2,338 research outputs found
A Contour Integral Representation for the Dual Five-Point Function and a Symmetry of the Genus Four Surface in R6
The invention of the "dual resonance model" N-point functions BN motivated
the development of current string theory. The simplest of these models, the
four-point function B4, is the classical Euler Beta function. Many standard
methods of complex analysis in a single variable have been applied to elucidate
the properties of the Euler Beta function, leading, for example, to analytic
continuation formulas such as the contour-integral representation obtained by
Pochhammer in 1890. Here we explore the geometry underlying the dual five-point
function B5, the simplest generalization of the Euler Beta function. Analyzing
the B5 integrand leads to a polyhedral structure for the five-crosscap surface,
embedded in RP5, that has 12 pentagonal faces and a symmetry group of order 120
in PGL(6). We find a Pochhammer-like representation for B5 that is a contour
integral along a surface of genus five. The symmetric embedding of the
five-crosscap surface in RP5 is doubly covered by a symmetric embedding of the
surface of genus four in R6 that has a polyhedral structure with 24 pentagonal
faces and a symmetry group of order 240 in O(6). The methods appear
generalizable to all N, and the resulting structures seem to be related to
associahedra in arbitrary dimensions.Comment: 43 pages and 44 figure
A multi-lake comparative analysis of the General Lake Model (GLM): Stress-testing across a global observatory network
The modelling community has identified challenges for the integration and assessment of lake models due to the diversity of modelling approaches and lakes. In this study, we develop and assess a one-dimensional lake model and apply it to 32 lakes from a global observatory network. The data set included lakes over broad ranges in latitude, climatic zones, size, residence time, mixing regime and trophic level. Model performance was evaluated using several error assessment metrics, and a sensitivity analysis was conducted for nine parameters that governed the surface heat exchange and mixing efficiency. There was low correlation between input data uncertainty and model performance and predictions of temperature were less sensitive to model parameters than prediction of thermocline depth and Schmidt stability. The study provides guidance to where the general model approach and associated assumptions work, and cases where adjustments to model parameterisations and/or structure are required
Benzothiazole and Pyrrolone Flavivirus Inhibitors Targeting the Viral Helicase
The flavivirus nonstructural protein 3 (NS3) is a protease and helicase, and on the basis of its similarity to its homologue encoded by the hepatitis C virus (HCV), the flavivirus NS3 might be a promising drug target. Few flavivirus helicase inhibitors have been reported, in part, because few specific inhibitors have been identified when nucleic acid unwinding assays have been used to screen for helicase inhibitors. To explore the possibility that compounds inhibiting NS3-catalyzed ATP hydrolysis might function as antivirals even if they do not inhibit RNA unwinding in vitro, we designed a robust dengue virus (DENV) NS3 ATPase assay suitable for high-throughput screening. Members of two classes of inhibitory compounds were further tested in DENV helicase-catalyzed RNA unwinding assays, assays monitoring HCV helicase action, subgenomic DENV replicon assays, and cell viability assays and for their ability to inhibit West Nile virus (Kunjin subtype) replication in cells. The first class contained analogues of NIH molecular probe ML283, a benzothiazole oligomer derived from the dye primuline, and they also inhibited HCV helicase and DENV NS3-catalyzed RNA unwinding. The most intriguing ML283 analogue inhibited DENV NS3 with an IC50 value of 500 nM and was active against the DENV replicon. The second class contained specific DENV ATPase inhibitors that did not inhibit DENV RNA unwinding or reactions catalyzed by HCV helicase. Members of this class contained a 4-hydroxy-3-(5-methylfuran-2-carbonyl)-2H-pyrrol-5-one scaffold, and about 20 μM of the most potent pyrrolone inhibited both DENV replicons and West Nile virus replication in cells by 50%
Manipulating a qubit through the backaction of sequential partial measurements and real-time feedback
Quantum measurements not only extract information from a system but also
alter its state. Although the outcome of the measurement is probabilistic, the
backaction imparted on the measured system is accurately described by quantum
theory. Therefore, quantum measurements can be exploited for manipulating
quantum systems without the need for control fields. We demonstrate
measurement-only state manipulation on a nuclear spin qubit in diamond by
adaptive partial measurements. We implement the partial measurement via tunable
correlation with an electron ancilla qubit and subsequent ancilla readout. We
vary the measurement strength to observe controlled wavefunction collapse and
find post-selected quantum weak values. By combining a novel quantum
non-demolition readout on the ancilla with real-time adaption of the
measurement strength we realize steering of the nuclear spin to a target state
by measurements alone. Besides being of fundamental interest, adaptive
measurements can improve metrology applications and are key to
measurement-based quantum computing.Comment: 6 pages, 4 figure
TeV Particle Astrophysics II: Summary comments
A unifying theme of this conference was the use of different approaches to
understand astrophysical sources of energetic particles in the TeV range and
above. In this summary I review how gamma-ray astronomy, neutrino astronomy and
(to some extent) gravitational wave astronomy provide complementary avenues to
understanding the origin and role of high-energy particles in energetic
astrophysical sources.Comment: 6 pages, 4 figures; Conference summary talk for "TeV Particle
Astrophysics II" at University of Wisconsin, Madison, 28-31 August 200
Denitrification and nitrous oxide emissions from riparian forests soils exposed to prolonged nitrogen runoff
Compared to upland forests, riparian forest soils have greater potential to remove nitrate (NO3) from agricultural run-off through denitrification. It is unclear, however, whether prolonged exposure of riparian soils to nitrogen (N) loading will affect the rate of denitrification and its end products. This research assesses the rate of denitrification and nitrous oxide (N2O) emissions from riparian forest soils exposed to prolonged nutrient run-off from plant nurseries and compares these to similar forest soils not exposed to nutrient run-off. Nursery run-off also contains high levels of phosphate (PO4). Since there are conflicting reports on the impact of PO4 on the activity of denitrifying microbes, the impact of PO4 on such activity was also investigated. Bulk and intact soil cores were collected from N-exposed and non-exposed forests to determine denitrification and N2O emission rates, whereas denitrification potential was determined using soil slurries. Compared to the non-amended treatment, denitrification rate increased 2.7- and 3.4-fold when soil cores collected from both N-exposed and non-exposed sites were amended with 30 and 60 μg NO3-N g-1 soil, respectively. Net N2O emissions were 1.5 and 1.7 times higher from the N-exposed sites compared to the non-exposed sites at 30 and 60 μg NO3-N g-1 soil amendment rates, respectively. Similarly, denitrification potential increased 17 times in response to addition of 15 μg NO3-N g-1 in soil slurries. The addition of PO4 (5 μg PO4–P g-1) to soil slurries and intact cores did not affect denitrification rates. These observations suggest that prolonged N loading did not affect the denitrification potential of the riparian forest soils; however, it did result in higher N2O emissions compared to emission rates from non-exposed forests
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RCAN1 knockout and overexpression recapitulate an ensemble of rest-activity and circadian disruptions characteristic of Down syndrome, Alzheimer's disease, and normative aging
Regulator of calcineurin 1 (RCAN1) is overexpressed in Down syndrome (DS), but RCAN1 levels are also increased in Alzheimer’s disease (AD) and normal aging. AD is highly comorbid among individuals with DS and is characterized in part by progressive neurodegeneration that resembles accelerated aging. Importantly, abnormal RCAN1 levels have been demonstrated to promote memory deficits and pathophysiology that appear symptomatic of DS, AD, and aging. Anomalous diurnal rest-activity patterns and circadian rhythm disruptions are also common in DS, AD, and aging and have been implicated in facilitating age-related cognitive decline and AD progression. However, no prior studies have assessed whether RCAN1 dysregulation may also promote the age-associated alteration of rest-activity profiles and circadian rhythms, which could in turn contribute to neurodegeneration in DS, AD, and aging.
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Internalization Dissociates β2-Adrenergic Receptors
G protein-coupled receptors (GPCRs) self-associate as dimers or higher-order oligomers in living cells. The stability of associated GPCRs has not been extensively studied, but it is generally thought that these receptors move between the plasma membrane and intracellular compartments as intact dimers or oligomers. Here we show that β2-adrenergic receptors (β2ARs) that self-associate at the plasma membrane can dissociate during agonist-induced internalization. We use bioluminescence-resonance energy transfer (BRET) to monitor movement of β2ARs between subcellular compartments. BRET between β2ARs and plasma membrane markers decreases in response to agonist activation, while at the same time BRET between β2ARs and endosome markers increases. Energy transfer between β2ARs is decreased in a similar manner if either the donor- or acceptor-labeled receptor is mutated to impair agonist binding and internalization. These changes take place over the course of 30 minutes, persist after agonist is removed, and are sensitive to several inhibitors of arrestin- and clathrin-mediated endocytosis. The magnitude of the decrease in BRET between donor- and acceptor-labeled β2ARs suggests that at least half of the receptors that contribute to the BRET signal are physically segregated by internalization. These results are consistent with the possibility that β2ARs associate transiently with each other in the plasma membrane, or that β2AR dimers or oligomers are actively disrupted during internalization
Stem Cell Transplantation and Long-Term Survival for Primary Immunodeficiencies: Outcomes Among the Donor Sources and Different Diagnostic Groups
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