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We study the chaotic motion of a semi-classical optomechanical system coupled to a non-Markovian environment with a finite correlation time. By studying the emergence of chaos using the Lyapunov exponent with the changing non-Markovian parameter, we show that the non-Markovian environment can significantly enhance chaos. It is observed that a non-Markovian environment characterized by the Ornstein-Uhlenbeck type noise can modify the generation of chaos with different environmental memory times. As a comparison, the crossover properties from Markov to non-Markovian regimes are also discussed. Our findings indicate that the quantum memory effects on the onset of chaos may become a useful property to be investigated in quantum manipulations and control.

Far-red cyanobacteriochromes (CBCRs) are bilin-based photosensory proteins that promise to be novel optical agents in optogenetics and deep tissue imaging. Recent structural studies of a far-red CBCR 2551g3 have revealed a unique all-Z,syn chromophore conformation in the far-red-absorbing Pfr state. Understanding the photoswitching mechanism through bilin photoisomerization is important for developing novel biomedical applications. Here, we employ femtosecond spectroscopy and site-directed mutagenesis to systematically characterize the dynamics of wild-type 2551g3 and four critical mutants in the 15Z Pfr state. We captured local relaxations in several picoseconds and isomerization dynamics in hundreds of picoseconds. Most mutants exhibited faster local relaxation, while their twisting dynamics and photoproducts depend on specific protein-chromophore interactions around the D-ring and C-ring. These results collectively reveal a unique dynamic pattern of excited-state evolution arising from a relatively rigid protein environment, thereby elucidating the molecular mechanism of Pfr-state photoisomerization in far-red CBCRs.

Global concerns over energy availability and the environment impose an urgent requirement for sustainable manufacturing, usage, and disposal of electronic components. Piezoelectric and photovoltaic components are being extensively used. They contain the hazardous element, Pb (e.g., in widely used and researched Pb(Zr,Ti)O 3 and halide perovskites), but they are not being properly recycled or reused. This work demonstrates the fabrication of upside-down composite sensor materials using crushed ceramic particles recycled from broken piezoceramics, polycrystalline halide perovskite powder collected from waste dye-sensitized solar cells, and crystal particles of a Cd-based perovskite composition, C 6 H 5 N(CH 3 ) 3 CdBr 3 x . The piezoceramic and halide perovskite particles are used as filler and binder, respectively, to show a proof of concept for the chemical and microstructural compatibility between the oxide and halide perovskite compounds while being recycled simultaneously. Production of the recycled and reusable materials requires only a marginal energy budget while achieving a very high material densification of >92%, as well as a 40% higher piezoelectric voltage coefficient, i.e., better sensing capability, than the pristine piezoceramics. This work thus offers an energy- and environmentally friendly approach to the recycling of hazardous elements as well as giving a second life to waste piezoelectric and photovoltaic components.3(1- x ) . The piezoceramic and halide perovskite particles are used as filler and binder, respectively, to show a proof of concept for the chemical and microstructural compatibility between the oxide and halide perovskite compounds while being recycled simultaneously. Production of the recycled and reusable materials requires only a marginal energy budget while achieving a very high material densification of >92%, as well as a 40% higher piezoelectric voltage coefficient, i.e., better sensing capability, than the pristine piezoceramics. This work thus offers an energy- and environmentally friendly approach to the recycling of hazardous elements as well as giving a second life to waste piezoelectric and photovoltaic components., (© 2023 The Authors. Small Methods published by Wiley‐VCH GmbH.)

How do words change their meaning? Although semantic evolution is driven by a variety of distinct factors, including linguistic, societal, and technological ones, we find that there is one law that holds universally across five major Indo-European languages: that semantic evolution is subdiffusive. Using an automated pipeline of diachronic distributional semantic embedding that controls for underlying symmetries, we show that words follow stochastic trajectories in meaning space with an anomalous diffusion exponent α = 0.45 ± 0.05 across languages, in contrast with diffusing particles that follow α = 1. Randomization methods indicate that preserving temporal correlations in semantic change directions is necessary to recover strongly subdiffusive behavior; however, correlations in change sizes play an important role too. We furthermore show that strong subdiffusion is a robust phenomenon under a wide variety of choices in data analysis and interpretation, such as the choice of fitting an ensemble average of displacements or averaging best-fit exponents of individual word trajectories., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Asztalos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The anti-seizure medication vigabatrin (VGB) is effective for controlling seizures, especially infantile spasms. However, use is limited by VGB-associated visual field loss (VAVFL). The mechanisms by which VGB causes VAVFL remains unknown. Average peripapillary retinal nerve fibre layer (ppRNFL) thickness correlates with the degree of visual field loss (measured by mean radial degrees). Duration of VGB exposure, maximum daily VGB dose, and male sex are associated with ppRNFL thinning. Here we test the hypothesis that common genetic variation is a predictor of ppRNFL thinning in VGB exposed individuals. Identifying pharmacogenomic predictors of ppRNFL thinning in VGB exposed individuals could potentially enable safe prescribing of VGB and broader use of a highly effective drug., Methods: Optical coherence topography (OCT) and GWAS data were processed from VGB-exposed individuals ( n  = 71) recruited through the EpiPGX Consortium. We conducted quantitative GWAS analyses for the following OCT measurements: (1) average ppRNFL, (2) inferior quadrant, (3) nasal quadrant, (4) superior quadrant, (5) temporal quadrant, (6) inferior nasal sector, (7) nasal inferior sector, (8) superior nasal sector, and (9) nasal superior sector. Using the summary statistics from the GWAS analyses we conducted gene-based testing using VEGAS2. We conducted nine different PRS analyses using the OCT measurements. To determine if VGB-exposed individuals were predisposed to having a thinner RNFL, we calculated their polygenic burden for retinal thickness. PRS alleles for retinal thickness were calculated using published summary statistics from a large-scale GWAS of inner retinal morphology using the OCT images of UK Biobank participants., Results: The GWAS analyses did not identify a significant association after correction for multiple testing. Similarly, the gene-based and PRS analyses did not reveal a significant association that survived multiple testing., Conclusion: We set out to identify common genetic predictors for VGB induced ppRNFL thinning. Results suggest that large-effect common genetic predictors are unlikely to exist for ppRNFL thinning (as a marker of VAVFL). Sample size was a limitation of this study. However, further recruitment is a challenge as VGB is rarely used today because of this adverse reaction. Rare variants may be predictors of this adverse drug reaction and were not studied here., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Boothman, Clayton, McCormack, Driscoll, Stevelink, Moloney, Krause, Kunz, Diehl, O’Brien, Sills, de Haan, Zara, Koeleman, Depondt, Marson, Stefansson, Stefansson, Craig, Johnson, Striano, Lerche, Furney, Delanty, Consortium, Sisodiya and Cavalleri.)

The fate and motion of cells is influenced by a variety of physical characteristics of their microenvironments. Traditionally, mechanobiology focuses on external mechanical phenomena such as cell movement and environmental sensing. However, cells are inherently dynamic, where internal waves and internal oscillations are a hallmark of living cells observed under a microscope. We propose that these internal mechanical rhythms provide valuable information about cell health. Therefore, it is valuable to capture the rhythms inside cells and quantify how drugs or physical interventions affect a cell's internal dynamics. One of the key dynamical entities inside cells is the microtubule network. Typically, microtubule dynamics are measured by end-protein tracking. In contrast, this paper introduces an easy-to-implement approach to measure the lateral motion of the microtubule filaments embedded within dense networks with (at least) confocal resolution image sequences. Our tool couples the computer vision algorithm Optical Flow with an anisotropic, rotating Laplacian of Gaussian filtering to characterize the lateral motion of dense microtubule networks. We then showcase additional image analytics used to understand the effect of microtubule orientation and regional location on lateral motion. We argue that our tool and these additional metrics provide a fuller picture of the active forcing environment within cells.

Recent validation experiments on laser irradiation of polymer foils with and without implanted golden nanoparticles are discussed. First we analyze characteristics of craters, formed in the target after its interaction with the laser beam. Preliminary experimental results show significant production of deuterons when both the energy of laser pulse and concentration of nanoparticles are high enough. We consider the deuteron production via the nuclear transmutation reactions p+C→d+X where protons are accelerated by the Coulomb field generated in the target plasma. We argue that maximal proton energy can be above threshold values for these reactions and the deuteron yield may noticeably increase due to presence of nanoparticles.

Cardiovascular disease is the leading cause of death globally. An advanced understanding of cardiovascular disease mechanisms is required to improve therapeutic strategies and patient risk stratification. State-of-the-art, large-scale, single-cell and single-nucleus transcriptomics facilitate the exploration of the cardiac cellular landscape at an unprecedented level, beyond its descriptive features, and can further our understanding of the mechanisms of disease and guide functional studies. In this Review, we provide an overview of the technical challenges in the experimental design of single-cell and single-nucleus transcriptomics studies, as well as a discussion of the type of inferences that can be made from the data derived from these studies. Furthermore, we describe novel findings derived from transcriptomics studies for each major cardiac cell type in both health and disease, and from development to adulthood. This Review also provides a guide to interpreting the exhaustive list of newly identified cardiac cell types and states, and highlights the consensus and discordances in annotation, indicating an urgent need for standardization. We describe advanced applications such as integration of single-cell data with spatial transcriptomics to map genes and cells on tissue and define cellular microenvironments that regulate homeostasis and disease progression. Finally, we discuss current and future translational and clinical implications of novel transcriptomics approaches, and provide an outlook of how these technologies will change the way we diagnose and treat heart disease., (© 2022. Springer Nature Limited.)

In this paper, the history, present status, and future of density-functional theory (DFT) is informally reviewed and discussed by 70 workers in the field, including molecular scientists, materials scientists, method developers and practitioners. The format of the paper is that of a roundtable discussion, in which the participants express and exchange views on DFT in the form of 302 individual contributions, formulated as responses to a preset list of 26 questions. Supported by a bibliography of 777 entries, the paper represents a broad snapshot of DFT, anno 2022.

Infection due to the Chikungunya virus (CHIKV) has taken the life of lots of people; and researchers are working to find the vaccine or promisng drug candidates against this viral infection. In this work, the authors have designed one component reaction based on the thia-/oxa-azolidineone and created a library of 2000 molecules based on the product obtained. Further, the compounds were screened through the docking using iGemdock against the non-structural protein 2 (nsp2) of CHIKV. Molecular docking gives the binding energy (BE) or energy for the formation of the complex between the designed compound and nsp2 of CHIKV; and CMPD222 gave the lowest energy. This is based on the energy obtained from van der Waal's interaction, hydrogen bonding and electrostatic instructions. Further, molecular dynamics simulations (MDS) of nsp2 of CHIKV with and without screened compound (222) were performed to validate the docking results and the change in free energy for the formation of the complex is -10.8327 kcal/mol. To explore the potential of CMPD222, the MDS of the CMPD222-nsp2 of CHIKV were performed at different temperatures (325, 350, 375 and 400 K) to understand the inhibition of the protease. MM-GBSA calculations were performed to determined change in entropy, change in enthalpy and change in free energy to understand the inhibition. Maximum inhibition of nsp2 of CHIKV with CMPD222 is observed at 375 K with a change in free energy of -19.3754 kcal/mol.Communicated by Ramaswamy H. Sarma.

Purpose: Programmable ventriculoperitoneal shunts (pVP shunts) are increasingly utilized for intraventricular chemotherapy, radioimmunotherapy, and/or cellular therapy. Shunt adjustments allow optimization of drug concentrations in the thecal space with minimization in the peritoneum. This report assesses the success of the pVP shunt as an access device for intraventricular therapies. Quantifying intrathecal drug delivery using scintigraphy by pVP shunt model has not been previously reported., Methods: We performed a single-institution, retrospective analysis on patients with CNS tumors and pVP shunts from 2003 to 2020, noting shunt model. pVP flow was evaluated for consideration of compartmental radioimmunotherapy (cRIT) using In-111-DTPA scintigraphy. Scintigraphy studies at 2-4 h and at 24 h quantified ventricular-thecal and peritoneal drug activity., Results: Twenty-two CSF flow studies were administered to 15 patients (N = 15) with diagnoses including medulloblastoma, metastatic neuroblastoma, pineoblastoma, and choroid plexus carcinoma. Six different types of pVP models were noted. 100% of the studies demonstrated ventriculo-thecal drug activity. 27% (6 of 22) of the studies had no peritoneal uptake visible by imaging. 73% (16 of 22) of the studies had minimal relative peritoneal uptake (< 12%). 27% (6 of 22) of the studies demonstrated moderate relative peritoneal uptake (12-37%). No studies demonstrated peritoneal uptake above 37%., Conclusions: All patients had successful drug delivery of In-111-DTPA to the ventriculo-thecal space. 73% of the patients had minimal relative (< 12%) peritoneal drug uptake. Though efficacy varies by shunt model, low numbers preclude conclusions regarding model superiority. CSF flow scintigraphy studies assesses drug distribution of In-111-DTPA, informing CSF flow for delivery of intraventricular therapies., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Multiply excited states in semiconductor quantum dots feature intriguing physics and play a crucial role in nanocrystal-based technologies. While photoluminescence provides a natural probe to investigate these states, room-temperature single-particle spectroscopy of their emission has proved elusive due to the temporal and spectral overlap with emission from the singly excited and charged states. Here, we introduce biexciton heralded spectroscopy enabled by a single-photon avalanche diode array based spectrometer. This allows us to directly observe biexciton-exciton emission cascades and measure the biexciton binding energy of single quantum dots at room temperature, even though it is well below the scale of thermal broadening and spectral diffusion. Furthermore, we uncover correlations hitherto masked in ensembles of the biexciton binding energy with both charge-carrier confinement and fluctuations of the local electrostatic potential. Heralded spectroscopy has the potential of greatly extending our understanding of charge-carrier dynamics in multielectron systems and of parallelization of quantum optics protocols.

Background: Baseline urinary incontinence (UI) strongly modulates UI recovery after adjuvant/salvage radiotherapy (ART/SRT), inducing clinicians to postpone it "as much as possible", maximizing UI recovery but possibly reducing efficacy. This series aims to analyze the trend of UI recovery and its predictors at radiotherapy start., Methods: A population of 408 patients treated with ART/SRT enrolled in a cohort study (ClinicalTrials.gov #NCT02803086) aimed at developing predictive models of radiation-induced toxicities. Self-reported UI and personality traits, evaluated by means of the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-SF) and Eysenck Personality Questionnaire - Revised (EPQ-R) questionnaires, were assessed at ART/SRT start. Several endpoints based on baseline ICIQ-SF were investigated: frequency and amount of urine loss (ICIQ3 and ICIQ4, respectively), "objective" UI (ICIQ3 + 4), "subjective" UI (ICIQ5), and "TOTAL" UI (ICIQ3 +4 + 5). The relationship between each endpoint and time from prostatectomy to radiotherapy (TTRT) was investigated. The association between clinical and personality variables and each endpoint was tested by uni- and multivariable logistic regression., Results: TTRT was the strongest predictor for all endpoints ( p -values ≤ 0.001); all scores improved between 4 and 8 months after prostatectomy, without any additional long-term recovery. Neuroticism independently predicted subjective UI, TOTAL UI, and daily frequency., Conclusions: Early UI recovery mostly depends on TTRT with no further improvement after 8 months from prostatectomy. Higher levels of neuroticism may overestimate UI.

We report on the light sterile neutrino search from the first four-week science run of the KATRIN experiment in 2019. Beta-decay electrons from a high-purity gaseous molecular tritium source are analyzed by a high-resolution MAC-E filter down to 40 eV below the endpoint at 18.57 keV. We consider the framework with three active neutrinos and one sterile neutrino. The analysis is sensitive to the mass, m&#95;{4}, of the fourth mass state for m&#95;{4}^{2}≲1000  eV^{2} and to active-to-sterile neutrino mixing down to |U&#95;{e4}|^{2}≳2×10^{-2}. No significant spectral distortion is observed and exclusion bounds on the sterile mass and mixing are reported. These new limits supersede the Mainz results for m&#95;{4}^{2}≲1000  eV^{2} and improve the Troitsk bound for m&#95;{4}^{2}<30  eV^{2}. The reactor and gallium anomalies are constrained for 100<Δm&#95;{41}^{2}<1000  eV^{2}.

Cardiovascular disease is the leading cause of death worldwide. Advanced insights into disease mechanisms and therapeutic strategies require a deeper understanding of the molecular processes involved in the healthy heart. Knowledge of the full repertoire of cardiac cells and their gene expression profiles is a fundamental first step in this endeavour. Here, using state-of-the-art analyses of large-scale single-cell and single-nucleus transcriptomes, we characterize six anatomical adult heart regions. Our results highlight the cellular heterogeneity of cardiomyocytes, pericytes and fibroblasts, and reveal distinct atrial and ventricular subsets of cells with diverse developmental origins and specialized properties. We define the complexity of the cardiac vasculature and its changes along the arterio-venous axis. In the immune compartment, we identify cardiac-resident macrophages with inflammatory and protective transcriptional signatures. Furthermore, analyses of cell-to-cell interactions highlight different networks of macrophages, fibroblasts and cardiomyocytes between atria and ventricles that are distinct from those of skeletal muscle. Our human cardiac cell atlas improves our understanding of the human heart and provides a valuable reference for future studies.

Alternatives to lead- and tin-based perovskites for photovoltaics and optoelectronics are sought that do not suffer from the disadvantages of toxicity and low device efficiency of present-day materials. Here we report a study of the double perovskite Cs 2 TeI 6 , which we have synthesized in the thin film form for the first time. Exhaustive trials concluded that spin coating CsI and TeI 4 using an antisolvent method produced uniform films, confirmed as Cs 2 TeI 6 by XRD with Rietveld analysis. They were stable up to 250 °C and had an optical band gap of ∼1.5 eV, absorption coefficients of ∼6 × 10 4 cm -1 , carrier lifetimes of ∼2.6 ns (unpassivated 200 nm film), a work function of 4.95 eV, and a p-type surface conductivity. Vibrational modes probed by Raman and FTIR spectroscopy showed resonances qualitatively consistent with DFT Phonopy -calculated spectra, offering another route for phase confirmation. It was concluded that the material is a candidate for further study as a potential optoelectronic or photovoltaic material., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

In this study, we report an inexpensive, green, and one-pot synthesis method for highly fluorescent carbon quantum dots (CQDs) using mango (Mangifera indica: M. indica) leaves to develop an efficient sensing platform for metal ions. The CQDs synthesized from M. indica leaves via pyrolysis treatment at 300 °C for 3 h were characterized by various spectroscopic and electron microscopy techniques for their structural, morphological, and optical properties. Accordingly, the synthesized CQDs showed an absorption peak at 213 nm to confirm the p-p* transition of the carbon core state, while the CQD particles were spherical with a size less than 10 nm. The prepared CQDs showed excellent fluorescent properties with blue emission spectra (around 525 nm) upon excitation at 435 nm. The synthesized CQDs had the prodigious sensing potential to detect Fe 2+ ions in water with a limit of detection of 0.62 ppm. Additionally, their sensing capability was tested using a real sample (e.g., Livogen tablet). Moreover, the synthesized CQDs showed substantial stability over a long period (three months). Thus, this study provides an inexpensive and facile method for CQD-based sensing of Fe 2+ ions with a photoluminescence quenching mechanism., Competing Interests: Declaration of competing interest This experimental research work is original and was carried out at the authors' institute. This work possesses no intellectual or financial conflict of interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The central goals of mechanobiology are to understand how cells generate force and how they respond to environmental mechanical stimuli. A full picture of these processes requires high-resolution, volumetric imaging with time-correlated force measurements. Here we present an instrument that combines an open-top, single-objective light sheet fluorescence microscope with an atomic force microscope (AFM), providing simultaneous volumetric imaging with high spatiotemporal resolution and high dynamic range force capability (10 pN - 100 nN). With this system we have captured lysosome trafficking, vimentin nuclear caging, and actin dynamics on the order of one second per single-cell volume. To showcase the unique advantages of combining Line Bessel light sheet imaging with AFM, we measured the forces exerted by a macrophage during FcɣR-mediated phagocytosis while performing both sequential two-color, fixed plane and volumetric imaging of F-actin. This unique instrument allows for a myriad of novel studies investigating the coupling of cellular dynamics and mechanical forces.

The loss of criticality in the form of weak first-order transitions or the end of the conformal window in gauge theories can be described as the merging of two fixed points that move to complex values of the couplings. When the complex fixed points are close to the real axis, the system typically exhibits walking behavior with Miransky (or Berezinsky-Kosterlitz-Thouless) scaling. We present a novel realization of these phenomena at strong coupling by means of the gauge/gravity duality, and give evidence for the conjectured existence of complex conformal field theories at the fixed points.

We report the first detection of gravitational lensing due to galaxy clusters using only the polarization of the cosmic microwave background (CMB). The lensing signal is obtained using a new estimator that extracts the lensing dipole signature from stacked images formed by rotating the cluster-centered Stokes QU map cutouts along the direction of the locally measured background CMB polarization gradient. Using data from the SPTpol 500  deg^{2} survey at the locations of roughly 18 000 clusters with richness λ≥10 from the Dark Energy Survey (DES) Year-3 full galaxy cluster catalog, we detect lensing at 4.8σ. The mean stacked mass of the selected sample is found to be (1.43±0.40)×10^{14}M&#95;{⊙} which is in good agreement with optical weak lensing based estimates using DES data and CMB-lensing based estimates using SPTpol temperature data. This measurement is a key first step for cluster cosmology with future low-noise CMB surveys, like CMB-S4, for which CMB polarization will be the primary channel for cluster lensing measurements.

The Cu (3 to 15 at%) is incorporated into ZnO thin film by atomic beam co-sputtering has been investigated for enhancement in room temperature ferromagnetism and green photo-luminance. These Cu-ZnO thin films examined with Raman spectroscopy, X-Ray Diffraction (XRD), UV-Visible spectroscopy, Hall measurement, magnetic force microscopy (MFM) and magnetic hysteresis. Raman spectroscopy, XRD confirms wurtzite structure and improvement in the crystallinity of ZnO upto 7% Cu. Further increase in Cu concentration results in growth in Cu nanoparticles. On increasing Cu concentration, there is decrement in transparency and increase in band gap with increase in n-type carrier concentration as confirmed from UV-Visible and Hall measurement studies. Magnetic measurement exhibited unique feature of room temperature ferromagnetic ordering in undoped and doped sample upto 3% Cu. The enhancement in magnetic moment as well as green emission in photoluminescence response with increase in Cu doping indicates that generation of large defects in ZnO by Cu doping, which can be attributed to combined effect of the presence of oxygen vacancies and/or structural inhomogeneity as well as formation of bound magnetic polarons. Importantly, synthesised Cu doped ZnO thin films can be used as spin LEDs and switchable spin-laser diodes.

We develop and validate a nonempirical generalized gradient approximation (GGA) exchange (X) density functional that performs as well as the SCAN (strongly constrained and appropriately normed) meta-GGA on standard thermochemistry tests. Additionally, the new functional (NCAP, nearly correct asymptotic potential) yields Kohn-Sham eigenvalues that are useful approximations of the density functional theory (DFT) ionization potential theorem values by inclusion of a systematic derivative discontinuity shift of the X potential. NCAP also enables time-dependent DFT (TD-DFT) calculations of good-quality polarizabilities, hyper-polarizabilities, and one-Fermion excited states without modification (calculated or ad hoc) of the long-range behavior of the exchange potential or other patches. NCAP is constructed by reconsidering the imposition of the asymptotic correctness of the X potential (-1/ r) as a constraint. Inclusion of derivative discontinuity and approximate integer self-interaction correction treatments along with first-principles determination of the effective second-order gradient expansion coefficient yields a major advance over our earlier correct asymptotic potential functional [CAP; J. Chem. Phys. 2015 , 142 , 054105 ]. The new functional reduces a spurious bump in the CAP atomic exchange potential and moves it to distances irrelevantly far from the nucleus (outside the tail of essentially all practical basis functions). It therefore has nearly correct atomic exchange-potential behavior out to rather large finite distances r from the nucleus but eventually goes as - c/ r with an estimated value for the constant c of around 0.3, so as to achieve other important properties of exact DFT exchange within the restrictions of the GGA form. We illustrate the results with the Ne atom optimized effective potentials and with standard molecular benchmark test data sets for thermochemical, structural, and response properties.

Parotid gland (PG) shrinkage and neck volume reduction during radiotherapy of head and neck (H&N) cancer patients is a clinical issue that has prompted interest in adaptive radiotherapy (ART). This study focuses on the difference between planned dose and delivered dose and the possible effects of an efficient replanning strategy during the course of treatment. Six patients with H&N cancer treated by tomotherapy were retrospectively enrolled. Thirty daily dose distributions (D MVCT ) were calculated on pretreatment megavoltage computed tomography (MVCT) scans. Deformable Image Registration which matched daily MVCT with treatment planning kilovoltage computed tomography was performed. Using the resulting deformation vector field, all daily D MVCT were deformed to the planning kilovoltage computed tomography and resulting doses were accumulated voxel per voxel. Cumulative D MVCT was compared to planned dose distribution performing γ-analysis (2 mm, 2% of 2.2 Gy). Two single-intervention ART strategies were executed on the 18th fraction whose previous data had suggested to be a suitable timepoint for a single replanning intervention: (1) replanning on the original target and deformed organ at risks (OARs) (a "safer" approach regarding tumor coverage) and (2) replanning on both deformed target and deformed OARs. D MVCT showed differences between planned and delivered doses (3D-γ 2mm/2%-passing rate = 85 ± 1%, p < 0.001). Voxel by voxel dose accumulation showed an increase in average dose of warped PG of 3.0 Gy ± 3.3 Gy. With ART the average dose of warped PG decreased by 3.2 Gy ± 1.7 Gy in comparison to delivered dose without replanning when both target and OARs were deformed. Average dose of warped PG decreased by 2.0 Gy ± 1.4 Gy when only OARs were deformed. Anatomical variations lead to increased doses to PGs. Efficient single-intervention ART-strategies with replanning on the 18th MVCT result a reduced PG dose. A strategy with deformation of both target and OAR resulted in the lowest PG dose, while formally maintaining PTV coverage. Deformation of only OAR nevertheless reduces PG dose and has less uncertainties regarding PTV coverage., (Copyright © 2019 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

We study the entropy production that is associated with the growing or shrinking of a small granule in, for instance, a colloidal suspension or in an aggregating polymer chain. A granule will fluctuate in size when the energy of binding is comparable to k B T , which is the "quantum" of Brownian energy. Especially for polymers, the conformational energy landscape is often rough and has been commonly modeled as being self-similar in its structure. The subdiffusion that emerges in such a high-dimensional, fractal environment leads to a Fokker-Planck Equation with a fractional time derivative. We set up such a so-called fractional Fokker-Planck Equation for the aggregation into granules. From that Fokker-Planck Equation, we derive an expression for the entropy production of a growing granule.

In this paper, we have reported a simple and efficient method for the synthesis of uniform, highly conducting single or few layer molybdenum disulfide (MoS2) on large scale. Scanning Electron Microscopy (SEM) and High Resolution Transmission Electron Microscopy (HRTEM) have been used for the confirmation of mono or few layered nature of the as-synthesized MoS2 sheets. X-ray Photoelectron Spectroscopy (XPS), X-Ray Diffraction (XRD) and Raman Spectroscopy have also been used to study the elemental, phase, and molecular composition of the sample. Optical properties of as-synthesized sample have been probed by measuring absorption and photoluminescence spectra which also compliment the formation of mono and few layers MoS2 Current-voltage (I-V ) characteristics of as-synthesized sample in the pellet form reveal that MoS2 sheets have an ohmic character and found to be highly conducting. Besides characterizing the as-synthesized sample, we have also proposed the mechanism and factors which play a decisive role in formation of high quality MoS2 sheets.

Nematic cells patterned with square arrays of strength m = ±1 topological defects were examined as a function of cell thickness (3 < h < 7.5 μm), temperature, and applied voltage. Thicker cells tend to exhibit an escape or partial escape of the nematic director as a means of mitigating the elastic energy cost near the defect cores, whereas thinner cells tend to favor splitting of the integer defects into pairs of half-integer strength defects. On heating the sample into the isotropic phase and cooling back into the nematic, some apparently split defects can reappear as unsplit integer defects, or vice versa. This is consistent with the system's symmetry, which requires a first order transition between the two relaxation mechanisms.

Identifying patients at risk of poor outcome after mild traumatic brain injury (MTBI) is essential to aid prognostics and treatment. Diffuse axonal injury (DAI) may be the primary pathologic feature of MTBI but is normally not detectable by conventional imaging technology. This lack of sensitivity of clinical imaging techniques has impeded a pathophysiologic understanding of the long-term cognitive and emotional consequences of MTBI, which often remain unnoticed and are attributed to factors other than the injury. Diffusion tensor imaging (DTI) is sensitive to microstructural properties of brain tissue and has been suggested to be a promising candidate for the detection of DAI in vivo. In this study, we report strong associations between brain white matter DTI and self-reported cognitive, somatic and emotional symptoms at 12 months post-injury in 134 MTBI patients. The anatomical distribution suggested global associations, in line with the diffuse symptomatology, although the strongest effects were found in frontal regions including the genu of the corpus callosum and the forceps minor. These findings support the hypothesis that DTI may provide increased sensitivity to the diffuse pathophysiology of MTBI and suggest an important role of advanced Magnetic Resonance Imaging (MRI) in trauma care.

The interface between biological matter and inorganic materials is a widely investigated research topic due to possible applications in biomedicine and nanotechnology. In this context, the molecular level adsorption mechanism that drives specific recognition between small peptide sequences and inorganic surfaces represents an important topic likely to provide much information useful for designing bioderived materials. Here, we investigate the dynamics at the interface between a Ti-binding peptide sequence (AMRKLPDAPGMHC) and a TiO 2 anatase surface by using molecular dynamics (MD) simulations. In the simulations the adsorption mechanism is characterized by diffusion of the peptide from the bulk water phase toward the TiO 2 surface, followed by the anchoring of the peptide to the surface. The anchoring is mediated by the interfacial water layers by means of the charged groups of the side chains of the peptide. The peptide samples anchored and dissociated states from the surface and its conformation is not affected by the surface when anchored.

The ability to simultaneously detect JAK2 V617F and MPL W515K/L mutations would substantially improve the early diagnosis of myeloproliferative neoplasms (MPNs) and decrease the risk of arterial thrombosis. The goal of this study is to achieve a point of care testing platform for simultaneous analysis of major genetic alterations in MPN. Here, we report a microfluidic platform including a glass capillary containing polypropylene matrix that extracts genomic DNA from a drop of whole blood, a microchip for simultaneous multi-gene mutation screening, and a handheld battery-powered heating device. The µmLchip system was successfully used for point-of-care identification of the JAK2 V617F and MPL W515K/L mutations. The µmLchip assays were then validated by mutation analysis with samples from 100 MPN patients who had previously been analyzed via unlabeled probe melting curve analysis or real-time PCR. The results from the µmLchip were in perfect agreement with those from the other methods, except for one discrepant result that was negative in the unlabeled probe melting curve analysis but positive in the µmLchip. After T-A cloning, sequences of cloned PCR products revealed JAK2 V617F mutation in the sample. The portable microfluidic platform may be very attractive in developing point-of-care diagnostics for MPL W515K/L and JAK2 V617F mutations.

Objective: Obese girls with polycystic ovarian syndrome (PCOS) have decreased insulin sensitivity (IS), muscle mitochondrial dysfunction and increased liver fat, which may contribute to their increased risk for type 2 diabetes. Less is known regarding normal-weight girls with PCOS., Methods: Normal-weight girls with PCOS [n =18, age 15.9 ± 1.8 years, body mass index (BMI) percentile 68 ± 18] and normal-weight controls (NWC; n = 20; age 15.0 ± 2.1 years, BMI percentile 60 ± 21) were studied. Tissue-specific IS was assessed with a four-phase hyperinsulinemic-euglycemic clamp with isotope tracers and a 2-hour oral glucose tolerance test (OGTT). Hepatic fat was determined using magnetic resonance imaging. Postexercise muscle mitochondrial function was assessed with 31 P MR spectroscopy., Results: Both groups had similar demographics, anthropomorphics, physical attributes, habitual physical activity levels and fasting laboratory values, except for increased total testosterone and DHEAS in PCOS. Clamp-assessed peripheral IS was lower in PCOS (10.4 ± 2.4 mg/kg/min vs 12.7 ± 2.1; P = 0.024). The 120-minute OGTT insulin and glucose concentrations were higher in PCOS (114 IU/mL ± 26 vs 41 ± 25, P = <0.001 and 119 ± 22 mg/dL vs 85 ± 23, P = 0.01, respectively). Muscle mitochondrial ADP and phosphocreatine time constants were slower in PCOS. Despite a higher percentage liver fat in PCOS, hepatic IS was similar between groups, as was adipose IS., Conclusions: Normal-weight girls with PCOS have decreased peripheral IS and muscle mitochondrial dysfunction, abnormal glucose disposal, relative postprandial hyperinsulinemia, and increased hepatic fat compared to NWC. Despite a normal BMI, multiple aspects of metabolism appear altered in normal-weight girls with PCOS.

Acoustophoresis, the ability to acoustically manipulate particles and cells inside a microfluidic channel, is a critical enabling technology for cell-sorting applications. However, one of the major impediments for routine use of acoustophoresis at clinical laboratory has been the reliance on the inherent physical properties of cells for separation. Here, we present a microfluidic-based microBubble-Activated Acoustic Cell Sorting (BAACS) method that rely on the specific binding of target cells to microbubbles conjugated with specific antibodies on their surface for continuous cell separation using ultrasonic standing wave. In acoustophoresis, cells being positive acoustic contrast particles migrate to pressure nodes. On the contrary, air-filled polymer-shelled microbubbles being strong negative acoustic contrast particles migrate to pressure antinodes and can be used to selectively migrate target cells. As a proof of principle, we demonstrate the separation of cancer cell line in a suspension with better than 75% efficiency. Moreover, 100% of the microbubble-cell conjugates migrated to the anti-node. Hence a better upstream affinity-capture has the potential to provide higher sorting efficiency. The BAACS technique expands the acoustic cell manipulation possibilities and offers cell-sorting solutions suited for applications at point of care.

This study is intended to develop a screening method for female breast cancer (BRC) from whole blood using Raman spectroscopy. A multivariate partial least squares (PLS) regression model is developed which is based upon Raman spectra of BRC-positive and healthy participants. It yields coefficients of regression at the corresponding Raman shifts. These coefficients represent the changes in molecular structures which are associated with the progress of disease. The present study pointed out some specific molecules which differentiated BRC-positive and healthy groups. In the BRC-positive group, a rising trend of calcium oxalate, calcium hydroxyapatite, phosphatidylserine and qunoid ring, and a lowering trend of tryptophan, tyrosine, and proline were observed in PLS-based coefficients of regression. The R-square value of the model was found to be 0.987, which is accepted clinically. The model was tested for the prediction of 50 randomly collected samples at a cutoff value of 0.5 with the gray region defined in the range of 0.4-0.6. Goodness of fit was estimated using accuracy, sensitivity, specificity, receiver operating characteristic (ROC) curve, and area under ROC curve. All of these parameters were found to be very promising.

Materials that luminesce after excitation with ionizing radiation are extensively applied in physics, medicine, security, and industry. Lanthanide dopants are known to trigger crystal scintillation through their fast d-f emissions; the same is true for other important applications as lasers or phosphors for lighting. However, this ability can be seriously compromised by unwanted anomalous emissions often found with the most common lanthanide activators. We report high-resolution X-ray-excited optical (IR to UV) luminescence spectra of CaF 2 :Yb and SrF 2 :Yb samples excited at 8949 eV and 80 K. Ionizing radiation excites the known anomalous emission of ytterbium in the CaF 2 host but not in the SrF 2 host. Wave function-based ab initio calculations of host-to-dopant electron transfer and Yb 2+ /Yb 3+ intervalence charge transfer explain the difference. The model also explains the lack of anomalous emission in Yb-doped SrF 2 excited by VUV radiation.

With the first direct detection of gravitational waves, the advanced laser interferometer gravitational-wave observatory (LIGO) has initiated a new field of astronomy by providing an alternative means of sensing the universe. The extreme sensitivity required to make such detections is achieved through exquisite isolation of all sensitive components of LIGO from non-gravitational-wave disturbances. Nonetheless, LIGO is still susceptible to a variety of instrumental and environmental sources of noise that contaminate the data. Of particular concern are noise features known as glitches , which are transient and non-Gaussian in their nature, and occur at a high enough rate so that accidental coincidence between the two LIGO detectors is non-negligible. Glitches come in a wide range of time-frequency-amplitude morphologies, with new morphologies appearing as the detector evolves. Since they can obscure or mimic true gravitational-wave signals, a robust characterization of glitches is paramount in the effort to achieve the gravitational-wave detection rates that are predicted by the design sensitivity of LIGO. This proves a daunting task for members of the LIGO Scientific Collaboration alone due to the sheer amount of data. In this paper we describe an innovative project that combines crowdsourcing with machine learning to aid in the challenging task of categorizing all of the glitches recorded by the LIGO detectors. Through the Zooniverse platform, we engage and recruit volunteers from the public to categorize images of time-frequency representations of glitches into pre-identified morphological classes and to discover new classes that appear as the detectors evolve. In addition, machine learning algorithms are used to categorize images after being trained on human-classified examples of the morphological classes. Leveraging the strengths of both classification methods, we create a combined method with the aim of improving the efficiency and accuracy of each individual classifier. The resulting classification and characterization should help LIGO scientists to identify causes of glitches and subsequently eliminate them from the data or the detector entirely, thereby improving the rate and accuracy of gravitational-wave observations. We demonstrate these methods using a small subset of data from LIGO's first observing run.

Here we demonstrate the use of a functional dopant as a fast and simple way to tune the chemical affinity and selectivity of polypyrrole films. More specifically, a boronic-functionalised dopant, 4-N-Pentylphenylboronic Acid (PBA), was used to provide to polypyrrole films with enhanced affinity towards diols. In order to prove the proposed concept, two model systems were explored: (i) the capture and the electrochemical detection of dopamine and (ii) the adhesion of bacteria onto surfaces. The chemisensor, based on overoxidised polypyrrole boronic doped film, was shown to have the ability to capture and retain dopamine, thus improving its detection; furthermore the chemisensor showed better sensitivity in comparison with overoxidised perchlorate doped films. The adhesion of bacteria, Deinococcus proteolyticus, Escherichia coli, Streptococcus pneumoniae and Klebsiella pneumoniae, onto the boric doped polypyrrole film was also tested. The presence of the boronic group in the polypyrrole film was shown to favour the adhesion of sugar-rich bacterial cells when compared with a control film (Dodecyl benzenesulfonate (DBS) doped film) with similar morphological and physical properties. The presented single step synthesis approach is simple and fast, does not require the development and synthesis of functional monomers, and can be easily expanded to the electrochemical, and possibly chemical, fabrication of novel functional surfaces and interfaces with inherent pre-defined sensing and chemical properties., Competing Interests: The authors have declared that no competing interests exist.

A complete physical description of membrane remodeling processes, such as fusion or fission, requires knowledge of the underlying free energy landscapes, particularly in barrier regions involving collective shape changes, topological transitions, and high curvature, where Canham-Helfrich (CH) continuum descriptions may fail. To calculate these free energies using atomistic simulations, one must address not only the sampling problem due to high free energy barriers, but also an orthogonal sampling problem of combinatorial complexity stemming from the permutation symmetry of identical lipids. Here, we solve the combinatorial problem with a permutation reduction scheme to map a structural ensemble into a compact, nondegenerate subregion of configuration space, thereby permitting straightforward free energy calculations via umbrella sampling. We applied this approach, using a coarse-grained lipid model, to test the CH description of bending and found sharp increases in the bending modulus for curvature radii below 10 nm. These deviations suggest that an anharmonic bending term may be required for CH models to give quantitative energetics of highly curved states.

This work investigated the utility of performing efficiency calibration for environmental gamma spectrometry using the Monte Carlo based, free of charge GATE toolbox. The validity of this approach was tested by comparing output efficiency values of an in-house developed GATE-based program with experimental measurements covering various geometries and primary photon energies. The results of this comparison revealed relative deviations within ±20%, thus validating the employed computational approach. Moreover, the GATE-based method was able to predict quantities that are generally difficult to measure experimentally, such as the number of interactions preceding full energy absorption. These computationally obtained predictions were found to be in agreement with theory.