Adaptive design of nano-scale dielectric structures for photonics

Using adaptive algorithms, the design of nano-scale dielectric structures for photonic applications is explored. Widths of dielectric layers in a linear array are adjusted to match target responses of optical transmission as a function of energy. Two complementary approaches are discussed. The first approach uses adaptive local random updates and progressively adjusts individual dielectric layer widths. The second approach is based on global updating functions in which large subgroups of layers are adjusted simultaneously. Both schemes are applied to obtain specific target responses of the transmission function within selected energy windows, such as discontinuous cut-off or power-law decay filters close to a photonic band edge. These adaptive algorithms are found to be effective tools in the custom design of nano-scale photonic dielectric structures.Comment: 4 pages Revtex, 4 embedded EPS figure

Quantum Phase Transitions in Coupled Dimer Compounds

We study the critical properties in cubic systems of antiferromagnetically coupled spin dimers near magnetic-field induced quantum phase transitions. The quantum critical points in the zero-temperature phase diagrams are determined from quantum Monte Carlo simulations. Furthermore, scaling properties of the uniform magnetization and the staggered transverse magnetization across the quantum phase transition in magnetic fields are calculated. The critical exponents are derived from Ginzburg-Landau theory. We find excellent agreement between the quantum Monte Carlo simulations and the analytical results.Comment: 7 pages, 9 eps-figure

Effect of Combined Subsurface Structures and Steps on Hyporheic Exchange

The deployment of artificial structures in streambeds has been proposed as a way to enhance hyporheic exchange, and numerical models can be used to quantify their effects. In this study, combinations of different structures—that is, boxes, steps and a new type of subsurface structure (L-shaped structure)—were considered to evaluate their potential applicability on river restoration. Flow-3D and COMSOL were applied to simulate surface and subsurface flow, respectively. The performance of the structures was evaluated on the basis of hyporheic flow and residence time distributions. For the structure sizes here considered, results showed for steps (single step, combination of two steps) and L-shaped structures (single L-shaped structure, combination of two L-shaped structures) most hyporheic flowpaths return to the stream after 5 and 2.5 hr, respectively. Instead, shorter residence times (<0.25 hr) were found for boxes (single box, combination of two boxes). For combinations of steps and permeable boxes, the values of hyporheic flow per unit width are higher (0.35 and 0.3 m2/hr, respectively) than for the combination of L-shaped (0.06 m 2/hr). As a result, the combinations of steps and boxes are more effective in increasing hyporheic flow. However, when subsurface structures are combined with steps the resulting hyporheic exchange is dominated by the steps. Therefore, the combined use of in-stream and subsurface structures separately may increase their benefits for hyporheic exchange, but when steps are the other subsurface structures provide minor advantages

A review of the most important native medicinal plants of Iran effective on gastric acid

Gastrointestinal diseases such as gastric acid hypersecretion are highly prevalent. Gastrointestinal diseases manifest frequently with gastric and duodendal ulcers, gastritis, and dyspepsia which are due to impaired gastric acid secretion. Given the frequency of developing gastrointestinal diseases such as gastric acid hypersecretion and consequently gastric ulcer, the aim of this review article is to report the native medicinal plants of Iran that are used to decrease or neutralize gastric acid. Ziziphora clinopodioidesl, Achillea wilhelmsii, Allium sativum, Amirkabiria odoratissim, Heracleum persicum L. and Medicago sativa are the most native medicinal plants of Iran used to treat gastric acid hypersecretion. Certain compounds such as pulegon, cisisopulegon, cineol, thymol, alpha and betapinene, piperitenone, terpenoids, flavonoids, allicin, tannin, terpenoids, saponin, sterol, and leucoanthocyanin, 3, 4, and 7-trihydroxy flavonol, caffeic acid, and fetalid existing in these plants may be the main agents for reducing gastric acid

Antitumour activity of pembrolizumab in advanced mucosal melanoma: a post-hoc analysis of KEYNOTE-001, 002, 006.

BackgroundMucosal melanoma is an aggressive melanoma with poor prognosis. We assessed efficacy of pembrolizumab in patients with advanced mucosal melanoma in KEYNOTE-001 (NCT01295827), -002 (NCT01704287), and -006 (NCT01866319).MethodsPatients received pembrolizumab 2 mg/kg every 3 weeks (Q3W) or 10 mg/kg Q2W or Q3W. Response was assessed by independent central review per RECIST v1.1.Results1567 patients were treated and 84 (5%) had mucosal melanoma. Fifty-one of 84 were ipilimumab-naive. In patients with mucosal melanoma, the objective response rate (ORR) was 19% (95% CI 11-29%), with median duration of response (DOR) of 27.6 months (range 1.1 + to 27.6). Median progression-free survival (PFS) was 2.8 months (95% CI 2.7-2.8), with median overall survival (OS) of 11.3 months (7.7-16.6). ORR was 22% (95% CI 11-35%) and 15% (95% CI 5-32%) in ipilimumab-naive and ipilimumab-treated patients.ConclusionPembrolizumab provides durable antitumour activity in patients with advanced mucosal melanoma regardless of prior ipilimumab

Surface Charge-Switching Polymeric Nanoparticles for Bacterial Cell Wall-Targeted Delivery of Antibiotics

Bacteria have shown a remarkable ability to overcome drug therapy if there is a failure to achieve sustained bactericidal concentration or if there is a reduction in activity in situ. The latter can be caused by localized acidity, a phenomenon that can occur as a result of the combined actions of bacterial metabolism and the host immune response. Nanoparticles (NP) have shown promise in treating bacterial infections, but a significant challenge has been to develop antibacterial NPs that may be suitable for systemic administration. Herein we develop drug-encapsulated, pH-responsive, surface charge-switching poly(d,l-lactic-co-glycolic acid)-b-poly(l-histidine)-b-poly(ethylene glycol) (PLGA-PLH-PEG) nanoparticles for treating bacterial infections. These NP drug carriers are designed to shield nontarget interactions at pH 7.4 but bind avidly to bacteria in acidity, delivering drugs and mitigating in part the loss of drug activity with declining pH. The mechanism involves pH-sensitive NP surface charge switching, which is achieved by selective protonation of the imidazole groups of PLH at low pH. NP binding studies demonstrate pH-sensitive NP binding to bacteria with a 3.5 ± 0.2- to 5.8 ± 0.1-fold increase in binding to bacteria at pH 6.0 compared to 7.4. Further, PLGA-PLH-PEG-encapsulated vancomycin demonstrates reduced loss of efficacy at low pH, with an increase in minimum inhibitory concentration of 1.3-fold as compared to 2.0-fold and 2.3-fold for free and PLGA-PEG-encapsulated vancomycin, respectively. The PLGA-PLH-PEG NPs described herein are a first step toward developing systemically administered drug carriers that can target and potentially treat Gram-positive, Gram-negative, or polymicrobial infections associated with acidity.National Institutes of Health (U.S.) (Grant CA151884)National Institutes of Health (U.S.) (Grant EB003647)Prostate Cancer Foundation (Award in Nanotherapeutics)United States. Dept. of Defense (Prostate Cancer Research Program PC 051156)MIT-Portugal ProgramNational Science Foundation (U.S.). Graduate Research FellowshipNational Institutes of Health (U.S.) (Office of the Director Grant DP2OD008435

Controversies in Choledochal Malformation in Children:An International Survey among Pediatric Hepatobiliary Surgeons and Gastroenterologists

Background: While congenital choledochal malformation (CCM) is relatively well known within the pediatric surgical and pediatric gastroenterological communities, many controversies and questions remain. Methods: In this paper, we will discuss the results of an international Delphi survey among members of the European Reference Network RARE-LIVER and of the faculty of the Biliary Atresia and Related Diseases (BARD) network to identify the most common practices as well as controversies regarding diagnosis, treatment and follow-up of this still enigmatic disease. Results: Twenty-two individual respondents completed the survey. While there seems to be agreement on the definitions of CCM, preoperative workup, surgical approach and follow-up still vary considerably. The mainstay of treatment remains the removal of the entire extrahepatic biliary tract, clearance of debris both proximally and distally, followed by reconstruction with (according to 86% of respondents) a Roux-en-Y hepaticojejunostomy. Nonetheless, both laparoscopic and robotic-assisted resections are gaining ground with the suggestion that this might be facilitated by concentration of care and resources in specialized centers. However, long-term outcomes are still lacking. Conclusions: As even post-surgical CCM has to be considered as having premalignant potential, follow-up should be well-organized and continued into adulthood. This seems to be lacking in many centers. International cooperation for both benchmarking and research is paramount to improving care for this rare disease

Low- and High-Pressure Casting Aluminum Alloys: A Review

Low- pressure casting and high-pressure casting processes are the most common liquid-based technologies used to produce aluminum components. Processing conditions such as cooling rate and pressure level greatly influence the microstructure, mechanical properties, and heat treatment response of the Al alloys produced through these casting techniques. The performance of heat treatment depends on the alloy’s chemical composition and the casting condition such as the vacuum required for high-pressure casting, thus, highlighting the low-pressure casting application that does not require a vacuum. The level of pressure applied to fill the mold cavity can affect the formation of gas porosities and oxide films in the cast. Moreover, mechanical properties are influenced by the microstructure, i.e., secondary dendritic arm spacing, grain size, and the morphology of the secondary phases in the α-matrix. Thus, the current study evaluates the most current research developments performed to reduce these defects and to improve the mechanical performance of the casts produced by low- and high-pressure casting