Insulin analog preparations and their use in children and adolescents with type 1 diabetes mellitus.

Standard or 'traditional' human insulin preparations such as regular soluble insulin and neutral protamine Hagedorn (NPH) insulin have shortcomings in terms of their pharmacokinetic and pharmacodynamic properties that limit their clinical efficacy. Structurally modified insulin molecules or insulin 'analogs' have been developed with the aim of delivering insulin replacement therapy in a more physiological manner. In the last 10 years, five insulin analog preparations have become commercially available for clinical use in patients with type 1 diabetes mellitus: three 'rapid' or fast-acting analogs (insulin lispro, aspart, and glulisine) and two long-acting analogs (insulin glargine and detemir). This review highlights the specific pharmacokinetic properties of these new insulin analog preparations and focuses on their potential clinical advantages and disadvantages when used in children and adolescents with type 1 diabetes mellitus. The fast-acting analogs specifically facilitate more flexible insulin injection timing with regard to meals and activities, whereas the long-acting analogs have a more predictable profile of action and lack a peak effect. To date, clinical trials in children and adolescents have been few in number, but the evidence available from these and from other studies carried out in adults with type 1 diabetes suggest that they offer significant benefits in terms of reduced frequency of nocturnal hypoglycemia, better postprandial blood glucose control, and improved quality of life when compared with traditional insulins. In addition, insulin detemir therapy is unique in that patients may benefit from reduced risk of excessive weight, particularly during adolescence. Evidence for sustained long-term improvements in glycosylated hemoglobin, on the other hand, is modest. Furthermore, alterations to insulin/insulin-like growth factor I receptor binding characteristics have also raised theoretical concerns that insulin analogs may have an increased mitogenic potential and risk of tumor development, although evidence from both in vitro and in vivo animal studies do not support this assertion. Long-term surveillance has been recommended and further carefully designed prospective studies are needed to evaluate the overall benefits and clinical efficacy of insulin analog therapy in children and adolescents with type 1 diabetes.

Absence of branches from xylan in Arabidopsis gux mutants reveals potential for simplification of lignocellulosic biomass.

As one of the most abundant polysaccharides on Earth, xylan will provide more than a third of the sugars for lignocellulosic biofuel production when using grass or hardwood feedstocks. Xylan is characterized by a linear β(1,4)-linked backbone of xylosyl residues substituted by glucuronic acid, 4-O-methylglucuronic acid or arabinose, depending on plant species and cell types. The biological role of these decorations is unclear, but they have a major influence on the properties of the polysaccharide. Despite the recent isolation of several mutants with reduced backbone, the mechanisms of xylan synthesis and substitution are unclear. We identified two Golgi-localized putative glycosyltransferases, GlucUronic acid substitution of Xylan (GUX)-1 and GUX2 that are required for the addition of both glucuronic acid and 4-O-methylglucuronic acid branches to xylan in Arabidopsis stem cell walls. The gux1 gux2 double mutants show loss of xylan glucuronyltransferase activity and lack almost all detectable xylan substitution. Unexpectedly, they show no change in xylan backbone quantity, indicating that backbone synthesis and substitution can be uncoupled. Although the stems are weakened, the xylem vessels are not collapsed, and the plants grow to normal size. The xylan in these plants shows improved extractability from the cell wall, is composed of a single monosaccharide, and requires fewer enzymes for complete hydrolysis. These findings have implications for our understanding of the synthesis and function of xylan in plants. The results also demonstrate the potential for manipulating and simplifying the structure of xylan to improve the properties of lignocellulose for bioenergy and other uses.

A genetically mediated bias in decision making driven by failure of amygdala control.

Genetic variation at the serotonin transporter-linked polymorphic region (5-HTTLPR) is associated with altered amygdala reactivity and lack of prefrontal regulatory control. Similar regions mediate decision-making biases driven by contextual cues and ambiguity, for example the "framing effect." We hypothesized that individuals hemozygous for the short (s) allele at the 5-HTTLPR would be more susceptible to framing. Participants, selected as homozygous for either the long (la) or s allele, performed a decision-making task where they made choices between receiving an amount of money for certain and taking a gamble. A strong bias was evident toward choosing the certain option when the option was phrased in terms of gains and toward gambling when the decision was phrased in terms of losses (the frame effect). Critically, this bias was significantly greater in the ss group compared with the lala group. In simultaneously acquired functional magnetic resonance imaging data, the ss group showed greater amygdala during choices made in accord, compared with those made counter to the frame, an effect not seen in the lala group. These differences were also mirrored by differences in anterior cingulate-amygdala coupling between the genotype groups during decision making. Specifically, lala participants showed increased coupling during choices made counter to, relative to those made in accord with, the frame, with no such effect evident in ss participants. These data suggest that genetically mediated differences in prefrontal-amygdala interactions underpin interindividual differences in economic decision making.

Simulating early adoption of alternative fuel vehicles for sustainability

We quantify the conditions that might trigger wide spread adoption of alternative fuel vehicles (AFVs) to support energy policy. Empirical review shows that early adopters are heterogeneous motivated by financial benefits, environmental appeal, new technology, and vehicle reliability. A probabilistic Monte Carlo simulation model is used to assess consumer heterogeneity for early and mass market adopters. For early adopters full battery electric vehicles (BEVs) are competitive but unable to surpass diesels or hybrids due to purchase price premium and lack of charging availability. For mass adoption, simulations indicate that if the purchase price premium of a BEV closes to within 20% of an in-class internal combustion engine (ICE) vehicle, combined with a 60% increase in refuelling availability relative to the incumbent system, BEVs become competitive. But this depends on a mass market that values the fuel economy and CO2 reduction benefits associated with BEVs. We also find that the largest influence on early adoption is financial benefit rather than pro-environmental behaviour suggesting that AFVs should be marketed by appealing to economic benefits combined with pro-environmental behaviour to motivate adoption. Monte Carlo simulations combined with scenarios can give insight into diffusion dynamics for other energy demand-side technologies. © 2012 Elsevier Inc.

Time resolved measurement of cold start hc concentration using the fast FID

Understanding mixture formation phenomena during the first few cycles of an engine cold start is extremely important for achieving the minimum engine-out emission levels at the time when the catalytic converter is not yet operational. Of special importance is the structure of the charge (film, droplets and vapour) which enters the cylinder during this time interval as well as its concentration profile. However, direct experimental studies of the fuel behaviour in the inlet port have so far been less than fully successful due to the brevity of the process and lack of a suitable experimental technique. We present measurements of the hydrocarbon (HC) concentration in the manifold and port of a production SI engine using the Fast Response Flame Ionisation Detector (FRFID). It has been widely reported in the past few years how the FRFID can be used to study the exhaust and in-cylinder HC concentrations with a time resolution of a few degrees of crank angle, and the device has contributed significantly to the understanding of unburned HC emissions. Using the FRFID in the inlet manifold is difficult because of the presence of liquid droplets, and the low and fluctuating pressure levels, which leads to significant changes in the response time of the instrument. However, using recently developed procedures to correct for the errors caused by these effects, the concentration at the sampling point can be reconstructed to align the FRFID signal with actual events in the engine. © 1996 Society of Automotive Engineers, Inc.

Geometric optimization methods for independent component analysis applied on gene expression data

DNA microarrays provide a huge amount of data and require therefore dimensionality reduction methods to extract meaningful biological information. Independent Component Analysis (ICA) was proposed by several authors as an interesting means. Unfortunately, experimental data are usually of poor quality- because of noise, outliers and lack of samples. Robustness to these hurdles will thus be a key feature for an ICA algorithm. This paper identifies a robust contrast function and proposes a new ICA algorithm. © 2007 IEEE.

Application of scalar dissipation rate model to siemens DLE combustors

The standard design process for the Siemens Industrial Turbomachinery, Lincoln, Dry Low Emissions combustion systems has adopted the Eddy Dissipation Model with Finite Rate Chemistry for reacting computational fluid dynamics simulations. The major drawbacks of this model have been the over-prediction of temperature and lack of species data limiting the applicability of the model. A novel combustion model referred to as the Scalar Dissipation Rate Model has been developed recently based on a flamelet type assumption. Previous attempts to adopt the flamelet philosophy with alternative closure models have failed, with the prediction of unphysical phenomenon. The Scalar Dissipation Rate Model (SDRM) was developed from a physical understanding of scalar dissipation rate, signifying the rate of mixing of hot and cold fluids at scales relevant to sustain combustion, in flames and was validated using direct numerical simulations data and experimental measurements. This paper reports on the first industrial application of the SDRM to SITL DLE combustion system. Previous applications have considered ideally premixed laboratory scale flames. The industrial application differs significantly in the complexity of the geometry, unmixedness and operating pressures. The model was implemented into ANSYS-CFX using their inbuilt command language. Simulations were run transiently using Scale Adaptive Simulation turbulence model, which switches between Large Eddy Simulation and Unsteady Reynolds Averaged Navier Stokes using a blending function. The model was validated in a research SITL DLE combustion system prior to being applied to the actual industrial geometry at real operating conditions. This system consists of the SGT-100 burner with a glass square-sectioned combustor allowing for detailed diagnostics. This paper shows the successful validation of the SDRM against time averaged temperature and velocity within measurement errors. The successful validation allowed application of the SDRM to the SGT-100 twin shaft at the relevant full load conditions. Limited validation data was available due to the complexity of measurement in the real geometry. Comparison of surface temperatures and combustor exit temperature profiles showed an improvement compared to EDM/FRC model. Furthermore, no unphysical phenomena were predicted. This paper presents the successful application of the SDRM to the industrial combustion system. The model shows a marked improvement in the prediction of temperature over the EDM/FRC model previously used. This is of significant importance in the future applications of combustion CFD for understanding of hardware mechanical integrity, combustion emissions and dynamics of the flame. Copyright © 2012 by ASME.

Graphene nanoribbon blends with P3HT for organic electronics.

In organic field-effect transistors (OFETs) the electrical characteristics of polymeric semiconducting materials suffer from the presence of structural/morphological defects and grain boundaries as well as amorphous domains within the film, hindering an efficient transport of charges. To improve the percolation of charges we blend a regioregular poly(3-hexylthiophene) (P3HT) with newly designed N = 18 armchair graphene nanoribbons (GNRs). The latter, prepared by a bottom-up solution synthesis, are expected to form solid aggregates which cannot be easily interfaced with metallic electrodes, limiting charge injection at metal-semiconductor interfaces, and are characterized by a finite size, thus by grain boundaries, which negatively affect the charge transport within the film. Both P3HT and GNRs are soluble/dispersible in organic solvents, enabling the use of a single step co-deposition process. The resulting OFETs show a three-fold increase in the charge carrier mobilities in blend films, when compared to pure P3HT devices. This behavior can be ascribed to GNRs, and aggregates thereof, facilitating the transport of the charges within the conduction channel by connecting the domains of the semiconductor film. The electronic characteristics of the devices such as the Ion/Ioff ratio are not affected by the addition of GNRs at different loads. Studies of the electrical characteristics under illumination for potential use of our blend films as organic phototransistors (OPTs) reveal a tunable photoresponse. Therefore, our strategy offers a new method towards the enhancement of the performance of OFETs, and holds potential for technological applications in (opto)electronics.