The fundamental mechanism of vortex shedding past a curved cylinder has been investigated at a Reynolds number of 100 using three-dimensional spectral/
hp computations. Two different configurations ...are presented herein: in both cases the main component of the geometry is a circular cylinder whose centreline is a quarter of a ring and the inflow direction is parallel to the plane of curvature. In the first set of simulations the cylinder is forced to transversely oscillate at a fixed amplitude, while the oscillation frequency has been varied around the Strouhal value. Both geometries exhibit in-phase vortex shedding, with the vortex cores bent according to the body's curvature, although the wake topology is markedly different. In particular, the configuration that was found to suppress the vortex shedding in absence of forced motion exhibits now a primary instability in the near wake. A second set of simulations has been performed imposing an oscillatory roll to the curved cylinder, which is forced to rotate transversely around the axis of its bottom section. This case shows entirely different wake features from the previous one: the vortex shedding appears to be out-of-phase along the body's span, with straight cores that tend to twist after being shed and manifest a secondary spanwise instability. Further, the damping effect stemming from the transverse planar motion of the part of the cylinder parallel to the flow is no longer present, leading to a positive energy transfer from the fluid to the structure.
Variable x-ray and γ-ray emission is characteristic of the most extreme physical processes in the universe. We present multiwavelength observations of a unique γ-ray—selected transient detected by ...the Swift satellite, accompanied by bright emission across the electromagnetic spectrum, and whose properties are unlike any previously observed source. We pinpoint the event to the center of a small, star-forming galaxy at redshift z = 0.3534. Its high-energy emission has lasted much longer than any γ-ray burst, whereas its peak luminosity was ∼100 times higher than bright active galactic nuclei. The association of the outburst with the center of its host galaxy suggests that this phenomenon has its origin in a rare mechanism involving the massive black hole in the nucleus of that galaxy.
Kainate receptors (KARs) are involved in both NMDA receptor-independent long-term potentiation (LTP) and synaptic facilitation at mossy fibre synapses in the CA3 region of the hippocampus. However, ...the identity of the KAR subtypes involved remains controversial. Here we used a highly potent and selective GluK1 (formerly GluR5) antagonist (ACET) to elucidate roles of GluK1-containing KARs in these synaptic processes. We confirmed that ACET is an extremely potent GluK1 antagonist, with a Kb value of 1.4±0.2nM. In contrast, ACET was ineffective at GluK2 (formerly GluR6) receptors at all concentrations tested (up to 100μM) and had no effect at GluK3 (formerly GluR7) when tested at 1μM. The X-ray crystal structure of ACET bound to the ligand binding core of GluK1 was similar to the UBP310–GluK1 complex. In the CA1 region of hippocampal slices, ACET was effective at blocking the depression of both fEPSPs and monosynaptically evoked GABAergic transmission induced by ATPA, a GluK1 selective agonist. In the CA3 region of the hippocampus, ACET blocked the induction of NMDA receptor-independent mossy fibre LTP. To directly investigate the role of pre-synaptic GluK1-containing KARs we combined patch-clamp electrophysiology and 2-photon microscopy to image Ca2+ dynamics in individual giant mossy fibre boutons. ACET consistently reduced short-term facilitation of pre-synaptic calcium transients induced by 5 action potentials evoked at 20–25Hz. Taken together our data provide further evidence for a physiological role of GluK1-containing KARs in synaptic facilitation and LTP induction at mossy fibre–CA3 synapses.
Hypermethylation of multiple CpG islands is a common event in cancer. To assess the prognostic values of this epigenetic alteration, we developed Methylation Target Array (MTA), derived from the ...concept of tissue microarray, for simultaneous analysis of DNA hypermethylation in hundreds of tissue genomes. In MTA, linker-ligated CpG island fragments were digested with methylation-sensitive endonucleases and amplified with flanking primers. A panel of 468 MTA amplicons, which represented the whole repertoire of methylated CpG islands in 93 breast tumors, 20 normal breast tissues, and 4 breast cancer cell lines, were arrayed on nylon membrane for probe hybridization. Positive hybridization signals detected in tumor amplicons, but not in normal amplicons, were indicative of aberrant hypermethylation in tumor samples. This is attributed to aberrant sites that were protected from methylation-sensitive restriction and were amplified by PCR in tumor samples, while the same sites were restricted and could not be amplified in normal samples. Hypermethylation frequencies of the 10 genes tested in breast tumors and cancer cell lines were 60% for
GPC3
, 58% for
RASSF1A
, 32% for
3OST3B
, 30% for
HOXA5
, 28% for
uPA
, 25% for
WT1
, 23% for
BRCA1
, 9% for
DAPK1
, and 0% for
KL
. Furthermore, hypermethylation of 5 to 7 loci of these genes was significantly correlated with hormone receptor status, clinical stages, and ages at diagnosis of the patients analyzed. This novel approach thus provides an additional avenue for assessing clinicopathological consequences of DNA hypermethylation in breast cancer.
Pseudouridine (Ψ) is the most common noncanonical nucleotide present in naturally occurring RNA and serves a variety of roles in the cell, typically appearing where structural stability is crucial to ...function. Ψ residues are isomerized from native uridine residues by a class of highly conserved enzymes known as pseudouridine synthases. In order to quantify the thermodynamic impact of pseudouridylation on U-A base pairs, 24 oligoribonucleotides, 16 internal and eight terminal Ψ-A oligoribonucleotides, were thermodynamically characterized via optical melting experiments. The thermodynamic parameters derived from two-state fits were used to generate linearly independent parameters for use in secondary structure prediction algorithms using the nearest-neighbor model. On average, internally pseudouridylated duplexes were 1.7 kcal/mol more stable than their U-A counterparts, and terminally pseudouridylated duplexes were 1.0 kcal/mol more stable than their U-A equivalents. Due to the fact that Ψ-A pairs maintain the same Watson-Crick hydrogen bonding capabilities as the parent U-A pair in A-form RNA, the difference in stability due to pseudouridylation was attributed to two possible sources: the novel hydrogen bonding capabilities of the newly relocated imino group as well as the novel stacking interactions afforded by the electronic configuration of the Ψ residue. The newly derived nearest-neighbor parameters for Ψ-A base pairs may be used in conjunction with other nearest-neighbor parameters for accurately predicting the most likely secondary structure of A-form RNA containing Ψ-A base pairs.
The link between mineral resources and crustal‐rooted structures has been proposed for many of the world's most significant mineral provinces. Here we utilize a new approach by interpreting potential ...field data, including satellite gravity data, and high‐resolution continental‐scale magnetotelluric data, constrained with aeromagnetic, and seismic tomography and reflection data, to determine the distribution of crustal‐scale faults in the Archean to Proterozoic Gawler Craton (South Australia). The eastern flank of the craton hosts the supergiant Olympic Dam iron oxide‐copper‐gold (IOCG) deposit within a larger Olympic IOCG province. The central part of the craton contains gold‐only deposits, which define the Central Gawler Gold province. Both of these provinces are part of a Mesoproterozoic mineral system with an extensive hydrothermal alteration footprint, which formed during complicated tectonic mode switches. We show that both types of mineralization are located in proximity to crustal‐scale structures that appear to connect deep crustal fragments, which likely record the amalgamation of the Archean nucleus of the craton during the Neoarchean with subsequent reworking during the Mesoproterozoic. Many of these structures do not have a surface expression but coincide with gradients in magnetism, gravity, and electric resistivity anomalies, the latter data set suggesting they acted as fluid pathways extending to the lower crust. The results indicate that the first‐order controls on the distribution of IOCG and Central Gawler Gold metallogenic provinces are inherited from earlier tectonic events, which formed major crustal boundaries and related structures that are prone to reworking during later tectonism.
Key Points
The satellite gravity data provide clues to the regional framework of the Gawler Craton, which aligns with different geophysical data sets
The Gawler Craton is formed by a threefold Archean substratum that has undergone changes in the Proterozoic down to its deep crustal levels
Regional structures were reactivated through time and act as pathways for regional fluid flow throughout the craton
The flow of water along discontinuities, such as fractures or faults, is of paramount importance in understanding the hydrogeology of many geological settings. An experimental study was undertaken ...comprising two experiments on a 30° slip‐plane filled with kaolinite or Ball Clay gouge using a bespoke Angled Shear Rig (ASR). The gouge was initially loaded in equal step changes in vertical stress, followed by unloading of the sample in similar equal steps. This was followed by reloading to a new maximum stress, followed by unloading; the test history was therefore load‐unload‐reload‐unload (LURU). The transmissivity of the kaolinite and Ball Clay gouge showed a power‐law relationship with vertical stress. The LURU history showed considerable hysteresis, with flow effectively unchanged during unloading, even when vertical stress was close to zero. Reloading resulted in flow similar to that seen during unloading suggesting that the unloading‐reloading path is similar to the rebound‐reconsolidation line in classic soil mechanics. These observations show the importance of stress history on fracture flow; consideration of just the current stress acting upon a fracture may result in inaccuracies of predicted hydraulic flow. Once a new stress maximum was achieved the transmissivity of the fracture continued to reduce. No significant variation was seen in the flow response of kaolinite and Ball Clay gouge suggesting that the inclusion of illite and quartz did not have a significant influence on the form of the relationship between stress and flow, i.e. both described by a power‐law.
The association between severe mental illness (SMI) and cardiovascular and metabolic disease (CMD) is poorly understood. PCSK9 is expressed in systems critical to both SMI and CMD and influences ...lipid homeostasis and brain function. We systematically investigated relationships between genetic variation within the PCSK9 locus and risk for both CMD and SMI. UK Biobank recruited ~500,000 volunteers and assessed a wide range of SMI and CMD phenotypes. We used genetic data from white British ancestry individuals of UK Biobank. Genetic association analyses were conducted in PLINK, with statistical significance defined by the number of independent SNPs. Conditional analyses and linkage disequilibrium assessed the independence of SNPs and the presence of multiple signals. Two genetic risk scores of lipid-lowering alleles were calculated and used as proxies for putative lipid-lowering effects of PCSK9. PCSK9 variants were associated with central adiposity, venous thrombosis embolism, systolic blood pressure, mood instability, and neuroticism (all p < 1.16 × 10
). No secondary signals were identified. Conditional analyses and high linkage disequilibrium (r
= 0.98) indicated that mood instability and central obesity may share a genetic signal. Genetic risk scores suggested that the lipid-lowering effects of PCSK9 may be causal for greater mood instability and higher neuroticism. This is the first study to implicate the PCSK9 locus in mood-disorder symptoms and related traits, as well as the shared pathology of SMI and CMD. PCSK9 effects on mood may occur via lipid-lowering mechanisms. Further work is needed to understand whether repurposing PCSK9-targeting therapies might improve SMI symptoms and prevent CMD.
We use the Galaxy And Mass Assembly survey (GAMA) I data set combined with GALEX, Sloan Digital Sky Survey (SDSS) and UKIRT Infrared Deep Sky Survey (UKIDSS) imaging to construct the low-redshift (z ...< 0.1) galaxy luminosity functions in FUV, NUV, ugriz and YJHK bands from within a single well-constrained volume of 3.4 × 105 (Mpch-1)3. The derived luminosity distributions are normalized to the SDSS data release 7 (DR7) main survey to reduce the estimated cosmic variance to the 5per cent level. The data are used to construct the cosmic spectral energy distribution (CSED) from 0.1 to 2.1 μm free from any wavelength-dependent cosmic variance for both the elliptical and non-elliptical populations. The two populations exhibit dramatically different CSEDs as expected for a predominantly old and young population, respectively. Using the Driver et al. prescription for the azimuthally averaged photon escape fraction, the non-ellipticals are corrected for the impact of dust attenuation and the combined CSED constructed. The final results show that the Universe is currently generating (1.8 ± 0.3) × 1035h W Mpc-3 of which (1.2 ± 0.1) × 1035h W Mpc-3 is directly released into the inter-galactic medium and (0.6 ± 0.1) × 1035h W Mpc-3 is reprocessed and reradiated by dust in the far-IR. Using the GAMA data and our dust model we predict the mid- and far-IR emission which agrees remarkably well with available data. We therefore provide a robust description of the pre- and post-dust attenuated energy output of the nearby Universe from 0.1 μm to 0.6mm. The largest uncertainty in this measurement lies in the mid- and far-IR bands stemming from the dust attenuation correction and its currently poorly constrained dependence on environment, stellar mass and morphology. PUBLICATION ABSTRACT
BACKGROUND: Gynaecological laparotomies are associated with considerable adhesion-related burdens; however, few data are available concerning laparoscopic surgery. This study evaluated the ...epidemiology of adhesion-related readmissions following open and laparoscopic procedures. METHODS: Records from 24 046 patients undergoing gynaecological surgery in Scottish National Health Service hospitals during 1996 were assessed retrospectively. Cohorts comprised 15 197 patients undergoing laparoscopic surgery and 8849 patients undergoing laparotomies. Adhesion-related readmission episodes (directly and possibly related) were assessed over 4 years following initial surgery and were expressed as percentages of the number of initial procedures. RESULTS: Directly adhesion-related readmissions 1 year after initial laparoscopic surgery were: in the high-risk group (adhesiolysis and cyst drainage) 1.3%; medium-risk (therapeutic and diagnostic procedures not categorized as high- or low-risk) 1.5%; and low-risk (Fallopian tube sterilizations) 0.2%. Readmissions for laparotomy following surgery on the Fallopian tubes were 0.9%, ovaries 2.1%, uterus 0.6% and vagina 0%. Readmissions occurred at reduced rates in the second, third and fourth years after surgery. Exclusion of patients who underwent surgery within the previous 5 years resulted in reduced readmission rates following laparotomy and high-risk laparoscopy. CONCLUSIONS: With the exception of laparoscopic sterilizations, open and laparoscopic gynaecological surgery are associated with comparable risks of adhesion-related readmissions.
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