Electromagnetic Actuated Stiring in Microbioreactor Enabling Easier Multiplexing and Flexible Device Design

The development of a novel electromagnetically (EM) actuated stirring method, for use in microbioreactors, is reported. Mixing in microbioreactors is critical to ensure even distribution of nutrients to microorganisms and cells. Magnetically driven stirrer bars or peristaltic mixing are the most commonly utilised mixing methods employed in completely liquid-filled microbioreactors. However the circular reactor shape required for mixing with a stirrer bar and frequently used for peristaltically mixed microbioreactors presents difficulties for bubble-free priming in a microfluidic bioreactor. Moreover the circular shape and the hardware required for both types of mixing reduces the potential packing density of multiplexed reactors. We present a new method of mixing, displaying design flexibility by demonstrating mixing in circular and diamond-shaped reactors and a duplex diamond reactor and fermentation of the gram-positive bacteria S. carnosus in a diamond-shaped microbioreactor system. The results of the optimisation of this mixing method for performing fermentations alongside both batch and continuous culture fermentations are presentedPeer reviewe

A critical review: recent developments of natural fiber/rubber reinforced polymer composites

Recent advancements in the development of low-emission materials have become a global imperative to achieve net-zero emissions in efforts to limit the effects of climate change. The materials transition agenda not only aims to substitute emission-intensive materials but also incorporates emission reduction efforts into goods and applications. Natural fiber composites have received attention from both commercial and research communities because of their inherent eco-friendliness, lower cost, and lower energy consumption during processing than their synthetic counterparts. Additionally, rubber-reinforced polymer composites have generally shown promising results, particularly in resisting sudden deformation. Although studies combining waste rubber with natural fibers in polymer composites are nascent, with limited existing literature, this area demonstrates remarkable potential for the substitution of traditional synthetic composites. Therefore, this review outlines the recent developments in polymer composites incorporating the use of natural fibers and rubber in various forms. The use of rubber as a filler has been shown to enhance tensile strength and impact performance while enhancing the surface finish, however, conflicting studies were identified. Hybridizing waste rubber and natural fibers presents a promising path to further enhance the mechanical performance of composite materials. Emphasis has been placed on the use of fillers in various forms and on their inclusion in thermoset matrices. The future outlook and research opportunities are also presented in this review.</p

Type A aortic dissection: Has surgical outcome improved with time?

ObjectiveThe study objective was to determine whether developments in surgical, anesthetic, and perfusion techniques in the treatment of type A aortic dissection have resulted in improved clinical outcome.MethodsA consecutive series of 165 patients undergoing surgical repair of type A aortic dissection performed between April of 1992 and March of 2006 in a single center were analyzed. Operations were grouped in 2 time frames of equal length (before April of 1999 vs from April of 1999 onward).ResultsThere were 30 in-hospital deaths (18.2%), and the death rate was similar in the 2 time periods. Patients who underwent operation in the recent era compared with the earlier era were older (median 62 years [interquartile range 51–68] vs 59 years [45–68], P = .18), with a significantly higher incidence of concomitant coronary artery disease (13 [18%] vs 5 [7%], P = .03]) and significantly worse (moderate to poor) left ventricular function (33 [40%] vs 13 [18%], P = .002). The duration of circulatory arrest was shorter in the recent era (median 31 minutes [interquartile range 26.5–39] vs 37.5 minutes [31–45], P = .009), with a higher incidence of concomitant procedures (19 [21%] vs 10 [14%], P = .22). Except for total hospital stay, which increased over time, there were no significant differences in postoperative outcome.ConclusionDespite the adoption of techniques to improve outcome for patients with type A dissection, mortality remains unchanged. A deteriorating risk profile and factors relating to the disease process itself may explain this observation

Characterization of VPS34-IN1, a selective inhibitor of Vps34, reveals that the phosphatidylinositol 3-phosphate-binding SGK3 protein kinase is a downstream target of class III phosphoinositide 3-kinase

The Vps34 (vacuolar protein sorting 34) class III PI3K (phosphoinositide 3-kinase) phosphorylates PtdIns (phosphatidylinositol) at endosomal membranes to generate PtdIns(3)P that regulates membrane trafficking processes via its ability to recruit a subset of proteins possessing PtdIns(3)P-binding PX (phox homology) and FYVE domains. In the present study, we describe a highly selective and potent inhibitor of Vps34, termed VPS34-IN1, that inhibits Vps34 with 25 nM ICin vitro, but does not significantly inhibit the activity of 340 protein kinases or 25 lipid kinases tested that include all isoforms of class I as well as class II PI3Ks. Administration of VPS34-IN1 to cells induces a rapid dose-dependent dispersal of a specific PtdIns(3)P-binding probe from endosome membranes, within 1 min, without affecting the ability of class I PI3K to regulate Akt. Moreover, we explored whether SGK3 (serum- and glucocorticoid-regulated kinase-3), the only protein kinase known to interact specifically with PtdIns(3)P via its N-terminal PX domain, might be controlled by Vps34. Mutations disrupting PtdIns(3)P binding ablated SGK3 kinase activity by suppressing phosphorylation of the T-loop [PDK1 (phosphoinositide-dependent kinase 1) site] and hydrophobic motif (mammalian target of rapamycin site) residues. VPS34-IN1 induced a rapid ~50-60% loss of SGK3 phosphorylation within 1 min. VPS34-IN1 did not inhibit activity of the SGK2 isoform that does not possess a PtdIns(3)P-binding PX domain. Furthermore, class I PI3K inhibitors (GDC-0941 and BKM120) that do not inhibit Vps34 suppressed SGK3 activity by ~40%. Combining VPS34-IN1 and GDC-0941 reduced SGK3 activity ~80-90%. These data suggest SGK3 phosphorylation and hence activity is controlled by two pools of PtdIns(3)P. The first is produced through phosphorylation of PtdIns by Vps34 at the endosome. The second is due to the conversion of class I PI3K product, PtdIns(3,4,5)P3 into PtdIns(3)P, via the sequential actions of the PtdIns 5-phosphatases [SHIP1/2 (Src homology 2-domain-containing inositol phosphatase 1/2)] and PtdIns 4-phosphatase [INPP4B (inositol polyphosphate 4-phosphatase type II)]. VPS34-IN1 will be a useful probe to delineate physiological roles of the Vps34. Monitoring SGK3 phosphorylation and activity could be employed as a biomarker of Vps34 activity, in an analogous manner by which Akt is used to probe cellular class I PI3K activity. Combining class I (GDC-0941) and class III (VPS34-IN1) PI3K inhibitors could be used as a strategy to better analyse the roles and regulation of the elusive class II PI3K

Alzheimer disease genetic risk factor APOE e4, and cognitive abilities in 111,739 UK Biobank participants

Background: the apolipoprotein (APOE) e4 locus is a genetic risk factor for dementia. Carriers of the e4 allele may be more vulnerable to conditions that are independent risk factors for cognitive decline, such as cardiometabolic diseases. Objective: we tested whether any association with APOE e4 status on cognitive ability was larger in older ages or in those with cardiometabolic diseases. Subjects: UK Biobank includes over 500,000 middle- and older aged adults who have undergone detailed medical and cognitive phenotypic assessment. Around 150,000 currently have genetic data. We examined 111,739 participants with complete genetic and cognitive data. Methods: baseline cognitive data relating to information processing speed, memory and reasoning were used. We tested for interactions with age and with the presence versus absence of type 2 diabetes (T2D), coronary artery disease (CAD) and hypertension. Results: in several instances, APOE e4 dosage interacted with older age and disease presence to affect cognitive scores. When adjusted for potentially confounding variables, there was no APOE e4 effect on the outcome variables. Conclusions: future research in large independent cohorts should continue to investigate this important question, which has potential implications for aetiology related to dementia and cognitive impairment

A method for estimating the turbulent kinetic energy dissipation rate from a vertically pointing Doppler lidar, and independent evaluation from balloon-borne in situ measurements

A method of estimating dissipation rates from a vertically pointing Doppler lidar with high temporal and spatial resolution has been evaluated by comparison with independent measurements derived from a balloon-borne sonic anemometer. This method utilizes the variance of the mean Doppler velocity from a number of sequential samples and requires an estimate of the horizontal wind speed. The noise contribution to the variance can be estimated from the observed signal-to-noise ratio and removed where appropriate. The relative size of the noise variance to the observed variance provides a measure of the confidence in the retrieval. Comparison with in situ dissipation rates derived from the balloon-borne sonic anemometer reveal that this particular Doppler lidar is capable of retrieving dissipation rates over a range of at least three orders of magnitude. This method is most suitable for retrieval of dissipation rates within the convective well-mixed boundary layer where the scales of motion that the Doppler lidar probes remain well within the inertial subrange. Caution must be applied when estimating dissipation rates in more quiescent conditions. For the particular Doppler lidar described here, the selection of suitably short integration times will permit this method to be applicable in such situations but at the expense of accuracy in the Doppler velocity estimates. The two case studies presented here suggest that, with profiles every 4 s, reliable estimates of ϵ can be derived to within at least an order of magnitude throughout almost all of the lowest 2 km and, in the convective boundary layer, to within 50%. Increasing the integration time for individual profiles to 30 s can improve the accuracy substantially but potentially confines retrievals to within the convective boundary layer. Therefore, optimization of certain instrument parameters may be required for specific implementations

Summer Conference on ‘Nutrition at Key Stages of the Life Cycle’:Summer conference, Liverpool.

Nutritional requirements of individuals vary across the lifecycle, according to activity,age, and gender. To optimize human health, consideration of nutritional priorities at each stage is needed. This conference brought together multidisciplinary experts in maternal and child nutrition and health, cardiometabolic and plant-based nutrition, and dietitians involved in the care of vulnerable populations, plus nutritional metabolism, health, and ageing. The presentations highlighted the most important nutrition research in these areas, updating knowledge and suggesting how dietary advice and policy could be adapted to incorporate research findings. With the global increase in non-communicable disease (NCD) and nutrition being considered as a key modifiable risk factor for the prevention and management of NCD, this conference was much needed