Jacobi polynomial solutions of first kind integral equations for numerical conformal mapping

AbstractA numerical method is described for the conformal mapping of simply connected domains whose boundaries contains sharp corner points. The method is based on a first kind integral equation formulation due to Wendland [15]. On each component analytic arc of the boundary, the dominant singularities of the unknown source density ν are incorporated in a Jacobi weight function w, so that ν/w may be approximated by a finite Jacobi polynomial series. The coefficients in these series are determined by collocation. Numerical example illustrate the accuracy of the proposed technique

The treatment of corner and pole-type singularities in numerical conformal mapping techniques

AbstractThis paper is a report of recent developments concerning the nature and the treatment of singularities that affect certain numerical conformal mapping techniques. The paper also includes some new results on the nature of singularities that the mapping function may have in the complement of the closure of the domain under consideration

Cinacalcet corrects hypercalcemia in mice with an inactivating Gα11 mutation

Loss-of-function mutations of GNA11, which encodes G-protein subunit α11 (Gα11), a signaling partner for the calcium-sensing receptor (CaSR), result in familial hypocalciuric hypercalcemia type 2 (FHH2). FHH2 is characterized by hypercalcemia, inappropriately normal or raised parathyroid hormone (PTH) concentrations, and normal or low urinary calcium excretion. A mouse model for FHH2 that would facilitate investigations of the in vivo role of Gα11 and the evaluation of calcimimetic drugs, which are CaSR allosteric activators, is not available. We therefore screened DNA from > 10,000 mice treated with the chemical mutagen N-ethyl-N-nitrosourea (ENU) for GNA11 mutations and identified a Gα11 variant, Asp195Gly (D195G), which downregulated CaSR-mediated intracellular calcium signaling in vitro, consistent with it being a loss-of-function mutation. Treatment with the calcimimetic cinacalcet rectified these signaling responses. In vivo studies showed mutant heterozygous (Gna11+/195G) and homozygous (Gna11195G/195G) mice to be hypercalcemic with normal or increased plasma PTH concentrations and normal urinary calcium excretion. Cinacalcet (30mg/kg orally) significantly reduced plasma albumin-adjusted calcium and PTH concentrations in Gna11+/195G and Gna11195G/195G mice. Thus, our studies have established a mouse model with a germline loss-of-function Gα11 mutation that is representative for FHH2 in humans and demonstrated that cinacalcet can correct the associated abnormalities of plasma calcium and PTH

Gα11 mutation in mice causes hypocalcemia rectifiable by calcilytic therapy

Heterozygous germline gain-of-function mutations of G-protein subunit α11 (Gα11), a signaling partner for the calcium-sensing receptor (CaSR), result in autosomal dominant hypocalcemia type 2 (ADH2). ADH2 may cause symptomatic hypocalcemia with low circulating parathyroid hormone (PTH) concentrations. Effective therapies for ADH2 are currently not available and a mouse model for ADH2 would help in assessment of potential therapies. We hypothesised that a previously reported dark skin mouse mutant (Dsk7), which has a germline hypermorphic Gα11 mutation, Ile62Val, may be a model for ADH2 and allow evaluation of calcilytics, which are CaSR negative allosteric modulators, as a targeted therapy for this disorder. Mutant Dsk7/+ and Dsk7/Dsk7 mice were shown to have hypocalcemia and reduced plasma PTH concentrations, similar to ADH2 patients. In vitro studies showed the mutant Val62 Gα11 to upregulate CaSR-mediated intracellular calcium and MAPK signaling, consistent with a gain-offunction. Treatment with NPS-2143, a calcilytic compound, normalised these signaling responses. In vivo, NPS-2143 induced a rapid and marked rise in plasma PTH and calcium concentrations in Dsk7/Dsk7 and Dsk7/+ mice, which became normocalcemic. Thus, these studies have established Dsk7 mice, which harbor a germline gain-of-function Gα11 mutation, as a model for ADH2; and demonstrated calcilytics as a potential targeted therapy

The Alvarez impact theory of mass extinction; limits to its applicability and the „great expectations syndrome”

For the past three decades, the Alvarez impact theory of mass extinction, causally related to catastrophic meteorite impacts, has been recurrently applied to multiple extinction boundaries. However, these multidisciplinary research efforts across the globe have been largely unsuccessful to date, with one outstanding exception: the Cretaceous-Paleogene boundary. The unicausal impact scenario as a leading explanation, when applied to the complex fossil record, has resulted in force-fitting of data and interpretations ("great expectations syndrome". The misunderstandings can be grouped at three successive levels of the testing process, and involve the unreflective application of the impact paradigm: (i) factual misidentification, i.e., an erroneous or indefinite recognition of the extraterrestrial record in sedimentological, physical and geochemical contexts, (ii) correlative misinterpretation of the adequately documented impact signals due to their incorrect dating, and (iii) causal overestimation when the proved impact characteristics are doubtful as a sufficient trigger of a contemporaneous global cosmic catastrophe. Examples of uncritical belief in the simple cause-effect scenario for the Frasnian-Famennian, Permian-Triassic, and Triassic-Jurassic (and the Eifelian-Givetian and Paleocene-Eocene as well) global events include mostly item-1 pitfalls (factual misidentification), with Ir enrichments and shocked minerals frequently misidentified. Therefore, these mass extinctions are still at the first test level, and only the F-F extinction is potentially seen in the context of item-2, the interpretative step, because of the possible causative link with the Siljan Ring crater (53 km in diameter). The erratically recognized cratering signature is often marked by large timing and size uncertainties, and item-3, the advanced causal inference, is in fact limited to clustered impacts that clearly predate major mass extinctions. The multi-impact lag-time pattern is particularly clear in the Late Triassic, when the largest (100 km diameter) Manicouagan crater was possibly concurrent with the end-Carnian extinction (or with the late Norian tetrapod turnover on an alternative time scale). The relatively small crater sizes and cratonic (crystalline rock basement) setting of these two craters further suggest the strongly insufficient extraterrestrial trigger of worldwide environmental traumas. However, to discuss the kill potential of impact events in a more robust fashion, their location and timing, vulnerability factors, especially target geology and palaeogeography in the context of associated climate-active volatile fluxes, should to be rigorously assessed. The current lack of conclusive impact evidence synchronous with most mass extinctions may still be somewhat misleading due to the predicted large set of undiscovered craters, particularly in light of the obscured record of oceanic impact events

A First Search for coincident Gravitational Waves and High Energy Neutrinos using LIGO, Virgo and ANTARES data from 2007

We present the results of the first search for gravitational wave bursts associated with high energy neutrinos. Together, these messengers could reveal new, hidden sources that are not observed by conventional photon astronomy, particularly at high energy. Our search uses neutrinos detected by the underwater neutrino telescope ANTARES in its 5 line configuration during the period January - September 2007, which coincided with the fifth and first science runs of LIGO and Virgo, respectively. The LIGO-Virgo data were analysed for candidate gravitational-wave signals coincident in time and direction with the neutrino events. No significant coincident events were observed. We place limits on the density of joint high energy neutrino - gravitational wave emission events in the local universe, and compare them with densities of merger and core-collapse events.Comment: 19 pages, 8 figures, science summary page at http://www.ligo.org/science/Publication-S5LV_ANTARES/index.php. Public access area to figures, tables at https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=p120000

A mouse model with a frameshift mutation in the nuclear factor I/X (NFIX) gene has phenotypic features of Marshall-Smith Syndrome

The nuclear factor I/X (NFIX) gene encodes a ubiquitously expressed transcription factor whose mutations lead to two allelic disorders characterized by developmental, skeletal, and neural abnormalities, namely, Malan syndrome (MAL) and Marshall–Smith syndrome (MSS). NFIX mutations associated with MAL mainly cluster in exon 2 and are cleared by nonsense-mediated decay (NMD) leading to NFIX haploinsufficiency, whereas NFIX mutations associated with MSS are clustered in exons 6–10 and escape NMD and result in the production of dominant-negative mutant NFIX proteins. Thus, different NFIX mutations have distinct consequences on NFIX expression. To elucidate the in vivo effects of MSS-associated NFIX exon 7 mutations, we used CRISPR-Cas9 to generate mouse models with exon 7 deletions that comprised: a frameshift deletion of two nucleotides (Nfix Del2); in-frame deletion of 24 nucleotides (Nfix Del24); and deletion of 140 nucleotides (Nfix Del140). Nfix+/Del2, Nfix+/Del24, Nfix+/Del140, NfixDel24/Del24, and NfixDel140/Del140 mice were viable, normal, and fertile, with no skeletal abnormalities, but NfixDel2/Del2 mice had significantly reduced viability (p < 0.002) and died at 2–3 weeks of age. Nfix Del2 was not cleared by NMD, and NfixDel2/Del2 mice, when compared to Nfix+/+ and Nfix+/Del2 mice, had: growth retardation; short stature with kyphosis; reduced skull length; marked porosity of the vertebrae with decreased vertebral and femoral bone mineral content; and reduced caudal vertebrae height and femur length. Plasma biochemistry analysis revealed NfixDel2/Del2 mice to have increased total alkaline phosphatase activity but decreased C-terminal telopeptide and procollagen-type-1-N-terminal propeptide concentrations compared to Nfix+/+ and Nfix+/Del2 mice. NfixDel2/Del2 mice were also found to have enlarged cerebral cortices and ventricular areas but smaller dentate gyrus compared to Nfix+/+ mice. Thus, NfixDel2/Del2 mice provide a model for studying the in vivo effects of NFIX mutants that escape NMD and result in developmental abnormalities of the skeletal and neural tissues that are associated with MSS

Search for gravitational waves from Scorpius X-1 in the second Advanced LIGO observing run with an improved hidden Markov model

We present results from a semicoherent search for continuous gravitational waves from the low-mass x-ray binary Scorpius X-1, using a hidden Markov model (HMM) to track spin wandering. This search improves on previous HMM-based searches of LIGO data by using an improved frequency domain matched filter, the J-statistic, and by analyzing data from Advanced LIGO's second observing run. In the frequency range searched, from 60 to 650 Hz, we find no evidence of gravitational radiation. At 194.6 Hz, the most sensitive search frequency, we report an upper limit on gravitational wave strain (at 95% confidence) of h095%=3.47×10-25 when marginalizing over source inclination angle. This is the most sensitive search for Scorpius X-1, to date, that is specifically designed to be robust in the presence of spin wandering. © 2019 American Physical Society

Erratum: "A Gravitational-wave Measurement of the Hubble Constant Following the Second Observing Run of Advanced LIGO and Virgo" (2021, ApJ, 909, 218)

[no abstract available