Pseudo-Killing Spinors, Pseudo-supersymmetric p-branes, Bubbling and Less-bubbling AdS Spaces

We consider Einstein gravity coupled to an n-form field strength in D dimensions. Such a theory cannot be supersymmetrized in general, we nevertheless propose a pseudo-Killing spinor equation and show that the AdS X Sphere vacua have the maximum number of pseudo-Killing spinors, and hence are fully pseudo-supersymmetric. We show that extremal p-branes and their intersecting configurations preserve fractions of the pseudo-supersymmetry. We study the integrability condition for general (D,n) and obtain the additional constraints that are required so that the existence of the pseudo-Killing spinors implies the Einstein equations of motion. We obtain new pseudo-supersymmetric bubbling AdS_5 X S^5 spaces that are supported by a non-self-dual 5-form. This demonstrates that non-supersymmegtric conformal field theories may also have bubbling states of arbitrary droplets of free fermions in the phase space. We also obtain an example of less-bubbling AdS geometry in D=8, whose bubbling effects are severely restricted by the additional constraint arising from the integrability condition.Comment: typos corrected, extra comments and references added, version appeared in JHE

Missense Mutation R338W in ARHGEF9 in a Family with X-linked Intellectual Disability with Variable Macrocephaly and Macro-Orchidism

Non-syndromal X-linked intellectual disability (NS-XLID) represents a broad group of clinical disorders in which ID is the only clinically consistent manifestation. Although in many cases either chromosomal linkage data or knowledge of the >100 existing XLID genes has assisted mutation discovery, the underlying cause of disease remains unresolved in many families. We report the resolution of a large family (K8010) with NS-XLID, with variable macrocephaly and macro-orchidism. Although a previous linkage study had mapped the locus to Xq12-q21, this region contained too many candidate genes to be analyzed using conventional approaches. However, X-chromosome exome sequencing, bioinformatics analysis and segregation analysis revealed a novel missense mutation (c.1012C>T; p.R338W) in ARHGEF9. This gene encodes collybistin (CB), a neuronal GDP-GTP exchange factor previously implicated in several cases of XLID, as well as clustering of gephyrin and GABAA receptors at inhibitory synapses. Molecular modeling of the CB R338W substitution revealed that this change results in the substitution of a long electropositive side-chain with a large non-charged hydrophobic side-chain. The R338W change is predicted to result in clashes with adjacent amino acids (K363 and N335) and disruption of electrostatic potential and local folding of the PH domain, which is known to bind phosphatidylinositol-3-phosphate (PI3P/PtdIns-3-P). Consistent with this finding, functional assays revealed that recombinant CB CB2SH3- (R338W) was deficient in PI3P binding and was not able to translocate EGFP-gephyrin to submembrane microaggregates in an in vitro clustering assay. Taken together, these results suggest that the R338W mutation in ARHGEF9 is the underlying cause of NS-XLID in this family

BPS States, Refined Indices, and Quiver Invariants

For D=4 BPS state construction, counting, and wall-crossing thereof, quiver quantum mechanics offers two alternative approaches, the Coulomb phase and the Higgs phase, which sometimes produce inequivalent counting. The authors have proposed, in arXiv:1205.6511, two conjectures on the precise relationship between the two, with some supporting evidences. Higgs phase ground states are naturally divided into the Intrinsic Higgs sector, which is insensitive to wall-crossings and thus an invariant of quiver, plus a pulled-back ambient cohomology, conjectured to be an one-to-one image of Coulomb phase ground states. In this note, we show that these conjectures hold for all cyclic quivers with Abelian nodes, and further explore angular momentum and R-charge content of individual states. Along the way, we clarify how the protected spin character of BPS states should be computed in the Higgs phase, and further determine the entire Hodge structure of the Higgs phase cohomology. This shows that, while the Coulomb phase states are classified by angular momentum, the Intrinsic Higgs states are classified by R-symmetry.Comment: 51 pages, 5 figure

Galactic and Extragalactic Samples of Supernova Remnants: How They Are Identified and What They Tell Us

Supernova remnants (SNRs) arise from the interaction between the ejecta of a supernova (SN) explosion and the surrounding circumstellar and interstellar medium. Some SNRs, mostly nearby SNRs, can be studied in great detail. However, to understand SNRs as a whole, large samples of SNRs must be assembled and studied. Here, we describe the radio, optical, and X-ray techniques which have been used to identify and characterize almost 300 Galactic SNRs and more than 1200 extragalactic SNRs. We then discuss which types of SNRs are being found and which are not. We examine the degree to which the luminosity functions, surface-brightness distributions and multi-wavelength comparisons of the samples can be interpreted to determine the class properties of SNRs and describe efforts to establish the type of SN explosion associated with a SNR. We conclude that in order to better understand the class properties of SNRs, it is more important to study (and obtain additional data on) the SNRs in galaxies with extant samples at multiple wavelength bands than it is to obtain samples of SNRs in other galaxiesComment: Final 2016 draft of a chapter in "Handbook of Supernovae" edited by Athem W. Alsabti and Paul Murdin. Final version available at https://doi.org/10.1007/978-3-319-20794-0_90-

Protein dynamics and conformational selection in bidirectional signal transduction

Protein conformational dynamics simultaneously allow promiscuity and specificity in binding. The multiple conformations of the free EphA4 ligand-binding domain observed in two new EphA4 crystal structures provide a unique insight into the conformational dynamics of EphA4 and its signaling pathways. The heterogeneous ensemble and loop dynamics explain how the EphA4 receptor is able to bind multiple A- and B-ephrin ligands and small molecules via conformational selection, which helps to fine-tune cellular signal response in both receptor and ligand cells

Theoretical Investigations into Self-Organized Ordered Metallic Semi-Clusters Arrays on Metallic Substrate

Using the energy minimization calculations based on an interfacial potential and a first-principles total energy method, respectively, we show that (2 × 2)/(3 × 3) Pb/Cu(111) system is a stable structure among all the [(n − 1) × (n − 1)]/(n × n) Pb/Cu(111) (n = 2, 3,…, 12) structures. The electronic structure calculations indicate that self-organized ordered Pb semi-clusters arrays are formed on the first Pb monolayer of (2 × 2)/(3 × 3) Pb/Cu(111), which is due to a strain-release effect induced by the inherent misfits. The Pb semi-clusters structure can generate selective adsorption of atoms of semiconductor materials (e.g., Ge) around the semi-clusters, therefore, can be used as a template for the growth of nanoscale structures with a very short periodic length (7.67 Å)

Histone deacetylase adaptation in single ventricle heart disease and a young animal model of right ventricular hypertrophy.

BackgroundHistone deacetylase (HDAC) inhibitors are promising therapeutics for various forms of cardiac diseases. The purpose of this study was to assess cardiac HDAC catalytic activity and expression in children with single ventricle (SV) heart disease of right ventricular morphology, as well as in a rodent model of right ventricular hypertrophy (RVH).MethodsHomogenates of right ventricle (RV) explants from non-failing controls and children born with a SV were assayed for HDAC catalytic activity and HDAC isoform expression. Postnatal 1-day-old rat pups were placed in hypoxic conditions, and echocardiographic analysis, gene expression, HDAC catalytic activity, and isoform expression studies of the RV were performed.ResultsClass I, IIa, and IIb HDAC catalytic activity and protein expression were elevated in the hearts of children born with a SV. Hypoxic neonatal rats demonstrated RVH, abnormal gene expression, elevated class I and class IIb HDAC catalytic activity, and protein expression in the RV compared with those in the control.ConclusionsThese data suggest that myocardial HDAC adaptations occur in the SV heart and could represent a novel therapeutic target. Although further characterization of the hypoxic neonatal rat is needed, this animal model may be suitable for preclinical investigations of pediatric RV disease and could serve as a useful model for future mechanistic studies

The shadow knows: using shadows to investigate the structure of the pretransitional disk of HD 100453

This is the final version of the article. Available from American Astronomical Society via the DOI in this record.We present GPI polarized intensity imagery of HD 100453 in Y-, J-, and K1 bands which reveals an inner gap ($9 - 18$ au), an outer disk ($18-39$ au) with two prominent spiral arms, and two azimuthally-localized dark features also present in SPHERE total intensity images (Wagner 2015). SED fitting further suggests the radial gap extends to $1$ au. The narrow, wedge-like shape of the dark features appears similar to predictions of shadows cast by a inner disk which is misaligned with respect to the outer disk. Using the Monte Carlo radiative transfer code HOCHUNCK3D (Whitney 2013), we construct a model of the disk which allows us to determine its physical properties in more detail. From the angular separation of the features we measure the difference in inclination between the disks 45$^{\circ}$, and their major axes, PA = 140$^{\circ}$ east of north for the outer disk and 100$^{\circ}$for the inner disk. We find an outer disk inclination of $25 \pm 10^{\circ}$ from face-on in broad agreement with the Wagner 2015 measurement of 34$^{\circ}$. SPHERE data in J- and H-bands indicate a reddish disk which points to HD 100453 evolving into a young debris disk.Based in part on data obtained at the Gemini Observatory via the time exchange program between Gemini and the Subaru Telescope (GS-2015A-C-1). The Gemini Observatory is operated by the Association of Universities for Research in Astronomy, Inc., under a cooperative agreement with the NSF on behalf of the Gemini partnership: the National Science Foundation (United States), the National Research Council (Canada), CONICYT (Chile), Ministerio de Ciencia, Tecnología e Innovación Productiva (Argentina), and Ministério da Ciência, Tecnologia e Inovação (Brazil). M.T. is partly supported by JSPS KAKENHI 2680016. C.A.G. is supported under NASA Origins of Solar Systems Funding via NNG16PX39P. Y.H. is supported by Jet Propulsion Laboratory, California Institute of Technology under a contract from NASA. M.S. is supported by NASA Exoplanet Research Program NNX16AJ75G. J.K. acknowledges support from Philip Leverhulme Prize (PLP-2013-110, PI: Stefan Kraus). S.K. acknowledges support from an ERC Starting Grant (Grant Agreement No. 639889). We also thank the referee for their comments and suggestions which added clarity to this paper

Gate-tunable black phosphorus spin valve with nanosecond spin lifetimes

Two-dimensional materials offer new opportunities for both fundamental science and technological applications, by exploiting the electron spin. While graphene is very promising for spin communication due to its extraordinary electron mobility, the lack of a band gap restricts its prospects for semiconducting spin devices such as spin diodes and bipolar spin transistors. The recent emergence of 2D semiconductors could help overcome this basic challenge. In this letter we report the first important step towards making 2D semiconductor spin devices. We have fabricated a spin valve based on ultra-thin (5 nm) semiconducting black phosphorus (bP), and established fundamental spin properties of this spin channel material which supports all electrical spin injection, transport, precession and detection up to room temperature (RT). Inserting a few layers of boron nitride between the ferromagnetic electrodes and bP alleviates the notorious conductivity mismatch problem and allows efficient electrical spin injection into an n-type bP. In the non-local spin valve geometry we measure Hanle spin precession and observe spin relaxation times as high as 4 ns, with spin relaxation lengths exceeding 6 um. Our experimental results are in a very good agreement with first-principles calculations and demonstrate that Elliott-Yafet spin relaxation mechanism is dominant. We also demonstrate that spin transport in ultra-thin bP depends strongly on the charge carrier concentration, and can be manipulated by the electric field effect

A phase 1b open-label dose-finding study of ustekinumab in young adults with type 1 diabetes

Aim We assessed the safety of ustekinumab (a monoclonal antibody used in psoriasis to target the IL-12 and IL-23 pathways) in a small cohort of recent-onset (<100 days of diagnosis) adults with type 1 diabetes (T1D) by conducting a pilot open-label dose-finding and mechanistic study (NCT02117765) at the University of British Columbia. Methods We sequentially enrolled 20 participants into four subcutaneous dosing cohorts: i) 45mg loading-weeks 0/4/16, ii) 45mg maintenance-weeks 0/4/16/28/40, iii) 90mg loading-weeks 0/4/16 and iv) 90mg maintenance-weeks 0/4/16/28/40. The primary endpoint was safety as assessed by an independent data and safety monitoring board (DSMB) but we also measured mixed meal tolerance test C-peptide, insulin use/kg, and HbA1c. Immunophenotyping was performed to assess immune cell subsets and islet antigen-specific T cell responses. Results Although several adverse events were reported, only two (bacterial vaginosis and hallucinations) were thought to be possibly related to drug administration by the study investigators. At 1 year, the 90mg maintenance dosing cohort had the smallest mean decline in C-peptide AUC (0.1pmol/mL). Immunophenotyping showed that ustekinumab reduced the percentage of circulating Th17, Th1 and Th17.1 cells and proinsulin-specific T cells that secreted IFN-γ and IL-17A. Conclusion Ustekinumab was deemed safe to progress to efficacy studies by the DSMB at doses used to treat psoriasis in adults with T1D. A 90mg maintenance dosing schedule reduced proinsulin-specific IFN-γ and IL-17A-producing T cells. Further studies are warranted to determine if ustekinumab can prevent C-peptide AUC decline and induce a clinical response