Influence of AgNO3 on somatic embryo induction and development in Manchurian ash (Fraxinus mandshurica Rupr.)

In this present study, we explored the effects of silver nitrate (AgNO3) on somatic embryo induction and the development from immature zygotic embryos in Manchurian ash (Fraxinus mandshurica Rupr.). AgNO3 played a minor role on in vitro embryo induction frequency and in the number of somatic embryos per explant. However, 1 mg L–1 AgNO3 enhanced synchronization and significantly inhibited abnormal somatic embryo formation suggesting that AgNO3 might serve an important function in controlling the development of somatic embryos in Manchurian ash. Our results provided foundation for a future more efficient somatic embryogenesis and regeneration protocol.Key words: Abnormality, Fraxinus mandshurica, silver nitrate, somatic embryogenesis, synchronization

Towards Physical Hybrid Systems

Some hybrid systems models are unsafe for mathematically correct but physically unrealistic reasons. For example, mathematical models can classify a system as being unsafe on a set that is too small to have physical importance. In particular, differences in measure zero sets in models of cyber-physical systems (CPS) have significant mathematical impact on the mathematical safety of these models even though differences on measure zero sets have no tangible physical effect in a real system. We develop the concept of "physical hybrid systems" (PHS) to help reunite mathematical models with physical reality. We modify a hybrid systems logic (differential temporal dynamic logic) by adding a first-class operator to elide distinctions on measure zero sets of time within CPS models. This approach facilitates modeling since it admits the verification of a wider class of models, including some physically realistic models that would otherwise be classified as mathematically unsafe. We also develop a proof calculus to help with the verification of PHS.Comment: CADE 201

Are old running shoes detrimental to your feet? A pedobarographic study

<p>Abstract</p> <p>Background</p> <p>Footwear characteristics have been implicated in fatigue and foot pain. The recommended time for changing running shoes is every 500 miles. The aim of our study was to assess and compare plantar peak pressures and pressure time integrals in new and old running shoes.</p> <p>Findings</p> <p>This was a prospective study involving 11 healthy female volunteers with no previous foot and ankle problems. New running shoes were provided to the participants. Plantar pressures were measured using the Novel Pedar system while walking with new and participants' personal old running shoes. Plantar pressures were measured in nine areas of the feet. Demographic data, age of old running shoes, Body Mass Index (BMI), peak pressures and pressure-time integral were acquired. The right and left feet were selected at random and assessed separately. Statistical analysis was done using the paired t test to compare measurements between old and new running shoes.</p> <p>The mean peak pressures were higher in new running shoes (330.5 ± 79.6 kiloPascals kPa) when compared to used old running shoes (304 ± 58.1 kPa) (p = 0.01). The pressure-time integral was significantly higher in the new running shoes (110 ± 28.3 kPa s) compared to used old running shoes (100.7 ± 24.0 kPa s) (p = 0.01).</p> <p>Conclusion</p> <p>Plantar pressure measurements in general were higher in new running shoes. This could be due to the lack of flexibility in new running shoes. The risk of injury to the foot and ankle would appear to be higher if running shoes are changed frequently. We recommend breaking into new running shoes slowly using them for mild physical activity.</p

A Pair of Dopamine Neurons Target the D1-Like Dopamine Receptor DopR in the Central Complex to Promote Ethanol-Stimulated Locomotion in Drosophila

Dopamine is a mediator of the stimulant properties of drugs of abuse, including ethanol, in mammals and in the fruit fly Drosophila. The neural substrates for the stimulant actions of ethanol in flies are not known. We show that a subset of dopamine neurons and their targets, through the action of the D1-like dopamine receptor DopR, promote locomotor activation in response to acute ethanol exposure. A bilateral pair of dopaminergic neurons in the fly brain mediates the enhanced locomotor activity induced by ethanol exposure, and promotes locomotion when directly activated. These neurons project to the central complex ellipsoid body, a structure implicated in regulating motor behaviors. Ellipsoid body neurons are required for ethanol-induced locomotor activity and they express DopR. Elimination of DopR blunts the locomotor activating effects of ethanol, and this behavior can be restored by selective expression of DopR in the ellipsoid body. These data tie the activity of defined dopamine neurons to D1-like DopR-expressing neurons to form a neural circuit that governs acute responding to ethanol

Therapeutic DNA vaccine induces broad T cell responses in the gut and sustained protection from viral rebound and AIDS in SIV-infected rhesus macaques.

Immunotherapies that induce durable immune control of chronic HIV infection may eliminate the need for life-long dependence on drugs. We investigated a DNA vaccine formulated with a novel genetic adjuvant that stimulates immune responses in the blood and gut for the ability to improve therapy in rhesus macaques chronically infected with SIV. Using the SIV-macaque model for AIDS, we show that epidermal co-delivery of plasmids expressing SIV Gag, RT, Nef and Env, and the mucosal adjuvant, heat-labile E. coli enterotoxin (LT), during antiretroviral therapy (ART) induced a substantial 2-4-log fold reduction in mean virus burden in both the gut and blood when compared to unvaccinated controls and provided durable protection from viral rebound and disease progression after the drug was discontinued. This effect was associated with significant increases in IFN-γ T cell responses in both the blood and gut and SIV-specific CD8+ T cells with dual TNF-α and cytolytic effector functions in the blood. Importantly, a broader specificity in the T cell response seen in the gut, but not the blood, significantly correlated with a reduction in virus production in mucosal tissues and a lower virus burden in plasma. We conclude that immunizing with vaccines that induce immune responses in mucosal gut tissue could reduce residual viral reservoirs during drug therapy and improve long-term treatment of HIV infection in humans

Low-dose TNF augments fracture healing in normal and osteoporotic bone by up-regulating the innate immune response

The mechanism by which trauma initiates healing remains unclear. Precise understanding of these events may define interventions for accelerating healing that could be translated to the clinical arena. We previously reported that addition of low-dose recombinant human TNF (rhTNF) at the fracture site augmented fracture repair in a murine tibial fracture model. Here, we show that local rhTNF treatment is only effective when administered within 24h of injury, when neutrophils are the major inflammatory cell infiltrate. Systemic administration of anti-TNF impaired fracture healing. Addition of rhTNF enhanced neutrophil recruitment and promoted recruitment of monocytes through CCL2 production. Conversely, depletion of neutrophils or inhibition of the chemokine receptor CCR2 resulted in significantly impaired fracture healing. Fragility, or osteoporotic, fractures represent a major medical problem as they are associated with permanent disability and premature death. Using a murine model of fragility fractures, we found that local rhTNF treatment improved fracture healing during the early phase of repair. If translated clinically, this promotion of fracture healing would reduce the morbidity and mortality associated with delayed patient mobilization

A novel investigation into the application of non-destructive evaluation for vibration assessment and analysis of in-service pipes

Flow induced vibrations that are close to resonance frequencies are a major problem in all oil and gas processing industries, so all piping systems require regular condition monitoring and inspection to assess changes in their dynamic characteristics and structural integrity in order to prevent catastrophic failures. One of the main causes of pipe failure is weak support causing low frequency high amplitude flow-induced vibration. This causes wear and tear, especially near joints due to their dissimilar stiffness resulting in fatigue failure of joints caused by vibration-induced high cyclic stress. Other contributing factors in pipe failure are poor or inadequate design, poor workmanship during installation or maintenance and inadequate or weak and flexible support. These pipes are usually required to work non-stop for 24 hours a day 7 days a week for weeks, months or years at a time. Regular monitoring and in-service dynamic analysis should ensure continuous and safe operation. A novel method of non-destructive testing and evaluation of these pipes, while in service, is proposed in this paper. This technique will enable early detection and identification of the root causes of any impending failure due to excess vibration as a result of cyclic force induced by the flow. The method pinpoints the location of the impending failure prior to condition-based maintenance procedures. The technique relies on the combined application of Operating Deflection Shapes (ODS) analysis and computational mechanics utilizing Finite Element Analysis (FEA), i.e. linear elastic stress analysis. Any structural modification to the pipes and their supports can then be applied virtually and their effects on the system can be analysed. The effect on vibration levels is assessed and verified. The effect of any change in the forces corresponding to changes in the Differential Pressure (DP) at constant flow rate through the pipes can then be estimated. It was concluded that maintaining the differential pressure above some “critical” threshold ensures the pipe operates under the allowable dynamic stress for a theoretically “indefinite” life cycle

Identification of hypoxanthine as a urine marker for non-Hodgkin lymphoma by low-mass-ion profiling

<p>Abstract</p> <p>Background</p> <p>Non-Hodgkin lymphoma (NHL) is a hematologic malignancy for which good diagnostic markers are lacking. Despite continued improvement in our understanding of NHL, efforts to identify diagnostic markers have yielded dismal results. Here, we translated low-mass-ion information in urine samples from patients with NHL into a diagnostic marker.</p> <p>Methods</p> <p>To minimize experimental error, we tested variable parameters before MALDI-TOF analysis of low-mass ions in urine. Urine from 30 controls and 30 NHL patients was analyzed as a training set for NHL prediction. All individual peak areas were normalized to total area up to 1000 m/z. The training set analysis was repeated four times. Low-mass peaks that were not affected by changes in experimental conditions were collected using MarkerView™ software. Human Metabolome Database (HMDB) searches and ESI LC-MS/MS analyses were used to identify low-mass ions that exhibited differential patterns in control and NHL urines. Identified low-mass ions were validated in a blinded fashion in 95 controls and 66 NHL urines to determine their ability to discriminate NHL patients from controls.</p> <p>Results</p> <p>The 30 highest-ranking low-mass-ion peaks were selected from the 60-urine training set, and three low-mass-ion peaks with high intensity were selected for identification. Of these, a 137.08-m/z ion showed lower mass-peak intensity in urines of NHL patients, a result that was validated in a 161-urine blind validation set (95 controls and 66 NHL urines). The 130.08-m/z ion was identified from HMDB searches and ESI LC-MS/MS analyses as hypoxanthine (HX). The HX concentration in urines of NHL patients was significantly decreased (P < 0.001) and was correlated with the mass-peak area of the 137.08-m/z ion. At an HX concentration cutoff of 17.4 μM, sensitivity and specificity were 79.2% and 78.4%, respectively.</p> <p>Conclusions</p> <p>The present study represents a good example of low-mass-ion profiling in the setting of disease screening using urine. This technique can be a powerful non-invasive diagnostic tool with high sensitivity and specificity for NHL screening. Furthermore, HX identified in the study may be a useful single urine marker for NHL screening.</p

De novo mutations in SMCHD1 cause Bosma arhinia microphthalmia syndrome and abrogate nasal development

Bosma arhinia microphthalmia syndrome (BAMS) is an extremely rare and striking condition characterized by complete absence of the nose with or without ocular defects. We report here that missense mutations in the epigenetic regulator SMCHD1 mapping to the extended ATPase domain of the encoded protein cause BAMS in all 14 cases studied. All mutations were de novo where parental DNA was available. Biochemical tests and in vivo assays in Xenopus laevis embryos suggest that these mutations may behave as gain-of-function alleles. This finding is in contrast to the loss-of-function mutations in SMCHD1 that have been associated with facioscapulohumeral muscular dystrophy (FSHD) type 2. Our results establish SMCHD1 as a key player in nasal development and provide biochemical insight into its enzymatic function that may be exploited for development of therapeutics for FSHD