ABSTRACT We present an extension to a Sunyaev–Zel’dovich Effect (SZE) selected cluster catalogue based on observations from the South Pole Telescope (SPT); this catalogue extends to lower signal to ...noise than the previous SPT–SZ catalogue and therefore includes lower mass clusters. Optically derived redshifts, centres, richnesses, and morphological parameters together with catalogue contamination and completeness statistics are extracted using the multicomponent matched filter (MCMF) algorithm applied to the S/N > 4 SPT–SZ candidate list and the Dark Energy Survey (DES) photometric galaxy catalogue. The main catalogue contains 811 sources above S/N = 4, has 91 per cent purity, and is 95 per cent complete with respect to the original SZE selection. It contains in total 50 per cent more clusters and twice as many clusters above z = 0.8 in comparison to the original SPT-SZ sample. The MCMF algorithm allows us to define subsamples of the desired purity with traceable impact on catalogue completeness. As an example, we provide two subsamples with S/N > 4.25 and S/N > 4.5 for which the sample contamination and cleaning-induced incompleteness are both as low as the expected Poisson noise for samples of their size. The subsample with S/N > 4.5 has 98 per cent purity and 96 per cent completeness and is part of our new combined SPT cluster and DES weak-lensing cosmological analysis. We measure the number of false detections in the SPT-SZ candidate list as function of S/N, finding that it follows that expected from assuming Gaussian noise, but with a lower amplitude compared to previous estimates from simulations.
Endogenous protein quality control machinery has long been suspected of influencing the onset and progression of neurodegenerative diseases characterized by accumulation of misfolded proteins. ...Huntington's disease (HD) is a fatal neurodegenerative disorder caused by an expansion of a polyglutamine (polyQ) tract in the protein huntingtin (htt), which leads to its aggregation and accumulation in inclusion bodies. Here, we demonstrate in a mouse model of HD that deletion of the molecular chaperones Hsp70.1 and Hsp70.3 significantly exacerbated numerous physical, behavioral and neuropathological outcome measures, including survival, body weight, tremor, limb clasping and open field activities. Deletion of Hsp70.1 and Hsp70.3 significantly increased the size of inclusion bodies formed by mutant htt exon 1, but surprisingly did not affect the levels of fibrillar aggregates. Moreover, the lack of Hsp70s significantly decreased levels of the calcium regulated protein c-Fos, a marker for neuronal activity. In contrast, deletion of Hsp70s did not accelerate disease in a mouse model of infectious prion-mediated neurodegeneration, ruling out the possibility that the Hsp70.1/70.3 mice are nonspecifically sensitized to all protein misfolding disorders. Thus, endogenous Hsp70s are a critical component of the cellular defense against the toxic effects of misfolded htt protein in neurons, but buffer toxicity by mechanisms independent of the deposition of fibrillar aggregates.
Ocular complications in cryptococcal meningitis (CM) are commonly attributed to elevated intracranial pressure (ICP). We report a case of reversible vision loss complicating AIDS-related CM with a ...normal ICP. We review other cases of blindness in CM with normal ICP and the potential role of corticosteroids as treatment.
A gamma-ray-based, active (A) and passive (P) computed tomography (CT) technology has been developed that locates, identifies and quantifies gamma-ray emitting isotopes, transuranic (TRU) and others, ...in nuclear waste drums. ACT uses a collimated external source and a HPGe detector to measure selected mono-energetic gamma-rays that are attenuated by waste-drum contents; a separate PCT measurement uses the HPGe detector to record the spectra of gamma-rays emitted from within a drum. The ACT attenuation images and the PCT emission spectra are coupled to quantitatively assay drum contents for ∼0.1–200
g of TRU isotopes. Calibration requires a single measurement of a known radioactive standard; construction of waste-drum surrogates is not required. Fixed and mobile systems demonstrated compliance with a DOE quality assurance program via several independent blind tests.
A Bell test is a randomized trial that compares experimental observations against the philosophical worldview of local realism
, in which the properties of the physical world are independent of our ...observation of them and no signal travels faster than light. A Bell test requires spatially distributed entanglement, fast and high-efficiency detection and unpredictable measurement settings
. Although technology can satisfy the first two of these requirements
, the use of physical devices to choose settings in a Bell test involves making assumptions about the physics that one aims to test. Bell himself noted this weakness in using physical setting choices and argued that human 'free will' could be used rigorously to ensure unpredictability in Bell tests
. Here we report a set of local-realism tests using human choices, which avoids assumptions about predictability in physics. We recruited about 100,000 human participants to play an online video game that incentivizes fast, sustained input of unpredictable selections and illustrates Bell-test methodology
. The participants generated 97,347,490 binary choices, which were directed via a scalable web platform to 12 laboratories on five continents, where 13 experiments tested local realism using photons
, single atoms
, atomic ensembles
and superconducting devices
. Over a 12-hour period on 30 November 2016, participants worldwide provided a sustained data flow of over 1,000 bits per second to the experiments, which used different human-generated data to choose each measurement setting. The observed correlations strongly contradict local realism and other realistic positions in bipartite and tripartite
scenarios. Project outcomes include closing the 'freedom-of-choice loophole' (the possibility that the setting choices are influenced by 'hidden variables' to correlate with the particle properties
), the utilization of video-game methods
for rapid collection of human-generated randomness, and the use of networking techniques for global participation in experimental science.
The lack of sensitive and robust behavioral assessments of pain in preclinical models has been a major limitation for both pain research and the development of novel analgesics. Here, we demonstrate ...a novel data acquisition and analysis platform that provides automated, quantitative, and objective measures of naturalistic rodent behavior in an observer-independent and unbiased fashion. The technology records freely behaving mice, in the dark, over extended periods for continuous acquisition of 2 parallel video data streams: (1) near-infrared frustrated total internal reflection for detecting the degree, force, and timing of surface contact and (2) simultaneous ongoing video graphing of whole-body pose. Using machine vision and machine learning, we automatically extract and quantify behavioral features from these data to reveal moment-by-moment changes that capture the internal pain state of rodents in multiple pain models. We show that these voluntary pain-related behaviors are reversible by analgesics and that analgesia can be automatically and objectively differentiated from sedation. Finally, we used this approach to generate a paw luminance ratio measure that is sensitive in capturing dynamic mechanical hypersensitivity over a period and scalable for high-throughput preclinical analgesic efficacy assessment.
Psoriasis is a common inflammatory disorder of the skin and other organs. We have determined that mutations in CARD14, encoding a nuclear factor of kappa light chain enhancer in B cells (NF-kB) ...activator within skin epidermis, account for PSORS2. Here, we describe fifteen additional rare missense variants in CARD14, their distribution in seven psoriasis cohorts (>6,000 cases and >4,000 controls), and their effects on NF-kB activation and the transcriptome of keratinocytes. There were more CARD14 rare variants in cases than in controls (burden test p value = 0.0015). Some variants were only seen in a single case, and these included putative pathogenic mutations (c.424G>A p.Glu142Lys and c.425A>G p.Glu142Gly) and the generalized-pustular-psoriasis mutation, c.413A>C (p.Glu138Ala); these three mutations lie within the coiled-coil domain of CARD14. The c.349G>A (p.Gly117Ser) familial-psoriasis mutation was present at a frequency of 0.0005 in cases of European ancestry. CARD14 variants led to a range of NF-kB activities; in particular, putative pathogenic variants led to levels >2.5× higher than did wild-type CARD14. Two variants (c.511C>A p.His171Asn and c.536G>A p.Arg179His) required stimulation with tumor necrosis factor alpha (TNF-α) to achieve significant increases in NF-kB levels. Transcriptome profiling of wild-type and variant CARD14 transfectants in keratinocytes differentiated probably pathogenic mutations from neutral variants such as polymorphisms. Over 20 CARD14 polymorphisms were also genotyped, and meta-analysis revealed an association between psoriasis and rs11652075 (c.2458C>T p.Arg820Trp; p value = 2.1 × 10−6). In the two largest psoriasis cohorts, evidence for association increased when rs11652075 was conditioned on HLA-Cw∗0602 (PSORS1). These studies contribute to our understanding of the genetic basis of psoriasis and illustrate the challenges faced in identifying pathogenic variants in common disease.
A summary of data and results from the first neutron images produced by the National Ignition Facility (NIF), Lawrence Livermore National Laboratory, Livermore, CA, USA are presented. An overview of ...the neutron imaging technique is presented, as well as a synopsis of the data collected and measurements made to date. Data form directly driven, DT filled microballoons, as well as, indirectly driven, cryogenically layered ignition experiments are presented. The data presented show that the primary cores from directly driven implosions are approximately twice as large, 64 {+-} 3 {mu}m, as indirect cores 25 {+-} 4 and 29 {+-} 4 {mu}m and more asymmetric, P2/P0 = 47% vs. -14% and 7%. Further, comparison with the size and shape of X-ray image data on the same implosions show good agreement, indicating X-ray emission is dominated by the hot regions of the implosion.
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