101 research outputs found
A Non-Singular One-Loop Wave Function of the Universe From a New Eigenvalue Asymptotics in Quantum Gravity
Recent work on Euclidean quantum gravity on the four-ball has proved
regularity at the origin of the generalized zeta-function built from
eigenvalues for metric and ghost modes, when diffeomorphism-invariant boundary
conditions are imposed in the de Donder gauge. The hardest part of the analysis
involves one of the four sectors for scalar-type perturbations, the eigenvalues
of which are obtained by squaring up roots of a linear combination of Bessel
functions of integer adjacent orders, with a coefficient of linear combination
depending on the unknown roots. This paper obtains, first, approximate analytic
formulae for such roots for all values of the order of Bessel functions. For
this purpose, both the descending series for Bessel functions and their uniform
asymptotic expansion at large order are used. The resulting generalized
zeta-function is also built, and another check of regularity at the origin is
obtained. For the first time in the literature on quantum gravity on manifolds
with boundary, a vanishing one-loop wave function of the Universe is found in
the limit of small three-geometry, which suggests a quantum avoidance of the
cosmological singularity driven by full diffeomorphism invariance of the
boundary-value problem for one-loop quantum theory.Comment: 21 Pages, Latex and .eps files with JHEP3 style. The discussion in
Section 5 has been improved, and Ref. 26 has been adde
The Grizzly, March 2, 2006
Omega Chi Hosts Red Cross Blood Drive • Alumna of Sigma Gamma Rho Honored with Stamp • Georgetown Professor Speaks About Abortion • Ursinus Hosts Job and Internship Fair • Introducing the IUD • Centre Pompidou: Modern Art • Breaking Stereotypes • WVOU Spotlight: Bloc Party • Opinions: Red Cross Guidelines Demonstrate Questionable Requirements • Letter to the Editor • Is the Juice Worth the Squeeze?https://digitalcommons.ursinus.edu/grizzlynews/1708/thumbnail.jp
The Grizzly, October 12, 2006
Editorial: Call to Responsibility • Letter of Apology • New Shopping Center Near Campus • Spring Registration Just Around the Corner • Preventing Sexual Assault • Sexual Assault Awareness on Campus • New Incentive Program Underway for CAB • Ursinus Students Evoke Shakespeare\u27s Spirit in Two Gentlemen of Verona • Degas: His Work, His Vision, His Camera • Opinions: On Habeas Corpus; Hurt Feelings; Fundamental Importance of Negative Campaigning • Bears Pull Out Victory in Second Half Comeback • Men\u27s Soccer Capture First Win • A Look Into Ursinus College Fall Athleticshttps://digitalcommons.ursinus.edu/grizzlynews/1721/thumbnail.jp
The Tarantula Venom Peptide Eo1a Binds to the Domain II S3-S4 Extracellular Loop of Voltage-Gated Sodium Channel NaV1.8 to Enhance Activation
Venoms from cone snails and arachnids are a rich source of peptide modulators of voltage-gated sodium (NaV) channels, however relatively few venom-derived peptides with activity at the mammalian NaV1.8 subtype have been isolated. Here, we describe the discovery and functional characterisation of β-theraphotoxin-Eo1a, a peptide from the venom of the Tanzanian black and olive baboon tarantula Encyocratella olivacea that modulates NaV1.8. Eo1a is a 37-residue peptide that increases NaV1.8 peak current (EC50 894 ± 146 nM) and causes a large hyperpolarising shift in both the voltage-dependence of activation (ΔV50-20.5 ± 1.2 mV) and steady-state fast inactivation (ΔV50-15.5 ± 1.8 mV). At a concentration of 10 μM, Eo1a has varying effects on the peak current and channel gating of NaV1.1-NaV1.7, although its activity is most pronounced at NaV1.8. Investigations into the binding site of Eo1a using NaV1.7/NaV1.8 chimeras revealed a critical contribution of the DII S3-S4 extracellular loop of NaV1.8 to toxin activity. Results from this work may form the basis for future studies that lead to the rational design of spider venom-derived peptides with improved potency and selectivity at NaV1.8
The health impacts of waste incineration: a systematic review
Introduction: Waste incineration is increasingly used to reduce waste volume and produce electricity. Several incinerators have recently been proposed in Australia and community groups are concerned about health impacts. An overview of the evidence on health effects has been needed. Method: A systematic review of English language literature for waste incinerators and health using PRISMA methodology. Results: A range of adverse health effects were identified, including significant associations with some neoplasia, congenital anomalies, infant deaths and miscarriage, but not for other diseases. Ingestion was the dominant exposure pathway for the public. Newer incinerator technologies may reduce exposure. Discussion: Despite these findings, diverse chemicals, poor study methodologies and inconsistent reporting of incinerator technology specifications precludes firmer conclusions about safety. Conclusion: Older incinerator technology and infrequent maintenance schedules have been strongly linked with adverse health effects. More recent incinerators have fewer reported ill effects, perhaps because of inadequate time for adverse effects to emerge. A precautionary approach is required. Waste minimisation is essential. Implications for public health: Public health practitioners can offer clearer advice about adverse health effects from incinerators. We suggest improved research design and methods to make future studies more robust and comparable. We offer ideas for better policy and regulation. Key words: waste, health, cancer, incineration, toxi
Rare Copy Number Variants in \u3cem\u3eNRXN1\u3c/em\u3e and \u3cem\u3eCNTN6\u3c/em\u3e Increase Risk for Tourette Syndrome
Tourette syndrome (TS) is a model neuropsychiatric disorder thought to arise from abnormal development and/or maintenance of cortico-striato-thalamo-cortical circuits. TS is highly heritable, but its underlying genetic causes are still elusive, and no genome-wide significant loci have been discovered to date. We analyzed a European ancestry sample of 2,434 TS cases and 4,093 ancestry-matched controls for rare (\u3c 1% frequency) copy-number variants (CNVs) using SNP microarray data. We observed an enrichment of global CNV burden that was prominent for large (\u3e 1 Mb), singleton events (OR = 2.28, 95% CI [1.39–3.79], p = 1.2 × 10−3) and known, pathogenic CNVs (OR = 3.03 [1.85–5.07], p = 1.5 × 10−5). We also identified two individual, genome-wide significant loci, each conferring a substantial increase in TS risk (NRXN1 deletions, OR = 20.3, 95% CI [2.6–156.2]; CNTN6 duplications, OR = 10.1, 95% CI [2.3–45.4]). Approximately 1% of TS cases carry one of these CNVs, indicating that rare structural variation contributes significantly to the genetic architecture of TS
Pain-causing stinging nettle toxins target TMEM233 to modulate NaV1.7 function
Voltage-gated sodium (NaV) channels are critical regulators of neuronal excitability and are targeted by many toxins that directly interact with the pore-forming α subunit, typically via extracellular loops of the voltage-sensing domains, or residues forming part of the pore domain. Excelsatoxin A (ExTxA), a pain-causing knottin peptide from the Australian stinging tree Dendrocnide excelsa, is the first reported plant-derived NaV channel modulating peptide toxin. Here we show that TMEM233, a member of the dispanin family of transmembrane proteins expressed in sensory neurons, is essential for pharmacological activity of ExTxA at NaV channels, and that co-expression of TMEM233 modulates the gating properties of NaV1.7. These findings identify TMEM233 as a previously unknown NaV1.7-interacting protein, position TMEM233 and the dispanins as accessory proteins that are indispensable for toxin-mediated effects on NaV channel gating, and provide important insights into the function of NaV channels in sensory neurons
Synaptic processes and immune-related pathways implicated in Tourette syndrome
Tourette syndrome (TS) is a neuropsychiatric disorder of complex genetic architecture involving multiple interacting genes. Here, we sought to elucidate the pathways that underlie the neurobiology of the disorder through genome-wide analysis. We analyzed genome-wide genotypic data of 3581 individuals with TS and 7682 ancestry-matched controls and investigated associations of TS with sets of genes that are expressed in particular cell types and operate in specific neuronal and glial functions. We employed a self-contained, set-based association method (SBA) as well as a competitive gene set method (MAGMA) using individual-level genotype data to perform a comprehensive investigation of the biological background of TS. Our SBA analysis identified three significant gene sets after Bonferroni correction, implicating ligand-gated ion channel signaling, lymphocytic, and cell adhesion and transsynaptic signaling processes. MAGMA analysis further supported the involvement of the cell adhesion and trans-synaptic signaling gene set. The lymphocytic gene set was driven by variants in FLT3, raising an intriguing hypothesis for the involvement of a neuroinflammatory element in TS pathogenesis. The indications of involvement of ligand-gated ion channel signaling reinforce the role of GABA in TS, while the association of cell adhesion and trans-synaptic signaling gene set provides additional support for the role of adhesion molecules in neuropsychiatric disorders. This study reinforces previous findings but also provides new insights into the neurobiology of TS
The Atacama Cosmology Telescope: Modeling the Gas Thermodynamics in BOSS CMASS galaxies from Kinematic and Thermal Sunyaev-Zel'dovich Measurements
The thermal and kinematic Sunyaev-Zel'dovich effects (tSZ, kSZ) probe the
thermodynamic properties of the circumgalactic and intracluster medium (CGM and
ICM) of galaxies, groups, and clusters, since they are proportional,
respectively, to the integrated electron pressure and momentum along the
line-of-sight. We present constraints on the gas thermodynamics of CMASS
galaxies in the Baryon Oscillation Spectroscopic Survey (BOSS) using new
measurements of the kSZ and tSZ signals obtained in a companion paper.
Combining kSZ and tSZ measurements, we measure within our model the amplitude
of energy injection , where is the stellar
mass, to be , and the amplitude of the
non-thermal pressure profile to be (2),
indicating that less than 20% of the total pressure within the virial radius is
due to a non-thermal component. We estimate the effects of including baryons in
the modeling of weak-lensing galaxy cross-correlation measurements using the
best fit density profile from the kSZ measurement. Our estimate reduces the
difference between the original theoretical model and the weak-lensing galaxy
cross-correlation measurements in arXiv:1611.08606 by half, but does not fully
reconcile it. Comparing the kSZ and tSZ measurements to cosmological
simulations, we find that they under predict the CGM pressure and to a lesser
extent the CGM density at larger radii. This suggests that the energy injected
via feedback models in the simulations that we compared against does not
sufficiently heat the gas at these radii. We do not find significant
disagreement at smaller radii. These measurements provide novel tests of
current and future simulations. This work demonstrates the power of joint, high
signal-to-noise kSZ and tSZ observations, upon which future cross-correlation
studies will improve.Comment: Accepted for publication in Physical Review D. Editors' Suggestion.
New Fig. 1-2, Tab.
Histone Deacetylase Inhibitor Romidepsin Induces HIV Expression in CD4 T Cells from Patients on Suppressive Antiretroviral Therapy at Concentrations Achieved by Clinical Dosing
Persistent latent reservoir of replication-competent proviruses in memory CD4 T cells is a major obstacle to curing HIV infection. Pharmacological activation of HIV expression in latently infected cells is being explored as one of the strategies to deplete the latent HIV reservoir. In this study, we characterized the ability of romidepsin (RMD), a histone deacetylase inhibitor approved for the treatment of T-cell lymphomas, to activate the expression of latent HIV. In an in vitro T-cell model of HIV latency, RMD was the most potent inducer of HIV (EC50 = 4.5 nM) compared with vorinostat (VOR; EC50 = 3,950 nM) and other histone deacetylase (HDAC) inhibitors in clinical development including panobinostat (PNB; EC50 = 10 nM). The HIV induction potencies of RMD, VOR, and PNB paralleled their inhibitory activities against multiple human HDAC isoenzymes. In both resting and memory CD4 T cells isolated from HIV-infected patients on suppressive combination antiretroviral therapy (cART), a 4-hour exposure to 40 nM RMD induced a mean 6-fold increase in intracellular HIV RNA levels, whereas a 24-hour treatment with 1 μM VOR resulted in 2- to 3-fold increases. RMD-induced intracellular HIV RNA expression persisted for 48 hours and correlated with sustained inhibition of cell-associated HDAC activity. By comparison, the induction of HIV RNA by VOR and PNB was transient and diminished after 24 hours. RMD also increased levels of extracellular HIV RNA and virions from both memory and resting CD4 T-cell cultures. The activation of HIV expression was observed at RMD concentrations below the drug plasma levels achieved by doses used in patients treated for T-cell lymphomas. In conclusion, RMD induces HIV expression ex vivo at concentrations that can be achieved clinically, indicating that the drug may reactivate latent HIV in patients on suppressive cART
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