3,793 research outputs found

    Wireless electrical–molecular quantum signalling for cancer cell apoptosis

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    Quantum biological tunnelling for electron transfer is involved in controlling essential functions for life such as cellular respiration and homoeostasis. Understanding and controlling the quantum effects in biology has the potential to modulate biological functions. Here we merge wireless nano-electrochemical tools with cancer cells for control over electron transfer to trigger cancer cell death. Gold bipolar nanoelectrodes functionalized with redox-active cytochrome c and a redox mediator zinc porphyrin are developed as electric-field-stimulating bio-actuators, termed bio-nanoantennae. We show that a remote electrical input regulates electron transport between these redox molecules, which results in quantum biological tunnelling for electron transfer to trigger apoptosis in patient-derived cancer cells in a selective manner. Transcriptomics data show that the electric-field-induced bio-nanoantenna targets the cancer cells in a unique manner, representing electrically induced control of molecular signalling. The work shows the potential of quantum-based medical diagnostics and treatments

    Numerical and experimental investigation of static shaft Wankel expander for compressed-air energy storage

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    Compressed air energy storage (CAES) is a promising technology for storing mechanical and electrical energy using the gas power cycle. The expansion device is a critical component of the CAES that determines the overall performance of the system. Standard Wankel expander (SWE) is one of the volumetric expanders which has several advantages including low vibration, ability to produce high power output, low manufacturing cost and less moving parts. However, SWE requires valves for timing the inlet and outlet flow and a balancing system to ensure reliable operation. Static shaft Wankel expander (SSWE) is an attractive solution to enable valves’ removal and the need for balancing system. This paper presents a detailed experimental and numerical investigation of an SSWE performance at various operating pressures and temperatures for CAES application. An advanced computational fluid dynamic simulation model taking into account the dynamic motion of the SSWE and utilising real gas air properties. A compressed air test rig was constructed and instrumented with temperature, flow rate, pressure and torque sensors. Experimental testing at temperatures 20 °C to 80 °C and pressures of 1.5 bara to 3 bara was conducted and compared to the CFD simulations results. Correlations were developed for the friction power loss. Experimental results showed that the developed SSWE can produce power output of 504 W at 80 °C and 3 bara and its isentropic efficiency reached 71 % at 60 °C and 2 bara.<br/

    Sistema Informático para el control de trámite documentario de reembolso de la prestación económica de sepelio en la oficina de Seguros 2023

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    A lo largo de la historia, los trámites documentarios y los procesos administrativos en el sector público han sido conocidos por su lentitud y esta situación se ha visto agravada con la llegada de la pandemia de COVID-19, lo que ha ralentizado aún más dichos procesos. A pesar de encontrarnos en pleno siglo XXI, no se han producido cambios significativos en este ámbito. Esta situación fue la principal motivación para llevar a cabo la presente investigación. El objetivo de este estudio fue aplicar el marco de trabajo de la norma ISO 30300 en los procesos de trámite documentario de las entidades públicas, adoptando sus buenas prácticas. Además, se utilizó un diseño de estudio experimental (preexperimental), tomando registros mensuales de las solicitudes de prestación económica de sepelio en diferentes establecimientos de salud del sector de Comas. Como resultado de la investigación, se observó una falta de interés en la investigación sobre la gestión documental. No obstante, en los pocos estudios realizados, las recomendaciones fueron favorables, ya que se encontró que la implementación de la norma ISO 30300 ayuda a cumplir los objetivos establecidos por las organizaciones. En conclusión, se pudo comprobar que la aplicación de las normas ISO 30301 en las empresas tiene un impacto significativo en su entorno tanto interno como externo. Frente a las problemáticas y evaluaciones a las que se enfrentan, las empresas que han adoptado estas normas han respondido de manera satisfactoria, marcando una diferencia con respecto a otras

    Development and validation of innovative sequencing tools for the fast and efficient detection of plant virus

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    Plant viruses are a major cause of crop losses and decreased agricultural productivity worldwide. Rapid and accurate detection of plant viruses is essential for the implementation of effective control measures. Traditional methods of plant virus detection, such as serological and molecular assays, often present very good performance criteria but they are targeted, and they don’t detect new viruses or divergent strains of known viruses. Overall, developing and validating innovative sequencing tools for fast and efficient detection of plant viruses gained a lot of leverage. Indeed, high throughput sequencing (HTS) tests followed by bioinformatic analyses can detect several viruses at once (including novel ones) and then characterise their genomes. This very high inclusivity allows better monitoring of agricultural pest presence than traditional methods. In addition, the sensitivity of HTS viral detection is theoretically higher than molecular and serological tests, meaning that low-level infection can be traced more efficiently. HTS tests have several drawbacks: the price, the high technical requirements and the cross-contamination of sequences between samples nevertheless. The cost of viral detection by sequencing is higher than traditional methods, but the cost gap is reducing over time as HTS is more and more affordable. More technical skills are required for sequencing and analysis of a sample for virus detection, but the laboratory and bioinformatic protocols are becoming simpler and easier to learn and apply. Cross-contamination between samples is a recurrent phenomenon that is challenging the operational activities of laboratories aiming to detect plant pests. The high sensitivity of HTS has a drawback as it means that cross-contamination is an even more pressing issue than with traditional methods. Cross-contamination is probably one of the main issues when using HTS for viral detection. Indeed, if an unexpected genetic material transfer happens between two samples in the laboratory, one virus can be sequenced in the other sample. Since sequencing sensitivity is high, HTS is more prone to detect this cross-contaminating virus. That may lead to a false positive virus detection (as it is really in the bioinformatic data) while it was not present in the plant. The specificities of HTS technologies (high sensitivity, high inclusivity but with the complexity of laboratory and bioinformatics steps) make their validation difficult compared to traditional tests. Therefore, this thesis describes the side-by-side comparison between traditional tests and HTS technologies for virus indexing of Musa germplasm collection. In addition, an alien control (a specific type of external control) has been used for the first time to II monitor cross-contamination in HTS. In addition, a newly described alien-based filter algorithm, called Cont-ID, has been developed and applied to find the most appropriate limit of detection that should be applied for accurate virus detection taking into account the risk of false negatives and false positives. That way, the detection prediction's confidence can be high enough to be considered for its use in plant virus diagnosis. As written above, HTS technologies can also characterise the genome of the detected viruses. Through variant analysis, the different virus variants can be highlighted. A performance testing was conducted to better understand the difficulties and therefore improve the variants' characterisation. This thesis has therefore addressed several drawbacks limiting potentially the use of HTS technologies for plant virus detection and genome characterisation. It has delivered several milestones to contribute to these technologies' wider and more reliable applications for plant virus detection. Overall, it has reinforced its high potential for improving the control and management of plant virus diseases.2. Zero hunge

    Characterising novel genetic causes of growth failure

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    To identify novel genetic causes of growth failure, I developed a unique, targeted whole gene panel for rapid and accurate genetic testing of patients with short stature and features of Growth Hormone Insensitivity (GHI) or unexplained short stature. This included 64 genes of interest, including those in the GH-IGF1 pathway and genes linked to conditions with overlapping features. In parallel, I also assessed these patients for copy number variants. Using custom bioinformatic pipelines to filter these data sets and a variety of in silico prediction programs, I identified interesting novel genetic defects in both known and candidate growth genes. I then performed functional analysis of these defects to determine if they affected gene structure/function and could explain the patient phenotype. I identified several novel splicing mutations in the Growth Hormone Receptor (GHR) causing a spectrum of GHI. These include a novel mutation deep within intron 6 GHR that leads to mis-splicing and pseudoexon inclusion. Pseudoexon inclusion leads to frameshift of the GHR and thus causes a non-functional Growth Hormone Receptor and severe GHI. I discovered two novel heterozygous GHR mutations in patients with milder GHI phenotypes. These mutations both led to mis-splicing of exon 9 of the GHR and act in a dominant negative effect on the GHR, reducing the efficacy of signalling and explaining their milder phenotypes. I identified a rare novel heterozygous IGF1 variant that I hypothesised would impair IGF-1 cleavage causing functional IGF-1 deficiency. Our patient cohort was enriched for low frequency CNVs, particularly in patients with subtle features of Silver Russell Syndrome. This is the first study to assess CNVs in patients with GHI. From my CNV analysis, I identified CHD1L and HMGA2 as key candidate growth genes and functionally assessed several patient variants identified within our cohort

    Application of multi-scale computational techniques to complex materials systems

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    The applications of computational materials science are ever-increasing, connecting fields far beyond traditional subfields in materials science. This dissertation demonstrates the broad scope of multi-scale computational techniques by investigating multiple unrelated complex material systems, namely scandate thermionic cathodes and the metallic foam component of micrometeoroid and orbital debris (MMOD) shielding. Sc-containing scandate cathodes have been widely reported to exhibit superior properties compared to previous thermionic cathodes; however, knowledge of their precise operating mechanism remains elusive. Here, quantum mechanical calculations were utilized to map the phase space of stable, highly-faceted and chemically-complex W nanoparticles, accounting for both finite temperature and chemical environment. The precise processing conditions required to form the characteristic W nanoparticle observed experimentally were then distilled. Metallic foams, a central component of MMOD shielding, also represent a highly-complex materials system, albeit at a far higher length scale than W nanoparticles. The non-periodic, randomly-oriented constituent ligaments of metallic foams and similar materials create a significant variability in properties that is generally difficult to model. Rather than homogenizing the material such that its unique characteristic structural features are neglected, here, a stochastic modeling approach is applied that integrates complex geometric structure and utilizes continuum calculations to predict the resulting probabilistic distributions of elastic properties. Though different in many aspects, scandate cathodes and metallic foams are united by complexity that is impractical, even dangerous, to ignore and well-suited to exploration with multi-scale computational methods

    SIMULATING CONSUMABLE ORDER FULFILLMENT VIA ADDITIVE MANUFACTURING TECHNOLOGIES

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    Operational availability of naval aircraft through material readiness is critical to ensuring combat power. Supportability of aircraft is a crucial aspect of readiness, influenced by several factors including access to 9B Cognizance Code (COG) aviation consumable repair parts at various supply echelons. Rapidly evolving additive manufacturing (AM) technologies are transforming supply chain dynamics and the traditional aircraft supportability construct. As of June 2022, there are 595 AM assets within the Navy’s inventory—all for research and development purposes. This report simulates 9B COG aviation consumable fulfillment strategies within the U.S. Indo-Pacific sustainment network for a three-year span, inclusive of traditional supply support avenues and a developed set of user-variable capability inputs. Simulated probabilistic demand configurations are modeled from historical trends that exploit a heuristic methodology to assign a “printability” score to each 9B COG requirement, accounting for uncertainty, machine failure rates, and other continuous characteristics of the simulated orders. The results measure simulated lead time across diverse planning horizons in both current and varied operationalized AM sustainment network configurations. This research indicates a measurable lead time reduction of approximately 10% across all 9B order lead times when AM is employed as an order fulfillment source for only 0.5% of orders.NPS Naval Research ProgramThis project was funded in part by the NPS Naval Research Program.Lieutenant Commander, United States NavyApproved for public release. Distribution is unlimited

    Specificity of the innate immune responses to different classes of non-tuberculous mycobacteria

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    Mycobacterium avium is the most common nontuberculous mycobacterium (NTM) species causing infectious disease. Here, we characterized a M. avium infection model in zebrafish larvae, and compared it to M. marinum infection, a model of tuberculosis. M. avium bacteria are efficiently phagocytosed and frequently induce granuloma-like structures in zebrafish larvae. Although macrophages can respond to both mycobacterial infections, their migration speed is faster in infections caused by M. marinum. Tlr2 is conservatively involved in most aspects of the defense against both mycobacterial infections. However, Tlr2 has a function in the migration speed of macrophages and neutrophils to infection sites with M. marinum that is not observed with M. avium. Using RNAseq analysis, we found a distinct transcriptome response in cytokine-cytokine receptor interaction for M. avium and M. marinum infection. In addition, we found differences in gene expression in metabolic pathways, phagosome formation, matrix remodeling, and apoptosis in response to these mycobacterial infections. In conclusion, we characterized a new M. avium infection model in zebrafish that can be further used in studying pathological mechanisms for NTM-caused diseases
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