A High-Order Ultra-Weak Variational Formulation for Electromagnetic Waves Utilizing Curved Elements

The Ultra Weak Variational Formulation (UWVF) is a special Trefftz discontinuous Galerkin method, here applied to the time-harmonic Maxwell's equations. The method uses superpositions of plane waves to represent solutions element by element on a finite element mesh. We discuss the use of our parallel UWVF implementation called ParMax, and concentrate on methods for obtaining high order solutions in the presence of scatterers with piecewise smooth boundaries. In particular, we show how curved surface triangles can be incorporated in the UWVF. This requires quadrature to assemble the system matrices. We also show how to implement a total field and scattered field approach, together with the transmission conditions across an interface to handle resistive sheets. We note also that a wide variety of element shapes can be used, that the elements can be large compared to the wavelength of the radiation, and that a matrix free version is easy to implement (although computationally costly). Our contributions are illustrated by several numerical examples showing that curved elements can improve the efficiency of the UWVF, and that the method accurately handles resistive screens as well as PEC and penetrable scatterers. Using large curved elements and the matrix free approach, we are able to simulate scattering from an aircraft at X-band frequencies. The innovations here demonstrate the applicability of the UWVF for industrial examples

The Dynamics of Shock Dispersion and Interactions in Supersonic Freestreams with Counterflowing Jets

An active flow control concept using counterflowing jets to significantly modify the external flowfields and strongly weaken or disperse the shock-waves of supersonic and hypersonic vehicles to reduce the aerothermal loads and wave drag was investigated. Experiments were conducted in a trisonic blow-down wind-tunnel, complemented by pre-test computational fluid dynamics (CFD) analysis of a 2.6% scale model of Apollo capsule, with and without counterflowing jets, in Mach 3.48 and 4.0 freestreams, to assess the potential aerothermal and aerodynamic benefits of this concept. The model was instrumented with heat flux gauges, thermocouples and pressure taps, and employed five counterflowing jet nozzles (three sonic and other two supersonic with design Mach numbers of 2.44 and 2.94) and nozzle exit diameters ranging from 0.25 to 0.5 inch. Schlieren data show that at low jet flow rates of 0.05 and 0.1lb(sub m)/sec, the interactions result in a long penetration mode (LPM) jet, while the short penetration mode (SPM) jet is observed at flow rates greater than 0.1 lb(sub m)/sec., consistent with the pre-test CFD predictions. For the LPM, the jet appears to be nearly fully-expanded, resulting in a very unsteady and oscillatory flow structure in which the bow shock becomes highly dispersed such that it is no longer discernable. Higher speed camera Schlieren data reveal the shock to be dispersed into striations of compression waves, which suddenly coalesce to a weaker bow shock with a larger standoff distance as the flow rate reached a critical value. The pronounced shock dispersion could significantly impact the aerodynamic performance (L/D) and heat flux reduction of spacecraft in atmospheric entry and re-entry, and could also attenuate the entropy layer in hypersonic blunt body flows. For heat transfer, the results show significant reduction in heat flux, even giving negative heat flux for some of the SPM interactions, indicating that the flow wetting the model is cooling, instead of heating the model, which could significantly impact the requirements and design of thermal protection system. These findings strongly suggest that the application of counterflowing jets as active flow control could have strong impact on supersonic and hypersonic vehicle design and performance

Competition between neighbouring topogenic signals during membrane protein insertion into the ER membrane

To better define the mechanism of membrane protein insertion into the membrane of the endoplasmic reticulum, we measured the kinetics of translocation across microsomal membranes of the N-terminal lumenal tail and the lumenal domain following the second transmembrane segment (TM2) in the multispanning mouse protein Cig30. In the wild-type protein, the N-terminal tail translocates across the membrane before the downstream lumenal domain. Addition of positively charged residues to the N-terminal tail dramatically slows down its translocation and allows the downstream lumenal domain to translocate at the same time as or even before the N-tail. When TM2 is deleted, or when the loop between TM1 and TM2 is lengthened, addition of positively charged residues to the N-terminal tail causes TM1 to adopt an orientation with its N-terminal end in the cytoplasm. We suggest that the topology of the TM1-TM2 region of Cig30 depends on a competition between TM1 and TM2 such that the transmembrane segment that inserts first into the ER membrane determines the final topology

Treatment of squamous cell carcinoma of the uterine cervix with radiation therapy alone: long-term survival, late complications, and incidence of second cancers

The objective of this retrospective study was to determine the survival rate, incidence of late complications, and incidence of second cancers when radiation therapy alone is used for carcinoma of the uterine cervix. Between 1971 and 1995, 1495 patients with squamous cell carcinoma of the uterine cervix (stages I–IV) were treated with radiation therapy alone in our hospital. Radiation therapy consisted of a combination of high-dose-rate intracavitary brachytherapy and external beam radiotherapy. The cumulative 5-year survival rates for stages Ib, II, and III/IVa carcinoma were 93.5, 77.0, and 60.3%, respectively, and the 10-year survival rates were 90.9, 74.5, and 56.1%, respectively. Local control rates for stages Ib, II, and III/IVa carcinoma were 92.0, 79.4 and 64.2%, respectively. Eighty-two (5.5%) patients suffered grade III/IV or V (fatal) complications. A second cancer developed in 13 (0.87%) patients. Second cancers were observed most frequently in the rectum (five cases), colon (three cases), and uterine body (two cases). Long-term follow-up data revealed that our method of radiation therapy alone for locally advanced carcinoma of the uterine cervix is effective, with low incidences of late complications and second cancers

Nuclear magnetic resonance spectroscopy for structural characterization of bioactive compounds

The structural assignment of a new natural product molecule is not only to establish the 3D structure of a compound, but potentially to provide the basis for research in a multitude of disciplines, ultimately generating new therapeutic agents and/or new understanding of disease biology. The development of modern spectroscopic techniques has transformed the structure assignment process, which previously was essentially based on chemical degradation or derivatization followed by partial or total synthesis. Notably, it was only in the specialization era of the spectroscopic structural assignment of natural products that the field of marine natural products chemistry took shape. Today the processes of marine and terrestrial natural product isolation and structural determination are frequently streamlined and expeditious due to the spectacular advances in chromatographic and spectroscopic technologies as well as chemical synthesis. The NMR spectroscopy is a powerful tool in structure elucidation because the properties it displays can be related to the molecular structure. The chemical environment of a particular nucleus is associated with the chemical shift (d, ppm), and the area of a resonance, usually presented as its relative integral, is related to the number of nuclei giving rise to the NMR signal. The interactions between individual nuclei, mediated by electrons in a chemical bond, determine the coupling constant (J, Hz). In this chapter we will present the techniques commonly used, basic concepts, and how they are useful for chemists in the structural elucidation of mainly bioactive marine natural products. Its complex planar structure is determined by 1H and 13C NMR analysis strongly supported by other 1D (DEPT) and 2D (COSY, TOCSY, HSQC/HMQC, HMBC) NMR techniques. The stereochemistry is generally based on NOE experiments (NOE difference, NOESY, and ROESY), 1H–1H and 1H–13C coupling constants, chiral derivatizing agents, and also in empirical procedures comparing the chemical shifts of unknown vicinal and proximal centers with libraries of configurationally known stereomodels. However, the most reliable option to assign all the 3D structure of a marine natural product still is their total synthesis. The use of NMR hyphenated with other chromatographic and spectroscopic techniques and microcoil probes and narrow diameter tube probes for the structural elucidation of bioactive marine natural products, mainly associated with the quantitative NMR determinations, will be also briefly described. The chapter will finish with a description of the structural characterization of several types of marine natural products using all the referred NMR techniques followed by a small reference to the misassignments that still are very common

CANDELS: The Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey

The Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey (CANDELS) is designed to document the first third of galactic evolution, over the approximate redshift (z) range 8--1.5. It will image >250,000 distant galaxies using three separate cameras on the Hubble Space Telescope, from the mid-ultraviolet to the near-infrared, and will find and measure Type Ia supernovae at z>1.5 to test their accuracy as standardizable candles for cosmology. Five premier multi-wavelength sky regions are selected, each with extensive ancillary data. The use of five widely separated fields mitigates cosmic variance and yields statistically robust and complete samples of galaxies down to a stellar mass of 10^9 M_\odot to z \approx 2, reaching the knee of the ultraviolet luminosity function (UVLF) of galaxies to z \approx 8. The survey covers approximately 800 arcmin^2 and is divided into two parts. The CANDELS/Deep survey (5\sigma\ point-source limit H=27.7 mag) covers \sim 125 arcmin^2 within GOODS-N and GOODS-S. The CANDELS/Wide survey includes GOODS and three additional fields (EGS, COSMOS, and UDS) and covers the full area to a 5\sigma\ point-source limit of H \gtrsim 27.0 mag. Together with the Hubble Ultra Deep Fields, the strategy creates a three-tiered "wedding cake" approach that has proven efficient for extragalactic surveys. Data from the survey are nonproprietary and are useful for a wide variety of science investigations. In this paper, we describe the basic motivations for the survey, the CANDELS team science goals and the resulting observational requirements, the field selection and geometry, and the observing design. The Hubble data processing and products are described in a companion paper.Comment: Submitted to Astrophysical Journal Supplement Series; Revised version, subsequent to referee repor

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

What is the level of evidence for the use of currently available technologies in facilitating the self-management of difficulties associated with ADHD in children and young people? A systematic review

A number of technologies to help self-manage Attention Deficit Hyperactivity Disorder (ADHD) in children and young people (YP) have been developed. This review will assess the level of evidence for the use of such technologies. The review was undertaken in accordance with the general principles recommended in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. 7545 studies were screened. Fourteen studies of technology that aim to manage difficulties associated with ADHD in children and YP were included. Primary outcome measures were measures that assessed difficulties related to ADHD. Databases searched were MEDLINE, Web of Science (Core collection), CINAHL, the Cochrane Library, ProQuest ASSIA, PsycINFO and Scopus. The methodological quality of the studies was assessed. This review highlights the potential for the use of technology in paediatric ADHD self-management. However, it also demonstrates that current research lacks robustness; using small sample sizes, non-validated outcome measures and little psychoeducation component. Future research is required to investigate the value of technology in supporting children and YP with ADHD and a focus psychoeducation is needed

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Expression of Fluorescently Tagged Proteins in Pichia pastoris

The aim of this study was to recombinantly express Pyriform Spidroin 1 (PySp1) and Protein Kinase C (PKC1) in the yeast Pichia pastoris. PySp1 is a spider silk protein that we believe can be expressed and secreted in large amounts by Pichia pastoris for potential industrial and medical purposes. Because PKC1 is involved in intracellular signaling, the localization of PKC1 in Pichia pastoris could provide a better understanding of the ability of Pichia pastoris to super secrete. EGFP fusion proteins were quantified and analyzed by Western Blot and fluorescent microscopy