Measuring Thread Timing to Assess the Feasibility of Early-bird Message Delivery

Early-bird communication is a communication/computation overlap technique that combines fine-grained communication with partitioned communication to improve application run-time. Communication is divided among the compute threads such that each individual thread can initiate transmission of its portion of the data as soon as it is complete rather than waiting for all of the threads. However, the benefit of early-bird communication depends on the completion timing of the individual threads. In this paper, we measure and evaluate the potential overlap, the idle time each thread experiences between finishing their computation and the final thread finishing. These measurements help us understand whether a given application could benefit from early-bird communication. We present our technique for gathering this data and evaluate data collected from three proxy applications: MiniFE, MiniMD, and MiniQMC. To characterize the behavior of these workloads, we study the thread timings at both a macro level, i.e., across all threads across all runs of an application, and a micro level, i.e., within a single process of a single run. We observe that these applications exhibit significantly different behavior. While MiniFE and MiniQMC appear to be well-suited for early-bird communication because of their wider thread distribution and more frequent laggard threads, the behavior of MiniMD may limit its ability to leverage early-bird communication

Translocation or just location? Pseudopodia affect fluorescent signals

The use of fluorescent probes is one of the most powerful techniques for gaining spatial and temporal knowledge of dynamic events within living cells. Localized increases in the signal from cytosolic fluorescent protein constructs, for example, are frequently used as evidence for translocation of proteins to specific sites within the cell. However, differences in optical and geometrical properties of cytoplasm can influence the recorded intensity of the probe signal. Pseudopodia are especially problematic because their cytoplasmic properties can cause abrupt increases in fluorescent signal of both GFP and fluorescein. Investigators should therefore be cautious when interpreting fluorescence changes within a cell, as these can result from either translocation of the probe or changes in the optical properties of the milieu surrounding the probe

Determinants of Leukocyte Margination in Rectangular Microchannels

Microfabrication of polydimethylsiloxane (PDMS) devices has provided a new set of tools for studying fluid dynamics of blood at the scale of real microvessels. However, we are only starting to understand the power and limitations of this technology. To determine the applicability of PDMS microchannels for blood flow analysis, we studied white blood cell (WBC) margination in channels of various geometries and blood compositions. We found that WBCs prefer to marginate downstream of sudden expansions, and that red blood cell (RBC) aggregation facilitates the process. In contrast to tubes, WBC margination was restricted to the sidewalls in our low aspect ratio, pseudo-2D rectangular channels and consequently, margination efficiencies of more than 95% were achieved in a variety of channel geometries. In these pseudo-2D channels blood rheology and cell integrity were preserved over a range of flow rates, with the upper range limited by the shear in the vertical direction. We conclude that, with certain limitations, rectangular PDMS microfluidic channels are useful tools for quantitative studies of blood rheology

Leukocyte trafficking in alveoli and airway passages

Many pulmonary diseases preferentially affect the large airways or the alveoli. Although the mechanisms are often particular to each disease process, site-specific differences in leukocyte trafficking and the regulation of inflammation also occur. Differences in the process of margination, sequestration, adhesion, and migration occur that can be attributed to differences in anatomy, hemodynamics, and the expression of proteins. The large airways are nourished by the bronchial circulation, whereas the pulmonary circulation feeds the distal lung parenchyma. The presence of different cell types in large airways from those in alveoli might contribute to site-specific differences in the molecular regulation of the inflammatory process

A prospective service evaluation of acceptance and commitment therapy for patients with refractory epilepsy

Objective: The aims of this service evaluation were to explore the effectiveness of a psychotherapeutic treatment for patients with epilepsy based on the acceptance and commitment therapy (ACT) approach and to assess whether this treatment is likely to be cost-effective. Method: We conducted an uncontrolled prospective study of consecutive patients with refractory epilepsy referred for outpatient psychological treatment to a single psychotherapist because of emotional difficulties related to their seizure disorder. Participants were referred by consultant neurologists, neuropsychologists, or epilepsy nurses, completed a set of validated self-report questionnaires (Short Form - 12 version 2, Generalized Anxiety Disorder - 7, Neurological Disorders Depression Inventory for Epilepsy, Work and Social Adjustment Scale, and Rosenberg Self-Esteem Scale), and reported their seizure frequency at referral, the end of therapy, and six months posttherapy. Patients received a maximum of 20 sessions of one-to-one psychological treatment supported by a workbook. Cost-effectiveness was estimated based on the calculation of quality-adjusted life year (QALY) gains associated with the intervention. Results: Sixty patients completed the prepsychotherapy and postpsychotherapy questionnaires, among whom 41 also provided six-month follow-up data. Patients received six to 20 sessions of psychotherapy (mean = 11.5, S.D. = 9.6). Psychotherapy was associated with significant medium to large positive effects on depression, anxiety, quality of life, self-esteem, and work and social adjustment ( ps < .001), which were sustained six months after therapy. The mean cost of the psychotherapy was £445.6, and, assuming that benefits were maintained for at least six months after the end of therapy, the cost per QALY was estimated to be £11,140 (€14,119, $18,016; the cost per QALY would be half this amount if the benefits lasted one year). Conclusion: The findings of this pilot study indicate that the described psychotherapeutic intervention may be a cost-effective treatment for patients with epilepsy. The results suggest that a randomized controlled trial of the psychotherapy program is justified

Tyrosine Sulfation of Native Mouse Psgl-1 Is Required for Optimal Leukocyte Rolling on P-Selectin In Vivo

We recently demonstrated that tyrosine sulfation is an important contributor to monocyte recruitment and retention in a mouse model of atherosclerosis. P-selectin glycoprotein ligand-1 (Psgl-1) is tyrosine-sulfated in mouse monocyte/macrophages and its interaction with P-selectin is important in monocyte recruitment in atherosclerosis. However, whether tyrosine sulfation is required for the P-selectin binding function of mouse Psgl-1 is unknown. Here we test the function of native Psgl-1 expressed in leukocytes lacking endogenous tyrosylprotein sulfotransferase (TPST) activity.Psgl-1 function was assessed by examining P-selectin dependent leukocyte rolling in post-capillary venules of C57BL6 mice transplanted with hematopoietic progenitors from wild type (WT → B6) or Tpst1;Tpst2 double knockout mice (Tpst DKO → B6) which lack TPST activity. We observed that rolling flux fractions were lower and leukocyte rolling velocities were higher in Tpst DKO → B6 venules compared to WT → B6 venules. Similar results were observed on immobilized P-selectin in vitro. Finally, Tpst DKO leukocytes bound less P-selectin than wild type leukocytes despite equivalent surface expression of Psgl-1.These findings provide direct and convincing evidence that tyrosine sulfation is required for optimal function of mouse Psgl-1 in vivo and suggests that tyrosine sulfation of Psgl-1 contributes to the development of atherosclerosis

Endothelial Cells Obtained from Patients Affected by Chronic Venous Disease Exhibit a Pro-Inflammatory Phenotype

The inflammatory properties of vein endothelium in relation to chronic venous disease (CVD) have been poorly investigated. Therefore, new insights on the characteristics of large vein endothelium would increase our knowledge of large vessel physiopathology. METHODOLOGY/PRINCIPAL FINDINGS: Surgical specimens of veins were obtained from the tertiary venous network (R3) and/or saphenous vein (SF) of patients affected by CVD and from control individuals. Highly purified venous endothelial cell (VEC) cultures obtained from CVD patients were characterized for morphological, phenotypic and functional properties compared to control VEC. An increase of CD31/PECAM-1, CD146 and ICAM-1 surface levels was documented at flow cytometry in pathological VEC with respect to normal controls. Of note, the strongest expression of these pro-inflammatory markers was observed in VEC obtained from patients with more advanced disease. Similarly, spontaneous cell proliferation and resistance to starvation was higher in pathological than in normal VEC, while the migratory response of VEC showed an opposite trend, being significantly lower in VEC obtained from pathological specimens. In addition, in keeping with a higher baseline transcriptional activity of NF-kB, the release of the pro-inflammatory cytokines osteoprotegerin (OPG) and vascular endothelial growth factor (VEGF) was higher in pathological VEC cultures with respect to control VEC. Interestingly, there was a systemic correlation to these in vitro data, as demonstrated by higher serum OPG and VEGF levels in CVD patients with respect to normal healthy controls. CONCLUSION/SIGNIFICANCE: Taken together, these data indicate that large vein endothelial cells obtained from CVD patients exhibit a pro-inflammatory phenotype, which might significantly contribute to systemic inflammation in CVD patients

Hydrodynamic Regulation of Monocyte Inflammatory Response to an Intracellular Pathogen

Systemic bacterial infections elicit inflammatory response that promotes acute or chronic complications such as sepsis, arthritis or atherosclerosis. Of interest, cells in circulation experience hydrodynamic shear forces, which have been shown to be a potent regulator of cellular function in the vasculature and play an important role in maintaining tissue homeostasis. In this study, we have examined the effect of shear forces due to blood flow in modulating the inflammatory response of cells to infection. Using an in vitro model, we analyzed the effects of physiological levels of shear stress on the inflammatory response of monocytes infected with chlamydia, an intracellular pathogen which causes bronchitis and is implicated in the development of atherosclerosis. We found that chlamydial infection alters the morphology of monocytes and trigger the release of pro-inflammatory cytokines TNF-α, IL-8, IL-1β and IL-6. We also found that the exposure of chlamydia-infected monocytes to short durations of arterial shear stress significantly enhances the secretion of cytokines in a time-dependent manner and the expression of surface adhesion molecule ICAM-1. As a functional consequence, infection and shear stress increased monocyte adhesion to endothelial cells under flow and in the activation and aggregation of platelets. Overall, our study demonstrates that shear stress enhances the inflammatory response of monocytes to infection, suggesting that mechanical forces may contribute to disease pathophysiology. These results provide a novel perspective on our understanding of systemic infection and inflammation

Leukotriene biosynthesis inhibition ameliorates acute lung injury following hemorrhagic shock in rats

<p>Abstract</p> <p>Background</p> <p>Hemorrhagic shock followed by resuscitation is conceived as an insult frequently induces a systemic inflammatory response syndrome and oxidative stress that results in multiple-organ dysfunction syndrome including acute lung injury. MK-886 is a leukotriene biosynthesis inhibitor exerts an anti inflammatory and antioxidant activity.</p> <p>Objectives</p> <p>The objective of present study was to assess the possible protective effect of MK-886 against hemorrhagic shock-induced acute lung injury via interfering with inflammatory and oxidative pathways.</p> <p>Materials and methods</p> <p>Eighteen adult Albino rats were assigned to three groups each containing six rats: group I, sham group, rats underwent all surgical instrumentation but neither hemorrhagic shock nor resuscitation was done; group II, Rats underwent hemorrhagic shock (HS) for 1 hr then resuscitated with Ringer's lactate (1 hr) (induced untreated group, HS); group III, HS + MK-886 (0.6 mg/kg i.p. injection 30 min before the induction of HS, and the same dose was repeated just before reperfusion period). At the end of experiment (2 hr after completion of resuscitation), blood samples were collected for measurement of serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). The trachea was then isolated and bronchoalveolar lavage fluid (BALF) was carried out for measurement of leukotriene B₄(LTB₄), leukotriene C₄(LTC₄) and total protein. The lungs were harvested, excised and the left lung was homogenized for measurement of malondialdehyde (MDA) and reduced glutathione (GSH) and the right lung was fixed in 10% formalin for histological examination.</p> <p>Results</p> <p>MK-886 treatment significantly reduced the total lung injury score compared with the HS group (<it>P </it>< 0.05). MK-886 also significantly decreased serum TNF-α & IL-6; lung MDA; BALF LTB₄, LTC₄& total protein compared with the HS group (<it>P </it>< 0.05). MK-886 treatment significantly prevented the decrease in the lung GSH levels compared with the HS group (<it>P </it>< 0.05).</p> <p>Conclusions</p> <p>The results of the present study reveal that MK-886 may ameliorate lung injury in shocked rats via interfering with inflammatory and oxidative pathways implicating the role of leukotrienes in the pathogenesis of hemorrhagic shock-induced lung inflammation.</p