728 research outputs found

    Absolute and differential measurement of water vapor supersaturation using a commercial thin-film sensor

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    We describe a technique for measuring the water vapor supersaturation of normal air over a temperature range of –40<~T<~0 °C. The measurements use an inexpensive commercial hygrometer which is based on a thin-film capacitive sensor. The time required for the sensor to reach equilibrium was found to increase exponentially with decreasing sensor temperature, exceeding 2 min for T = –30 °C; however, the water vapor sensitivity of the device remained high down to this temperature. After calibrating our measurement procedure, we found residual scatter in the data corresponding to an uncertainty in the absolute water vapor pressure of about ±15%. This scatter was due mainly to long-term drift, which appeared to be intrinsic to the capacitive thin-film sensor. The origin of this drift is not clear, but it effectively limits the applicability of this instrument for absolute measurements. We also found, however, that the high sensitivity of the thin-film sensor makes it rather well suited for differential measurements. By comparing supersaturated and saturated air at the same temperature we obtained a relative measurement uncertainty of about ±1.5%, an order of magnitude better than the absolute measurements

    Thymoquinone overcomes chemoresistance and enhances the anticancer effects of bortezomib through abrogation of NF-κB regulated gene products in multiple myeloma xenograft mouse model

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    Multiple myeloma (MM) is a B cell malignancy characterized by clonal proliferation of plasma cells in the bone marrow. With the advent of novel targeted agents, the median survival rate has increased to 5 -7 years. However, majority of patients with myeloma suffer relapse or develop chemoresistance to existing therapeutic agents. Thus, there is a need to develop novel alternative therapies for the treatment of MM. Thus in the present study, we investigated whether thymoquinone (TQ), a bioactive constituent of black seed oil, could suppress the proliferation and induce chemosensitization in human myeloma cells and xenograft mouse model. Our results show that TQ inhibited the proliferation of MM cells irrespective of their sensitivity to doxorubicin, melphalan or bortezomib. Interestingly, TQ treatment also resulted in a significant inhibition in the proliferation of CD138+ cells isolated from MM patient samples in a concentration dependent manner. TQ also potentiated the apoptotic effects of bortezomib in various MM cell lines through the activation of caspase-3, resulting in the cleavage of PARP. TQ treatment also inhibited chemotaxis and invasion induced by CXCL12 in MM cells. Furthermore, in a xenograft mouse model, TQ potentiated the antitumor effects of bortezomib (p < 0.05, vehicle versus bortezomib + TQ; p < 0.05, bortezomib versus bortezomib + TQ), and this correlated with modulation of various markers for survival and angiogenesis, such as Ki-67, vascular endothelial growth factor (VEGF), Bcl-2 and p65 expression. Overall, our results demonstrate that TQ can enhance the anticancer activity of bortezomib in vitro and in vivo and may have a substantial potential in the treatment of MM

    Globally optimal shape and spin pole determination with lightcurve inversion

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    Light-curve inversion is an established technique in determining the shape and spin states of an asteroid. However, the front part of the processing pipeline, which recovers the spin pole and area of each facet, is a non-convex optimization problem. Hence, an y local iterative optimization scheme can only promise a locally optimal solution. Apart from the obvious downsides of getting a non-optimal solution and the need for an initialization scheme, another major implication is that it creates an ambiguous scenario –which is to be blamed for the remaining residual? The inaccuracy of the modelling, the integrity of the data, or the non-global algorithm? We address the last uncertainty in this paper by embedding the spin pole and area vector determination module in a deterministic global optimization framework. To the best of our knowledge, this is the first attempt to solve these parameters globally . Specifically , given calibrated light-curve data, a scattering model for the object, and spin period, our method outputs the globally optimal spin pole and area vector solutions. One theoretical contribution of this paper is the introduction of a lower bound error function that is derived based on (1) the geometric relationship between the incident and scattered light on a surface and (2) the uncertainty of the gap between the observed and estimated brightness at a particular epoch in a light curve. We validated our method’s ability in achieving global minimum with both simulated and real light-curve data. We also tested our method on the real light curves of four asteroids.Chee-Kheng Chng, Michele Sasdelli, and Tat-Jun Chi

    Pacritinib (SB1518), a JAK2/FLT3 inhibitor for the treatment of acute myeloid leukemia

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    FMS-like tyrosine kinase 3 (FLT3) is the most commonly mutated gene found in acute myeloid leukemia (AML) patients and its activating mutations have been proven to be a negative prognostic marker for clinical outcome. Pacritinib (SB1518) is a tyrosine kinase inhibitor (TKI) with equipotent activity against FLT3 (IC50=22 n) and Janus kinase 2 (JAK2, IC50=23 n). Pacritinib inhibits FLT3 phosphorylation and downstream STAT, MAPK and PI3 K signaling in FLT3-internal-tandem duplication (ITD), FLT3-wt cells and primary AML blast cells. Oral administration of pacritinib in murine models of FLT3-ITD-driven AML led to significant inhibition of primary tumor growth and lung metastasis. Upregulation of JAK2 in FLT3-TKI-resistant AML cells was identified as a potential mechanism of resistance to selective FLT3 inhibition. This resistance could be overcome by the combined FLT3 and JAK2 activities of pacritinib in this cellular model. Our findings provide a rationale for the clinical evaluation of pacritinib in AML including patients resistant to FLT3-TKI therapy

    Generalized Weyl solutions in d=5 Einstein-Gauss-Bonnet theory: the static black ring

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    We argue that the Weyl coordinates and the rod-structure employed to construct static axisymmetric solutions in higher dimensional Einstein gravity can be generalized to the Einstein-Gauss-Bonnet theory. As a concrete application of the general formalism, we present numerical evidence for the existence of static black ring solutions in Einstein-Gauss-Bonnet theory in five spacetime dimensions. They approach asymptotically the Minkowski background and are supported against collapse by a conical singularity in the form of a disk. An interesting feature of these solutions is that the Gauss-Bonnet term reduces the conical excess of the static black rings. Analogous to the Einstein-Gauss-Bonnet black strings, for a given mass the static black rings exist up to a maximal value of the Gauss-Bonnet coupling constant α\alpha'. Moreover, in the limit of large ring radius, the suitably rescaled black ring maximal value of α\alpha' and the black string maximal value of α\alpha' agree.Comment: 43 pages, 14 figure

    I4U Submission to NIST SRE 2018: Leveraging from a Decade of Shared Experiences

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    The I4U consortium was established to facilitate a joint entry to NIST speaker recognition evaluations (SRE). The latest edition of such joint submission was in SRE 2018, in which the I4U submission was among the best-performing systems. SRE'18 also marks the 10-year anniversary of I4U consortium into NIST SRE series of evaluation. The primary objective of the current paper is to summarize the results and lessons learned based on the twelve sub-systems and their fusion submitted to SRE'18. It is also our intention to present a shared view on the advancements, progresses, and major paradigm shifts that we have witnessed as an SRE participant in the past decade from SRE'08 to SRE'18. In this regard, we have seen, among others, a paradigm shift from supervector representation to deep speaker embedding, and a switch of research challenge from channel compensation to domain adaptation.Comment: 5 page

    Commuting and wellbeing: A critical overview of the literature with implications for policy and future research

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    © 2019, © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This review provides a critical overview of what has been learnt about commuting’s impact on subjective wellbeing (SWB). It is structured around a conceptual model which assumes commuting can affect SWB over three time horizons: (i) during the journey; (ii) immediately after the journey; and (iii) over the longer term. Our assessment of the evidence shows that mood is lower during the commute than other daily activities and stress can be induced by congestion, crowding and unpredictability. People who walk or cycle to work are generally more satisfied with their commute than those who travel by car and especially those who use public transport. Satisfaction decreases with duration of commute, regardless of mode used, and increases when travelling with company. After the journey, evidence shows that the commute experience “spills over” into how people feel and perform at work and home. However, a consistent link between commuting and life satisfaction overall has not been established. The evidence suggests that commuters are generally successful in trading off the drawbacks of longer and more arduous commute journeys against the benefits they bring in relation to overall life satisfaction, but further research is required to understand the decision making involved. The evidence review points to six areas that warrant policy action and research: (i) enhancing the commute experience; (ii) increasing commute satisfaction; (iii) reducing the impacts of long duration commutes; (iv) meeting commuter preferences; (v) recognising flexibility and constraints in commuting routines and (vi) accounting for SWB impacts of commuting in policy making and appraisal

    Molecular diagnosis of scabies using a novel probe-based polymerase chain reaction assay targeting high-copy number repetitive sequences in the Sarcoptes scabiei genome

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    Background The suboptimal sensitivity and specificity of available diagnostic methods for scabies hampers clinical management, trials of new therapies and epidemiologic studies. Additionally, parasitologic diagnosis by microscopic examination of skin scrapings requires sample collection with a sharp scalpel blade, causing discomfort to patients and difficulty in children. Polymerase chain reaction (PCR)-based diagnostic assays, combined with non-invasive sampling methods, represent an attractive approach. In this study, we aimed to develop a real-time probe-based PCR test for scabies, test a non-invasive sampling method and evaluate its diagnostic performance in two clinical settings. Methodology/Principal findings High copy-number repetitive DNA elements were identified in draft Sarcoptes scabiei genome sequences and used as assay targets for diagnostic PCR. Two suitable repetitive DNA sequences, a 375 base pair microsatellite (SSR5) and a 606 base pair long tandem repeat (SSR6), were identified. Diagnostic sensitivity and specificity were tested using relevant positive and negative control materials and compared to a published assay targeting the mitochondrial cox1 gene. Both assays were positive at a 1:100 dilution of DNA from a single mite; no amplification was observed in DNA from samples from 19 patients with other skin conditions nor from house dust, sheep or dog mites, head and body lice or from six common skin bacterial and fungal species. Moderate sensitivity of the assays was achieved in a pilot study, detecting 5/7 (71.4% [95% CI: 29.0% - 96.3%]) of clinically diagnosed untreated scabies patients). Greater sensitivity was observed in samples collected by FLOQ swabs compared to skin scrapings. Conclusions/Significance This newly developed qPCR assay, combined with the use of an alternative non-invasive swab sampling technique offers the possibility of enhanced diagnosis of scabies. Further studies will be required to better define the diagnostic performance of these tests
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