4,599 research outputs found
UK security will both gain and suffer from Brexit. The EU will only lose
Although the EU was not, in the beginning, a security mechanism, states have increasingly co-operated on security, foreign policy and defence. Their endeavours have had mixed results that at times have been seen as a drag on Britain’s autonomy. What practical effect will Brexit have on the way Britain collects intelligence, defends itself and deals with China and Russia? Philip HJ Davies considers the implications
Troglitazone reverses the multiple drug resistance phenotype in cancer cells
A major problem in treating cancer is the development of drug resistance. We previously demonstrated doxorubicin (DOX) resistance in K562 human leukemia cells that was associated with upregulation of glyoxalase 1 (GLO-1) and histone H3 expression. The thiazolidinedione troglitazone (TRG) downregulated GLO-1 expression and further upregulated histone H3 expression and post-translational modifications in these cells, leading to a regained sensitivity to DOX. Given the pleiotropic effects of epigenetic changes in cancer development, we hypothesized that TRG may downregulate the multiple drug resistance (MDR) phenotype in a variety of cancer cells. To test this, MCF7 human breast cancer cells and K562 cells were cultured in the presence of low-dose DOX to establish DOX-resistant cell lines (K562/DOX and MCF7/DOX). The MDR phenotype was confirmed by Western blot analysis of the 170 kDa P-glycoprotein (Pgp) drug efflux pump multiple drug resistance protein 1 (MDR-1), and the breast cancer resistance protein (BCRP). TRG markedly decreased expression of both MDR-1 and BCRP in these cells, resulting in sensitivity to DOX. Silencing of MDR-1 expression also sensitized MCF7/DOX cells to DOX. Use of the specific and irreversible peroxisome proliferator-activated receptor gamma (PPARγ) inhibitor GW9662 in the nanomolar range not only demonstrated that the action of TRG on MCF/DOX was PPARγ-independent, but indicated that PPARγ may play a role in the MDR phenotype, which is antagonized by TRG. We conclude that TRG is potentially a useful adjunct therapy in chemoresistant cancers
A review of the electrical properties of semiconductor nanowires: Insights gained from terahertz conductivity spectroscopy
Accurately measuring and controlling the electrical properties of semiconductor nanowires is of paramount importance in the development of novel nanowire-based devices. In light of this, terahertz (THz) conductivity spectroscopy has emerged as an ideal non-contact technique for probing nanowire electrical conductivity and is showing tremendous value in the targeted development of nanowire devices. THz spectroscopic measurements of nanowires enable charge carrier lifetimes, mobilities, dopant concentrations and surface recombination velocities to be measured with high accuracy and high throughput in a contact-free fashion. This review spans seminal and recent studies of the electronic properties of nanowires using THz spectroscopy. A didactic description of THz time-domain spectroscopy, optical pump–THz probe spectroscopy, and their application to nanowires is included. We review a variety of technologically important nanowire materials, including GaAs, InAs, InP, GaN and InN nanowires, Si and Ge nanowires, ZnO nanowires, nanowire heterostructures, doped nanowires and modulation-doped nanowires. Finally, we discuss how THz measurements are guiding the development of nanowire-based devices, with the example of single-nanowire photoconductive THz receivers.The authors gratefully acknowledge EPSRC (UK) for research funding. H J Joyce gratefully acknowledges the Royal Commission for the Exhibition of 1851 for her research fellowship.This is the final version of the article. It first appeared from IOP via https://doi.org/10.1088/0268-1242/31/10/10300
Wearable in-ear PPG: detailed respiratory variations enable classification of COPD
An ability to extract detailed spirometry-like breath-ing waveforms from wearable sensors promises to greatly improve respiratory health monitoring. Photoplethysmography (PPG) has been researched in depth for estimation of respiration rate, given that it varies with respiration through overall intensity, pulse amplitude and pulse interval. We compare and contrast the extraction of these three respiratory modes from both the ear canal and finger and show a marked improvement in the respiratory power for respiration induced intensity variations and pulse amplitude variations when recording from the ear canal. We next employ a data driven multi-scale method, noise assisted multivariate empirical mode decomposition (NA-MEMD), which allows for simultaneous analysis of all three respiratory modes to extract detailed respiratory waveforms from in-ear PPG. For rigour, we considered in-ear PPG recordings from healthy subjects, both older and young, patients with chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) and healthy subjects with artificially obstructed breathing. Specific in-ear PPG waveform changes are observed for COPD, such as a decreased inspiratory duty cycle and an increased inspiratory magnitude, when compared with expiratory magnitude. These differences are used to classify COPD from healthy and IPF waveforms with a sensitivity of 87% and an overall accuracy of 92%. Our findings indicate the promise of in-ear PPG for COPD screening and unobtrusive respiratory monitoring in ambulatory scenarios and in consumer wearables
In-ear SpO2 for classification of cognitive workload
The brain is the most metabolically active organ in the body, which increases its metabolic activity, and thus oxygen consumption, with increasing cognitive demand. This motivates us to question whether increased cognitive workload may be measurable through changes in blood oxygen saturation. To this end, we explore the feasibility of cognitive workload tracking based on in-ear SpO2 measurements, which are known to be both robust and exhibit minimal delay. We consider cognitive workload assessment based on an N-back task with randomised order. It is shown that the 2-back and 3-back tasks (high cognitive workload) yield either the lowest median absolute SpO2 or largest median decrease in SpO2 in all of the subjects, indicating a measurable and statistically significant decrease in blood oxygen in response to increased cognitive workload. This makes it possible to classify the four N-back task categories, over 5 second epochs, with a mean accuracy of 90.6%, using features derived from in-ear pulse oximetry, including SpO2, pulse rate and respiration rate. These findings suggest that in-ear SpO2 measurements provide sufficient information for the reliable classification of cognitive workload over short time windows, which promises a new avenue for real time cognitive workload tracking
Imaging with therapeutic acoustic wavelets–short pulses enable acoustic localization when time of arrival is combined with delay and sum
—Passive acoustic mapping (PAM) is an algorithm that reconstructs the location of acoustic sources using an array of receivers. This technique can monitor therapeutic ultrasound procedures to confirm the spatial distribution and amount of microbubble activity induced. Current PAM algorithms have an excellentlateral resolution but have a poor axial resolution, making it difficult to distinguish acoustic sources within the ultrasound beams. With recent studies demonstrating that short-length and low-pressure pulses—acoustic wavelets—have the therapeutic function, we hypothesizedthat the axial resolution could be improved with a quasi-pulse-echo approach and that the resolution improvement would depend on the wavelet’s pulse length. This article describes an algorithm that resolves acoustic sources axially using time of flight and laterally using delayand-sum beamforming, which we named axial temporal position PAM (ATP-PAM). The algorithm accommodates a rapid short pulse (RaSP) sequence that can safely deliver drugs across the blood–brain barrier. We developed our algorithm with simulations (k-wave) and in vitro experiments for one-, two-, and five-cycle pulses, comparing our resolution against that of two current PAM algorithms. We then tested ATP-PAM in vivo and evaluated whether the reconstructed acoustic sources mapped to drug deliver
Expanding the Anti-Phl p 7 Antibody Toolkit: An Anti-Idiotype Nanobody Inhibitor.
We have previously produced a toolkit of antibodies, comprising recombinant human antibodies of all but one of the human isotypes, directed against the polcalcin family antigen Phl p 7. In this work, we complete the toolkit of human antibody isotypes with the IgD version of the anti-Phl p 7 monoclonal antibody. We also raised a set of nanobodies against the IgD anti-Phl p 7 antibody and identify and characterize one paratope-specific nanobody. This nanobody also binds to the IgE isotype of this antibody, which shares the same idiotype, and orthosterically inhibits the interaction with Phl p 7. The 2.1 Å resolution X-ray crystal structure of the nanobody in complex with the IgD Fab is described
Crystal structures of the human IgD Fab reveal insights into CH1 domain diversity
Antibodies of the IgD isotype remain the least well characterized of the mammalian immunoglobulin isotypes. Here we report three-dimensional structures for the Fab region of IgD, based on four different crystal structures, at resolutions of 1.45–2.75 Å. These IgD Fab crystals provide the first high-resolution views of the unique Cδ1 domain. Structural comparisons identify regions of conformational diversity within the Cδ1 domain, as well as among the homologous domains of Cα1, Cγ1 and Cμ1. The IgD Fab structure also possesses a unique conformation of the upper hinge region, which may contribute to the overall disposition of the very long linker sequence between the Fab and Fc regions found in human IgD. Structural similarities observed between IgD and IgG, and differences with IgA and IgM, are consistent with predicted evolutionary relationships for the mammalian antibody isotypes
The Development of a Semtex-H Simulant for Terahertz Spectroscopy
The development and use of terahertz (THz) frequency spectroscopy systems for security screening has shown an increased growth over the past 15 years. In order to test these systems in real-world situations, safe simulants of illicit materials, such as Semtex-H, are required. Ideally, simulants should mimic key features of the material of interest, such that they at least resemble or even appear indistinguishable from the materials of interest to the interrogating technique(s), whilst not having hazardous or illicit properties. An ideal simulant should have similar physical properties (malleability, density, surface energy and volatility to the material of interest); be non-toxic and easy to clean and decontaminate from surfaces; be recyclable or disposable; and be useable in a public environment. Here, we present a method for developing such an explosive simulant (for Semtex-H) based on a database of THz spectra of common organic molecules, and the use of a genetic algorithm to select a mixture of compounds automatically to form such a simulant. Whilst we focus on a security application, this work could be applied to various other contexts, where the material of interest is dangerous, impractical or costly. We propose four mixtures that could then be used to test the spectral response of any instrument, working at terahertz frequencies, without the need for an explosive substance
Quantified moorland vegetation and assessment of the role of burning over the past five millennia
© 2017 International Association for Vegetation Science. Aims: To apply the Landscape Reconstruction Algorithm (LRA) to pollen count data from multiple sites to estimate local vegetation abundance and compare with charcoal-derived records of burning. Location: Exmoor, southwest England, UK. Methods: Pollen count data from 16 sites were transformed to estimates of distance-weighted vegetation abundance using the LRA (REVEALS and LOVE models), correcting for bias in pollen production and dispersal. Charcoal concentration data from six sites were normalized using Box-Cox transformation to produce z-scores. Moving-window correlation was undertaken to compare pollen percentage values for key taxa (Calluna, Poaceae) and localized burning. Estimates of distance-vegetation abundance (LRA output) and time-averaged charcoal z-scores were compared to assess the role of burning as a driver for upland vegetation cover. Results: Comparison of pollen percentage and normalized charcoal z-scores show little correlation between vegetation cover and burning. Estimates of distance-weighted vegetation abundance and normalized charcoal data show relationships between vegetation change and burning at four of the six sites. The relationships are site-specific: three sites suggest burning promoted grass-dominated vegetation, at one site burning promoted heather-dominated vegetation, and in two sites there is no apparent relationship. Conclusions: The patterning of vegetation within uplands is a crucial part of ecosystem service delivery, and contemporary and future management benefits from understanding of 'long-term' development, i.e. patterns over millennia. The correction of biases within pollen production and dispersal to produce local vegetation estimates has demonstrated spatial heterogeneity in vegetation cover on Exmoor that is not otherwise evident in the pollen percentage data (which retain a strong influence of the regional vegetation cover). The relationship between LRA-derived vegetation cover and burning is not apparent in comparisons between pollen percentage data and charcoal records. This implies that studies that use pollen proportional data alone can misrepresent the relationship between vegetation cover and fire. This study demonstrates that fire has been an important part of the development of this cultural landscape
- …