4,115 research outputs found
Sub-wavelength terahertz beam profiling of a THz source via an all-optical knife-edge technique
Terahertz technologies recently emerged as outstanding candidates for a variety of applications in such sectors as security, biomedical, pharmaceutical, aero spatial, etc. Imaging the terahertz field, however, still remains a challenge, particularly when sub-wavelength resolutions are involved. Here we demonstrate an all-optical technique for the terahertz near-field imaging directly at the source plane. A thin layer (<100 nm-thickness) of photo carriers is induced on the surface of the terahertz generation crystal, which acts as an all-optical, virtual blade for terahertz near-field imaging via a knife-edge technique. Remarkably, and in spite of the fact that the proposed approach does not require any mechanical probe, such as tips or apertures, we are able to demonstrate the imaging of a terahertz source with deeply sub-wavelength features (<30 μm) directly in its emission plane
Higher premorbid serum testosterone predicts COVID-19-related mortality risk in men.
Objective: Men are at greater risk from COVID-19 than women. Older, overweight men, and those with type 2 diabetes, have lower testosterone concentrations and poorer COVID-19-related outcomes. We analysed the associations of premorbid serum testosterone concentrations, not confounded by the effects of acute SARS-CoV-2 infection, with COVID-19-related mortality risk in men. Design: This study is a United Kingdom Biobank prospective cohort study of community-dwelling men aged 40-69 years. Methods: Serum total testosterone and sex hormone-binding globulin (SHBG) were measured at baseline (2006-2010). Free testosterone values were calculated (cFT). the incidence of SARS-CoV-2 infections and deaths related to COVID-19 were ascertained from 16 March 2020 to 31 January 2021 and modelled using time-stratified Cox regression. Results: In 159 964 men, there were 5558 SARS-CoV-2 infections and 438 COVID-19 deaths. Younger age, higher BMI, non-White ethnicity, lower educational attainment, and socioeconomic deprivation were associated with incidence of SARS-CoV-2 infections but total testosterone, SHBG, and cFT were not. Adjusting for potential confounders, higher total testosterone was associated with COVID-19-related mortality risk (overall trend P = 0.008; hazard ratios (95% CIs) quintile 1, Q1 vs Q5 (reference), 0.84 (0.65-1.12) Q2:Q5, 0.82 (0.63-1.10); Q3:Q5, 0.80 (0.66-1.00); Q4:Q5, 0.82 (0.75-0.93)). Higher SHBG was also associated with COVID-19 mortality risk (P = 0.008), but cFT was not (P = 0.248). Conclusions: Middle-aged to older men with the highest premorbid serum total testosterone and SHBG concentrations are at greater risk of COVID-19-related mortality. Men could be advised that having relatively high serum testosterone concentrations does not protect against future COVID-19-related mortality. Further investigation of causality and potential underlying mechanisms is warranted
Use of Recombinant Adenovirus Vectored Consensus IFN-α to Avert Severe Arenavirus Infection
Several arenaviruses can cause viral hemorrhagic fever, a severe disease with case-fatality rates in hospitalized individuals ranging from 15-30%. Because of limited prophylaxis and treatment options, new medical countermeasures are needed for these viruses classified by the National Institutes of Allergy and Infectious Diseases (NIAID) as top priority biodefense Category A pathogens. Recombinant consensus interferon alpha (cIFN-α) is a licensed protein with broad clinical appeal. However, while cIFN-α has great therapeutic value, its utility for biodefense applications is hindered by its short in vivo half-life, mode and frequency of administration, and costly production. To address these limitations, we describe the use of DEF201, a replication-deficient adenovirus vector that drives the expression of cIFN-α, for pre- and post-exposure prophylaxis of acute arenaviral infection modeled in hamsters. Intranasal administration of DEF201 24 h prior to challenge with Pichindé virus (PICV) was highly effective at protecting animals from mortality and preventing viral replication and liver-associated disease. A significant protective effect was still observed with a single dosing of DEF201 given two weeks prior to PICV challenge. DEF201 was also efficacious when administered as a treatment 24 to 48 h post-virus exposure. The protective effect of DEF201 was largely attributed to the expression of cIFN-α, as dosing with a control empty vector adenovirus did not protect hamsters from lethal PICV challenge. Effective countermeasures that are highly stable, easily administered, and elicit long lasting protective immunity are much needed for arena and other viral infections. The DEF201 technology has the potential to address all of these issues and may serve as a broad-spectrum antiviral to enhance host defense against a number of viral pathogens
Sudden drop of fractal dimension of electromagnetic emissions recorded prior to significant earthquake
The variation of fractal dimension and entropy during a damage evolution
process, especially approaching critical failure, has been recently
investigated. A sudden drop of fractal dimension has been proposed as a
quantitative indicator of damage localization or a likely precursor of an
impending catastrophic failure. In this contribution, electromagnetic emissions
recorded prior to significant earthquake are analysed to investigate whether
they also present such sudden fractal dimension and entropy drops as the main
catastrophic event is approaching. The pre-earthquake electromagnetic time
series analysis results reveal a good agreement to the theoretically expected
ones indicating that the critical fracture is approaching
Fracturing ranked surfaces
Discretized landscapes can be mapped onto ranked surfaces, where every
element (site or bond) has a unique rank associated with its corresponding
relative height. By sequentially allocating these elements according to their
ranks and systematically preventing the occupation of bridges, namely elements
that, if occupied, would provide global connectivity, we disclose that bridges
hide a new tricritical point at an occupation fraction , where
is the percolation threshold of random percolation. For any value of in the
interval , our results show that the set of bridges has a
fractal dimension in two dimensions. In the limit , a self-similar fracture is revealed as a singly connected line
that divides the system in two domains. We then unveil how several seemingly
unrelated physical models tumble into the same universality class and also
present results for higher dimensions
Correlation functions quantify super-resolution images and estimate apparent clustering due to over-counting
We present an analytical method to quantify clustering in super-resolution
localization images of static surfaces in two dimensions. The method also
describes how over-counting of labeled molecules contributes to apparent
self-clustering and how the effective lateral resolution of an image can be
determined. This treatment applies to clustering of proteins and lipids in
membranes, where there is significant interest in using super-resolution
localization techniques to probe membrane heterogeneity. When images are
quantified using pair correlation functions, the magnitude of apparent
clustering due to over-counting will vary inversely with the surface density of
labeled molecules and does not depend on the number of times an average
molecule is counted. Over-counting does not yield apparent co-clustering in
double label experiments when pair cross-correlation functions are measured. We
apply our analytical method to quantify the distribution of the IgE receptor
(Fc{\epsilon}RI) on the plasma membranes of chemically fixed RBL-2H3 mast cells
from images acquired using stochastic optical reconstruction microscopy (STORM)
and scanning electron microscopy (SEM). We find that apparent clustering of
labeled IgE bound to Fc{\epsilon}RI detected with both methods arises from
over-counting of individual complexes. Thus our results indicate that these
receptors are randomly distributed within the resolution and sensitivity limits
of these experiments.Comment: 22 pages, 5 figure
Bridging Time Scales in Cellular Decision Making with a Stochastic Bistable Switch
Cellular transformations which involve a significant phenotypical change of
the cell's state use bistable biochemical switches as underlying decision
systems. In this work, we aim at linking cellular decisions taking place on a
time scale of years to decades with the biochemical dynamics in signal
transduction and gene regulation, occuring on a time scale of minutes to hours.
We show that a stochastic bistable switch forms a viable biochemical mechanism
to implement decision processes on long time scales. As a case study, the
mechanism is applied to model the initiation of follicle growth in mammalian
ovaries, where the physiological time scale of follicle pool depletion is on
the order of the organism's lifespan. We construct a simple mathematical model
for this process based on experimental evidence for the involved genetic
mechanisms. Despite the underlying stochasticity, the proposed mechanism turns
out to yield reliable behavior in large populations of cells subject to the
considered decision process. Our model explains how the physiological time
constant may emerge from the intrinsic stochasticity of the underlying gene
regulatory network. Apart from ovarian follicles, the proposed mechanism may
also be of relevance for other physiological systems where cells take binary
decisions over a long time scale.Comment: 14 pages, 4 figure
Matrix metalloproteinase-9 activity and a downregulated Hedgehog pathway impair blood-brain barrier function in an <i>in vitro</i> model of CNS tuberculosis
Central nervous system tuberculosis (CNS TB) has a high mortality and morbidity associated with severe inflammation. The blood-brain barrier (BBB) protects the brain from inflammation but the mechanisms causing BBB damage in CNS TB are uncharacterized. We demonstrate that Mycobacterium tuberculosis (Mtb) causes breakdown of type IV collagen and decreases tight junction protein (TJP) expression in a co-culture model of the BBB. This increases permeability, surface expression of endothelial adhesion molecules and leukocyte transmigration. TJP breakdown was driven by Mtb-dependent secretion of matrix metalloproteinase (MMP)-9. TJP expression is regulated by Sonic hedgehog (Shh) through transcription factor Gli-1. In our model, the hedgehog pathway was downregulated by Mtb-stimulation, but Shh levels in astrocytes were unchanged. However, Scube2, a glycoprotein regulating astrocyte Shh release was decreased, inhibiting Shh delivery to brain endothelial cells. Activation of the hedgehog pathway by addition of a Smoothened agonist or by addition of exogenous Shh, or neutralizing MMP-9 activity, decreased permeability and increased TJP expression in the Mtb-stimulated BBB co-cultures. In summary, the BBB is disrupted by downregulation of the Shh pathway and breakdown of TJPs, secondary to increased MMP-9 activity which suggests that these pathways are potential novel targets for host directed therapy in CNS TB
Robust isothermal electric switching of interface magnetization: A route to voltage-controlled spintronics
Roughness-insensitive and electrically controllable magnetization at the
(0001) surface of antiferromagnetic chromia is observed using magnetometry and
spin-resolved photoemission measurements and explained by the interplay of
surface termination and magnetic ordering. Further, this surface in placed in
proximity with a ferromagnetic Co/Pd multilayer film. Exchange coupling across
the interface between chromia and Co/Pd induces an electrically controllable
exchange bias in the Co/Pd film, which enables a reversible isothermal (at room
temperature) shift of the global magnetic hysteresis loop of the Co/Pd film
along the magnetic field axis between negative and positive values. These
results reveal the potential of magnetoelectric chromia for spintronic
applications requiring non-volatile electric control of magnetization.Comment: Single PDF file: 27 pages, 6 figures; version of 12/30/09; submitted
to Nature Material
- …