AKT activation controls cell survival in response to HDAC6 inhibition.

HDAC6 is emerging as an important therapeutic target for cancer. We investigated mechanisms responsible for survival of tumor cells treated with a HDAC6 inhibitor. Expression of the 20 000 genes examined did not change following HDAC6 treatment in vivo. We found that HDAC6 inhibition led to an increase of AKT activation (P-AKT) in vitro, and genetic knockdown of HDAC6 phenocopied drug-induced AKT activation. The activation of AKT was not observed in PTEN null cells; otherwise, PTEN/PIK3CA expression per se did not predict HDAC6 inhibitor sensitivity. Interestingly, HDAC6 inhibitor treatment led to inactivating phosphorylation of PTEN (P-PTEN Ser380), which likely led to the increased P-AKT in cells that express PTEN. Synergy was observed with phosphatidylinositol 3-kinases (PI3K) inhibitor treatment in vitro, accompanied by increased caspase 3/7 activity. Furthermore, combination of HDAC6 inhibitor with a PI3K inhibitor caused substantial tumor growth inhibition in vivo compared with either treatment alone, also detectable by Ki-67 immunostaining and (18)F-FLT positron emission tomography (PET). In aggregate AKT activation appears to be a key survival mechanism for HDAC6 inhibitor treatment. Our findings indicate that dual inhibition of HDAC6 and P-AKT may be necessary to substantially inhibit growth of solid tumors

The Role of Non-Governmental Organizations on HIV/AIDS Mitigation in Morogoro Municipality, Tanzania

HIV/AIDS pandemic has caused widespread negative socio-economic impacts in Tanzania. The epidemic is restraining development efforts of many households and the nation at large. Despite the mushrooming number of NGOs established to combat the epidemic, the prevalence of HIV infection is still high. This study was conducted so as to assess the effectiveness of NGOs on HIV/AIDS mitigation in Morogoro Municipality. A cross-sectional research design which employs a survey method was used. A sample 120 respondents was picked randomly and 17 NGOs were picked with the aid of table of random numbers. Purposive sampling was used to select members for a FGD and key informants. Data was collected using questionnaires, interview guide, FGD and key informants. Quantitative data were analysed using a Statistical Package for Social Sciences program. To determine the effectiveness of NGOs, descriptive and inferential statistics were employed. Structural and content analysis was used to analyse data from FGD and key informants. The study revealed challenges constraining the performance of NGOs which include; operating under meagre funds and donor dependency, incompetent staff, inappropriate approaches on HIV/AIDS message delivery, and poor networking. The study concludes that, NGOs are very important for mitigating HIV/AIDS despite the shortcomings revealed.Key words: HIV/AIDS, NGOs, mitigatio

Theory and application of reverberated direct and indirect noise

The generation of a temperature disturbance in a flow is accompanied by the production of acoustic waves (direct noise), and of an entropy perturbation. If this entropy perturbation is accelerated or decelerated (as is the case through a nozzle or flow restriction), additional acoustic waves are generated (indirect noise). Several studies have demonstrated this mechanism in controlled conditions by using Entropy Wave Generators, in which entropy waves are generated and convected through a nozzle, leading to direct and indirect noise. An analytical analysis of the direct and indirect noise produced by the generation and acceleration of entropy waves in a reflective environment is presented. The e ect of reverberation (repeated acoustic reflections) on low-frequency perturbations (characteristic of Entropy Wave Generators) is determined analytically. These results are then implemented in a set of limit cases, showing the limit behaviours of such systems. The analytical model is applied to the case of the Cambridge Entropy Wave Generator experiment, in which entropy waves are generated by an electric heater and accelerated through a subsonic ori ce plate. Due to the clear time separation of direct and indirect noise in the experimental results, direct and indirect noise transfer functions can be extracted from the experimental data for the rst time, and compared directly with existing theoretical models. The backward-propagating indirect noise generated at an ori ce plate is shown to be signi cantly higher than predicted by existing theoretical models for isentropic nozzles.EPSRC EP/K02924X/1

Influence of fermentation and cowpea steaming on some quality characteristics of maize-cowpea blends

Fermentation and cowpea steaming can be used to improve the protein quality and quantity of fermented maize dough. In the production of maize-cowpea blends, it is important that the quality characteristics are evaluated to determine their functionality in the products. A 5x4x2x2factorial experiment with cowpea level, fermentation time, cowpea steaming time and fermentation method as the variable was performed. The cowpeas were dehulled, steamed, dried at 65EC for 24 hours and milled into flours. Maize was soaked in water (18 hours), drained and milled into flour. The maize-cowpea blends were made into a 50% moisture dough, fermented for the specified periods, dried at 65EC and milled into flour. Samples were evaluated for pH, titratable acidity, water absorption and sugars. The pH and titratable acidity of the samples were affected by fermentation time, steaming time, and the levels of cowpeas in the blend. Cowpeas was the main source of glucose/galactose.Fermentation caused a reduction in stacchyose and glucose/galactose. The mixing of cowpea flour with fermented maize dough prior to drying (single component fermentation) gave similar effects on sugar concentrations as detected in the co-fermented samples (multi-component fermentation).Fermentation and steamed cowpea fortification can be used to produce high protein fermented cereal foods with reduced anti-nutritional factors

Measurements of the effect of boundary conditions on upstream and downstream noise arising from entropy spots

Pressure fluctuations in combustors arise either directly from the heat release rate perturbations of the flame (direct noise), or indirectly from the acceleration of entropy, vorticity or compositional perturbations through nozzles or turbine guide vanes (indirect noise). In this work, the generation of synthetic entropy spots via the Joule effect produces direct noise, and their acceleration through orifice plates and nozzles produces indirect noise. These acoustic waves reverberate, reflecting several times at the boundaries to add up to the measured pressure. Single travelling pulses are isolated by the introduction of a semiinfinite tube that acts as an anechoic termination for a limited time-window. It is shown how the shape of the converging nozzle does not affect the reflection of the direct noise wave, confirming the hypothesis of a compact nozzle. Further, it is demonstrated that the assumption of an isentropic nozzle does not hold, but that an alternative theory which takes into account the partial acoustic energy dissipation offers good agreement with the experiments. Finally, it is shown that the reflected indirect noise is underpredicted by isentropic theories. An extension of the present work is indicated for the measurement of the transmissivity of indirect noise.Francesca De Domenico is supported by the Honorary Vice-Chancellor’s Award and a Qualcomm/DTA Studentship (University of Cambridge). Erwan Rolland is supported by an EPSRC DTA studentship (University of Cambridge). Experiments were partly funded by EPSRC grant EP/K02924X/1

Acoustic and entropic transfer functions of a generalised subsonic nozzle

The knowledge of the acoustic and entropic transfer functions at the boundaries of combustors is crucial to understand the fate of flame-generated pressure perturbations and to predict and prevent the emergence of combustion instabilities. Traditional models often rely on the isentropic assumption for nozzle guide vanes. In real systems, however, pressure losses and local flow recirculations may occur, as evidenced by drops in the static pressure. In this work we relax the isentropic assumption and derive a parametric model to predict the acoustic and entropic transfer functions of generalised convergent-divergent nozzles with subsonic-to-sonic throat conditions in the low frequency domain. By tuning two parameters, this model can retrieve the impedance of three limit cases known from the literature: the isentropic nozzle, the orifice plate and the convergent nozzle duct termination. The generalised model also includes the conversion of entropy to sound through orifice plates and non-isentropic nozzles, yet to be considered in the literature. These analytical results are then compared with the experimental data acquired in the Cambridge Entropy Generator. The comparison highlights the need to correctly account for the losses in the system to properly explain the transfer functions of nozzles, as isentropic predictions differ substantially from the acquired experimental data.Qualcom

Low frequency generation, transmission and reflection of direct and indirect perturbations through nozzles

Pressure perturbations arise in combustors from direct noise related to the change in density in flames, as well as the indirect (entropic) noise associated with the acceleration of non-homogeneous regions of flow through nozzles. In this paper we review our recent work on quantifying the relative contributions of direct and indirect noise generated from perturbations in temperature and composition, and the resulting transmitted and reflected pressure perturbations. We show that (a) isentropic models are inadequate to capture the acoustic and entropic transfer functions across a nozzle; (b) corrections to non-isentropic behaviour are possible using existing models for orifices using a single parameter accounting for losses; (c) the behaviour of low frequency entropic noise generated in a chamber can be entirely accounted for when reverberation is taken into account; and (d) indirect noise due to compositional fluctuations can be as large as entropic noise arising from temperature fluctuations. The findings have implications for both the study of entropy noise in model systems, as well as for understanding how to separate the origins of noise in practical systems. In particular, the role of compositional noise in gas turbines (regarding for example the role of cooling in rich-quench-lean turbines) and the role of non-isentropic effects is not accounted for in current models, and should be revisited in the light of current findings.QUALCOM

Lipid Profile and High Maternal Body Mass Index is Associated with Preeclampsia: A Case-Control Study of the Cape Coast Metropolis

Background: Preeclampsia is a leading cause of maternal mortality worldwide and a serious health problem that affects the majority of women. Aim: We investigated the association between lipid profile and maternal obesity among preeclamptic women in the Cape Coast Metropolis. Subject and Methods: This case.control study involved 60 preeclamptics and 50 healthy pregnant controls matched for age and gestational weeks consecutively recruited from two major hospitals in the Cape Coast Metropolis. Blood samples were collected after overnight fasting and enzymatic spectrophotometric tests used to estimate lipid concentrations.The independent samples t.test, Chi.square, and Pearsonfs correlation were used in the analysis of data gathered.Results: Serum triglyceride (TG) (P = 0.04), very low density lipoprotein (VLDL) (P = 0.02), TC (P = 0.01) and low density lipoprotein (LDL) (P = 0.03) levels were higher in preeclamptic participants than in the controls. High density lipoprotein concentration showed no significant variation between the two groups (P = 0.83). Preeclamptic women were more obese (P = 0.07). High body mass index (OR = 1.501; CI = 0.926.2.106, P = 0.01), high TG level (OR = 5.026; CI = 0.794-31.818, P = 0.01), were associated with preeclampsia.Conclusion: Lipid abnormalities, mostly elevated levels of TG, TC, LDL, andVLDL are present in preeclamptics. High TG levels and maternal obesity are associated with preeclampsia among pregnant women in the Cape Coast Metropolis.Keywords: Body mass index, Dyslipidemia, High blood pressure, Pre-eclampsia, Proteinuri