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We suggest a new strategy for creating stimuli-responsive bio-integrated optical nanostructures based on Mie-resonant silicon nanoparticles covered by an ensemble of similarity negatively charged polyelectrolytes (heparin and sodium polystyrene sulfonate). The dynamic tuning of the nanostructures' optical response is due to light-induced heating of the nanoparticles and swelling of the polyelectrolyte shell. The resulting hydrophilic/hydrophobic transitions significantly change the shell thickness and reversible shift of the scattering spectra for individual nanoparticles up to 60 nm. Our findings bring novel opportunities for the application of smart nanomaterials in nanomedicine and bio-integrated nanophotonics.

Two-way enriched design (TED) is a novel approach addressing placebo response in clinical trials. It is a two-stage, randomized, placebo-controlled trial design with enrichment in placebo non-responders and treatment responders at the second stage. All data from the first stage and data from placebo non-responders and treatment responders in the second stage are used for the final analysis of the treatment effect. The existing methods for the analysis of TED data include score tests with one, two, and three degrees of freedom. All these methods are only applicable to binary outcomes. However, there is an interest in continuous outcomes in clinical trials in psychiatry. In this manuscript, we apply some novel methods, including a repeated measures model, a weighted repeated measures model with weights from propensity score, and weights from K-means clustering, to analyze TED data for both binary outcomes and continuous outcomes. The simulation study indicates that the repeated measures model performs consistently well in preserving the type I error and achieving the minimum mean standard error as well as a higher power. The performance of the weighted repeated measures model with weights from K-means clustering improves with increasing sample size. Investigators can choose from these analytic approaches under different scenarios.

Reciprocal space engineering allows tailoring the scattering response of media with a low refractive-index contrast. Here it is shown that a quasiperiodic leveled-wave structure with well-defined reciprocal space and random real space distribution can be engineered to open a complete photonic bandgap (CPBG) for any refractive-index contrast. For these structures, an analytical estimation is derived, which predicts that there is an optimal number of Bragg peaks for any refractive-index contrast. A finite 2D or 3D CPBG is expected at this optimal number even for an arbitrarily small refractive-index contrast. Results of numerical simulations of dipole emission in 2D and 3D structures support the estimations. In 3D simulations, an emission suppression of almost 10 dB is demonstrated with a refractive index down to 1.38. The 3D structures are realized by additive manufacturing on millimeter scale for a material with a refractive index of n ≈ 1.59. Measurements confirm a strong suppression of microwave transmission in the expected frequency range.

Excitation of the non-radiative eigenmodes in photonics and metamaterials above their light cone, that is, the bound states in the continuum (BICs), has drawn fundamental and technological interest. However, the current studies on photonic BICs are mainly restricted to the characterization of the eigenmodes with fixed point group. Here, a fourfold rotationally symmetric (C4v) array of silicon resonators in a square lattice is investigated that reveals the traditional symmetry-protected (Γ-state) and accidental (off-Γ) BICs in the momentum space. Upon symmetry-breaking, BICs at Γ-state transform into quasi-states with decaying quality factors that obey the inverse-square law α−2 as a function of the structural asymmetry parameter α. Surprisingly, at larger asymmetries, multiple new states of extended BICs are observed beyond typical inverse-square law behavior. The structural asymmetry of a resonator provides an important degree of freedom for exploring the Friedrich–Wintgen and new accidental BICs that are topologically protected by robust polarization vortices. The extended family of sharp BIC resonances in all-dielectric silicon metasurfaces is extremely important for scalable applications in terahertz sensing, higher harmonic generation, and ultralow-power switching. Ministry of Education (MOE) The authors acknowledge the financial support from the Singapore Ministry of Education (MOE) Academic Research Fund (AcRF) Tier 1 grant RG96/19, Tier 2 grant MOE2017-T2-1-110, and Tier 3 grant MOE2016-T3-1-006.

Background Neuromuscular electrical stimulation (NMES) is a highly sought after but poorly studied treatment for dysphagia among patients with head and neck cancer with dysphagia. This study investigated the efficacy of NMES in this patient population. Methods In this double-blinded, randomized controlled trial, 170 patients with head and neck cancer experiencing posttreatment dysphagia were randomized into active NMES + swallow exercise versus sham NMES + swallow exercise groups. Outcomes after a 12-week program included changes in fluoroscopy measures, diet, and quality of life. Results After the 12-week program, the active NMES group had significantly worse Penetration Aspiration Scale scores than the sham group. Both groups reported significantly better diet and quality of life. No other measures were significant. Conclusion NMES did not add benefit to traditional swallow exercises. Unfortunately, swallow exercises were not effective by themselves either. For patients with head and neck cancer with moderate to severe dysphagia caused by radiation therapy, current behavioral therapies are of limited help in reversing long-term dysphagia. © 2015 Wiley Periodicals, Head Neck 38: E1221–E1231, 2016

To better understand the spatial structure of Amur tigers (Panthera tigris altaica) at the southern edge of their range we fitted 14 tigers (6♀♀ and 8♂♂) with 15 GPS-Argos collars between 2008 and 2011 in 2 study sites: the Ussuriskii Reserve of southern Sikhote-Alin and the Land of the Leopard National Park in southwest Primorye, Russian Far East. Fixed kernel estimates of male home ranges were larger than those of female home ranges (P < 0.05 [mean 95% fixed kernel(♀) = 401 ± 205 km(2) ; mean 95% fixed kernel(♂) = 778 ± 267 km(2)]). The home range size of females varied greatly, but on average was similar to estimates derived from earlier work further north. Low overlap of adjacent home ranges suggested that females retained exclusive territories. Real core areas of females overlapped only slightly, and remained stable over multiple years. The home ranges of adult males were smaller than those of males to the north, and in contrast to previous studies, high overlap among males indicated the absence of territoriality. Nonetheless, real core areas of males did not overlap, suggesting some spatial separation. In comparison to other tiger populations and other areas of the Russian Far East, the sex ratio in our 2 study areas was highly skewed towards males. We believe this skewed sex ratio resulted in the dissolution of territoriality of males due to an inability to defend individual females, with males resorting to scramble competition for mates. Continued monitoring of these sites to determine whether shifts in the sex ratio might result in a return to male territoriality would provide confirmation of our tentative hypothesis.

The soft corals of the genus Xenia are common for Indo-Pacific reef ecosystems. Lipid class, fatty acid (FA), phospho- and phosphonolipid molecular species compositions were identified for the first time in the soft coral Xenia sp. from Vietnam. Total lipids consisted predominantly of waxes, monoalkyl diacylglycerols, triacylglycerols, sterols, and polar lipids (21.4, 7.7, 14.2, 10.5, and 36.7 %, respectively). Sesquiterpene alcohol, valerenenol, was found. Acids 16:0, 18:3n-6, 20:4n-6, and 20:5n-3 dominated in total FA. The markers of zooxanthellae (18:4n-3 and 18:5n-3) and octocorals (24:5n-6 and 24:6n-3) were detected. Acids 18:5n-3, 20:4n-6, 22:4n-6, and 24:5n-6 concentrated in FA of polar lipids, whereas 14:0, 16:0, 16:1n-7, 18:2n-6, and 18:3n-6 were the major FA of neutral lipids. ChoGpl, EtnGpl, SerGpl, CAEP, PtdIns, and lyso ChoGpl constituted 39.5, 20.8, 20.5, 9.7, 4.3, and 5.3 %, respectively, of the sum of phospho- and phosphonolipids. Thirty-two molecular species of phospholipids and ceramide aminoethylphosphonate (CAEP) were determined by high resolution tandem mass spectrometry. Lyso 18:0e PakCho (4.1 %), 18:0e/20:4 PakCho (20.5 %), 18:1e/20:4 PlsEtn (18.0 %), 18:0e/24:5 PakSer (14.0 %), and 16:0 CAEP (9.6 %) were the major molecular species. EtnGpl and PtdIns mainly consisted of alkenyl acyl and diacyl forms, respectively. Alkyl acyl forms predominated in ChoGpl and SerGpl. Acid 24:5n-6 was a principal FA in SerGpl, whereas 20:4n-6 was more abundant in ChoGpl and EtnGpl. PtdIns contained various C20-24 PUFA. In the context of chemotaxonomy of corals, Xenia sp. has the lipid composition typical for soft corals and the FA profile similar to that of alcyonarians with the high level of 18:3n-6.

The Sequential Parallel Comparison Design (SPCD) is one of the novel approaches addressing placebo response. The analysis of SPCD data typically classifies subjects as ‘placebo responders’ or ‘placebo non-responders’. Most current methods employed for analysis of SPCD data utilize only a part of the data collected during the trial. A repeated measures model was proposed for analysis of continuous outcomes that permitted the inclusion of information from all subjects into the treatment effect estimation. We describe here a new approach using a weighted repeated measures model that further improves the utilization of data collected during the trial, allowing the incorporation of information that is relevant to the placebo response, and dealing with the problem of possible misclassification of subjects. Our simulations show that when compared to the unweighted repeated measures model method, our approach performs as well or, under certain conditions, better, in preserving the type I error, achieving adequate power and minimizing the mean squared error. Copyright © 2015 John Wiley & Sons, Ltd.

Iloprost, an inhaled synthetic prostacyclin analogue, improves hemodynamic and clinical status with minimal systemic adversity in patients with pulmonary arterial hypertension. Our single-site, prospective case series aimed to determine the effects of iloprost in subjects with group 2 pulmonary hypertension and heart failure with preserved ejection fraction. Patients referred to Boston Medical Center for initial evaluation of suspected pulmonary hypertension received a test dose of 2.5 μg inhaled iloprost, followed by two subsequent doses of 5 μg. Hemodynamic measurements were recorded for each inhalation after 15, 30, 60, and 90 minutes. Results were analyzed via paired t test and signed-rank test. Eight subjects fulfilled criteria and elected to enter the study. There was a reduction of pulmonary arterial pressure (by an average of 7.0 mmHg [P = 0.005] and 4.7 mmHg [P = 0.021] with the first and second 5-μg inhalations, respectively) and pulmonary vascular resistance (by an average of 161.9 dyn·s/cm(5) [P = 0.019] and 95.0 dyn·s/cm(5) [P = 0.014] with the first and second 5-μg inhalations, respectively). There were trends for increased cardiac output and decreased oxygen saturation. There were no changes in other vital or hemodynamic parameters, including pulmonary capillary wedge pressure. All patients completed each cycle of iloprost administration without preestablished termination criteria. In patients with pulmonary hypertension and heart failure with preserved ejection fraction, inhaled iloprost resulted in acute reduction of pulmonary arterial pressure and pulmonary vascular resistance. Further evaluation of iloprost in this subset of patients is warranted.

Coupling of diffracted waves in gratings with the waveguide modes gives rise to the guided mode resonances (GMRs). The GMRs provide designer linewidth and resonance intensity amidst a broad background, and thus have been widely used for numerous applications in visible and infrared spectral regions. Here, terahertz GMRs are demonstrated in low‐loss, all‐dielectric metasurfaces, which are periodic square lattices of silicon cuboids on quartz substrates. The silicon cuboid lattice simultaneously acts as a diffraction grating and an in‐plane slab waveguide, thereby resulting in the formation of terahertz GMRs. At oblique incidence, two distinct frequency detuned GMRs are observed. The frequency difference between these two GMRs increases at larger angle of incidence. However, extremely small angle of incidence causes destructive interference between these counter‐propagating GMRs that leads to a nonradiative symmetry‐protected bound state in the continuum. GMRs in all‐dielectric silicon metasurfaces can have potential applications in the realization of efficient terahertz devices such as high‐Q transmission filters with angular spectral selectivity, ultrafast modulators, and free‐space couplers. MOE (Min. of Education, S’pore) Accepted version

Previous authors have proposed the sequential parallel comparison design (SPCD) to address the issue of high placebo response rate in clinical trials. The original use of SPCD focused on binary outcomes, but recent use has since been extended to continuous outcomes that arise more naturally in many fields, including psychiatry. Analytic methods proposed to date for analysis of SPCD trial continuous data included methods based on seemingly unrelated regression and ordinary least squares. Here, we propose a repeated measures linear model that uses all outcome data collected in the trial and accounts for data that are missing at random. An appropriate contrast formulated after the model has been fit can be used to test the primary hypothesis of no difference in treatment effects between study arms. Our extensive simulations show that when compared with the other methods, our approach preserves the type I error even for small sample sizes and offers adequate power and the smallest mean squared error under a wide variety of assumptions. We recommend consideration of our approach for analysis of data coming from SPCD trials.

CdSe/ZnSe QD structure was investigated by current deep level transient spectroscopy (DLTS) with Laplace transform cooperated with atomic force microscopy (AFM). Cathodoluminescence (CL) measurements were carried out too. Basing on Laplace current DLTS with AFM and CL data an activation energy of electron emission from the quantized levels in a small group of CdSe QDs was measured. We have demonstrated the advanced capabilities of the new method of studying the electrical properties of nano-objects. (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Here we report the data on the few layer graphene films grown by a chemical vapour deposition on nickel foils and transferred onto desirable substrates for different applications. The experimental conditions have been optimized to prepare a really single graphene layer. A strong influence of the growth conditions onto the number of graphene layers has been revealed. Raman spectroscopy was used to confirm the formation of the single graphene layer with a little amount of defects. To estimate a transmittance of graphene films the optical absorption spectra have been measured. A number of graphene layers in different samples has been estimated on the base of an optical absorbance of a monolayer graphene (2.3% of the incident light intensity). (© 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

The E3 ubiquitin ligase CHIP (C-terminus of Hsc70-interacting protein) is believed to be a central player in the cellular triage decision, as it links the molecular chaperones Hsp70/Hsc70 and Hsp90 to the ubiquitin proteasomal degradation pathway. To better understand the decision process, we determined the affinity of CHIP for Hsp70 and Hsp90 using isothermal titration calorimetry. We analyzed the influence of CHIP on the ATPase cycles of both chaperones in the presence of co-chaperones and a substrate, and determined the ubiquitination efficacy of CHIP in the presence of the chaperones. We found that CHIP has a sixfold higher affinity for Hsp90 compared with Hsc70. CHIP had no influence on ADP dissociation or ATP association, but reduced the Hsp70 cochaperone Hdj1-stimulated single-turnover ATPase rates of Hsc70 and Hsp70. CHIP did not influence the ATPase cycle of Hsp90 in the absence of co-chaperones or in the presence of the Hsp90 cochaperones Aha1 or p23. Polyubiquitination of heat-denatured luciferase and the native substrate p53 was much more efficient in the presence of Hsc70 and Hdj1 than in the presence of Hsp90, indicating that CHIP preferentially ubiquitinates Hsp70-bound substrates.

SummaryIn plants, the first committed enzyme for glutathione biosynthesis, c-glutamylcysteine ligase (GCL), is undermultiple controls. The recent elucidation of GCL structure from Brassica juncea (BjGCL) has revealed thepresence of two intramolecular disulfide bridges (CC1, CC2), which both strongly impact on GCL activityin vitro. Here we demonstrate that cysteines of CC1 are confined to plant species from the Rosids clade, andare absent in other plant families. Conversely, cysteines of CC2 involved in the monomer–dimer transition inBjGCL are not only conserved in the plant kingdom, but are also conserved in the evolutionarily relateda- (and some c-) proteobacterial GCLs. Focusing on the role of CC2 for GCL redox regulation, we haveextended our analysis to all available plant (31; including moss and algal) and related proteobacterial GCL(46) protein sequences. Amino acids contributing to the homodimer interface in BjGCL are highly conservedamong plant GCLs, but are not conserved in related proteobacterial GCLs. To probe the significance of thisdistinction, recombinant GCLs from Nicotiana tabacum (NtGCL), Agrobacterium tumefaciens (AtuGCL,a-proteobacteria) and Xanthomonas campestris (XcaGCL, c-proteobacteria) were analyzed for their redoxresponse. As expected, NtGCL forms a homodimer under oxidizing conditions, and is activated more thanthreefold. Conversely, proteobacterial GCLs remain monomeric under oxidizing and reducing conditions,and their activities are not inhibited by DTT, despite the presence of CC2. We conclude that although plantGCLs are evolutionarily related to proteobacterial GCLs, redox regulation of their GCLs via CC2-dependentdimerization has been acquired later in evolution, possibly as a consequence of compartmentation in theredox-modulated plastid environment.Keywords: glutathione, c-glutamylcysteine ligase, plants, a-proteobacteria, disulfide bridges, dimerization,redox control.IntroductionThe tripeptide glutathione (GSH) is the most abundant low-molecular-weight thiol in all mitochondria-bearing eukary-otes. In plants, GSH is involved in a plethora of cellularprocesses, including defence against reactive oxygen spe-cies (Foyer and Noctor, 2005; Mullineaux and Rausch, 2005),sequestration of heavy metals (Cobbett and Goldsbrough,2002; Freeman et al., 2004) and detoxification of xenobiotics(Dixonet al.,2002).GSHalsoplaysaroleintheregulationofdevelopmental processes, including cell division (Vernouxet al.,2000)andflowering(Ogawaet al.,2004).Furthermore,GSH is the major transport and storage form of reducedsulfur (Leustek and Saito, 1999). GSH is synthesized viatwo ATP-dependent reactions. c-Glutamylcysteine ligase(GCL = GSH1, E.C. 6.3.2.2) catalyzes the formation of apeptide bond between the c-carboxyl group of glutamateand the amino group of cysteine, to yield c-glutamylcyste-ine. This first step has been shown to be a major controlpoint under conditions of increased demand for GSH

In 1,079 infants monitored for >700,000 hr at home for apnea or bradycardia, we found an association between infants having multiple events exceeding conventional or a priori defined more extreme thresholds and less favorable developmental outcome at 1 year of age than infants with few or no events. If it is necessary to prevent such events to minimize risk for developmental morbidity, there is reason to determine whether there are disturbances in advance of the apnea or bradycardia that herald their onset. In the 85 infants with at least 1 extreme event and 1 conventional event, we hypothesized that apnea and bradycardia do not occur de novo but rather are preceded by cardiorespiratory and hemoglobin O2 saturation changes. We compared recorded time intervals preceding these events, and we analyzed three preceding time intervals for each conventional and extreme event, and each non-event recording: Time-2 hr: up to 2 hr before; Time-1 hr: up to 1 hr before; and Time-75 sec: the 75 sec immediately preceding each event. O2 saturation progressively decreased preceding both conventional and extreme events, and progressive increases occurred in heart and breathing rate variability. Duration of respiratory pauses and of periodic breathing progressively increased preceding conventional events, respiratory rate variability increased immediately preceding conventional events and at 1 hr preceding extreme events, and O2 saturation decreased immediately preceding both conventional and extreme events. Thus, conventional and extreme events do not occur de novo but rather are preceded by autonomic instability of the cardiorespiratory system. Pediatr Pulmonol. 2008; 43:87–98. © 2007 Wiley-Liss, Inc.

Interaction of light pulses of various durations and intensities with nanoscale photonic structures plays an important role in many applications of nanophotonics for high-density data storage, ultra-fast data processing, surface coloring and sensing. A design of optically tunable and reconfigurable structures made from different materials is based on many important physical effects and advances in material science, and it employs the resonant character of light interaction with nanostructures and strong field confinement at the nanoscale. Here we review the recent progress in physics of tunable and reconfigurable nanophotonic structures of different types. We start from low laser intensities that produce weak reversible changes in nanostructures, and then move to the discussion of non-reversible changes in photonic structures. We focus on three platforms based on metallic, dielectric and hybrid resonant photonic structures such as nanoantennas, nanoparticle oligomers and nanostructured metasurfaces. Main challenges and key advantages of each of the approaches focusing on applications in advanced photonic technologies are also discussed.

ZnCdS/ZnSSe SQW structure were investigated by current deep level transient spectroscopy (DLTS) with Laplace transform cooperated with atomic force microscopy (AFM) for the first time. Cathodoluminescence (CL) measurements were carried out also. Basing on Laplace current DLTS with AFM and CL data we estimated the conduction band offset of the ZnCdS/ZnSSe interface in the different regions of the structure. Size of the investigated region was commensurable with the diameter of cantilever tip. We demonstrated that Laplace current DLTS-spectrometer switched in the circuit of an AFM cantilever may be used for an investigation of nanostructures. (© 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)