position between $i_{c1}$ and $i_{c2}$ ($i_{c1}$$<$$i_{c2}$), the current increases, for $\beta_{0}$$<$$\beta_{0c1}$, with $\beta_{0}$ and becomes constant for $\beta_{0c1}$$<$$\beta_{0}$$<$$\beta_{0c2}$ and decreases with $\beta_{0}$ for $\beta_{0}$$>$$\beta_{0c2}$. In the later case the density undergoes two successive first order transitions; from high density to maximal current phase at $\beta_{0}$$=$$\beta_{0c1}$ and from intermediate density to the low one at $\beta_{0}$$=$$\beta_{0c2}$. In the case of two ways out located respectively at the positions $i_{1}$ and $i_{2}$, the two successive transitions occur only when the distance $i_{2}$-$i_{1}$ separating the two ways is smaller than a critical distance $d_{c}$. Phase diagrams in the ($\alpha,\beta_{0}$), ($\beta,\beta_{0}$) and ($i_{1},\beta_{0}$) planes are established. It is found that the transitions between Free traffic, Congested traffic and maximal current phase are first order

Toward a High-Frequency Pulsed-Detonation Actuator

This paper describes the continued development of an actuator, energized by pulsed detonations, that provides a pulsed jet suitable for flow control in high-speed applications. A high-speed valve, capable of delivering a pulsed stream of reactants a mixture of H2 and air at rates of up to 1500 pulses per second, has been constructed. The reactants burn in a resonant tube and the products exit the tube as a pulsed jet. High frequency pressure transducers have been used to monitor the pressure fluctuations in the device at various reactant injection frequencies, including both resonant and off-resonant conditions. Pulsed detonations have been demonstrated in the lambda/4 mode of an 8 inch long tube at approx. 600 Hz. The pulsed jet at the exit of the device has been observed using shadowgraph and an infrared camera

Quenched Narrow-Line Laser Cooling of 40Ca to Near the Photon Recoil Limit

We present a cooling method that should be generally applicable to atoms with narrow optical transitions. This technique uses velocity-selective pulses to drive atoms towards a zero-velocity dark state and then quenches the excited state to increase the cooling rate. We demonstrate this technique of quenched narrow-line cooling by reducing the 1-D temperature of a sample of neutral 40Ca atoms. We velocity select and cool with the 1S0(4s2) to 3P1(4s4p) 657 nm intercombination line and quench with the 3P1(4s4p) to 1S0(4s5s) intercombination line at 553 nm, which increases the cooling rate eight-fold. Limited only by available quenching laser power, we have transferred 18 % of the atoms from our initial 2 mK velocity distribution and achieved temperatures as low as 4 microK, corresponding to a vrms of 2.8 cm/s or 2 recoils at 657 nm. This cooling technique, which is closely related to Raman cooling, can be extended to three dimensions.Comment: 5 pages, 4 figures; Submitted to PRA Rapid Communication

Повышение ресурса безопасной эксплуатации промысловых трубопроводов на основе применения неметаллических труб

Основным результатом исследовательской работы является выбор оптимального материала для промыслового трубопровода, который обеспечит защиту от коррозии, а также увеличит ресурс безопасной эксплуатации нефтегазопровода при минимальных затратах материальных ресурсов на строительство и эксплуатацию промыслового нефтегазопроводаThe main result of the research is the selection of the optimal material for the field pipeline, which will provide protection against corrosion, as well as increase the resource for safe operation of the oil and gas pipeline with minimal expenditure of material resources for the construction and operation of the field pipelin

Endovascular baroreflex amplification and the effect on sympathetic nerve activity in patients with resistant hypertension: A proof-of-principle study

Background: First in human studies suggest that endovascular baroreflex amplification (EVBA) lowers blood pressure (BP). To explore potential mechanisms for BP reduction, this study examines the effects of EVBA on muscle sympathetic nerve activity (MSNA) and baroreceptor sensitivity (BRS). // Methods: In a single-center sub-study of the CALM-DIEM study (Controlling And Lowering blood pressure with the MobiusHD—Defining Efficacy Markers), 14 patients with resistant hypertension were treated with EVBA. Microneurography and non-invasive continuous BP measurements were performed at baseline and three months after MobiusHD implantation. The primary outcome was change in MSNA. Secondary outcomes were change in baroreflex sensitivity (BRS), cardiovascular responses to a sympathetic stimulus, BP, heart rate (HR) and heart rate variability (HRV). // Results: The primary endpoint was obtained in 10 of 14 patients enrolled in the sub-study. MSNA burst frequency and burst incidence decreased in 6 of 10 patients: mean change -4.1 bursts/min (95% confidence interval -12.2 to 4.0) and -3.8 bursts/100 heartbeats (-15.2 to 7.7). MSNA spike frequency and spike count decreased in 8 of 10 patients: mean change -2.8 spikes/sec (-7.3 to 1.8) and -3.0 spikes/heartbeat (-6.1 to 0.1). Change in MSNA and BP were not correlated. Office BP decreased by -14/-6 mmHg (-27 to -2/-15 to 3). We observed a trend towards decreased HR (-5 bpm, -10 to 1) and increased total power HRV (623 msec2, 78 to 1168). In contrast, BRS and cardiovascular responses remained unchanged after EVBA. // Conclusions: In this proof-of-principle study, EVBA did not significantly decrease MSNA in patients with resistant hypertension. EVBA did not impair baroreflex function

Postoperative Immune Suppression in Visceral Surgery: Characterisation of an Intestinal Mouse Model

Background: Postoperatively acquired immune dysfunction is associated with a higher mortality rate in case of septic complications. As details of this severe clinical problem are still unknown, animal models are essential to characterise the mechanisms involved. Methods: Mice were laparotomised and the small intestine was pressed smoothly in antegrade direction. For extension of trauma, the intestine was manipulated three times consecutively. Following this, the ex vivo cytokine release of splenocytes was determined. The degree of surgical trauma was analysed by detection of HMGB1 and IL-6 in serum and by neutrophil staining in the muscularis mucosae. Results: We adapted the previously described animal model of intestinal manipulation to provide a model of surgically induced immune dysfunction. Following intestinal manipulation, the mice showed elevated serum levels of HMGB1 and IL-6 and increased infiltration of granulocytes into the muscularis mucosae. Ex vivo cytokine release by splenocytes was suppressed in the postoperative period. The degree of suppression correlated with the extent of surgical trauma. Conclusions: In this study, we describe a surgically induced immune dysfunction animal model, in which a significant surgical trauma is followed by an immune dysfunction. This model may be ideal for the characterisation of the postoperative immune dysfunction syndrome