Change in focus due to motion

The physical properties of a system at rest are not the same when the system is in motion. These relativistic effects, such as changes of length and mass, are usually minute when the velocity of the system is small compared to the speed of light and therefore of little practical interest. However, this paper reports changes of the velocity of light in a moving medium which lead to changes in refractive index and therefore focal length that are not small. The change in focal length can be as much as a fraction of a millimeter when the velocity of the system is as low 1/10,000th the speed of ltght. Conceivably these effects could cause \u27 defocusing of optical instruments carried on space flights

High Linearity Millimeter Wave Power Amplifiers with Novel Linearizer Techniques

Millimeter-wave communications have experienced phenomenal growth in recent years when limited frequency spectrum is occupied by the ever-developing communication services. The power amplifier, as the key component in the transmitter/receiver module of communication systems, affects performance of the whole system directly and receives much attention. For minimized distortion and optimum system performance, the non-constant en- velope modulation schemes used in communication systems have challenging requirements on linearity. As linearity is related to communication quality directly, several linearization techniques, such as predistortion and feedforward, are applied to power amplifier design. Predistortion method has the advantages over other techniques in relatively simple struc- ture and reasonable linearity improvement. But current predistortion circuits have quite limited performance improvement and relatively large insertion loss, which indicate the need for further research. In most of millimeter-wave amplifier design, great effort has been spent on output power or gain, while linearity is often ignored. As almost all the predistortion circuits operate at the RF frequencies, the linearized millimeter-wave com- munication circuit is still relatively immature and very challenging. This project is dedicated to solve the linearity problem faced by millimeter-wave power amplifier in communication systems, which lacks of e®ective techniques in this field. Linearity improvement with the predistortion method will be the key issue in this project and some original ideas for predistortion circuit design will be applied to millimeter-wave amplifiers. In this thesis, several predistortion circuits with novel structure were proposed, which provide a new approach for linearity improvement for millimeter-wave power am- plifier. A millimeter-wave power ampli¯er for LMDS applications built on GaAs pHEMT technology was developed to a high engineering standard, which works as the test bench for linearization. Actual operation and parasitic elements at tens of gigahertz have been taken into consideration during the design. Firstly, two novel predistorter structures based on the amplifier were proposed, one is based on an amplifier with a fixed bias circuit and the other is based on an amplifier with a nonlinear signal dependant bias circuit. These novel structures can improve the linearity while improving other metrics simultaneously, which can effectively solve the problem of insertion loss faced by the conventional structures. Besides this, an original predistortion circuit design methodology derived from frequency to signal amplitude transformation was proposed. Based on this methodology, several transfer functions were proposed and related predistortion circuits were built to linearize the power amplifier. As this methodology is quite different from the traditional approach, it can improve the linearity signifficantly while other metrics are affected slightly and has a broad prospect for application

A SuperWASP Light Curve Displaying a Single Long-duration Transit: A Jupiter Size Exoplanet in a Very Distant Orbit?

We present the SuperWASP light curve of a 10th magnitude A7V star containing a single, well-defined U-shaped transit-like event lasting around 11 days with a depth of 1.1%. The star is otherwise non-variable throughout the 8 yr duration of the observations. If the event is modeled as an exoplanet transit, it is compatible with a 1.8 RJ exoplanet in a ∼205 au orbit with a period of ∼2200 yr

Enhanced Immune Responses by Skin Vaccination with Influenza Subunit Vaccine in Young Hosts

Skin has gained substantial attention as a vaccine target organ due to its immunological properties, which include a high density of professional antigen presenting cells (APCs). Previous studies have demonstrated the effectiveness of this vaccination route not only in animal models but also in adults. Young children represent a population group that is at high risk from influenza infection. As a result, this group could ben- efit significantly from influenza vaccine delivery approaches through the skin and the improved immune response it can induce. In this study, we compared the immune responses in young BALB/c mice upon skin delivery of influenza vaccine with vaccination by the conventional intramuscular route. Young mice that received 5 fLg of H1N1 A/Ca/07/09 influenza subunit vaccine using MN demonstrated an improved serum antibody response (IgG1 and IgG2a) when compared to the young IM group, accompanied by higher numbers of influenza-specific antibody secreting cells (ASCs) in the bone marrow. In addition, we observed increased activation of follicular helper T cells and formation of germinal centers in the regional lymph nodes in the MN immunized group, rapid clearance of the virus from their lungs as well as complete survival, compared with partial protection observed in the IM-vaccinated group. Our results support the hypothesis that influenza vaccine delivery through the skin would be beneficial for protecting the high-risk young population from influenza infection

Vascular Nox (NADPH oxidase) compartmentalization, protein hyperoxidation, and endoplasmic reticulum stress response in hypertension

Vascular Nox (NADPH oxidase)-derived reactive oxygen species and endoplasmic reticulum (ER) stress have been implicated in hypertension. However, relationships between these processes are unclear. We hypothesized that Nox isoforms localize in a subcellular compartment-specific manner, contributing to oxidative and ER stress, which influence the oxidative proteome and vascular function in hypertension. Nox compartmentalization (cell fractionation), O2− (lucigenin), H2O2 (amplex red), reversible protein oxidation (sulfenylation), irreversible protein oxidation (protein tyrosine phosphatase, peroxiredoxin oxidation), and ER stress (PERK [protein kinase RNA-like endoplasmic reticulum kinase], IRE1α [inositol-requiring enzyme 1], and phosphorylation/oxidation) were studied in spontaneously hypertensive rat (SHR) vascular smooth muscle cells (VSMCs). VSMC proliferation was measured by fluorescence-activated cell sorting, and vascular reactivity assessed in stroke-prone SHR arteries by myography. Noxs were downregulated by short interfering RNA and pharmacologically. In SHR, Noxs were localized in specific subcellular regions: Nox1 in plasma membrane and Nox4 in ER. In SHR, oxidative stress was associated with increased protein sulfenylation and hyperoxidation of protein tyrosine phosphatases and peroxiredoxins. Inhibition of Nox1 (NoxA1ds), Nox1/4 (GKT137831), and ER stress (4-phenylbutyric acid/tauroursodeoxycholic acid) normalized SHR vascular reactive oxygen species generation. GKT137831 reduced IRE1α sulfenylation and XBP1 (X-box binding protein 1) splicing in SHR. Increased VSMC proliferation in SHR was normalized by GKT137831, 4-phenylbutyric acid, and STF083010 (IRE1–XBP1 disruptor). Hypercontractility in the stroke-prone SHR was attenuated by 4-phenylbutyric acid. We demonstrate that protein hyperoxidation in hypertension is associated with oxidative and ER stress through upregulation of plasmalemmal-Nox1 and ER-Nox4. The IRE1–XBP1 pathway of the ER stress response is regulated by Nox4/reactive oxygen species and plays a role in the hyperproliferative VSMC phenotype in SHR. Our study highlights the importance of Nox subcellular compartmentalization and interplay between cytoplasmic reactive oxygen species and ER stress response, which contribute to the VSMC oxidative proteome and vascular dysfunction in hypertensio

Fifteen years of clinical liver transplantation

Liver transplantation in humans was first attempted more than 15 yr ago. The 1-yr survival has slowly improved until it has now reached about 50%. In our experience, 46 patients have lived for at least 1 yr, with the longest survival being 9 yr. The high acute mortality in early trials was due in many cases to technical and management errors and to the use of damaged organs. With elimination of such factors, survival increased. Further improvements will depend upon better immunosuppression. Orthotopic liver transplantation (liver replacement) is the preferred operation in most cases, but placement of an extra liver (auxiliary transplantation) may have a role under special circumstances. © 1979

In vivo microsampling to capture the elusive exposome

Bessonneau, V., Ings, J., McMaster, M., Smith, R., Bragg, L., Servos, M., & Pawliszyn, J. (2017). In vivo microsampling to capture the elusive exposome. Scientific Reports, 7, 44038. The final and definitive publication is available through Nature publishing Group via: http://dx.doi.org/10.1038/srep44038Loss and/or degradation of small molecules during sampling, sample transportation and storage can adversely impact biological interpretation of metabolomics data. In this study, we performed in vivo sampling using solid-phase microextraction (SPME) in combination with non-targeted liquid chromatography and high-resolution tandem mass spectrometry (LC-MS/MS) to capture the fish tissue exposome using molecular networking analysis, and the results were contrasted with molecular differences obtained with ex vivo SPME sampling. Based on 494 MS/MS spectra comparisons, we demonstrated that in vivo SPME sampling provided better extraction and stabilization of highly reactive molecules, such as 1-oleoyl-sn-glycero-3-phosphocholine and 1-palmitoleoyl-glycero-3-phosphocholine, from fish tissue samples. This sampling approach, that minimizes sample handling and preparation, offers the opportunity to perform longitudinal monitoring of the exposome in biological systems and improve the reliability of exposure-measurement in exposome-wide association studies.Environment Canada, Environmental Damages Fund (Grant EC-129114) provided to Environment Canada through the Joint Oil Sands Monitoring Program

A clinical and economic evaluation of Control of Hyperglycaemia in Paediatric intensive care (CHiP): a randomised controlled trial.

BACKGROUND: Early research in adults admitted to intensive care suggested that tight control of blood glucose during acute illness can be associated with reductions in mortality, length of hospital stay and complications such as infection and renal failure. Prior to our study, it was unclear whether or not children could also benefit from tight control of blood glucose during critical illness. OBJECTIVES: This study aimed to determine if controlling blood glucose using insulin in paediatric intensive care units (PICUs) reduces mortality and morbidity and is cost-effective, whether or not admission follows cardiac surgery. DESIGN: Randomised open two-arm parallel group superiority design with central randomisation with minimisation. Analysis was on an intention-to-treat basis. Following random allocation, care givers and outcome assessors were no longer blind to allocation. SETTING: The setting was 13 English PICUs. PARTICIPANTS: Patients who met the following criteria were eligible for inclusion: ≥ 36 weeks corrected gestational age; ≤ 16 years; in the PICU following injury, following major surgery or with critical illness; anticipated treatment > 12 hours; arterial line; mechanical ventilation; and vasoactive drugs. Exclusion criteria were as follows: diabetes mellitus; inborn error of metabolism; treatment withdrawal considered; in the PICU > 5 consecutive days; and already in CHiP (Control of Hyperglycaemia in Paediatric intensive care). INTERVENTION: The intervention was tight glycaemic control (TGC): insulin by intravenous infusion titrated to maintain blood glucose between 4.0 and 7.0 mmol/l. CONVENTIONAL MANAGEMENT (CM): This consisted of insulin by intravenous infusion only if blood glucose exceeded 12.0 mmol/l on two samples at least 30 minutes apart; insulin was stopped when blood glucose fell below 10.0 mmol/l. MAIN OUTCOME MEASURES: The primary outcome was the number of days alive and free from mechanical ventilation within 30 days of trial entry (VFD-30). The secondary outcomes comprised clinical and economic outcomes at 30 days and 12 months and lifetime cost-effectiveness, which included costs per quality-adjusted life-year. RESULTS: CHiP recruited from May 2008 to September 2011. In total, 19,924 children were screened and 1369 eligible patients were randomised (TGC, 694; CM, 675), 60% of whom were in the cardiac surgery stratum. The randomised groups were comparable at trial entry. More children in the TGC than in the CM arm received insulin (66% vs. 16%). The mean VFD-30 was 23 [mean difference 0.36; 95% confidence interval (CI) -0.42 to 1.14]. The effect did not differ among prespecified subgroups. Hypoglycaemia occurred significantly more often in the TGC than in the CM arm (moderate, 12.5% vs. 3.1%; severe, 7.3% vs. 1.5%). Mean 30-day costs were similar between arms, but mean 12-month costs were lower in the TGC than in CM arm (incremental costs -£3620, 95% CI -£7743 to £502). For the non-cardiac surgery stratum, mean costs were lower in the TGC than in the CM arm (incremental cost -£9865, 95% CI -£18,558 to -£1172), but, in the cardiac surgery stratum, the costs were similar between the arms (incremental cost £133, 95% CI -£3568 to £3833). Lifetime incremental net benefits were positive overall (£3346, 95% CI -£11,203 to £17,894), but close to zero for the cardiac surgery stratum (-£919, 95% CI -£16,661 to £14,823). For the non-cardiac surgery stratum, the incremental net benefits were high (£11,322, 95% CI -£15,791 to £38,615). The probability that TGC is cost-effective is relatively high for the non-cardiac surgery stratum, but, for the cardiac surgery subgroup, the probability that TGC is cost-effective is around 0.5. Sensitivity analyses showed that the results were robust to a range of alternative assumptions. CONCLUSIONS: CHiP found no differences in the clinical or cost-effectiveness of TGC compared with CM overall, or for prespecified subgroups. A higher proportion of the TGC arm had hypoglycaemia. This study did not provide any evidence to suggest that PICUs should stop providing CM for children admitted to PICUs following cardiac surgery. For the subgroup not admitted for cardiac surgery, TGC reduced average costs at 12 months and is likely to be cost-effective. Further research is required to refine the TGC protocol to minimise the risk of hypoglycaemic episodes and assess the long-term health benefits of TGC. TRIAL REGISTRATION: Current Controlled Trials ISRCTN61735247. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 26. See the NIHR Journals Library website for further project information