41 research outputs found

    A solution of the coincidence problem based on the recent galactic core black hole mass density increase

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    A mechanism capable to provide a natural solution to two major cosmological problems, i.e. the cosmic acceleration and the coincidence problem, is proposed. A specific brane-bulk energy exchange mechanism produces a total dark pressure, arising when adding all normal to the brane negative pressures in the interior of galactic core black holes. This astrophysically produced negative dark pressure explains cosmic acceleration and why the dark energy today is of the same order to the matter density for a wide range of the involved parameters. An exciting result of the analysis is that the recent rise of the galactic core black hole mass density causes the recent passage from cosmic deceleration to acceleration. Finally, it is worth mentioning that this work corrects a wide spread fallacy among brane cosmologists, i.e. that escaping gravitons result to positive dark pressure.Comment: 14 pages, 3 figure

    Molecular signatures for CCN1, p21 and p27 in progressive mantle cell lymphoma

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    Mantle cell lymphoma (MCL) is a comparatively rare non-Hodgkin’s lymphoma characterised by overexpression of cyclin D1.Many patients present with or progress to advanced stage disease within 3 years. MCL is considered an incurable disease withmedian survival between 3 and 4 years. We have investigated the role(s) of CCN1 (CYR61) and cell cycle regulators inprogressive MCL. We have used the human MCL cell lines REC1 G519 > JVM2 cells by RQ-PCR, depicting a decrease in CCN1expression with disease progression. Investigation of CCN1 isoform expression by western blotting showed that whilst expres-sion of full-length CCN1 was barely altered in the cell lines, expression of truncated forms (18–20 and 28–30 kDa) decreasedwith disease progression. We have then demonstrated that cyclin D1 and cyclin dependent kinase inhibitors (p21CIP1and p27KIP1)are also involved in disease progression. Cyclin D1 was highly expressed in REC1 cells (OD: 1.0), reduced to one fifth in G519cells (OD: 0.2) and not detected by western blotting in JVM2 cells. p27KIP1followed a similar profile of expression as cyclin D1.Conversely, p21CIP1was absent in the REC1 cells and showed increasing expression in G519 and JVM2 cells. Subcellularlocalization detected p21CIP1/p27KIP1primarily within the cytoplasm and absent from the nucleus, consistent with altered roles in treatment resistance. Dysregulation of the CCN1 truncated forms are associated with MCL progression. In conjunction withreduced expression of cyclin D1 and increased expression of p21, this molecular signature may depict aggressive disease andtreatment resistance

    Microfluidics as an Enabling Technology for Personalized Cancer Therapy

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    Tailoring patient‐specific treatments for cancer is necessary in order to achieve optimal results but requires new diagnostic approaches at affordable prices. Microfluidics has immense potential to provide solutions for this, as it enables the processing of samples that are not available in large quantities (e.g., cells from patient biopsies), is cost efficient, provides a high level of automation, and allows the set‐up of complex models for cancer studies. In this review, individual solutions in the fields of genetics, circulating tumor cell monitoring, biomarker analysis, phenotypic drug sensitivity tests, and systems providing controlled environments for disease modeling are discussed. An overview on how these early stage achievements can be combined or developed further is showcased, and the required translational steps before microfluidics becomes a routine tool for clinical applications are critically discussed

    An assessment of thermocline-control methods for packed-bed thermal-energy storage in CSP plants, Part 2: Assessment strategy and results

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    Three thermocline-control (TCC) methods are assessed through numerical simulations for a thermal-energy storage (TES) filled with a packed bed of rocks. Two previously suggested methods are based on extracting or injecting heat-transfer fluid (HTF) through ports, while the third is a novel method based on mixing HTF streams. The assessment was carried out using simulations with a model that resolves the packed bed in one dimension. Simulations of stand-alone TES with maximum allowed outflow temperature differences of 10% at quasi-steady conditions showed that the mixing method with three ports led to the largest utilization factors – the fraction of the maximum storage capacity that is actually utilized – of 90.8% and 85.1% for molten salt (MS) and compressed air (CA) as HTF, respectively. These represent relative improvements of 38.8% and 73.4% compared to the baseline configurations without TCC. The increased utilization factors come at the expense of small decreases in the cycle exergy efficiency. For the mixing method with three ports, the exergy efficiencies were 97.3% and 95.6% for MS and CA, respectively. Simulations of a TES with MS as HTF integrated into a CSP plant operating on a Rankine steam cycle showed that TCC increases the annually averaged plant efficiency and the annual net electricity generated solely from thermal energy supplied by the TES. These results suggest that the small decreases in the exergy efficiency of the TES are outweighed by the large increases in the utilization factor.ISSN:0038-092XISSN:1471-125

    An assessment of thermocline-control methods for packed-bed thermal-energy storage in CSP plants, Part 1: Method descriptions

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    Thermocline thermal-energy storage (TES) suffers from so-called thermocline degradation, which refers to the flattening of temperature gradients in the TES with successive charging-discharging cycles. Thermocline degradation increases the variations of the heat-transfer fluid (HTF) outflow temperatures, decreases storage utilization factors, and increases specific TES material costs. Methods that prevent or reduce thermocline degradation by changing the operation of the storage are called thermocline-control (TCC) methods. The assessment of TCC methods is the main objective of this work. Three TCC methods that were chosen for this assessment are described in this paper. Two methods, based on either extracting or injecting HTF through ports, were derived from previously published methods while the third method, based on mixing multiple HTF streams, one of which is extracted through a port, is novel. In a companion paper (GeissbĂŒhler et al., Solar Energy, submitted 2018), the three TCC methods are assessed for air and molten salt as HTF using simulations of stand-alone storages as well as storages integrated into a concentrated solar power plant.ISSN:0038-092XISSN:1471-125

    Targeted Perturb-seq enables genome-scale genetic screens in single cells

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    The transcriptome contains rich information on molecular, cellular and organismal phenotypes. However, experimental and statistical limitations constrain sensitivity and throughput of genetic screening with single-cell transcriptomics readout. To overcome these limitations, we introduce targeted Perturb-seq (TAP-seq), a sensitive, inexpensive and platform-independent method focusing single-cell RNA-seq coverage on genes of interest, thereby increasing the sensitivity and scale of genetic screens by orders of magnitude. TAP-seq permits routine analysis of thousands of CRISPR-mediated perturbations within a single experiment, detects weak effects and lowly expressed genes, and decreases sequencing requirements by up to 50-fold. We apply TAP-seq to generate perturbation-based enhancer–target gene maps for 1,778 enhancers within 2.5% of the human genome. We thereby show that enhancer–target association is jointly determined by three-dimensional contact frequency and epigenetic states, allowing accurate prediction of enhancer targets throughout the genome. In addition, we demonstrate that TAP-seq can identify cell subtypes with only 100 sequencing reads per cell

    Roadmap on organic–inorganic hybrid perovskite semiconductors and devices

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    Metal halide perovskites are the first solution processed semiconductors that can compete in their functionality with conventional semiconductors, such as silicon. Over the past several years, perovskite semiconductors have reported breakthroughs in various optoelectronic devices, such as solar cells, photodetectors, light emitting and memory devices, and so on. Until now, perovskite semiconductors face challenges regarding their stability, reproducibility, and toxicity. In this Roadmap, we combine the expertise of chemistry, physics, and device engineering from leading experts in the perovskite research community to focus on the fundamental material properties, the fabrication methods, characterization and photophysical properties, perovskite devices, and current challenges in this field. We develop a comprehensive overview of the current state-of-the-art and offer readers an informed perspective of where this field is heading and what challenges we have to overcome to get to successful commercialization.publishe
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