Data Analysis WorkbeNch (DAWN) Basham, Mark; Filik, Jacob; Wharmby, Michael T. ...
Journal of synchrotron radiation,
20/May , Volume:
22, Issue:
3
Journal Article
Peer reviewed
Open access
Synchrotron light source facilities worldwide generate terabytes of data in numerous incompatible data formats from a wide range of experiment types. The Data Analysis WorkbeNch (DAWN) was developed ...to address the challenge of providing a single visualization and analysis platform for data from any synchrotron experiment (including single‐crystal and powder diffraction, tomography and spectroscopy), whilst also being sufficiently extensible for new specific use case analysis environments to be incorporated (e.g. ARPES, PEEM). In this work, the history and current state of DAWN are presented, with two case studies to demonstrate specific functionality. The first is an example of a data processing and reduction problem using the generic tools, whilst the second shows how these tools can be targeted to a specific scientific area.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
A long duration gamma-ray burst, GRB 160530A, was detected by the Compton Spectrometer and Imager (COSI) during the 2016 COSI Super Pressure Balloon campaign. As a Compton telescope, COSI is ...inherently sensitive to the polarization of gamma-ray sources in the energy range 0.2-5.0 MeV. We measured the polarization of GRB 160530A using (1) a standard method (SM) based on fitting the distribution of azimuthal scattering angles with a modulation curve and (2) an unbinned, maximum likelihood method (MLM). In both cases, the measured polarization level was below the 99% confidence minimum detectable polarization levels of 72.3% 0.8% (SM) and 57.5% 0.8% (MLM). Therefore, COSI did not detect polarized gamma-ray emission from this burst. Our most constraining 90% confidence upper limit on the polarization level was 46% (MLM).
Variants of TREM2 are associated with Alzheimer’s disease (AD). To study whether increasing TREM2 gene dosage could modify the disease pathogenesis, we developed BAC transgenic mice expressing human ...TREM2 (BAC-TREM2) in microglia. We found that elevated TREM2 expression reduced amyloid burden in the 5xFAD mouse model. Transcriptomic profiling demonstrated that increasing TREM2 levels conferred a rescuing effect, which includes dampening the expression of multiple disease-associated microglial genes and augmenting downregulated neuronal genes. Interestingly, 5xFAD/BAC-TREM2 mice showed further upregulation of several reactive microglial genes linked to phagocytosis and negative regulation of immune cell activation. Moreover, these mice showed enhanced process ramification and phagocytic marker expression in plaque-associated microglia and reduced neuritic dystrophy. Finally, elevated TREM2 gene dosage led to improved memory performance in AD models. In summary, our study shows that a genomic transgene-driven increase in TREM2 expression reprograms microglia responsivity and ameliorates neuropathological and behavioral deficits in AD mouse models.
•Elevating TREM2 gene dosage altered microglial morphology and interaction with Aβ•Increasing TREM2 gene dosage reprograms microglial responsivity in AD mouse brains•Transcriptomic profiling identified three groups of TREM2 gene-dosage-dependent genes•Extra TREM2 gene dosage ameliorates neuropathology and memory deficits in AD mice
Augmenting TREM2 gene dosage in AD mouse models leads to reduced amyloid burden and neuropathology and improved memory performance. Gene expression profiling reveals a reprogrammed disease-associated microglial response that may underlie the phenotypic improvement in AD models.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
From the Surface Velocity Program (SVP) drifter current and QuikSCAT wind data, the relationship between the observed near‐surface current vectors and surface wind vectors for the northwestern ...Pacific Ocean under high winds (20–50 m s−1) are obtained with quantitative estimations of near‐surface drift ratio (current speed versus wind speed)r(∼2%) and near‐surface drift angleα (∼0°–10° to the right of the winds). These estimations keep unchanged after removing the surface geostrophic component. From the SVP drifter current and daily WindSat wind data, the estimated ris still approximately 2%. Three linear regression equations are obtained between the observed near‐surface current speeds and the surface wind stress for the high wind range.
Key Points
Data observed for low and high wind speeds are combined as a regression formula
The near‐surface drift angles under high wind speeds are shown
Elevated body mass index (BMI) is heritable and associated with many health conditions that impact morbidity and mortality. The study of the genetic association of BMI across a broad range of common ...disease conditions offers the opportunity to extend current knowledge regarding the breadth and depth of adiposity-related diseases. We identify 906 (364 novel) and 41 (6 novel) genome-wide significant loci for BMI among participants of European (N~1.1 million) and African (N~100,000) ancestry, respectively. Using a BMI genetic risk score including 2446 variants, 316 diagnoses are associated in the Million Veteran Program, with 96.5% showing increased risk. A co-morbidity network analysis reveals seven disease communities containing multiple interconnected diseases associated with BMI as well as extensive connections across communities. Mendelian randomization analysis confirms numerous phenotypes across a breadth of organ systems, including conditions of the circulatory (heart failure, ischemic heart disease, atrial fibrillation), genitourinary (chronic renal failure), respiratory (respiratory failure, asthma), musculoskeletal and dermatologic systems that are deeply interconnected within and across the disease communities. This work shows that the complex genetic architecture of BMI associates with a broad range of major health conditions, supporting the need for comprehensive approaches to prevent and treat obesity.
Background
The prevalence of gastroesophageal reflux disease (GERD) and laryngopharyngeal reflux (LPR) in post‐irradiated patients with nasopharyngeal carcinoma (NPC) is unknown.
Materials and ...methods
In a cross‐sectional study, 31 NPC and 12 control patients completed questionnaires for GERD/LPR before esophageal manometry and 24‐h pH monitoring. The DeMeester score and reflux finding score (RFS) were used to define GERD and LPR, respectively. Risk factors were identified.
Results
51.6% of NPC and 8.3% of control patients, and 77.4% of NPC and 33% of control patients, were GERD‐positive and LPR‐positive, respectively. The GERD/LPR questionnaire failed to identify either condition in patients with NPC. No parameter differences in esophageal manometry or pneumonia incidence were noted between GERD/LPR‐positive and GERD/LPR‐negative patients. Post radiotherapy duration, high BMI, lack of chemotherapy, and dysphagia were positive risk factors for GERD/LPR.
Conclusions
A high prevalence of GERD/LPR in patients with post‐irradiated NPC exists, but reflux symptoms are inadequate for diagnosis.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Multiple membrane organelles require cholesterol for proper function within cells. The Niemann-Pick type C (NPC) proteins export cholesterol from endosomes to other membrane compartments, including ...the endoplasmic reticulum (ER), plasma membrane (PM), trans-Golgi network (TGN), and mitochondria, to meet their cholesterol requirements. Defects in NPC cause malfunctions in multiple membrane organelles and lead to an incurable neurological disorder. Acyl-coenzyme A:cholesterol acyltransferase 1 (ACAT1), a resident enzyme in the ER, converts cholesterol to cholesteryl esters for storage. In mutant NPC cells, cholesterol storage still occurs in an NPC-independent manner. Here we report the interesting finding that in a mutant Npc1 mouse (Npc1nmf), Acat1 gene (Soat1) knockout delayed the onset of weight loss, motor impairment, and Purkinje neuron death. It also improved hepatosplenic pathology and prolonged lifespan by 34%. In mutant NPC1 fibroblasts, ACAT1 blockade (A1B) increased cholesterol content associated with TGN-rich membranes and mitochondria, while decreased cholesterol content associated with late endosomes. A1B also restored proper localization of syntaxin 6 and golgin 97 (key proteins in membrane trafficking at TGN) and improved the levels of cathepsin D (a key protease in lysosome and requires Golgi/endosome transport for maturation) and ABCA1 (a key protein controlling cholesterol release at PM). This work supports the hypothesis that diverting cholesterol from storage can benefit multiple diseases that involve cholesterol deficiencies in cell membranes.
Given the limited resources and capabilities of states to maintain cyber security, a variety of co‐production efforts have been made by individuals or by collectives, of varying degrees of ...organization and coordination. This article identifies different forms of citizen co‐production of cyber security and notes the risk of unintended consequences. Safeguards and principles are proposed in order to facilitate constructive citizen/netizen co‐production of cyber security. Although co‐production of security can contribute to social control, only those activities within the bounds of the law should be encouraged. Activities of private citizens/netizens that test the limits of legality should be closely circumscribed.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, PRFLJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract
About 10–15% of all human cancer cells employ a telomerase-independent recombination-based telomere maintenance method, known as alternative lengthening of telomere (ALT), of which the full ...mechanism remains incompletely understood. While implicated in previous studies as the initiating signals for ALT telomere repair, the prevalence of non-canonical nucleic acid structures in ALT cancers remains unclear. Extending earlier reports, we observe higher levels of DNA/RNA hybrids (R-loops) in ALT-positive (ALT+) compared to telomerase-positive (TERT+) cells. Strikingly, we observe even more pronounced differences for an associated four-stranded nucleic acid structure, G-quadruplex (G4). G4 signals are found at the telomere and are broadly associated with telomere length and accompanied by DNA damage markers. We establish an interdependent relationship between ALT-associated G4s and R-loops and confirm that these two structures can be spatially linked into unique structures, G-loops, at the telomere. Additionally, stabilization of G4s and R-loops cooperatively enhances ALT-activity. However, co-stabilization at higher doses resulted in cytotoxicity in a synergistic manner. Nuclear G4 signals are significantly and reproducibly different between ALT+ and TERT+ low-grade glioma tumours. Together, we present G4 as a novel hallmark of ALT cancers with potential future applications as a convenient biomarker for identifying ALT+ tumours and as therapeutic targets.
BACKGROUND:Although the use of filling agents for soft-tissue augmentation has increased worldwide, most consensus statements do not distinguish between ethnic populations. There are, however, ...significant differences between Caucasian and Asian faces, reflecting not only cultural disparities, but also distinctive treatment goals. Unlike aesthetic patients in the West, who usually seek to improve the signs of aging, Asian patients are younger and request a broader range of indications.
METHODS:Members of the Asia-Pacific Consensus group—comprising specialists from the fields of dermatology, plastic surgery, anatomy, and clinical epidemiology—convened to develop consensus recommendations for Asians based on their own experience using cohesive polydensified matrix, hyaluronic acid, and calcium hydroxylapatite fillers.
RESULTS:The Asian face demonstrates differences in facial structure and cosmetic ideals. Improving the forward projection of the “T zone” (i.e., forehead, nose, cheeks, and chin) forms the basis of a safe and effective panfacial approach to the Asian face. Successful augmentation may be achieved with both (1) high- and low-viscosity cohesive polydensified matrix/hyaluronic acid and (2) calcium hydroxylapatite for most indications, although some constraints apply.
CONCLUSION:The Asia-Pacific Consensus recommendations are the first developed specifically for the use of fillers in Asian populations.
CLINCIAL QUESTION/LEVEL OF EVIDENCE:Therapeutic, V.
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