113 research outputs found
Coherent Patterning of Matter Waves with Subwavelength Localization
We propose the Subwavelength Localization via Adiabatic Passage (SLAP)
technique to coherently achieve state-selective patterning of matter waves well
beyond the diffraction limit. The SLAP technique consists in coupling two
partially overlapping and spatially structured laser fields to three internal
levels of the matter wave yielding state-selective localization at those
positions where the adiabatic passage process does not occur. We show that by
means of this technique matter wave localization down to the single nanometer
scale can be achieved. We analyze in detail the potential implementation of the
SLAP technique for nano-lithography with an atomic beam of metastable Ne* and
for coherent patterning of a two-component 87Rb Bose-Einstein condensate.Comment: 6 pages, 5 figure
Pulsed Direct And Constant Direct Currents In The Pilocarpine Iontophoresis Sweat Chloride Test
Background: The classic sweat test (CST) is the golden standard for cystic fibrosis (CF) diagnosis. Then, our aim was compare the production and volume of sweat, and side effects caused by pulsed direct current (PDC) and constant direct current (CDC). To determine the optimal stimulation time (ST) for the sweat collection. To verify the PDC as CF diagnosis option. Methods: Prospective study with cross-sectional experimental intervention. Experiment 1 (right arm): PDC and CDC. ST at 10 min and sweat collected at 30 min. Currents of 0.5; 0.75; 1.0 and 1.5 mA and frequencies of 0, 200, 1,000 and 5,000 Hz applied. Experiment 2 (left arm): current of 1.0 mA, ST at 5 and 10 min and sweat collected at 15 and 30 min with frequencies of 0; 200; 1,000 and 5,000 Hz applied Experiments 1 and 2 were performed with current density (CD) from 0.07 to 0.21 mA/cm2. Experiment 3: PDC was used in typical CF patients with two CFTR mutations screened and or with CF diagnosis by rectal biopsy and patients with atypical CF. Results: 48 subjects (79.16% female) with average of 29.54 ± 8.87 years old were enrolled. There was no statistical difference between the interaction of frequency and current in the sweat weight (p = 0.7488). Individually, positive association was achieved between weight sweat and stimulation frequency (p = 0.0088); and current (p = 0.0025). The sweat production was higher for 10 min of stimulation (p = 0.0023). The sweat collection was better for 30 min (p = 0.0019). The skin impedance was not influenced by ST and sweat collection (p > 0.05). The current frequency was inversely associated with the skin impedance (p < 0.0001). The skin temperature measured before stimulation was higher than after (p < 0.0001). In Experiment 3 (29 subjects) the PDC showed better kappa index compared to CDC (0.9218 versus 0.5205, respectively). Conclusions: The performance of the CST with CDC and PDC with CD of 0.14 to 0.21 mA/cm2 showed efficacy in steps of stimulation and collection of sweat, without side effects. The optimal stimulation time and sweat collection were, respectively, 10 and 30 min.141Di Sant'S Agnese, P.A., Darling, R.C., Perara, G.A., Shea, E., Abnormal electrolyte composition of sweat in cystic fibrosis of the pancreas (1953) Am J Dis Child, 86, pp. 618-619Gibson, L.E., Cooke, R.E., A test for concentration of electrolytes in sweat in cystic fibrosis of the pancreas utilizing pilocarpine by iontophoresis (1959) Pediatrics, 23, pp. 545-549Taylor, C.J., Hardcastle, J., Southern, K.W., Physiological measurements confirming the diagnosis of cystic fibrosis. The sweat test and measurements of transepithelial potential difference (2009) Paedia Resp Rev, 10, pp. 220-226Rosenstein, B.J., What is a cystic fibrosis diagnosis? 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Penrose limit, Spontaneous Symmetry Breaking and Holography in PP-Wave Background
We argue that the gauge theory dual to the Type IIB string theory in
ten-dimensional pp-wave background can be thought to `live' on an {\it
Euclidean} subspace spanning four of the eight transverse coordinates. We then
show that light-cone time evolution of the string is identifiable as the RG
flow of the gauge theory -- a relation facilitating `holography' of the pp-wave
background. The `holography' reorganizes the dual gauge theory into theories
defined over Hilbert subspaces of fixed R-charge. The reorganization breaks the
SO(4,2)SO(6) symmetry to a maximal subgroup SO(4) SO(4)
spontaneously. We argue that the low-energy string modes may be regarded as
Goldstone modes resulting from such symmetry breaking pattern.Comment: LateX 24 pages; v2 : new subsection added about relation to usual
Yang-Mills, references adde
The Vega debris disc: A view from Herschel
We present five band imaging of the Vega debris disc obtained using the Herschel Space Observatory. These data span a wavelength range of 70-500 mu m with full-width half-maximum angular resolutions of 5.6-36.9 ''. The disc is well resolved in all bands, with the ring structure visible at 70 and 160 mu m. Radial profiles of the disc surface brightness are produced, and a disc radius of 11 '' (similar to 85AU) is determined. The disc is seen to have a smooth structure thoughout the entire wavelength range, suggesting that the disc is in a steady state, rather than being an ephemeral structure caused by the recent collision of two large planetesimals
On the Holographic RG-flow and the Low-energy, Strong Coupling, Large N Limit
From the AdS/CFT correspondence, we learn that the classical evolution of
supergravity in the bulk can be reduced to a RG-flow equation for the dual
low-energy, strongly coupled and large N gauge theory on the boundary. This
result has been used to obtain interesting relations between the various terms
in the gravitational part of the boundary effective action, in particular the
term that affect the cosmological constant. It is found that once the
cosmological constant is cancelled in the UV theory, the RG-flow symmetry of
the boundary effective action automatically implies the existence of zero
cosmological constant solutions that extend all the way into the IR. Given the
standard (and well founded) contradiction between the RG-flow idea and the
observational evidence of a small cosmological constant, this is considered to
be an important progress, albeit incomplete, towards the final solution.
Motivated by this success, it would be interesting to see whether this
RG-stability extends outside the scope of strong 't Hooft coupling and large N
regime that are implicitly assumed in the de Boer-Verlinde-Verlinde
Hamilton-Jacobi formulation of the holographic RG-flow equations of the
boundary theory. In this paper, we address this question. Taking into account
the leading order corrections in the 1/N and parameters, we
derive new bulk/boundary relations, from which one can read all the local terms
in the boundary effective action. Next, we use the resulting constraints, to
examine whether the RG-stability of the cosmological constant extends to the
new coupling regime. It would be also interesting to use these constraints to
study the Randall-Sundrum scenario in this case.Comment: 27 pages, LateX, no figures, minor changes, typos corrected and added
more reference
CSF1R inhibitor JNJ-40346527 attenuates microglial proliferation and neurodegeneration in P301S mice
Neuroinflammation and microglial activation are significant processes in Alzheimer's disease pathology. Recent genome-wide association studies have highlighted multiple immune-related genes in association with Alzheimer's disease, and experimental data have demonstrated microglial proliferation as a significant component of the neuropathology. In this study, we tested the efficacy of the selective CSF1R inhibitor JNJ-40346527 (JNJ-527) in the P301S mouse tauopathy model. We first demonstrated the anti-proliferative effects of JNJ-527 on microglia in the ME7 prion model, and its impact on the inflammatory profile, and provided potential CNS biomarkers for clinical investigation with the compound, including pharmacokinetic/pharmacodynamics and efficacy assessment by TSPO autoradiography and CSF proteomics. Then, we showed for the first time that blockade of microglial proliferation and modification of microglial phenotype leads to an attenuation of tau-induced neurodegeneration and results in functional improvement in P301S mice. Overall, this work strongly supports the potential for inhibition of CSF1R as a target for the treatment of Alzheimer's disease and other tau-mediated neurodegenerative diseases
Inflammatory biomarkers in Alzheimer's disease plasma
Introduction: Plasma biomarkers for Alzheimer's disease (AD) diagnosis/stratification are a \u201cHoly Grail\u201d of AD research and intensively sought; however, there are no well-established plasma markers. Methods: A hypothesis-led plasma biomarker search was conducted in the context of international multicenter studies. The discovery phase measured 53 inflammatory proteins in elderly control (CTL; 259), mild cognitive impairment (MCI; 199), and AD (262) subjects from AddNeuroMed. Results: Ten analytes showed significant intergroup differences. Logistic regression identified five (FB, FH, sCR1, MCP-1, eotaxin-1) that, age/APO\u3b54 adjusted, optimally differentiated AD and CTL (AUC: 0.79), and three (sCR1, MCP-1, eotaxin-1) that optimally differentiated AD and MCI (AUC: 0.74). These models replicated in an independent cohort (EMIF; AUC 0.81 and 0.67). Two analytes (FB, FH) plus age predicted MCI progression to AD (AUC: 0.71). Discussion: Plasma markers of inflammation and complement dysregulation support diagnosis and outcome prediction in AD and MCI. Further replication is needed before clinical translation
Cabotegravir for HIV Prevention in Cisgender Men and Transgender Women
Background: Safe and effective long-acting injectable agents for preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection are needed to increase the options for preventing HIV infection. Methods: We conducted a randomized, double-blind, double-dummy, noninferiority trial to compare long-acting injectable cabotegravir (CAB-LA, an integrase strand-transfer inhibitor [INSTI]) at a dose of 600 mg, given intramuscularly every 8 weeks, with daily oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for the prevention of HIV infection in at-risk cisgender men who have sex with men (MSM) and in at-risk transgender women who have sex with men. Participants were randomly assigned (1:1) to receive one of the two regimens and were followed for 153 weeks. HIV testing and safety evaluations were performed. The primary end point was incident HIV infection. Results: The intention-to-treat population included 4566 participants who underwent randomization; 570 (12.5%) identified as transgender women, and the median age was 26 years (interquartile range, 22 to 32). The trial was stopped early for efficacy on review of the results of the first preplanned interim end-point analysis. Among 1698 participants from the United States, 845 (49.8%) identified as Black. Incident HIV infection occurred in 52 participants: 13 in the cabotegravir group (incidence, 0.41 per 100 person-years) and 39 in the TDF-FTC group (incidence, 1.22 per 100 person-years) (hazard ratio, 0.34; 95% confidence interval, 0.18 to 0.62). The effect was consistent across prespecified subgroups. Injection-site reactions were reported in 81.4% of the participants in the cabotegravir group and in 31.3% of those in the TDF-FTC group. In the participants in whom HIV infection was diagnosed after exposure to CAB-LA, INSTI resistance and delays in the detection of HIV infection were noted. No safety concerns were identified. Conclusions: CAB-LA was superior to daily oral TDF-FTC in preventing HIV infection among MSM and transgender women. Strategies are needed to prevent INSTI resistance in cases of CAB-LA PrEP failure
APOE ɛ4 exacerbates age-dependent deficits in cortical microstructure
The apolipoprotein E ɛ4 allele is the primary genetic risk factor for the sporadic type of Alzheimer’s disease. However, the mechanisms by which apolipoprotein E ɛ4 are associated with neurodegeneration are still poorly understood. We applied the Neurite Orientation Dispersion Model to characterize the effects of apolipoprotein ɛ4 and its interactions with age and education on cortical microstructure in cognitively normal individuals. Data from 1954 participants were included from the PREVENT-Dementia and ALFA (ALzheimer and FAmilies) studies (mean age = 57, 1197 non-carriers and 757 apolipoprotein E ɛ4 carriers). Structural MRI datasets were processed with FreeSurfer v7.2. The Microstructure Diffusion Toolbox was used to derive Orientation Dispersion Index maps from diffusion MRI datasets. Primary analyses were focused on (i) the main effects of apolipoprotein E ɛ4, and (ii) the interactions of apolipoprotein E ɛ4 with age and education on lobar and vertex-wise Orientation Dispersion Index and implemented using Permutation Analysis of Linear Models. There were apolipoprotein E ɛ4 × age interactions in the temporo-parietal and frontal lobes, indicating steeper age-dependent Orientation Dispersion Index changes in apolipoprotein E ɛ4 carriers. Steeper age-related Orientation Dispersion Index declines were observed among apolipoprotein E ɛ4 carriers with lower years of education. We demonstrated that apolipoprotein E ɛ4 worsened age-related Orientation Dispersion Index decreases in brain regions typically associated with atrophy patterns of Alzheimer’s disease. This finding also suggests that apolipoprotein E ɛ4 may hasten the onset age of dementia by accelerating age-dependent reductions in cortical Orientation Dispersion Index
MIBiG 3.0: a community-driven effort to annotate experimentally validated biosynthetic gene clusters
Microbial Biotechnolog
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