510 research outputs found
Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector
Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente
Maternal hypoxia decreases capillary supply and increases metabolic inefficiency leading to divergence in myocardial oxygen supply and demand
Maternal hypoxia is associated with a decrease in left ventricular capillary density while cardiac performance is preserved, implying a mismatch between metabolism and diffusive exchange. We hypothesised this requires a switch in substrate metabolism to maximise efficiency of ATP production from limited oxygen availability. Rat pups from pregnant females exposed to hypoxia (FIO2=0.12) at days 10-20 of pregnancy were grown to adulthood and working hearts perfused ex vivo. 14 C-labelled glucose and 3 H-palmitate were provided as substrates and metabolism quantified from recovery of 14CO2 and 3 H2O, respectively. Hearts of male offspring subjected to Maternal Hypoxia showed a 20% decrease in cardiac output (P<0.05), despite recording a 2-fold increase in glucose oxidation (P<0.01) and 2.5-fold increase (P<0.01) in palmitate oxidation. Addition of insulin to Maternal Hypoxic hearts, further increased glucose oxidation (P<0.01) and suppressed palmitate oxidation (P<0.05), suggesting preservation in insulin signalling in the heart. In vitro enzyme activity measurements showed that Maternal Hypoxia increased both total and the active component of cardiac pyruvate dehydrogenase (both P<0.01), although pyruvate dehydrogenase sensitivity to insulin was lost (NS), while citrate synthase activity declined by 30% (P<0.001) and acetyl-CoA carboxylase activity was unchanged by Maternal Hypoxia, indicating realignment of the metabolic machinery to optimise oxygen utilisation. Capillary density was quantified and oxygen diffusion characteristics examined, with calculated capillary domain area increased by 30% (P<0.001). Calculated metabolic efficiency decreased 4-fold (P<0.01) for Maternal Hypoxia hearts. Paradoxically, the decline in citrate synthase activity and increased metabolism suggest that the scope of individual mitochondria had declined, rendering the myocardium potentially more sensitive to metabolic stress. However, decreasing citrate synthase may be essential to preserve local PO2, minimising regions of hypoxia and hence maximising the area of myocardium able to preserve cardiac output following maternal hypoxia
Stochasticity of flow through microcirculation as a regulator of oxygen delivery
<p>Abstract</p> <p>Objective</p> <p>Observations of microcirculation reveal that the blood flow is subject to interruptions and resumptions. Accepting that blood randomly stops and resumes, one can show that the randomness could be a powerful means to match oxygen delivery with oxygen demand.</p> <p>Method</p> <p>The ability of the randomness to regulate oxygen delivery is based on two suppositions: (a) the probability for flow to stop does not depend on the time of uninterrupted flow, thus the number of interruptions of flow follows a Poisson distribution; (b) the probability to resume the flow does not depend on the time for flow being interrupted; meaning that time spent by erythrocytes at rest follows an exponential distribution. Thus the distribution of the time to pass an organ is a compound Poisson distribution. The Laplace transform of the given distribution gives the fraction of oxygen that passes the organ.</p> <p>Result</p> <p>Oxygen delivery to the tissues directly depends on characteristics of the irregularity of the flow through microcirculation.</p> <p>Conclusion</p> <p>By variation of vasomotion activity it is possible to change delivery of oxygen to a tissue by up to 8 times.</p
Revisiting the influence of institutional forces on the written business plan:A replication study
The present paper re-analyzes and extends a study on institutional forces and the written business plan (Honig and Karlsson in J Manag 30(1):29–48, 2004). We attempt to examine to what extent critical decision making is evident in model and variable choice, and whether the implications provided by systematic replication efforts may serve to provide additional and perhaps unrecognized theoretical and/or empirical observations. We find that the key result—formal business planning does not affect performance, does not hold. In fact, we find evidence that formal business planning affects survival but not profitability. The re-analysis also reveals, that institutional antecedents to formal planning appear to be fragile and prone to researcher biases due to different coding and assumptions. Our study underscores the consequences of access to original data and coding material, and to rely upon current methodological explanations for subsequent analyses
Polycyclic Aromatic Hydrocarbon Emission in the Central Regions of Three Seyferts and the Implication for Underlying Feedback Mechanisms
\ua9 2024. The Author(s). Published by the American Astronomical Society.We analyze JWST Mid-Infrared Instrument/Medium Resolution Spectrograph integral field unit observations of three Seyferts from the Galactic Activity, Torus, and Outflow Survey (GATOS) and showcase the intriguing polycyclic aromatic hydrocarbon (PAH) and emission-line characteristics in regions of ∼500 pc scales over or around their active galactic nuclei (AGN). Combing the measurements and model predictions, we find that the central regions containing a high fraction of neutral PAHs with small sizes, e.g., those in ESO137-G034, are in highly heated environments, due to collisional shock heating, with hard and moderately intense radiation fields. Such environments are proposed to result in inhibited growth or preferential erosion of PAHs, decreasing their average size and overall abundance. We additionally find that the central regions containing a high fraction of ionized PAHs with large sizes, e.g., those in MCG-05-23-016, are likely experiencing severe photoionization because of the radiative effects from the radiative shock precursor besides the AGN. The severe photoionization can contribute to the ionization and further destruction of PAHs. Overall, different Seyferts, even different regions in the same galaxy, e.g., those in NGC 3081, can contain PAH populations of different properties. Specifically, Seyferts that exhibit similar PAH characteristics to ESO137-G034 and MCG-05-23-016 also tend to have similar emission-line properties to them, suggesting that the explanations for PAH characteristics of ESO137-G034 and MCG-05-23-016 may also apply generally. These results have promising application in the era of JWST, especially in diagnosing different (i.e., radiative and kinetic) AGN feedback modes
Microstructural analysis of deformation-induced hypoxic damage in skeletal muscle
Deep pressure ulcers are caused by sustained mechanical loading and involve skeletal muscle tissue injury. The exact underlying mechanisms are unclear, and the prevalence is high. Our hypothesis is that the aetiology is dominated by cellular deformation (Bouten et al. in Ann Biomed Eng 29:153–63, 2001; Breuls et al. in Ann Biomed Eng 31:1357–364, 2003; Stekelenburg et al. in J App Physiol 100(6):1946–954, 2006) and deformation-induced ischaemia. The experimental observation that mechanical compression induced a pattern of interspersed healthy and dead cells in skeletal muscle (Stekelenburg et al. in J App Physiol 100(6):1946–954, 2006) strongly suggests to take into account the muscle microstructure in studying damage development. The present paper describes a computational model for deformation-induced hypoxic damage in skeletal muscle tissue. Dead cells stop consuming oxygen and are assumed to decrease in stiffness due to loss of structure. The questions addressed are if these two consequences of cell death influence the development of cell injury in the remaining cells. The results show that weakening of dead cells indeed affects the damage accumulation in other cells. Further, the fact that cells stop consuming oxygen after they have died, delays cell death of other cells
A Concept to Improve Care for People with Dementia
AbstractDementia is one of the severe causes of mortality in elder groups of human population, and the number of dementia patients is expected to increase all over the world. Globally, the cost to take care of patients with the illness is high. Moreover, the lives for dementia patients are commonly impacted by a variety of challenges, for example, in terms of communication, emotional behaviour, confusion and wandering. Therefore, the future aim is to develop a serious games package which can help to slow down the progression of dementia, better life for the patients and their loved one and reduce the use of medications and the cost for the government sectors. In this study, a conceptual model was formed to present the problems the dementia patients and their caregivers are facing, and non-pharmacological approaches are suggested to slow down the progression of dementia-related impairments and behavioural symptoms by using well-structured serious games with personalised data.Abstract
Dementia is one of the severe causes of mortality in elder groups of human population, and the number of dementia patients is expected to increase all over the world. Globally, the cost to take care of patients with the illness is high. Moreover, the lives for dementia patients are commonly impacted by a variety of challenges, for example, in terms of communication, emotional behaviour, confusion and wandering. Therefore, the future aim is to develop a serious games package which can help to slow down the progression of dementia, better life for the patients and their loved one and reduce the use of medications and the cost for the government sectors. In this study, a conceptual model was formed to present the problems the dementia patients and their caregivers are facing, and non-pharmacological approaches are suggested to slow down the progression of dementia-related impairments and behavioural symptoms by using well-structured serious games with personalised data
Overexpression of LASP-1 mediates migration and proliferation of human ovarian cancer cells and influences zyxin localisation
LIM and SH3 protein 1 (LASP-1), initially identified from human breast cancer, is a specific focal adhesion protein involved in cell proliferation and migration. In the present work, we analysed the effect of LASP-1 on biology and function of human ovarian cancer cell line SKOV-3 using small interfering RNA technique (siRNA).Transfection with LASP-1-specific siRNA resulted in a reduced protein level of LASP-1 in SKOV-3 cells. The siRNA-treated cells were arrested in G2/M phase of the cell cycle and proliferation of the tumour cells was suppressed by 60–90% corresponding to around 70% of the cells being transfected successfully as seen by immunofluorescence. Moreover, transfected tumour cells showed a 40% reduced migration. LASP-1 silencing is accompanied by a reduced binding of the LASP-1-binding partner zyxin to focal contacts without changes in actin stress fibre and microtubule organisation or focal adhesion morphology as observed by immunofluorescence. In contrast, silencing of zyxin is not influencing cell migration and had neither influence on LASP-1 expression nor actin cytoskeleton and focal contact morphology suggesting that LASP-1 is necessary and sufficient for recruiting zyxin to focal contacts.The data provide evidence for an essential role of LASP-1 in tumour cell growth and migration, possibly through influencing zyxin localization
Severity dependent distribution of impairments in PSP and CBS: Interactive visualizations
BACKGROUND: Progressive supranuclear palsy (PSP) -Richardson's Syndrome and Corticobasal Syndrome (CBS) are the two classic clinical syndromes associated with underlying four repeat (4R) tau pathology. The PSP Rating Scale is a commonly used assessment in PSP clinical trials; there is an increasing interest in designing combined 4R tauopathy clinical trials involving both CBS and PSP. OBJECTIVES: To determine contributions of each domain of the PSP Rating Scale to overall severity and characterize the probable sequence of clinical progression of PSP as compared to CBS. METHODS: Multicenter clinical trial and natural history study data were analyzed from 545 patients with PSP and 49 with CBS. Proportional odds models were applied to model normalized cross-sectional PSP Rating Scale, estimating the probability that a patient would experience impairment in each domain using the PSP Rating Scale total score as the index of overall disease severity. RESULTS: The earliest symptom domain to demonstrate impairment in PSP patients was most likely to be Ocular Motor, followed jointly by Gait/Midline and Daily Activities, then Limb Motor and Mentation, and finally Bulbar. For CBS, Limb Motor manifested first and ocular showed less probability of impairment throughout the disease spectrum. An online tool to visualize predicted disease progression was developed to predict relative disability on each subscale per overall disease severity. CONCLUSION: The PSP Rating Scale captures disease severity in both PSP and CBS. Modelling how domains change in relation to one other at varying disease severities may facilitate detection of therapeutic effects in future clinical trials
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