We use high‐resolution lidar microtopographic data and luminescence dating to constrain incremental Holocene–latest Pleistocene slip rates for the Wairau fault, a major dextral strike‐slip fault in ...the Marlborough Fault System, South Island, New Zealand. Our data come from two closely spaced study areas along the structurally simple, central portion of the fault: The well‐known Branch River terrace flight, and a previously undated series of offset risers and channel features several km to the east that we refer to as the Dunbeath site. Field work and mapping using lidar‐derived topography yields revised or novel measurements of nine fault offsets. We date those features using a post‐IR50‐IRSL225 infrared stimulated luminescence dating method, and a stratigraphically informed Bayesian age model. The dated slip history of the Wairau fault is further constrained using newly cataloged offset measurements collected along a ∼35 km stretch of the fault, and available paleoseismic data. Incremental slip rates are precisely computed using a Monte Carlo resampling scheme. Our results provide a nearly earthquake‐by‐earthquake record of incremental slip, with pronounced variations in incremental slip rate spanning multiple millennia and tens of m of slip. These extreme, multi‐millennial variations in fault slip rate have basic implications for earthquake occurrence, plate boundary lithosphere behavior, and probabilistic seismic hazard assessment.
Plain Language Summary
Fault slip rates reflect the myriad mechanical processes operating at depth, and are an important input in seismic hazard analyses. In this study, we measure how the Wairau fault in South Island, New Zealand, sped up and slowed down over multiple earthquake cycles throughout the past 15 thousand years. Using lidar laser topographic scans and field geologic techniques, we precisely measure a series of earthquake fault displacements ranging from ∼5 to 60 m, recorded in river terraces and other landscape features. We then use luminescence dating to determine when the faulted features were deposited and last exposed to sunlight. Employing fundamental principles of sedimentology, we accurately date the measured displacements, constructing a fault slip rate history. This slip history shows factor‐of‐three variations in fault slip rate spanning multiple earthquakes, implying the action of poorly understood mechanisms at depth. Interestingly, the slip history of the Wairau fault appears to correspond to that of the nearby Wellington fault, located >150 km away on the other side of the structurally complicated Cook Strait, suggesting that the two faults influence each other within the plate boundary system.
Key Points
Incremental slip rates of the Wairau fault, New Zealand, have varied by a factor of three or more since latest Pleistocene time
Slip history of the Wairau fault may be coordinated with that of the Wellington fault, 150 km distant along‐strike in southern North Island
Sustained and coordinated slip rate variations imply the influence of one or more as‐yet poorly understood shear zone mechanisms
Estrogen receptor-positive (ER+) breast cancers (BCs) constitute the most frequent BC subtype. The molecular landscape of ER+ relapsed disease is not well characterized. In this study, we aimed to ...describe the genomic evolution between primary (P) and matched metastatic (M) ER+ BCs after failure of adjuvant therapy.
A total of 182 ER+ metastatic BC patients with long-term follow-up were identified from a single institution. P tumor tissue was available for all patients, with 88 having matched M material. According to the availability of tumor material, samples were characterized using a 120 mutational hotspot qPCR, a 29 gene copy number aberrations (CNA) and a 400 gene expression panels. ESR1 mutations were assayed by droplet digital PCR. Molecular alterations were correlated with overall survival (OS) using the Cox proportional hazards regression models.
The median follow-up was 6.4 years (range 0.5–26.6 years). Genomic analysis of P tumors revealed somatic mutations in PIK3CA, KRAS, AKT1, FGFR3, HRAS and BRAF at frequencies of 41%, 6%, 5%, 2%, 1% and 2%, respectively, and CN amplification of CCND1, ZNF703, FGFR1, RSF1 and PAK1 at 23%, 19%, 17%, 12% and 11%, respectively. Mutations and CN amplifications were largely concordant between P and matched M (>84%). ESR1 mutations were found in 10.8% of the M but none of the P. Thirteen genes, among which ESR1, FOXA1, and HIF1A, showed significant differential expression between P and M. In P, the differential expression of 18 genes, among which IDO1, was significantly associated with OS (FDR < 0.1).
Despite the large concordance between P and matched M for the evaluated molecular alterations, potential actionable targets such as ESR1 mutations were found only in M. This supports the importance of characterizing the M disease. Other targets we identified, such as HIF1A and IDO1, warrant further investigation in this patient population.
We present optical continuum lags for two Seyfert 1 galaxies, MCG+08-11-011 and NGC 2617, using monitoring data from a reverberation mapping campaign carried out in 2014. Our light curves span the ...ugriz filters over four months, with median cadences of 1.0 and 0.6 days for MCG+08-11-011 and NGC 2617, respectively, combined with roughly daily X-ray and near-UV data from Swift for NGC 2617. We find lags consistent with geometrically thin accretion-disk models that predict a lag-wavelength relation of τ ∝ λ4/3. However, the observed lags are larger than predictions based on standard thin-disk theory by factors of 3.3 for MCG+08-11-011 and 2.3 for NGC 2617. These differences can be explained if the mass accretion rates are larger than inferred from the optical luminosity by a factor of 4.3 in MCG+08-11-011 and a factor of 1.3 in NGC 2617, although uncertainty in the SMBH masses determines the significance of this result. While the X-ray variability in NGC 2617 precedes the UV/optical variability, the long (2.6 day) lag is problematic for coronal reprocessing models.
Sorodiplophrys stercorea is a sorocarpic organism that utilizes filose pseudopodia for locomotion and absorptive nutrition. It has traditionally been considered to be a member of the Labyrinthulae ...based on its morphology. Its closest relatives were thought to be species in the taxon Diplophrys. Since the genus Diplophrys has been shown to be paraphyletic and S. stercorea has pseudopodia similar to some members of Rhizaria, we examined its relationship with other eukaryotes. We obtained four isolates from the dung of cow and horse, brought each into monoeukaryotic culture, and sequenced their SSU rRNA gene for phylogenetic analysis. All our isolates were shown to form a monophyletic group in the Labyrinthulae, nested in the Amphifiloidea clade. Our results demonstrate that Sorodiplophrys is more closely related to species of the genus Amphifila than to Diplophrys and represents an additional independent origin of sorocarpic multicellularity among eukaryotes. This study represents the first confirmed sorocarpic lifestyle in the Stramenopiles.
On 2006 May 5, a 4 s duration, low-energy, similar to 10 super(49) erg, gamma-ray burst (GRB) was observed, spatially associated with a z = 0.0804 galaxy. Here we report the discovery of the GRB ...optical afterglow and observations of its environment using Gemini South, the Hubble Space Telescope (HST), Chandra, Swift, and the Very Large Array. The optical afterglow of this GRB is spatially associated with a prominent star-forming region in the Sc-type galaxy 2dFGRS S173Z112. Its proximity to a star-forming region suggests that the progenitor delay time, from birth to explosion, is smaller than similar to 10 Myr. Our HST deep imaging rules out the presence of a supernova brighter than an absolute magnitude of about -11 (or -12.6 in the case of maximal extinction) at about 2 weeks after the burst and limits the ejected mass of radioactive super(56)Ni to be less than about 2 x 10 super(-4) M unk (assuming no extinction). Although it was suggested that GRB 060505 may belong to a new class of long-duration GRBs with no supernova, we argue that the simplest interpretation is that the physical mechanism responsible for this burst is the same as that for short-duration GRBs.
We present the results of a direct detection search for mirror dark matter interactions, using data collected from the Large Underground Xenon experiment during 2013, with an exposure of 95 ...live−days×118 kg. Here, the calculations of the mirror electron scattering rate in liquid xenon take into account the shielding effects from mirror dark matter captured within the Earth. Annual and diurnal modulation of the dark matter flux and atomic shell effects in xenon are also accounted for. Having found no evidence for an electron recoil signal induced by mirror dark matter interactions we place an upper limit on the kinetic mixing parameter over a range of local mirror electron temperatures between 0.1 and 0.9 keV. This limit shows significant improvement over the previous experimental constraint from orthopositronium decays and significantly reduces the allowed parameter space for the model. We exclude mirror electron temperatures above 0.3 keV at a 90% confidence level, for this model, and constrain the kinetic mixing below this temperature.
T-cell acute lymphoblastic leukemia (T-ALL) is a challenging clinical entity with high rates of induction failure and relapse. To discover the genetic changes occurring in T-ALL, and those ...contributing to relapse, we studied zebrafish (Danio rerio) T-ALL samples using array comparative genomic hybridization (aCGH). We performed aCGH on 17 T-ALLs from four zebrafish T-ALL models, and evaluated similarities between fish and humans by comparing all D. rerio genes with copy number aberrations (CNAs) with a cohort of 75 published human T-ALLs analyzed by aCGH. Within all D. rerio CNAs, we identified 893 genes with human homologues and found significant overlap (67%) with the human CNA dataset. In addition, when we restricted our analysis to primary T-ALLs (14 zebrafish and 61 human samples), 10 genes were recurrently altered in > 3 zebrafish cancers and ≥ 4 human cases, suggesting a conserved role for these loci in T-ALL transformation across species. We also conducted iterative allo-transplantation with three zebrafish malignancies. This technique selects for aggressive disease, resulting in shorter survival times in successive transplant rounds and modeling refractory and relapsed human T-ALL. Fifty-five percent of original CNAs were preserved after serial transplantation, demonstrating clonality between each primary and passaged leukemia. Cancers acquired an average of 34 new CNAs during passaging. Genes in these loci may underlie the enhanced malignant behavior of these neoplasias. We also compared genes from CNAs of passaged zebrafish malignancies with aCGH results from 50 human T-ALL patients who failed induction, relapsed or would eventually relapse. Again, many genes (88/164) were shared by both datasets. Further, nine recurrently altered genes in passaged D. rerio T-ALL were also found in multiple human T-ALL cases. These results suggest that zebrafish and human T-ALLs are similar at the genomic level, and are governed by factors that have persisted throughout evolution.
To synthesize the cofactor thiamin diphosphate (ThDP), plants must first hydrolyze thiamin monophosphate (ThMP) to thiamin, but dedicated enzymes for this hydrolysis step were unknown and widely ...doubted to exist. The classical thiamin-requiring th2-1 mutation in Arabidopsis thaliana was shown to reduce ThDP levels by half and to increase ThMP levels 5-fold, implying that the THIAMIN REQUIRING2 (TH2) gene product could be a dedicated ThMP phosphatase. Genomic and transcriptomic data indicated that TH2 corresponds to At5g32470, encoding a HAD (haloacid dehalogenase) family phosphatase fused to a TenA (thiamin salvage) family protein. Like the th2-1 mutant, an insertional mutant of At5g32470 accumulated ThMP, and the thiamin requirement of the th2-1 mutant was complemented by wild-type At5g32470. Complementation tests in Escherichia coli and enzyme assays with recombinant proteins confirmed that At5g32470 and its maize (Zea mays) orthologs GRMZM2G148896 and GRMZM2G078283 are ThMP-selective phosphatases whose activity resides in the HAD domain and that the At5g32470 TenA domain has the expected thiamin salvage activity. In vitro and in vivo experiments showed that alternative translation start sites direct the At5g32470 protein to the cytosol and potentially also to mitochondria. Our findings establish that plants have a dedicated ThMP phosphatase and indicate that modest (50%) ThDP depletion can produce severe deficiency symptoms.
Many scenarios of physics beyond the standard model predict the existence of new gauge singlets, which might be substantially lighter than the weak scale. The experimental constraints on additional ...scalars with masses in the MeV to GeV range could be significantly weakened if they interact predominantly with leptons rather than quarks. At an e+e− collider, such a leptophilic scalar (ϕL) would be produced predominantly through radiation from a τ lepton. We report herein a search for e+e−→τ+τ−ϕL, ϕL→ℓ+ℓ− (ℓ=e, μ) using data collected by the BABAR experiment at SLAC. No significant signal is observed, and we set limits on the ϕL coupling to leptons in the range 0.04<mϕL<7.0 GeV. These bounds significantly improve upon the current constraints, excluding almost entirely the parameter space favored by the observed discrepancy in the muon anomalous magnetic moment below 4 GeV at 90% confidence level.
Germline mutations in CDH1 are associated with hereditary diffuse gastric cancer; lobular breast cancer also occurs excessively in families with such condition.
To determine if CDH1 is a ...susceptibility gene for lobular breast cancer in women without a family history of diffuse gastric cancer, germline DNA was analysed for the presence of CDH1 mutations in 318 women with lobular breast cancer who were diagnosed before the age of 45 years or had a family history of breast cancer and were not known, or known not, to be carriers of germline mutations in BRCA1 or BRCA2. Cases were ascertained through breast cancer registries and high-risk cancer genetic clinics (Breast Cancer Family Registry, the kConFab and a consortium of breast cancer genetics clinics in the United States and Spain). Additionally, Multiplex Ligation-dependent Probe Amplification was performed for 134 cases to detect large deletions.
No truncating mutations and no large deletions were detected. Six non-synonymous variants were found in seven families. Four (4/318 or 1.3%) are considered to be potentially pathogenic through in vitro and in silico analysis.
Potentially pathogenic germline CDH1 mutations in women with early-onset or familial lobular breast cancer are at most infrequent.
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