Influence of central venous pressure upon sinus node responses to arterial baroreflex stimulation in man

Measurements were made of sinus node responses to arterial baroreceptor stimulation with phenylephrine injection or neck suction, before and during changes of central venous pressure provoked by lower body negative pressure or leg and lower truck elevation. Variations of central venous pressure between 1.1 and 9.0 mm Hg did not influence arterial baroreflex mediated bradycardia. Baroreflex sinus node responses were augmented by intravenous propranolol, but the level of responses after propranolol was comparable during the control state, lower body negative pressure, and leg and trunk elevation. Sinus node responses to very brief baroreceptor stimuli applied during the transitions of central venous pressure also were comparable in the three states. The authors conclude that physiological variations of central venous pressure do not influence sinus node responses to arterial baroreceptor stimulation in man

{SETH}-Based Lower Bounds for Subset Sum and Bicriteria Path

Subset-Sum and k-SAT are two of the most extensively studied problems in computer science, and conjectures about their hardness are among the cornerstones of fine-grained complexity. One of the most intriguing open problems in this area is to base the hardness of one of these problems on the other. Our main result is a tight reduction from k-SAT to Subset-Sum on dense instances, proving that Bellman's 1962 pseudo-polynomial $O^{*}(T)$-time algorithm for Subset-Sum on $n$ numbers and target $T$ cannot be improved to time $T^{1-\varepsilon}\cdot 2^{o(n)}$ for any $\varepsilon>0$, unless the Strong Exponential Time Hypothesis (SETH) fails. This is one of the strongest known connections between any two of the core problems of fine-grained complexity. As a corollary, we prove a "Direct-OR" theorem for Subset-Sum under SETH, offering a new tool for proving conditional lower bounds: It is now possible to assume that deciding whether one out of $N$ given instances of Subset-Sum is a YES instance requires time $(N T)^{1-o(1)}$. As an application of this corollary, we prove a tight SETH-based lower bound for the classical Bicriteria s,t-Path problem, which is extensively studied in Operations Research. We separate its complexity from that of Subset-Sum: On graphs with $m$ edges and edge lengths bounded by $L$, we show that the $O(Lm)$ pseudo-polynomial time algorithm by Joksch from 1966 cannot be improved to $\tilde{O}(L+m)$, in contrast to a recent improvement for Subset Sum (Bringmann, SODA 2017)

The Roots of Salafist Terror: An Analysis of the Growth of Violence in the Middle East from 1991-2010

Though originally ascertaining that both blowback and interest sharing were the primary causal factors giving rise to Salafist terrorism from 1991-2010, the project found evidence supporting the idea that the two concepts are related instead. Blowback, specifically from “direct interventions,” increases interest sharing by providing Salafist terrorist groups with the means to expand their objectives to make their fight seem like that of ordinary citizens thereby swelling their numbers. It can also lead to the unification of various groups who previously may have had no common goals. In turn these intertwining phenomenon lead to more attacks and damage done by Salafist terror groups. Blowback can particularly rear itself if the intervening state utilizes a level of force that is neither light nor heavy and falls within a middle ground of troop numbers. The intervening states in the Middle East pursued that avenue, which ultimately led to the increase in Salafist terrorism

Shiga toxin 1 elicits diverse biologic responses in mesangial cells

Shiga toxin 1 elicits diverse biologic responses in mesangial cells.BackgroundShiga toxin 1 (Stx1) is a causative agent in hemolytic uremic syndrome (HUS). Its receptor, the glycosphingolipid globotriaosylceramide (Gb3), is expressed on cultured human endothelial and mesangial cells. Mesangial cell injury in HUS ranges from mild cellular edema to severe mesangiolysis and eventual glomerulosclerosis. We hypothesized that, in addition to endothelial cells, mesangial cells are targets of Stx1.MethodsHuman mesangial cells were exposed to Stx1. Protein synthesis was measured using [35S]-methionine/cysteine. Cell viability was measured as the lysosomal uptake of Neutral Red. Monocyte chemotactic peptide (MCP-1) mRNA and protein were analyzed by Northern blotting and ELISA.ResultsStx1 (0.25 to 2500ng/ml) resulted in a dose-dependent inhibition of protein synthesis. This effect of Stx1 was potentiated by preincubation of the cells with interleukin-1α (IL-1α; 2ng/ml) or tumor necrosis-α (TNF-α; 500 U/ml). Stx1 had little effect on mesangial cell viability during the first 24hours of exposure to Stx1. However, prolonged incubation with Stx1 for 48 and 72hours resulted in a 68% and 80% decrease in cell-viability, respectively. Stx1 elicited a dose and time dependent increase in the levels of MCP-1 mRNA, an effect that was potentiated by preincubation with IL-1α.ConclusionThese data indicate that mesangial cells are susceptible to the effects of Stx1 in vitro. Stx1 exerts a spectrum of biologic effects on mesangial cells ranging from activation of chemokine genes to a lethal toxic injury. Immunoinflammatory cytokines potentiate the effects of Stx1. Thus, glomerular pathology in HUS may also result from a direct effect of Stx1 on mesangial cells

Simulations of Ductile Fracture in an Idealized Ship Grounding Scenario Using Phenomenological Damage and Cohesive Zone Models

Two complementary simulation methodologies for ductile fracture in large sheet metal components are presented and evaluated in this paper. The first approach is based on the phenomenological dilatational plasticity-damage model developed by Woelke and Abboud [68], which accounts for pressure-dependent volumetric damage growth through a scalar damage variable. The damage function represents phenomenologically micromechanical changes the material undergoes during the process of necking. Secondly, the cohesive zone model with an opening mode traction-separation law is employed to simulate the same ductile fracture problems accounting for significant variation of the multiaxial stress state along the crack path. Both methods are examined as to their capabilities to reproduce and predict the outcome of large scale experimental fracture tests of welded and unwelded ductile plates subjected to large-scale penetration, simulating an idealized ship grounding (Alsos and Amdahl, [1, 2]). The results of the current study indicate that, with appropriate calibration, both approaches can be successfully employed to simulate ductile fracture in structural components under multiaxial stress. The advantages and shortcomings of each approach is discussed from the point of view of post-test numerical investigation as well as its predictive capabilities as an engineering tool.Engineering and Applied Science

Sunlight exposure is just one of the factors which influence Vitamin D status

© The Royal Society of Chemistry and Owner Societies. Studies on the determinants of vitamin D status have tended to concentrate on input-exposure to ultraviolet B radiation and the limited sources in food. Yet, vitamin D status, determined by circulating concentrations of 25-hydroxyvitamin D (25(OH)D), can vary quite markedly in groups of people with apparently similar inputs of vitamin D. There are small effects of polymorphisms in the genes for key proteins involved in vitamin D production and metabolism, including 7-dehydrocholesterol reductase, which converts 7-dehydrocholesterol, the precursor of vitamin D, to cholesterol, CYP2R1, the main 25-hydroxylase of vitamin D, GC, coding for the vitamin D binding protein which transports 25(OH)D and other metabolites in blood and CYP24A1, which 24-hydroxylates both 25(OH)D and the hormone, 1,25-dihydroxyvitamin D. 25(OH)D has a highly variable half-life in blood. There is evidence that the half-life of 25(OH)D is affected by calcium intake and some therapeutic agents. Fat tissue seems to serve as a sink for the parent vitamin D, which is released mainly when there are reductions in adiposity. Some evidence is presented to support the proposal that skeletal muscle provides a substantial site of sequestration of 25(OH)D, protecting this metabolite from degradation by the liver, which may help to explain why exercise, not just outdoors, is usually associated with better vitamin D status

Distributed Edge Connectivity in Sublinear Time

We present the first sublinear-time algorithm for a distributed message-passing network sto compute its edge connectivity $\lambda$ exactly in the CONGEST model, as long as there are no parallel edges. Our algorithm takes $\tilde O(n^{1-1/353}D^{1/353}+n^{1-1/706})$ time to compute $\lambda$ and a cut of cardinality $\lambda$ with high probability, where $n$ and $D$ are the number of nodes and the diameter of the network, respectively, and $\tilde O$ hides polylogarithmic factors. This running time is sublinear in $n$ (i.e. $\tilde O(n^{1-\epsilon})$) whenever $D$ is. Previous sublinear-time distributed algorithms can solve this problem either (i) exactly only when $\lambda=O(n^{1/8-\epsilon})$ [Thurimella PODC'95; Pritchard, Thurimella, ACM Trans. Algorithms'11; Nanongkai, Su, DISC'14] or (ii) approximately [Ghaffari, Kuhn, DISC'13; Nanongkai, Su, DISC'14]. To achieve this we develop and combine several new techniques. First, we design the first distributed algorithm that can compute a $k$-edge connectivity certificate for any $k=O(n^{1-\epsilon})$ in time $\tilde O(\sqrt{nk}+D)$. Second, we show that by combining the recent distributed expander decomposition technique of [Chang, Pettie, Zhang, SODA'19] with techniques from the sequential deterministic edge connectivity algorithm of [Kawarabayashi, Thorup, STOC'15], we can decompose the network into a sublinear number of clusters with small average diameter and without any mincut separating a cluster (except the `trivial' ones). Finally, by extending the tree packing technique from [Karger STOC'96], we can find the minimum cut in time proportional to the number of components. As a byproduct of this technique, we obtain an $\tilde O(n)$-time algorithm for computing exact minimum cut for weighted graphs.Comment: Accepted at 51st ACM Symposium on Theory of Computing (STOC 2019

1,25-Dihydroxycholecalciferol (calcitriol) modifies uptake and release of 25-hydroxycholecalciferol in skeletal muscle cells in culture

© 2017 Elsevier Ltd The major circulating metabolite of vitamin D 3 , 25-hydroxycholecalciferol [25(OH)D], has a remarkably long half-life in blood for a (seco)steroid. Data from our studies and others are consistent with the hypothesis that there is a role for skeletal muscle in the maintenance of vitamin D status. Muscle cells internalise vitamin D-binding protein (DBP) from the circulation by means of a megalin/cubilin plasma membrane transport mechanism. The internalised DBP molecules then bind to actin and thus provide an intracellular array of high affinity binding sites for its specific ligand, 25(OH)D. There is evidence that the residence time for DBP in muscle cells is short and that it undergoes proteolytic degradation, releasing bound 25(OH)D. The processes of internalisation of DBP and its intracellular residence time, bound to actin, appear to be regulated. To explore whether 1,25-dihydroxycholecalciferol (calcitriol) has any effect on this process, cell cultures of myotubes and primary skeletal muscle fibers were incubated in a medium containing 10 −10 M calcitriol but with no added DBP. After 3 h pre-incubation with calcitriol, the net uptake of 25(OH)D by these calcitriol-treated cells over a further 4 h was significantly greater than that in vehicle-treated control cells. This was accompanied by a significant increase in intracellular DBP protein. However, after 16 h of pre-incubation with calcitriol, the muscle cells showed a significantly depressed ability to accumulate 25(OH)D compared to control cells over a further 4 or 16 hours. These effects of pre-incubation with calcitriol were abolished in fibers from VDR-knockout mice. The effect was also abolished by the addition of 4,4\u27-diisothiocyano-2,2\u27-stilbenedisulfonic acid (DIDS), which inhibits chloride channel opening. Incubation of C2 myotubes with calcitriol also significantly reduced retention of previously accumulated 25(OH)D after 4 or 8 h. It is concluded from these in vitro studies that calcitriol can modify the DBP-dependent uptake and release of 25(OH)D by skeletal muscle cells in a manner that suggests some inducible change in the function of these cells