Non-local signatures of the chiral magnetic effect in Dirac semimetal Bi0.97_{0.97}Sb0.03_{0.03}

The field of topological materials science has recently been focussing on three-dimensional Dirac semimetals, which exhibit robust Dirac phases in the bulk. However, the absence of characteristic surface states in accidental Dirac semimetals (DSM) makes it difficult to experimentally verify claims about the topological nature using commonly used surface-sensitive techniques. The chiral magnetic effect (CME), which originates from the Weyl nodes, causes an $\textbf{E}\cdot\textbf{B}$-dependent chiral charge polarization, which manifests itself as negative magnetoresistance. We exploit the extended lifetime of the chirally polarized charge and study the CME through both local and non-local measurements in Hall bar structures fabricated from single crystalline flakes of the DSM Bi$_{0.97}$Sb$_{0.03}$. From the non-local measurement results we find a chiral charge relaxation time which is over one order of magnitude larger than the Drude transport lifetime, underlining the topological nature of Bi$_{0.97}$Sb$_{0.03}$.Comment: 6 pages, 6 figures + 7 pages of supplemental materia

The Sex and Race Specific Relationship between Anthropometry and Body Fat Composition Determined from Computed Tomography: Evidence from the Multi-Ethnic Study of Atherosclerosis.

BackgroundFew studies have investigated the relationship of anthropometric measurements with computed tomography (CT) body fat composition, and even fewer determined if these relationships differ by sex and race.MethodsCT scans from 1,851 participants in the population based Multi-Ethnic Study of Atherosclerosis were assessed for visceral and subcutaneous fat areas by semi-automated segmentation of body compartments. Regression models were used to investigate relationships for anthropometry with visceral and subcutaneous fat separately by sex and race/ethnicity.ResultsParticipants were 50% female, 41% Caucasian, 13% Asian, 21% African American, and 25% Hispanic. For visceral fat, the positive relationship with weight (p = 0.028), waist circumference (p<0.001), waist to hip ratio (p<0.001), and waist to height ratio (p = 0.05) differed by sex, with a steeper slope for men. That is, across the range of these anthropometric measures the rise in visceral fat is faster for men than for women. Additionally, there were differences by race/ethnicity in the relationship with height (p<0.001), weight (p<0.001), waist circumference (p<0.001), hip circumference (p = 0.006), and waist to hip ratio (p = 0.001) with the Hispanic group having shallower slopes. For subcutaneous fat, interaction by sex was found for all anthropometric indices at p<0.05, but not for race/ethnicity.ConclusionThe relationship between anthropometry and underlying adiposity differs by sex and race/ethnicity. When anthropometry is used as a proxy for visceral fat in research, sex-specific models should be used

4π4\pi periodic Andreev bound states in a Dirac semimetal

Electrons in a Dirac semimetals possess linear dispersion in all three spatial dimensions, and form part of a developing platform of novel quantum materials. Bi$_{1-x}$Sb$_x$ supports a three-dimensional Dirac cone at the Sb-induced band inversion point. Nanoscale phase-sensitive junction technology is used to induce superconductivity in this Dirac semimetal. Radio frequency irradiation experiments reveal a significant contribution of 4$\pi$-periodic Andreev bound states to the supercurrent in Nb-Bi$_{0.97}$Sb$_{0.03}$-Nb Josephson junctions. The conditions for a substantial $4\pi$ contribution to the supercurrent are favourable because of the Dirac cone's topological protection against backscattering, providing very broad transmission resonances. The large g-factor of the Zeeman effect from a magnetic field applied in the plane of the junction, allows tuning of the Josephson junctions from 0 to $\pi$ regimes.Comment: Supplementary information is include

Progress toward superconductor electronics fabrication process with planarized NbN and NbN/Nb layers

To increase density of superconductor digital and neuromorphic circuits by 10x and reach integration scale of $10^8$ Josephson junctions (JJs) per chip, we developed a new fabrication process on 200-mm wafers, using self-shunted Nb/Al-AlOx/Nb JJs and kinetic inductors. The process has a layer of JJs, a layer of resistors, and 10 fully planarized superconducting layers: 8 Nb layers and 2 layers of high kinetic inductance materials, Mo$_2$N and NbN, with sheet inductance of 8 pH/sq and 3 pH/sq, respectively. NbN films were deposited by two methods: with $T_c$=15.5 K by reactive sputtering of a Nb target in Ar+N$_2$ mixture; with $T_c$ in the range from 9 K to 13 K by plasma-enhanced chemical vapor deposition (PECVD) using Tris(diethylamido)(tert-butylimido)niobium(V) metalorganic precursor. PECVD of NbN was investigated to obtain conformal deposition and filling narrow trenches and vias with high depth-to-width ratios, which was not possible to achieve using sputtering and other physical vapor deposition (PVD) methods at temperatures below $200 ^oC$ required to prevent degradation of Nb/Al-AlOx/Nb junctions. Nb layers with 200 nm thickness are used in the process layer stack as ground planes to maintain a high level of interlayer shielding and low intralayer mutual coupling, for passive transmission lines with wave impedances matching impedances of JJs, typically <=50 $\Omega$, and for low-value inductors. NbN and NbN/Nb bilayer are used for cell inductors. Using NbN/Nb bilayers and individual pattering of both layers to form inductors allowed us to minimize parasitic kinetic inductance associated with interlayer vias and connections to JJs as well as to increase critical currents of the vias. Fabrication details and results of electrical characterization of NbN films, wires, and vias, and comparison with Nb properties are given.Comment: 12 pages, 16 figures, 4 tables, 49 references. Submitted to IEEE TAS on Nov. 10, 202

Characterization of a Cdc42 Protein Inhibitor and Its Use as a Molecular Probe

Cdc42 plays important roles in cytoskeleton organization, cell cycle progression, signal transduction, and vesicle trafficking. Overactive Cdc42 has been implicated in the pathology of cancers, immune diseases, and neuronal disorders. Therefore, Cdc42 inhibitors would be useful in probing molecular pathways and could have therapeutic potential. Previous inhibitors have lacked selectivity and trended toward toxicity. We report here the characterization of a Cdc42-selective guanine nucleotide binding lead inhibitor that was identified by high throughput screening. A second active analog was identified via structure-activity relationship studies. The compounds demonstrated excellent selectivity with no inhibition toward Rho and Rac in the same GTPase family. Biochemical characterization showed that the compounds act as noncompetitive allosteric inhibitors. When tested in cellular assays, the lead compound inhibited Cdc42-related filopodia formation and cell migration. The lead compound was also used to clarify the involvement of Cdc42 in the Sin Nombre virus internalization and the signaling pathway of integrin VLA-4. Together, these data present the characterization of a novel Cdc42-selective allosteric inhibitor and a related analog, the use of which will facilitate drug development targeting Cdc42-related diseases and molecular pathway studies that involve GTPases.This work was supported by National Science Foundation (NSF) Grant MCB0956027 and National Institutes of Health Grant R03 MH081231-01 from the Molecular Libraries Program (to A. W. N.); University of New Mexico Center for Molecular Discovery Molecular Libraries Probe Production Centers (UNMCMD MLPCN) National Institutes of Health Grants U54MH084690 and R01HL081062 (to L. A. S.); UNM National Center for Research Resources (NCRR) Grant 5P20RR016480 (to L. G. H.); National Institutes of Health Grant R21 CA170375-01 through the NCI (to A. W. N., L. G. H., and J. E. G.); National Institutes of Health Grants NS066429 and AI092130 (to T. B.); and University of Kansas Specialized Chemistry Center (KUSCC) MLPCN National Institutes of Health Grant U54HG005031 (to J. A.)

Identification of a small molecule yeast TORC1 inhibitor with a flow cytometry-based multiplex screen

TOR (target of rapamycin) is a serine/threonine kinase, evolutionarily conserved from yeast to human, which functions as a fundamental controller of cell growth. The moderate clinical benefit of rapamycin in mTOR-based therapy of many cancers favors the development of new TOR inhibitors. Here we report a high throughput flow cytometry multiplexed screen using five GFPtagged yeast clones that represent the readouts of four branches of the TORC1 signaling pathway in budding yeast. Each GFP-tagged clone was differentially color-coded and the GFP signal of each clone was measured simultaneously by flow cytometry, which allows rapid prioritization of compounds that likely act through direct modulation of TORC1 or proximal signaling components. A total of 255 compounds were confirmed in dose-response analysis to alter GFP expression in one or more clones. To validate the concept of the high throughput screen, we have characterized CID 3528206, a small molecule most likely to act on TORC1 as it alters GFP expression in all five GFP clones in an analogous manner to rapamycin. We have shown that CID 3528206 inhibited yeast cell growth, and that CID 3528206 inhibited TORC1 activity both in vitro and in vivo with EC50s of 150 nM and 3.9 μM, respectively. The results of microarray analysis and yeast GFP collection screen further support the notion that CID 3528206 and rapamycin modulate similar cellular pathways. Together, these results indicate that the HTS has identified a potentially useful small molecule for further development of TOR inhibitors

Consuming cassava as a staple food places children 2-5 years old at risk for inadequate protein intake, an observational study in Kenya and Nigeria

<p>Abstract</p> <p>Background</p> <p>Inadequate protein intake is known to be deleterious in animals. Using WHO consensus documents for human nutrient requirements, the protein:energy ratio (P:E) of an adequate diet is > 5%. Cassava has a very low protein content. This study tested the hypothesis that Nigerian and Kenyan children consuming cassava as their staple food are at greater risk for inadequate dietary protein intake than those children who consume less cassava.</p> <p>Methods</p> <p>A 24 hour dietary recall was used to determine the food and nutrient intake of 656 Nigerian and 449 Kenyan children aged 2-5 years residing in areas where cassava is a staple food. Anthropometric measurements were conducted. Diets were scored for diversity using a 12 point score. Pearson's Correlation Coefficients were calculated to relate the fraction of dietary energy obtained from cassava with protein intake, P:E, and dietary diversity.</p> <p>Results</p> <p>The fraction of dietary energy obtained from cassava was > 25% in 35% of Nigerian children and 89% of Kenyan children. The mean dietary diversity score was 4.0 in Nigerian children and 4.5 in Kenyan children, although the mean number of different foods consumed on the survey day in Nigeria was greater than Kenya, 7.0 compared to 4.6. 13% of Nigerian and 53% of Kenyan children surveyed had inadequate protein intake. The fraction of dietary energy derived from cassava was negatively correlated with protein intake, P:E, and dietary diversity. Height-for age z score was directly associated with protein intake and negatively associated with cassava consumption using regression modeling that controlled for energy and zinc intake.</p> <p>Conclusions</p> <p>Inadequate protein intake was found in the diets of Nigerian and Kenyan children consuming cassava as a staple food. Inadequate dietary protein intake is associated with stunting in this population. Interventions to increase protein intake in this vulnerable population should be the focus of future work.</p

Gray matter injury associated with periventricular leukomalacia in the premature infant

Neuroimaging studies indicate reduced volumes of certain gray matter regions in survivors of prematurity with periventricular leukomalacia (PVL). We hypothesized that subacute and/or chronic gray matter lesions are increased in incidence and severity in PVL cases compared to non-PVL cases at autopsy. Forty-one cases of premature infants were divided based on cerebral white matter histology: PVL (n = 17) with cerebral white matter gliosis and focal periventricular necrosis; diffuse white matter gliosis (DWMG) (n = 17) without necrosis; and

Locus-specific epigenetic remodeling controls addiction- and depression-related behaviors

Chronic exposure to drugs of abuse or stress regulates transcription factors, chromatin-modifying enzymes and histone post-translational modifications in discrete brain regions. Given the promiscuity of the enzymes involved, it has not yet been possible to obtain direct causal evidence to implicate the regulation of transcription and consequent behavioral plasticity by chromatin remodeling that occurs at a single gene. We investigated the mechanism linking chromatin dynamics to neurobiological phenomena by applying engineered transcription factors to selectively modify chromatin at a specific mouse gene in vivo. We found that histone methylation or acetylation at the Fosb locus in nucleus accumbens, a brain reward region, was sufficient to control drug- and stress-evoked transcriptional and behavioral responses via interactions with the endogenous transcriptional machinery. This approach allowed us to relate the epigenetic landscape at a given gene directly to regulation of its expression and to its subsequent effects on reward behavior

Comparability of Results from Pair and Classical Model Formulations for Different Sexually Transmitted Infections

The “classical model” for sexually transmitted infections treats partnerships as instantaneous events summarized by partner change rates, while individual-based and pair models explicitly account for time within partnerships and gaps between partnerships. We compared predictions from the classical and pair models over a range of partnership and gap combinations. While the former predicted similar or marginally higher prevalence at the shortest partnership lengths, the latter predicted self-sustaining transmission for gonorrhoea (GC) and Chlamydia (CT) over much broader partnership and gap combinations. Predictions on the critical level of condom use (Cc) required to prevent transmission also differed substantially when using the same parameters. When calibrated to give the same disease prevalence as the pair model by adjusting the infectious duration for GC and CT, and by adjusting transmission probabilities for HIV, the classical model then predicted much higher Cc values for GC and CT, while Cc predictions for HIV were fairly close. In conclusion, the two approaches give different predictions over potentially important combinations of partnership and gap lengths. Assuming that it is more correct to explicitly model partnerships and gaps, then pair or individual-based models may be needed for GC and CT since model calibration does not resolve the differences