125 research outputs found
DOUBLE AND TRIPLE BOUNCING SPINNING SOCCER BALL
The trajectories of soccer ball penalty kicks that strike one of the goal-posts while rolling along the surface are simulated and analyzed using conservation of linear and angular momenta. The reflected trajectories upon collisions with the goalpost are calculated and used to determine whether double or triple bounces take place. The analysis is iterated for a range of initial launch speeds, angular velocities, and normal and tangential coefficients of restitution of the goalpost-ball collisions. It is observed that double bounces can take place for almost any combination of the above parameters if the soccer ball strikes the appropriate narrow sectors of the first goalpost. The corresponding parameter ranges and impact areas are considerably more restricted for generating triple bounces. The angular velocity and coefficients of restitution are found to significantly influence the occurrence of multiple bounces
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Oral versus intubated feeding and the effect on glycaemic and insulinaemic responses, gastric emptying and satiety
Cephalic phase responses (CPR) are important in early initiation of digestion and maximal absorption of nutrients prior to ingestion. Bypassing CPR has been shown to have consequences on metabolic responses that may influence satiety. The aim of this study was to investigate if using gastric intubation to bypass oro-pharyngeal and oesophageal exposure would reduce CPR including insulin and blood glucose and whether these impact on gastric emptying and satiety. Ten male subjects were tested on 2 occasions, 3-7 days apart after an overnight fast, in randomized order. Subjects were cannulated and intubated with a gastric tube for both tests. For test one, subjects ate 400 ml soup with a spoon and for test two the soup was infused into the stomach at an equivalent rate. Subsequently measurements of glycaemic (GR) and insulinaemic responses (IR) from cannula samples, breath samples for measurement of gastric emptying using the [(13)C] sodium acetate breath test and visual analogue scales (VAS) for satiety were taken over 180 min. There were differences in IR over the first 15 min (Oral: 169.0 +/- 22.1; Gastric 124.1 +/- 18.8; t(9) = 2.67; p = 0.028) but no difference in GR. There were differences in gastric emptying half time (Oral: 85.0 +/- 2.7; Gastric 79.4 +/- 3.3; t(9) = 2.40; p = 0.04) and ascension time (Oral: 68.2 +/- 2.2; Gastric 64.0 +/- 2.2; t(9) = 2.57; p = 0.03) with food taking longer to empty from the stomach on the Oral test day than on the Gastric test day. There was no significant difference in the satiety ratings. This study demonstrated that bypassing oro-pharyngeal and oesophageal exposure decreases the normal physiological CPR with detriment to IR and gastric emptying
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Effect of medium-chain TAG and exercise on satiety, energy intake and energy balance
The present study examined whether the combination of medium-chain triglycerides (MCT) along with exercise suppress energy intake to a greater extent than either intervention alone. Twelve participants consumed a porridge breakfast containing 165 kcal 692.9 kJ of either vegetable or MCT oil on two separate occasions; one followed by rest for 240 min, one followed by rest broken up with 1h of cycling at 65% VO2peak starting at 120 min. At 240 min, participants consumed a buffet lunch to satiation, and recorded their food intake for the rest of the day. Expired air samples (for calculation of energy expenditure (EE)) and subjective ratings of appetite on visual analogue scales were taken every 30 min, and gastric emptying (GE) breath samples were taken every 15 min. There was no effect of either breakfast or exercise condition on energy intake at any time point (P>0.05) or any effect on subjective appetite ratings (P>0.05). Exercise trials resulted in significantly higher EE than resting trials (2960.6 kJ, 95% CI [2528.9, 3392.2]; P<0.001), and MCT increased resting EE over 4h compared to long-chain triglycerides (LCT) (124.8 kJ, 95% CI [13.5, 236.0]; P=0.031). GE was accelerated by exercise, regardless of breakfast, but delayed by MCT in both resting and exercise trials. The results show that exercise causes energy deficits via increased EE without promoting dietary compensation. MCT has no effect on energy intake or satiety, but increases EE under resting conditions. There is no additive effect of MCT and exercise on EE, intake, or appetite ratings
Ibrutinib inhibits SDF1/CXCR4 mediated migration in AML
Pharmacological targeting of BTK using ibrutinib has recently shown encouraging clinical activity in a range of lymphoid malignancies. Recently we reported that ibrutinib inhibits human acute myeloid leukemia (AML) blast proliferation and leukemic cell adhesion to the surrounding bone marrow stroma cells. Here we report that in human AML ibrutinib, in addition, functions to inhibit SDF1/CXCR4-mediated AML migration at concentrations achievable in vivo. It has previously been shown that SDF1/CXCR4-induced migration is dependent on activation of downstream BTK in chronic lymphocytic leukaemia (CLL) and multiple myeloma. Here we show that SDF-1 induces BTK phosphorylation and downstream MAPK signalling in primary AML blast. Furthermore, we show that ibrutinib can inhibit SDF1-induced AKT and MAPK activation. These results reported here provide a molecular mechanistic rationale for clinically evaluating BTK inhibition in AML patients and suggests that in some AML patients the blasts count may initially rise in response to ibrutinib therapy, analgous to similar clinical observations in CLL
The bone marrow microenvironment – Home of the leukemic blasts
Acute Myeloid Leukaemia (AML) is a genetically, biologically and clinically heterogeneous set of diseases, which are characterised by an increased growth of abnormal myeloid progenitor cells within the bone marrow (BM). Ex-vivo AML exhibits a high level of spontaneous apoptosis. Furthermore, relapse for patients achieving remission occurs from minimal residual disease harboured within the BM microenvironment. Taken together, these observations illustrate the importance of the BM microenvironment in sustaining AML. While significant progress has been made elaborating the small-scale genetic mutations and larger-scale chromosomal translocations that contribute to the development of AML and its prognosis in response to treatment, less is understood about the complex microenvironment of the BM, which is known to be a key player in the pathogenesis of the disease. As we look towards future therapies, the consideration that the BM microenvironment is uniquely important as a niche for AML - coupled with the idea that leukaemic blasts are more likely to be genetically unstable and therefore evolve resistance to conventional chemotherapies - make the functions of the non-malignant cells of the BM attractive targets for therapy. In this review, we discuss the microanatomy of the BM and provide an overview of the evidence supporting the role of the BM microenvironment in creating conditions conducive to the survival and proliferation of AML blasts. Ultimately, we examine the therapeutic potential of uncoupling AML from the BM microenvironment
THE ROLE OF ANXIETY IN GOLF PUTTING PERFORMANCE
Anxiety’s influence on performance continues to be one of the main research interests for sport psychologists (Hanin, 2000). It is apparent, though, that there is a lack of empirical research characterising the multi-disciplinary effect of anxiety on sports performance. The current study aimed to ascertain biomechanical (accuracy, movement variability) and psychological (anxiety) markers to determine how anxiety affects golf putting
Rapamycin inhibition of baculovirus recombinant (BVr) ribosomal protein S6 kinase (S6K1) is mediated by an event other than phosphorylation
<p>Abstract</p> <p>Background</p> <p>Ribosomal protein S6 kinase 1(S6K1) is an evolutionary conserved kinase that is activated in response to growth factors and viral stimuli to influence cellular growth and proliferation. This downstream effector of target of rapamycin (TOR) signaling cascade is known to be directly activated by TOR- kinase mediated hydrophobic motif (HM) phosphorylation at Threonine 412 (T412). Selective loss of this phosphorylation by inactivation of TOR kinase or activation/recruitment of a phosphatase has accordingly been implicated in mediating inhibition by rapamycin.</p> <p>Findings</p> <p>We present evidence that baculovirus driven expression of S6K1 in insect cells (Sf9) fails to activate the enzyme and instead renders it modestly active representing 4-6 folds less activity than its fully active mammalian counterpart. Contrary to the contention that viral infection activates TOR signaling pathway, we report that BVr enzyme fails to exhibit putative TOR dependent phosphorylation at the HM and the resultant phosphorylation at the activation loop (AL) of the enzyme, correlating with the level of activity observed. Surprisingly, the BVr enzyme continued to exhibit sensitivity to rapamycin that remained unaffected by mutations compromised for TOR phosphorylation (T412A) or deletions compromised for TOR binding (ΔNH <sub>2-46</sub>/ΔCT<sub>104</sub>).</p> <p>Conclusions</p> <p>These data together with the ability of the BVr enzyme to resist inactivation by phosphatases indicate that inhibition by rapamycin is not mediated by any phosphorylation event in general and TOR dependent phosphorylation in particular.</p
POWER OUTPUT, MUSCLE ACTIVITY, AND FRONTAL AREA OF A CYCLIST IN DIFFERENT CYCLING POSITIONS
Nine cyclists completed three trials of cycling 25W below lactate threshold (LT) with 1) hands on top of the brake hoods (BH); 2) hands below the dropped, curved, portion of the handlebars (DH); and 3) using clip-on triathlon aerobars (AB). Each trial lasted three minutes and was immediately followed by a 20sec maximal sprint during which power output and muscle EMG were measured. Frontal projection area (FPA) differed across all three positions. EMG did not differ between positions during submax or sprint cycling. Submax power output also did not differ, but during the sprint AB was lower
than BH, while DH did not differ from the other conditions. Although power output was 8.1% less while cycling in the AB position than BH, its FPA was 17.4% less, indicating the AB position allows a savings in resistive power greater than that lost in power production
The transcription factor Hey and nuclear lamins specify and maintain cell identity
The inability of differentiated cells to maintain their identity is a hallmark of age-related diseases. We found that the transcription factor Hey supervises the identity of differentiated enterocytes (ECs) in the adult Drosophila midgut. Lineage tracing established that Hey-deficient ECs are unable to maintain their unique nuclear organization and identity. To supervise cell identity, Hey determines the expression of nuclear lamins, switching from a stem-cell lamin configuration to a differentiated lamin configuration. Moreover, continued Hey expression is required to conserve large-scale nuclear organization. During aging, Hey levels decline, and EC identity and gut homeostasis are impaired, including pathological reprograming and compromised gut integrity. These phenotypes are highly similar to those observed upon acute targeting of Hey or perturbation of lamin expression in ECs in young adults. Indeed, aging phenotypes were suppressed by continued expression of Hey in ECs, suggesting that a Hey-lamin network safeguards nuclear organization and differentiated cell identity
Inflammatory Differences in Plaque Erosion and Rupture in Patients With ST‐Segment Elevation Myocardial Infarction
Background: Plaque erosion causes 30% of ST‐segment elevation myocardial infarctions, but the underlying cause is unknown. Inflammatory infiltrates are less abundant in erosion compared with rupture in autopsy studies. We hypothesized that erosion and rupture are associated with significant differences in intracoronary cytokines in vivo. Methods and Results: Forty ST‐segment elevation myocardial infarction patients with <6 hours of chest pain were classified as ruptured fibrous cap (RFC) or intact fibrous cap (IFC) using optical coherence tomography. Plasma samples from the infarct‐related artery and a peripheral artery were analyzed for expression of 102 cytokines using arrays; results were confirmed with ELISA. Thrombectomy samples were analyzed for differential mRNA expression using quantitative real‐time polymerase chain reaction. Twenty‐three lesions were classified as RFC (58%), 15 as IFC (38%), and 2 were undefined (4%). In addition, 12% (12 of 102) of cytokines were differentially expressed in both coronary and peripheral plasma. I‐TAC was preferentially expressed in RFC (significance analysis of microarrays adjusted P<0.001; ELISA IFC 10.2 versus RFC 10.8 log2 pg/mL; P=0.042). IFC was associated with preferential expression of epidermal growth factor (significance analysis of microarrays adjusted P<0.001; ELISA IFC 7.42 versus RFC 6.63 log2 pg/mL, P=0.036) and thrombospondin 1 (significance analysis of microarrays adjusted P=0.03; ELISA IFC 10.4 versus RFC 8.65 log2 ng/mL, P=0.0041). Thrombectomy mRNA showed elevated I‐TAC in RFC (P=0.0007) epidermal growth factor expression in IFC (P=0.0264) but no differences in expression of thrombospondin 1. Conclusions: These results demonstrate differential intracoronary cytokine expression in RFC and IFC. Elevated thrombospondin 1 and epidermal growth factor may play an etiological role in erosion
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