Sunburst quantum Ising model under interaction quench: entanglement and role of initial state coherence

We study the non-equilibrium dynamics of an isolated bipartite quantum system, the sunburst quantum Ising model, under interaction quench. The pre-quench limit of this model is two non-interacting integrable systems, namely a transverse ising chain and finite number of isolated qubits. As a function of interaction strength, the spectral fluctuation property goes from Poisson to Wigner-Dyson statistics. We chose entanglement entropy as a probe to study the approach to thermalization or lack of it in post-quench dynamics. In the near-integrable limit, as expected, the linear entropy displays oscillatory behavior while in the chaotic limit, it saturates. Along with the chaotic nature of the time evolution generator, we show the importance of the role played by the coherence of the initial state in deciding the nature of thermalization. We further show that these findings are general by replacing the Ising ring with a disordered $XXZ$ model with disorder strength putting it in the many-body localized phase

Analyzing Drug Release Kinetics from Water-Soluble Polymers

The ability to develop predictive mathematical models of therapeutic release from pharmaceutical formulations has enormous potential to enhance our understanding of such systems and improve the controlled release of the payload. The current work describes the development and testing of a one-dimensional model of drug transport from amorphous, swelling/dissolving polymers. Model parameters such as the diffusivities of water and drug, the initial loading of the drug, the polymer dissolution rate, drug-polymer interactions, and the tablet thickness were varied, demonstrating the ability to tune the release to be controlled by either drug diffusion or polymer chain disentanglement. In addition, predictions of the concentration profiles of water and drug within the gel layer, the locations of the erosion and swelling boundaries, and gel layer thickness were obtained for diffusion- and disentanglement-controlled release. To highlight the generalizability of this model, multiple parameters were varied, and it was shown that increasing the diffusivities of water and drug and the initial drug loading and decreasing the polymer dissolution rate sufficiently resulted in diffusion-controlled release. The model was fit to experimental data for a model tablet system comprising of sodium diclofenac entrapped in a poly(vinyl pyrrolidone) matrix and yielded physically meaningful values of the model parameters. The work presented here demonstrates the predictive power of the model for rapid and rational design of future pharmaceutical formulations for controlled drug delivery

NTIRE 2020 Challenge on Spectral Reconstruction from an RGB Image

This paper reviews the second challenge on spectral reconstruction from RGB images, i.e., the recovery of whole- scene hyperspectral (HS) information from a 3-channel RGB image. As in the previous challenge, two tracks were provided: (i) a "Clean" track where HS images are estimated from noise-free RGBs, the RGB images are themselves calculated numerically using the ground-truth HS images and supplied spectral sensitivity functions (ii) a "Real World" track, simulating capture by an uncalibrated and unknown camera, where the HS images are recovered from noisy JPEG-compressed RGB images. A new, larger-than-ever, natural hyperspectral image data set is presented, containing a total of 510 HS images. The Clean and Real World tracks had 103 and 78 registered participants respectively, with 14 teams competing in the final testing phase. A description of the proposed methods, alongside their challenge scores and an extensive evaluation of top performing methods is also provided. They gauge the state-of-the-art in spectral reconstruction from an RGB image

Impact of Intratumor Heterogeneity and the Tumor Microenvironment in Shaping Tumor Evolution and Response to Therapy

Intratumor heterogeneity (ITH) is a crucial challenge in cancer treatment. The genotypic and phenotypic heterogeneity underlying diverse cancer types leads to subclonal variation, which may result in mixed or failed response to therapy. The heterogeneity at the tumor level, along with the tumor microenvironment (TME), often shapes tumor evolution and ultimately clinical outcome. Given that modern treatment paradigms increasingly expose patients with metastatic disease to multiple treatment modalities through the course of their disease, there exists a need to characterize robust and predictive biomarkers of response to therapy. In order to accurately characterize tumor evolution, we need to account for both intra-tumoral genomic factors as well as how these factors interact with the components of the tumor microenvironment to allow for response and resistance to various forms of therapy. Through multidimensional profiling of a tumor and its cellular ecosystem we assessed spatial heterogeneity in response to ICB in metastatic melanoma and highlighted the effects of copy number alterations being associated to varied immune phenotypes. We characterized localized regions of immune activation by both T and B cells however, sub-regions with chromosome 7 gain displayed a distinct lack of immunocytic infiltrate but evidence of neutrophil activation that was recapitulated in TCGA samples and was associated with lack of response to ICB across three separate cohorts. Through a longitudinal sampling strategy paired to a clinical trial, we characterized the impact of heterogeneity on therapy outcomes after combination ICB agents in multiple sarcoma histologies. Amongst the genomic, transcriptomic and immune-based molecular correlates analyzed, elevated intratumoral levels of B cells were most significantly correlated with response at both time-points, as measured by both gene expression and immunostaining. Responsive tumors were also associated with higher diversity and richness of the intratumoral T cell repertoire at baseline. In order to characterize the effects of the immune-tumor microenvironment, we used multiplex immunofluorescence to quantitatively analyze T-cell subsets and sequenced the T-cell receptors of matched Barrett’s Esophagus (BE) and Esophageal adenocarcinoma (EAC) samples from our patient cohort. Through our work we identified a more infiltrated and diverse immune microenvironment in EAC as compared to BE, however this was primarily characterized by an immunosuppressive T-cell infiltrate, the clonal expansion of which may have been limited with public antigenicity. In summary, our work frames the spatial and temporal molecular features of heterogeneity characterized across tumors and their surrounding microenvironment, and how their interplay in turn may influence disease progression, tumor evolution and response to therapy

Analyzing Drug Release Kinetics from Water-Soluble Polymers

The ability to develop predictive mathematical models of therapeutic release from pharmaceutical formulations has enormous potential to enhance our understanding of such systems and improve the controlled release of the payload. The current work describes the development and testing of a one-dimensional model of drug transport from amorphous, swelling/dissolving polymers. Model parameters such as the diffusivities of water and drug, the initial loading of the drug, the polymer dissolution rate, drug-polymer interactions, and the tablet thickness were varied, demonstrating the ability to tune the release to be controlled by either drug diffusion or polymer chain disentanglement. In addition, predictions of the concentration profiles of water and drug within the gel layer, the locations of the erosion and swelling boundaries, and gel layer thickness were obtained for diffusion- and disentanglement-controlled release. To highlight the generalizability of this model, multiple parameters were varied, and it was shown that increasing the diffusivities of water and drug and the initial drug loading and decreasing the polymer dissolution rate sufficiently resulted in diffusion-controlled release. The model was fit to experimental data for a model tablet system comprising of sodium diclofenac entrapped in a poly(vinyl pyrrolidone) matrix and yielded physically meaningful values of the model parameters. The work presented here demonstrates the predictive power of the model for rapid and rational design of future pharmaceutical formulations for controlled drug delivery.This document is the unedited Author’s version of a Submitted Work that was subsequently accepted for publication in Industrial and Engineering Chemistry Research, copyright © American Chemical Society after peer review. To access the final edited and published work see DOI: 10.1021/acs.iecr.8b05800.</p

Synthesis and characterization of rapidly-degrading polyanhydrides as vaccine adjuvants

There is a currently a need to develop adjuvants that are best suited to simultaneously enhance immune responses, induce immunologic memory, improve patient compliance (i.e., reduce doses and inflammation), and provide vaccine shelf stability for stockpiling and global deployment to challenging environments. Biodegradable polyanhydrides have been investigated extensively to overcome such challenges. It has been shown that controlling copolymer composition can result in chemistry-dependent immunomodulatory capabilities. These studies have revealed that copolymers rich in sebacic acid (SA) are highly internalized by antigen presenting cells and confer improved shelf stability of encapsulated proteins, while copolymers rich in 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG) also exhibit enhanced internalization by and activation of antigen presenting cells (APCs), in addition to providing superior retention of protein stability following encapsulation and release. However, to date CPTEG:SA copolymers have not been synthesized and described. In this work, we hypothesized that new copolymers composed of CPTEG and SA would combine the advantages of both monomers in terms of enhanced thermal properties, maintaining antigenicity of encapsulated proteins following nanoparticle synthesis, and superior cellular internalization and activation by APCs, demonstrated by the upregulation of costimulatory markers CD80, CD86, and CD40, as well as the secretion of proinflammatory cytokines IL-6, IL-1β, and TNF-α. Herein, we describe the synthesis and design of novel CPTEG:SA nanoparticles with improved thermal properties, payload stability, and internalization by antigen presenting cells for applications in vaccine delivery. The performance of these new CPTEG:SA formulations was compared to that of traditional polyanhydride copolymers.This document is the unedited Author’s version of a Submitted Work that was subsequently accepted for publication in ACS Biomaterials Science & Engineering, copyright © American Chemical Society after peer review. To access the final edited and published work see DOI: 10.1021/acsbiomaterials.9b01427. Posted with permission.</p

Sodium fluoride induces skeletal muscle atrophy via changes in mitochondrial and sarcomeric proteomes.

Sodium Fluoride (NaF) can change the expression of skeletal muscle proteins. Since skeletal muscle is rich in mitochondrial and contractile (sarcomeric) proteins, these proteins are sensitive to the effects of NaF, and the changes are dose-and time-dependent. In the current study, we have analysed the effect of high concentrations of NaF (80ppm) on mouse skeletal muscle at two different time points, i.e., 15 days and 60 days. At the end of the experimental time, the animals were sacrificed, skeletal muscles were isolated, and proteins were extracted and subjected to bioinformatic (Mass Spectrometric) analysis. The results were analysed based on changes in different mitochondrial complexes, contractile (sarcomeric) proteins, 26S proteasome, and ubiquitin-proteasome pathway. The results showed that the mitochondrial proteins of complex I, II, III, IV and V were differentially regulated in the groups treated with 80ppm of NaF for 15 days and 60 days. The network analysis indicated more changes in mitochondrial proteins in the group treated with the higher dose for 15 days rather than 60 days. Furthermore, differential expression of (sarcomeric) proteins, downregulation of 26S proteasome subunits, and differential expression in proteins related to the ubiquitin-proteasome pathway lead to muscle atrophy. The differential expression might be due to the adaptative mechanism to counteract the deleterious effects of NaF on energy metabolism. Data are available via ProteomeXchange with identifier PXD035014

Phytochemical and pharmacological aspects of genus haplophyllum (Rutaceae): A review

The genus Haplophyllum belongs to the large family of flowering plants, Rutaceae. The genus Haplophyllum comprises of about 133 species of low shrubs and perennial herbs in the subtropical and tropical regions of the northern hemisphere of the Old World, markedly in Iran, Turkey and Central Asia. Species from this genus contains a rich sources of secondary metabolites such as quinoline alkaloids, furoquinoline alkaloids, isoquinoline alkaloids, acridone alkaloids, amide alkaloids, quinolone alkaloids, lignans, arylnaphtalene lignans, lignan glycosides, flavonoids, coumarins, saponins, amides and sterols. Extracts and pure compounds isolated from Haplophyllum species have been experimentally shown to have various bioactivities such as antioxidant, anti-inflammatory, antimicrobial, insecticidal, antiprotozoal, molluscicidal, cytotoxic, anti-cancer and anti-HIV activities. This reviews compile the phytochemical constituents, various pharmacological activities of the different plants of the Haplophyllum genus and the NMR value of different compounds of Haplophyllum genus

Mental Health Issues in Madhya Pradesh: Insights from National Mental Health Survey of India 2016

Background: About 14% of the global mental health burden is contributed by India. However, there exists a disparity in mental health patterns, utilization, and prioritization among various Indian states. The state of Madhya Pradesh is a low performer among Indian states, ranking lower than the national average on the Human Development Index, Hunger Index, and Gross Domestic Product (GDP). The state also performes poorly on other health-related indicators. Objectives of Study: To estimate the prevalence and patterns of mental illnesses in the state of Madhya Pradesh, India. Material and Methods: This study used the multistage, stratified, random cluster sampling technique, with selection probability proportionate to size at each stage. A total of 3240 individuals 18 years and older were interviewed. The mixed-method study that was employed had both quantitative and qualitative components. The Mini International Neuropsychiatric Interview along with 10 other instruments were used. Results: The overall weighted prevalence for any mental illness was 13.9%, with 16.7% over the lifetime. The treatment gap for all of the mental health problems is very high (91%), along with high suicidal risk and substance use in the state. Conclusions: This study provides evidence of the huge burden of mental, behavioral, and substance use disorders as well as the treatment gap in Madhya Pradesh. This information is crucial for developing an effective prevention and control strategy. The high treatment gap in the state calls for coordinated efforts from all stakeholders, including policy makers, political leaders, health care professionals, and the society at large to give mental health care its due priority. These findings also highlight the need for multi-pronged interventions rooted in health policy directed at reducing the treatment gap in the short term and disease burden in the long run