249 research outputs found
Sum rule for the backward spin polarizability of the nucleon from a backward dispersion relation
A new sum rule for , the backward spin polarizability of the
nucleon, is derived from a backward-angle dispersion relation. Taking into
account single- and multi-pion photoproduction in the s-channel up to the
energy 1.5 GeV and resonances in the t-channel with mass below 1.5 GeV, it is
found for the proton and neutron that = -39.5 +/- 2.4 and
= 52.5 +/- 2.4, respectively, in units of 10^{-4} fm^4.Comment: 10 pages, 1 figure, revtex. Submitted to Phys. Lett.
Basal forebrain volume reliably predicts the cortical spread of Alzheimer\u27s degeneration
© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. Alzheimer\u27s disease neurodegeneration is thought to spread across anatomically and functionally connected brain regions. However, the precise sequence of spread remains ambiguous. The prevailing model used to guide in vivo human neuroimaging and non-human animal research assumes that Alzheimer\u27s degeneration starts in the entorhinal cortices, before spreading to the temporoparietal cortex. Challenging this model, we previously provided evidence that in vivo markers of neurodegeneration within the nucleus basalis of Meynert (NbM), a subregion of the basal forebrain heavily populated by cortically projecting cholinergic neurons, precedes and predicts entorhinal degeneration. There have been few systematic attempts at directly comparing staging models using in vivo longitudinal biomarker data, and none to our knowledge testing if comparative evidence generalizes across independent samples. Here we addressed the sequence of pathological staging in Alzheimer\u27s disease using two independent samples of the Alzheimer\u27s Disease Neuroimaging Initiative (n1 = 284; n2 = 553) with harmonized CSF assays of amyloid-b and hyperphosphorylated tau (pTau), and longitudinal structural MRI data over 2 years. We derived measures of grey matter degeneration in a priori NbM and the entorhinal cortical regions of interest. To examine the spreading of degeneration, we used a predictive modelling strategy that tests whether baseline grey matter volume in a seed region accounts for longitudinal change in a target region. We demonstrated that predictive spread favoured the NbM!entorhinal over the entorhinal!NbM model. This evidence generalized across the independent samples. We also showed that CSF concentrations of pTau/amyloid-b moderated the observed predictive relationship, consistent with evidence in rodent models of an underlying trans-synaptic mechanism of pathophysiological spread. The moderating effect of CSF was robust to additional factors, including clinical diagnosis. We then applied our predictive modelling strategy to an exploratory whole-brain voxel-wise analysis to examine the spatial specificity of the NbM!entorhinal model. We found that smaller baseline NbM volumes predicted greater degeneration in localized regions of the entorhinal and perirhinal cortices. By contrast, smaller baseline entorhinal volumes predicted degeneration in the medial temporal cortex, recapitulating a prior influential staging model. Our findings suggest that degeneration of the basal forebrain cholinergic projection system is a robust and reliable upstream event of entorhinal and neocortical degeneration, calling into question a prevailing view of Alzheimer\u27s disease pathogenesis
Exclusive 16O(γ,π-p) reaction in the Δ resonance region
We report the first exclusive (γ,π-p) measurements on a complex nucleus. The 16O(γ,π-p) reaction was measured at pion laboratory angles of 64° and 120°. Coincident protons were detected over the quasifree angular correlation range using a vertical array of seven plastic scintillator detectors spanning ±33° about the scattering plane. The cross sections are compared to factorized distorted-wave impulse approximation calculations; these provide a good description of the backward angle data, but are in serious disagreement with the forward angle data
A smac mimetic reduces TNF related apoptosis inducing ligand (TRAIL)-induced invasion and metastasis of cholangiocarcinoma cells.
UNLABELLED: Cholangiocarcinoma (CCA) cells paradoxically express tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a death ligand that, failing to kill CCA cells, instead promotes their tumorigenicity and especially the metastatic behaviors of cell migration and invasion. Second mitochondria-derived activator of caspase (smac) mimetics are promising cancer therapeutic agents that enhance proapoptotic death receptor signaling by causing cellular degradation of inhibitor of apoptosis (IAP) proteins. Our aim was to examine the in vitro and in vivo effects of the smac mimetic JP1584 in CCA. Despite JP1584-mediated loss of cellular inhibitor of apoptosis-1 (cIAP-1) and cIAP-2, TRAIL failed to induce apoptosis in KMCH-1, TFK-1, and BDEneu CCA cells; a finding consistent with a downstream block in death signaling. Because cIAP-1 and cIAP-2 also promote nuclear factor kappa B (NF-kappaB) activation by the canonical pathway, the effect of JP1584 on this signaling pathway was examined. Treatment with JP1584 inhibited TRAIL-induced NF-kappaB activation as well as TRAIL-mediated up-regulation of the NF-kappaB target gene, matrix metalloproteinase 7 (MMP7). JP1584 also reduced TRAIL-mediated CCA cell migration and invasion in vitro. Finally, in a syngeneic rat orthotopic CCA model, JP1584 administration reduced MMP7 messenger RNA levels and extrahepatic metastases.
CONCLUSION: : Although the smac mimetic JP1584 does not sensitize cells to apoptosis, it reduces TRAIL-induced CCA cell metastatic behavior. These data support the emerging concept that IAPs are prometastatic and represent targets for antimetastatic therapies
A dimensionally continued Poisson summation formula
We generalize the standard Poisson summation formula for lattices so that it
operates on the level of theta series, allowing us to introduce noninteger
dimension parameters (using the dimensionally continued Fourier transform).
When combined with one of the proofs of the Jacobi imaginary transformation of
theta functions that does not use the Poisson summation formula, our proof of
this generalized Poisson summation formula also provides a new proof of the
standard Poisson summation formula for dimensions greater than 2 (with
appropriate hypotheses on the function being summed). In general, our methods
work to establish the (Voronoi) summation formulae associated with functions
satisfying (modular) transformations of the Jacobi imaginary type by means of a
density argument (as opposed to the usual Mellin transform approach). In
particular, we construct a family of generalized theta series from Jacobi theta
functions from which these summation formulae can be obtained. This family
contains several families of modular forms, but is significantly more general
than any of them. Our result also relaxes several of the hypotheses in the
standard statements of these summation formulae. The density result we prove
for Gaussians in the Schwartz space may be of independent interest.Comment: 12 pages, version accepted by JFAA, with various additions and
improvement
The clustering instability of inertial particles spatial distribution in turbulent flows
A theory of clustering of inertial particles advected by a turbulent velocity
field caused by an instability of their spatial distribution is suggested. The
reason for the clustering instability is a combined effect of the particles
inertia and a finite correlation time of the velocity field. The crucial
parameter for the clustering instability is a size of the particles. The
critical size is estimated for a strong clustering (with a finite fraction of
particles in clusters) associated with the growth of the mean absolute value of
the particles number density and for a weak clustering associated with the
growth of the second and higher moments. A new concept of compressibility of
the turbulent diffusion tensor caused by a finite correlation time of an
incompressible velocity field is introduced. In this model of the velocity
field, the field of Lagrangian trajectories is not divergence-free. A mechanism
of saturation of the clustering instability associated with the particles
collisions in the clusters is suggested. Applications of the analyzed effects
to the dynamics of droplets in the turbulent atmosphere are discussed. An
estimated nonlinear level of the saturation of the droplets number density in
clouds exceeds by the orders of magnitude their mean number density. The
critical size of cloud droplets required for clusters formation is more than
m.Comment: REVTeX 4, 15 pages, 2 figures(included), PRE submitte
Study of Quasielastic Barrier Distributions as a Step towards the Synthesis of Superheavy Elements with Hot Fusion Reactions
The excitation functions for quasielastic scattering of Ne22+Cm248, Mg26+Cm248, and Ca48+U238 are measured using a gas-filled recoil ion separator. The quasielastic barrier distributions are extracted for these systems and are compared with coupled-channel calculations. The results indicate that the barrier distribution is affected dominantly by deformation of the actinide target nuclei, but also by vibrational or rotational excitations of the projectile nuclei, as well as neutron transfer processes before capture. From a comparison between the experimental barrier distributions and the evaporation residue cross sections for Sg (Z=106), Hs (108), Cn (112), and Lv (116), it is suggested that the hot fusion reactions take advantage of a compact collision, where the projectile approaches along the short axis of a prolately deformed nucleus. A new method is proposed to estimate the optimum incident energy to synthesize unknown superheavy nuclei using the barrier distribution.This research was partially supported by a Grantin-Aid for Specially Promoted Research, 19002005, from
the Ministry of Education, Culture, Sports, Science and
Technology of Japan, and by the U.S. DOE Office of
Nuclear Physics. T. T. thanks the RIKEN Junior Research
Associate Program
Enhanced glycemic control with combination therapy for type 2 diabetes in primary care
Type 2 diabetes mellitus is an increasingly common medical problem for primary care clinicians to address. Treatment of diabetes has evolved from simple replacement of insulin (directly or through insulin secretagogs) through capture of mechanisms such as insulin sensitizers, alpha-glucosidase inhibitors, and incretins. Only very recently has recognition of the critical role of the gastrointestinal system as a major culprit in glucose dysregulation been established. Since glycated hemoglobin A1c reductions provide meaningful risk reduction as well as improved quality of life, it is worthwhile to explore evolving paths for more efficient use of the currently available pharmacotherapies. Because diabetes is a progressive disease, even transiently successful treatment will likely require augmentation as the disorder progresses. Pharmacotherapies with complementary mechanisms of action will be necessary to achieve glycemic goals. Hence, clinicians need to be well informed about the various noninsulin alternatives that have been shown to be successful in glycemic goal attainment. This article reviews the benefits of glucose control, the current status of diabetes control, pertinent pathophysiology, available pharmacological classes for combination, limitations of current therapies, and suggestions for appropriate combination therapies, including specific suggestions for thresholds at which different strategies might be most effectively utilized by primary care clinicians
Emerging role of insulin with incretin therapies for management of type 2 diabetes
Type 2 diabetes mellitus (T2DM) is a progressive disease warranting intensification of treatment, as beta-cell function declines over time. Current treatment algorithms recommend metformin as the first-line agent, while advocating the addition of either basal-bolus or premixed insulin as the final level of intervention. Incretin therapy, including incretin mimetics or enhancers, are the latest group of drugs available for treatment of T2DM. These agents act through the incretin axis, are currently recommended as add-on agents either as second-or third-line treatment, without concurrent use of insulin. Given the novel role of incretin therapy in terms of reducing postprandial hyperglycemia, and favorable effects on weight with reduced incidence of hypoglycemia, we explore alternative options for incretin therapy in T2DM management. Furthermore, as some evidence alludes to incretins potentially increasing betacell mass and altering disease progression, we propose introducing these agents earlier in the treatment algorithm. In addition, we suggest the concurrent use of incretins with insulin, given the favorable effects especially in relation to weight gain
Dapagliflozin: a sodium glucose cotransporter 2 inhibitor in development for type 2 diabetes
Type 2 diabetes mellitus (T2DM) is a growing worldwide epidemic. Patients face lifelong therapy to control hyperglycemia and prevent the associated complications. There are many medications, with varying mechanisms, available for the treatment of T2DM, but almost all target the declining insulin sensitivity and secretion that are associated with disease progression. Medications with such insulin-dependent mechanisms of action often lose efficacy over time, and there is increasing interest in the development of new antidiabetes medications that are not dependent upon insulin. One such approach is through the inhibition of renal glucose reuptake. Dapagliflozin, the first of a class of selective sodium glucose cotransporter 2 inhibitors, reduces renal glucose reabsorption and is currently under development for the treatment of T2DM. Here, we review the literature relating to the preclinical and clinical development of dapagliflozin
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