1,320 research outputs found

    Acupuncture Point Localization Varies Among Acupuncturists

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    Background: Studies assessing the point-specific effect of acupuncture or the characteristics of acupuncture points (APs) tend to yield inconclusive results. In order to identify a possible confounding factor, we aimed to examine the variability in AP localization by means of a survey. Material and Methods: Attendees of the 14th ICMART (International Council of Medical Acupuncture and Related Techniques) congress as well as DAGfA (German Medical Society of Acupuncture) lecturers and students were asked to locate and mark the APs LI 10 and TH 5 on a research assistant's arm. Identified points were transferred into a coordinate system, and the respective bivariate distribution function was calculated. Additionally, participants filled out a questionnaire about their acupuncture education and experience, the acupuncture style and point localization techniques used most frequently, and their estimation of the size of an AP. Results: The areas of the ellipses, theoretically containing 95% of AP localizations, varied between 44.49 and 5.18 cm(2). The largest distance between 2 identified points was 8.45 cm for LI 10 and 5.3 cm for TH 5. Apart from being trained at the same school, no other factor could be identified that determined the variability in AP localization. Conclusion: Our results indicate that congruity of AP localization among experienced acupuncturists might be low. Although there are some limitations to our results, this possible bias should be taken into account when conducting acupuncture trials and interpreting results of previous acupuncture studies

    Physiological Functions of the COPI Complex in Higher Plants

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    COPI vesicles are essential to the retrograde transport of proteins in the early secretory pathway. The COPI coatomer complex consists of seven subunits, termed alpha-, beta-, beta'-, gamma-, delta-, epsilon-, and zeta-COP, in yeast and mammals. Plant genomes have homologs of these subunits, but the essentiality of their cellular functions has hampered the functional characterization of the subunit genes in plants. Here we have employed virus-induced gene silencing (VIGS) and dexamethasone (DEX)-inducible RNAI of the COPI subunit genes to study the in vivo functions of the COPI coatomer complex in plants. The beta'-, gamma-, and delta-COP subunits localized to the Golgi as GFP-fusion proteins and interacted with each other in the Golgi. Silencing of beta'-, gamma-, and delta-COP by VIGS resulted in growth arrest and acute plant death in Nicotiana benthamiana, with the affected leaf cells exhibiting morphological markers of programmed cell death. Depletion of the COPI subunits resulted in disruption of the Golgi structure and accumulation of autolysosome-like structures in earlier stages of gene silencing. In tobacco BY-2 cells, DEX-inducible RNAi of beta'-COP caused aberrant cell plate formation during cytokinesis. Collectively, these results suggest that COPI vesicles are essential to plant growth and survival by maintaining the Golgi apparatus and modulating cell plate formation.1196Ysciescopu

    Methods for determining the optimal arrangement of water deluge systems on offshore installations

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    Offshore installations are prone to fire and/or explosion accidents. Fires have particularly serious consequences due to their high temperatures and heat flux, which affect humans, structures and environments alike. Due to the hydrocarbon explosions caused by delayed ignition following gas dispersion, fires can be the result of immediate ignition after gas release. Accordingly, it can be difficult to decrease their frequency, which is an element of risk (risk=frequency×consequence), using an active protection system (APS) such as gas detectors capable of shutting down the operation. Thus, it is more efficient to reduce the consequence using a passive protection system (PSS) such as water spray. It is important to decide the number and location of water deluge systems, thus the aim of this study is to introduce a new procedure for optimising the locations of water deluge systems using the water deluge location index (WLI) proposed herein. The locations of water deluge systems are thus optimised based on the results of credible fire scenarios using a three-dimensional computational fluid dynamics (CFD) tool. The effects of water spray and the effectiveness of the WLI are investigated in comparison with uniformly distributed sprays

    Electrical Impedance of Acupuncture Meridians: The Relevance of Subcutaneous Collagenous Bands

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    Background: The scientific basis for acupuncture meridians is unknown. Past studies have suggested that acupuncture meridians are physiologically characterized by low electrical impedance and anatomically associated with connective tissue planes. We are interested in seeing whether acupuncture meridians are associated with lower electrical impedance and whether ultrasound-derived measures – specifically echogenic collagenous bands- can account for these impedance differences. Methods/Results: In 28 healthy subjects, we assessed electrical impedance of skin and underlying subcutaneous connective tissue using a four needle-electrode approach. The impedances were obtained at 10 kHz and 100 kHz frequencies and at three body sites- upper arm (Large Intestine meridian), thigh (Liver), and lower leg (Bladder). Meridian locations were determined by acupuncturists. Ultrasound images were obtained to characterize the anatomical features at each measured site. We found significantly reduced electrical impedance at the Large Intestine meridian compared to adjacent control for both frequencies. No significant decrease in impedance was found at the Liver or Bladder meridian. Greater subcutaneous echogenic densities were significantly associated with reduced impedances in both within-site (meridian vs. adjacent control) and between-site (arm vs. thigh vs. lower leg) analyses. This relationship remained significant in multivariabl

    Evolutionary Toggling of Vpx/Vpr Specificity Results in Divergent Recognition of the Restriction Factor SAMHD1

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    SAMHD1 is a host restriction factor that blocks the ability of lentiviruses such as HIV-1 to undergo reverse transcription in myeloid cells and resting T-cells. This restriction is alleviated by expression of the lentiviral accessory proteins Vpx and Vpr (Vpx/Vpr), which target SAMHD1 for proteasome-mediated degradation. However, the precise determinants within SAMHD1 for recognition by Vpx/Vpr remain unclear. Here we show that evolution of Vpx/Vpr in primate lentiviruses has caused the interface between SAMHD1 and Vpx/Vpr to alter during primate lentiviral evolution. Using multiple HIV-2 and SIV Vpx proteins, we show that Vpx from the HIV-2 and SIVmac lineage, but not Vpx from the SIVmnd2 and SIVrcm lineage, require the C-terminus of SAMHD1 for interaction, ubiquitylation, and degradation. On the other hand, the N-terminus of SAMHD1 governs interactions with Vpx from SIVmnd2 and SIVrcm, but has little effect on Vpx from HIV-2 and SIVmac. Furthermore, we show here that this difference in SAMHD1 recognition is evolutionarily dynamic, with the importance of the N- and C-terminus for interaction of SAMHD1 with Vpx and Vpr toggling during lentiviral evolution. We present a model to explain how the head-to-tail conformation of SAMHD1 proteins favors toggling of the interaction sites by Vpx/Vpr during this virus-host arms race. Such drastic functional divergence within a lentiviral protein highlights a novel plasticity in the evolutionary dynamics of viral antagonists for restriction factors during lentiviral adaptation to its hosts. © 2013 Fregoso et al

    Rapid generation of chromosome-specific alphoid DNA probes using the polymerase chain reaction

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    Non-isotopic in situ hybridization of chromosome-specific alphoid DNA probes has become a potent tool in the study of numerical aberrations of specific human chromosomes at all stages of the cell cycle. In this paper, we describe approaches for the rapid generation of such probes using the polymerase chain reaction (PCR), and demonstrate their chromosome specificity by fluorescence in situ hybridization to normal human metaphase spreads and interphase nuclei. Oligonucleotide primers for conserved regions of the alpha satellite monomer were used to generate chromosome-specific DNA probes from somatic hybrid cells containing various human chromosomes, and from DNA libraries from sorted human chromosomes. Oligonucleotide primers for chromosome-specific regions of the alpha satellite monomer were used to generate specific DNA probes for the pericentromeric heterochromatin of human chromosomes 1, 6, 7, 17 and X directly from human genomic DNA

    Brigatinib Versus Alectinib in ALK-Positive NSCLC After Disease Progression on Crizotinib: Results of Phase 3 ALTA-3 Trial.

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    INTRODUCTION: This open-label, phase 3 trial (ALTA-3; NCT03596866) compared efficacy and safety of brigatinib versus alectinib for ALK+ NSCLC after disease progression on crizotinib. METHODS: Patients with advanced ALK+ NSCLC that progressed on crizotinib were randomized 1:1 to brigatinib 180 mg once daily (7-d lead-in, 90 mg) or alectinib 600 mg twice daily, aiming to test superiority. The primary end point was blinded independent review committee-assessed progression-free survival (PFS). Interim analysis for efficacy and futility was planned at approximately 70% of 164 expected PFS events. RESULTS: The population (N = 248; brigatinib, n = 125; alectinib, n = 123) was notable for long median duration of prior crizotinib (16.0-16.8 mo) and low rate of ALK fusion in baseline circulating tumor DNA (ctDNA; 78 of 232 [34%]). Median blinded independent review committee-assessed PFS was 19.3 months with brigatinib and 19.2 months with alectinib (hazard ratio = 0.97 [95% confidence interval: 0.66-1.42], p = 0.8672]). The study met futility criterion. Overall survival was immature (41 events [17%]). Exploratory analyses pooled across the treatment groups revealed median PFS of 11.1 versus 22.5 months in patients with versus without ctDNA-detectable ALK fusion at baseline (hazard ratio: 0.48 [95% confidence interval: 0.32-0.71]). Treatment-related adverse events in more than 30% of patients (brigatinib, alectinib) were elevated levels of blood creatine phosphokinase (70%, 29%), aspartate aminotransferase (53%, 38%), and alanine aminotransferase (40%, 36%). CONCLUSIONS: Brigatinib was not superior to alectinib for PFS in crizotinib-pretreated ALK+ NSCLC. Safety was consistent with the well-established and unique profiles of each drug. The low proportion of patients with ctDNA-detectable ALK fusion may account for prolonged PFS with both drugs in ALTA-3

    Is every female equal? Caste biasing in tropical paper wasps

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    Item does not contain fulltextDiseases caused by nontuberculous mycobacteria are emerging in many settings. With an increased number of patients needing treatment, the role of drug susceptibility testing is again in the spotlight. This articles covers the history and methodology of drug susceptibility tests for nontuberculous mycobacteria, but focuses on the correlations between in vitro drug susceptibility, pharmacokinetics and in vivo outcomes of treatment. Among slow-growing nontuberculous mycobacteria, clear correlations have been established for macrolides and amikacin (Mycobacterium avium complex) and for rifampicin (Mycobacterium kansasii). Among rapid-growing mycobacteria, correlations have been established in extrapulmonary disease for aminoglycosides, cefoxitin and co-trimoxazole. In pulmonary disease, correlations are less clear and outcomes of treatment are generally poor, especially for Mycobacterium abscessus. The clinical significance of inducible resistance to macrolides among rapid growers is an important topic. The true role of drug susceptibility testing for nontuberculous mycobacteria still needs to be addressed, preferably within clinical trials
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