118 research outputs found

    IoT Based Virtual Reality Game for Physio-therapeutic Patients

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    Biofeedback therapy trains the patient to control voluntarily the involuntary process of their body. This non-invasive and non-drug treatment is also used as a means to rehabilitate the physical impairments that may follow a stroke, a traumatic brain injury or even in neurological aspects within occupational therapy. The idea behind this study is based on using immersive gaming as a tool for physical rehabilitation that combines the idea of biofeedback and physical computing to get a patient emotionally involved in a game that requires them to do the exercises in order to interact with the game. This game is aimed towards addressing the basic treatment for ‘Frozen Shoulder’. In this work, the physical motions are captured by the wearable ultrasonic sensor attached temporarily to the various limbs of the patient. The data received from the sensors are then sent to the game via serial wireless communication. There are two main aspects to this study: motion capturing and game design. The current status of the application is a single ultrasonic detector. The experimental result shows that physio-therapeutic patients are benefited through the IoT based virtual reality game

    Expanding Benzoxazole-Based Inosine 5?-Monophosphate Dehydrogenase (IMPDH) Inhibitor Structure–Activity As Potential Antituberculosis Agents

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    New drugs and molecular targets are urgently needed to address the emergence and spread of drug-resistant tuberculosis. Mycobacterium tuberculosis (Mtb) inosine 5?-monophosphate dehydrogenase 2 (MtbIMPDH2) is a promising yet controversial potential target. The inhibition of MtbIMPDH2 blocks the biosynthesis of guanine nucleotides, but high concentrations of guanine can potentially rescue the bacteria. Herein we describe an expansion of the structure–activity relationship (SAR) for the benzoxazole series of MtbIMPDH2 inhibitors and demonstrate that minimum inhibitory concentrations (MIC) of ?1 ?M can be achieved. The antibacterial activity of the most promising compound, 17b (Q151), is derived from the inhibition of MtbIMPDH2 as demonstrated by conditional knockdown and resistant strains. Importantly, guanine does not change the MIC of 17b, alleviating the concern that guanine salvage can protect Mtb in vivo. These findings suggest that MtbIMPDH2 is a vulnerable target for tuberculosis

    Potential for pancreatic maturation of differentiating human embryonic stem cells is sensitive to the specific pathway of definitive endoderm commitment

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    This study provides a detailed experimental and mathematical analysis of the impact of the initial pathway of definitive endoderm (DE) induction on later stages of pancreatic maturation. Human embryonic stem cells (hESCs) were induced to insulin-producing cells following a directed-differentiation approach. DE was induced following four alternative pathway modulations. DE derivatives obtained from these alternate pathways were subjected to pancreatic progenitor (PP) induction and maturation and analyzed at each stage. Results indicate that late stage maturation is influenced by the initial pathway of DE commitment. Detailed quantitative analysis revealed WNT3A and FGF2 induced DE cells showed highest expression of insulin, are closely aligned in gene expression patterning and have a closer resemblance to pancreatic organogenesis. Conversely, BMP4 at DE induction gave most divergent differentiation dynamics with lowest insulin upregulation, but highest glucagon upregulation. Additionally, we have concluded that early analysis of PP markers is indicative of its potential for pancreatic maturation. © 2014 Jaramillo et al

    Large-scale Synthesis of β-SiC Nanochains and Their Raman/Photoluminescence Properties

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    Although the SiC/SiO2 nanochain heterojunction has been synthesized, the chained homogeneous nanostructure of SiC has not been reported before. Herein, the novel β-SiC nanochains are synthesized assisted by the AAO template. The characterized results demonstrate that the nanostructures are constructed by spheres of 25–30 nm and conjoint wires of 15–20 nm in diameters. Raman and photoluminescence measurements are used to explore the unique optical properties. A speed-alternating vapor–solid (SA-VS) growth mechanism is proposed to interpret the formation of this typical nanochains. The achieved nanochains enrich the species of one-dimensional (1D) nanostructures and may hold great potential applications in nanotechnology

    Trichostatin A Selectively Suppresses the Cold-Induced Transcription of the ZmDREB1 Gene in Maize

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    Post-translational modifications of histone proteins play a crucial role in responding to environmental stresses. Histone deacetylases (HDACs) catalyze the removal of an acetyl group from histones and are generally believed to be a transcriptional repressor. In this paper, we report that cold treatment highly induces the up-regulation of HDACs, leading to global deacetylation of histones H3 and H4. Treatment of maize with the HDAC inhibitor trichostatin A (TSA) under cold stress conditions strongly inhibits induction of the maize cold-responsive genes ZmDREB1 and ZmCOR413. However, up-regulation of the ZmICE1 gene in response to cold stress is less affected. The expression of drought and salt induced genes, ZmDBF1 and rab17, is almost unaffected by TSA treatment. Thus, these observations show that HDACs may selectively activate transcription. The time course of TSA effects on the expression of ZmDREB1 and ZmCOR413 genes indicates that HDACs appear to directly activate the ZmDREB1 gene, which in turn modulates ZmCOR413 expression. After cold treatment, histone hyperacetylation and DNA demethylation occurs in the ICE1 binding region, accompanied by an increase in accessibility to micrococcal nuclease (MNase). The two regions adjacent to the ICE1 binding site remain hypoacetylated and methylated. However, during cold acclimation, TSA treatment increases the acetylation status and accessibility of MNase and decreases DNA methylation at these two regions. However, TSA treatment does not affect histone hyperacetylation and DNA methylation levels at the ICE1 binding regions of the ZmDREB1 gene. Altogether, our findings indicate that HDACs positively regulate the expression of the cold-induced ZmDREB1 gene through histone modification and chromatin conformational changes and that this activation is both gene and site selective

    Comparative SNP and Haplotype Analysis Reveals a Higher Genetic Diversity and Rapider LD Decay in Tropical than Temperate Germplasm in Maize

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    Understanding of genetic diversity and linkage disequilibrium (LD) decay in diverse maize germplasm is fundamentally important for maize improvement. A total of 287 tropical and 160 temperate inbred lines were genotyped with 1943 single nucleotide polymorphism (SNP) markers of high quality and compared for genetic diversity and LD decay using the SNPs and their haplotypes developed from genic and intergenic regions. Intronic SNPs revealed a substantial higher variation than exonic SNPs. The big window size haplotypes (3-SNP slide-window covering 2160 kb on average) revealed much higher genetic diversity than the 10 kb-window and gene-window haplotypes. The polymorphic information content values revealed by the haplotypes (0.436–0.566) were generally much higher than individual SNPs (0.247–0.259). Cluster analysis classified the 447 maize lines into two major groups, corresponding to temperate and tropical types. The level of genetic diversity and subpopulation structure were associated with the germplasm origin and post-domestication selection. Compared to temperate lines, the tropical lines had a much higher level of genetic diversity with no significant subpopulation structure identified. Significant variation in LD decay distance (2–100 kb) was found across the genome, chromosomal regions and germplasm groups. The average of LD decay distance (10–100 kb) in the temperate germplasm was two to ten times larger than that in the tropical germplasm (5–10 kb). In conclusion, tropical maize not only host high genetic diversity that can be exploited for future plant breeding, but also show rapid LD decay that provides more opportunity for selection

    Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade.

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    The genomes of cancers deficient in mismatch repair contain exceptionally high numbers of somatic mutations. In a proof-of-concept study, we previously showed that colorectal cancers with mismatch repair deficiency were sensitive to immune checkpoint blockade with antibodies to programmed death receptor-1 (PD-1). We have now expanded this study to evaluate the efficacy of PD-1 blockade in patients with advanced mismatch repair-deficient cancers across 12 different tumor types. Objective radiographic responses were observed in 53% of patients, and complete responses were achieved in 21% of patients. Responses were durable, with median progression-free survival and overall survival still not reached. Functional analysis in a responding patient demonstrated rapid in vivo expansion of neoantigen-specific T cell clones that were reactive to mutant neopeptides found in the tumor. These data support the hypothesis that the large proportion of mutant neoantigens in mismatch repair-deficient cancers make them sensitive to immune checkpoint blockade, regardless of the cancers\u27 tissue of origin

    Plant 45S rDNA Clusters Are Fragile Sites and Their Instability Is Associated with Epigenetic Alterations

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    Our previous study demonstrated that 45S ribosomal DNA (45S rDNA) clusters were chromosome fragile sites expressed spontaneously in Lolium. In this study, fragile phenotypes of 45S rDNA were observed under aphidicolin (APH) incubation in several plant species. Further actinomycin D (ActD) treatment showed that transcriptional stress might interfere with chromatin packaging, resulting in 45S rDNA fragile expression. These data identified 45S rDNA sites as replication-dependent as well as transcription-dependent fragile sites in plants. In the presence of ActD, a dramatic switch to an open chromatin conformation and accumulated incomplete 5′ end of the external transcribed spacer (5′ETS) transcripts were observed, accompanied by decreased DNA methylation, decreased levels of histone H3, and increased histone acetylation and levels of H3K4me2, suggesting that these epigenetic alterations are associated with failure of 45S rDNA condensation. Furthermore, the finding that γ-H2AX was accumulated at 45S rDNA sites following ActD treatment suggested that the DNA damage signaling pathway was associated with the appearance of 45S rDNA fragile phenotypes. Our data provide a link between 45S rDNA transcription and chromatin-packaging defects and open the door for further identifying the molecular mechanism involved

    Frugal Innovation for Supply Chain Sustainability in SMEs: Multi-method Research Design

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    In this study we attempt to establish the missing links between supply chain sustainability and frugal innovation. Our study motivations stem from two facets of the emerging markets: firstly, the institutional barriers and secondly, the resource constraints. We argue that there is a synergy in the concepts of frugal innovation and sustainability in supply chains and there is a need to further explore this synergy. Furthermore, we claim that even in the wake of many success stories in the frugal innovative supply chain management practices from emerging markets such as India, there are very few, if any, attempts made to understand the implications of a sustainability oriented frugal innovations in the particular context. To address this gap we develop a model to establish the linkage between sustainable supply chains and frugal innovations. Our proposed conceptual framework depicts the hierarchy and interlinks of the identified enablers in developing sustainability oriented frugal innovative capabilities in supply chains. Furthermore, we have empirically validated our theoretical framework using survey data. We observed that most of the interpretive links are supported. These findings extend the understanding of frugal innovation for supply chain sustainability using multi-method research design, while also providing theoretically guidance to managers in the development of frugal innovation capability to achieve sustainability in supply chain in resource constrained environment
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