Experimental Tests of Discrete Strengthened Elements of Machine-Building Structures

Computer simulation and bench tests of components and full-scale structures of internal combustion engine are performed in order to evaluate discrete and continual strengthening technology. The contact pressure distributions, friction coefficients, wear, roughness and hardness of the contacting surfaces of the tested machine parts were determined. The numerical characteristics that determine the effectiveness of such combined strengthening method are established. Conceptual fundamentals of discrete continual strengthening have been developed. Positive effects in the “load – contact – friction – wear” chain were found due to the proposed strengthening method. The positive effect of the coordination of micro and macroscale processes and states of loaded parts, which are strengthened by the discrete and continuous method, is also established. It is confirmed that the entire set of tribo-mechanical characteristics is improved with such strengthening, in contrast to traditional methods, an application of which results in improvement in some characteristics at the cost of the others

Galanin and galanin receptors in embryonic stem cells: Accidental or essential?

Galanin is a peptide consisting of 29 (mouse) or 30 (human) amino acids that was recently identified in undifferentiated mouse embryonic stem (ES) cells through transcriptome analyses. Galanin is known to have important modulatory roles in neuronal cells, but it is currently unclear what biological role, if any, galanin has in stem cells. Here we show that galanin transcripts represent a distinguishing molecular feature of embryonic stem cell lines and that all three galanin receptors subtypes are expressed in mouse ES cells (Gal-R2 > Gal-R3 ≫ Gal-R1). Based on cell culture data, galanin in a dose-dependent manner appears to regulate growth characteristics of ES cells, at least partially, through interactions with leukemia inhibitory factor (LIF), a cytokine implicated in the self-renewal process of ES cells. The regulation of ES cell growth can therefore be added to the list of biological processes regulated by this peptide.link_to_subscribed_fulltex

Linkage of pluripotent stem cell-associated transcripts to regulatory gene networks

These journal issues entitled: Stem Cells, Tissue Regeneration and Repair (free suppl.)Knowledge of the transcriptional circuitry responsible for pluripotentiality and self-renewal in embryonic stem cells is tantamount to understanding early mammalian development and a prerequisite to determining their therapeutic potential. Various techniques have employed genomics to identify transcripts that were abundant in stem cells, in an attempt to define the molecular basis of 'stemness'. In this study, we have extended traditional genomic analyses to identify cis-elements that might be implicated in the control of embryonic stem cell-restricted gene promoters. The strategy relied on the generation of a problem-specific list from serial analysis of gene expression profiles and subsequent promoter analyses to identify frameworks of multiple cis-elements conserved in space and orientation among genes from the problem-specific list. Subsequent experimental data suggest that 2 novel transcription factors, B-Myb and Maz, predicted from these models, are implicated either in the maintenance of the undifferentiated stem cell state or in early steps of differentiation. Copyright © 2008 S. Karger AG.link_to_OA_fulltex

Fugetaxis: active movement of leukocytes away from a chemokinetic agent

Chemotaxis or active movement of leukocytes toward a stimulus has been shown to occur in response to chemokinetic agents including members of the recently identified superfamily of proteins called chemokines. Leukocyte chemotaxis is thought to play a central role in a wide range of physiological and pathological processes including the homing of immune cells to lymph nodes and the accumulation of these cells at sites of tissue injury and pathogen or antigen challenge. We have recently identified a novel biological mechanism, which we term fugetaxis (fugere, to flee from; taxis, movement) or chemorepulsion, which describes the active movement of leukocytes away from chemokinetic agents including the chemokine, stromal cell derived factor-1, and the HIV-1 envelope protein, gp120. In this article, we review the evidence that supports the observation that leukocyte fugetaxis occurs in vitro and in vivo and suggestions that this novel mechanism can be exploited to modulate the immune response. We propose that leukocyte fugetaxis plays a critical role in both physiological and pathological processes in which leukocytes are either excluded or actively repelled from specific sites in vivo including thymic emigration, the establishment of immune privileged sites and immune evasion by viruses and cancer. We believe that current data support the thesis that a greater understanding of leukocyte fugetaxis will lead to the development of novel therapeutic approaches for a wide range of human diseases

A Comparative Effectiveness Meta-Analysis of Drugs for the Prophylaxis of Migraine Headache

OBJECTIVE: To compare the effectiveness and side effects of migraine prophylactic medications. DESIGN: We performed a network meta-analysis. Data were extracted independently in duplicate and quality was assessed using both the JADAD and Cochrane Risk of Bias instruments. Data were pooled and network meta-analysis performed using random effects models. DATA SOURCES: PUBMED, EMBASE, Cochrane Trial Registry, bibliography of retrieved articles through 18 May 2014. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included randomized controlled trials of adults with migraine headaches of at least 4 weeks in duration. RESULTS: Placebo controlled trials included alpha blockers (n = 9), angiotensin converting enzyme inhibitors (n = 3), angiotensin receptor blockers (n = 3), anticonvulsants (n = 32), beta-blockers (n = 39), calcium channel blockers (n = 12), flunarizine (n = 7), serotonin reuptake inhibitors (n = 6), serotonin norepinephrine reuptake inhibitors (n = 1) serotonin agonists (n = 9) and tricyclic antidepressants (n = 11). In addition there were 53 trials comparing different drugs. Drugs with at least 3 trials that were more effective than placebo for episodic migraines included amitriptyline (SMD: -1.2, 95% CI: -1.7 to -0.82), -flunarizine (-1.1 headaches/month (ha/month), 95% CI: -1.6 to -0.67), fluoxetine (SMD: -0.57, 95% CI: -0.97 to -0.17), metoprolol (-0.94 ha/month, 95% CI: -1.4 to -0.46), pizotifen (-0.43 ha/month, 95% CI: -0.6 to -0.21), propranolol (-1.3 ha/month, 95% CI: -2.0 to -0.62), topiramate (-1.1 ha/month, 95% CI: -1.9 to -0.73) and valproate (-1.5 ha/month, 95% CI: -2.1 to -0.8). Several effective drugs with less than 3 trials included: 3 ace inhibitors (enalapril, lisinopril, captopril), two angiotensin receptor blockers (candesartan, telmisartan), two anticonvulsants (lamotrigine, levetiracetam), and several beta-blockers (atenolol, bisoprolol, timolol). Network meta-analysis found amitriptyline to be better than several other medications including candesartan, fluoxetine, propranolol, topiramate and valproate and no different than atenolol, flunarizine, clomipramine or metoprolol. CONCLUSION: Several drugs good evidence supporting efficacy. There is weak evidence supporting amitriptyline\u27s superiority over some drugs. Selection of prophylactic medication should be tailored according to patient preferences, characteristics and side effect profiles