1,303 research outputs found
Broadly Neutralizing Bovine Antibodies: Highly Effective New Tools against Evasive Pathogens?
Potent antibody-mediated neutralization is critical for an organism to combat the vast array of pathogens it will face during its lifetime. Due to the potential genetic diversity of some viruses, such as HIV-1 and influenza, standard neutralizing antibodies are often ineffective or easily evaded as their targets are masked or rapidly mutated. This has thwarted efforts to both prevent and treat HIV-1 infections and means that entirely new formulations are required to vaccinate against influenza each year. However, some rare antibodies isolated from infected individuals confer broad and potent neutralization. A subset of these broadly neutralizing antibodies possesses a long complementarity-determining 3 region of the immunoglobulin heavy chain (CDR H3). This feature generates unique antigen binding site configurations that can engage conserved but otherwise inaccessible epitope targets thus neutralizing many viral variants. Remarkably, ultralong CDR H3s are a common feature of the cow antibody repertoire and are encoded by a single variable, diversity, joining (VDJ) recombination that is extensively diversified prior to antigen exposure. Recently, it was shown that cows rapidly generate a broadly neutralizing response upon exposure to HIV-1 and this is primarily mediated by these novel ultralong antibody types. This review summarises the current knowledge of these unusual CDR H3 structures and discusses their known and potential future uses
Liouville-space R-matrix-Floquet description of atomic radiative processes involving autoionizing states in the presence of intense electromagnetic fields
A reduced-density-operator description is developed for coherent optical phenomena in many-electron atomic systems, utilizing a Liouville-space, multiple-mode Floquet–Fourier representation. The Liouville-space formulation provides a natural generalization of the ordinary Hilbert-space (Hamiltonian) R-matrix-Floquet method, which has been developed for multi-photon transitions and laser-assisted electron–atom collision processes. In these applications, the R-matrix-Floquet method has been demonstrated to be capable of providing an accurate representation of the complex, multi-level structure of many-electron atomic systems in bound, continuum, and autoionizing states. The ordinary Hilbert-space (Hamiltonian) formulation of the R-matrix-Floquet method has been implemented in highly developed computer programs, which can provide a non-perturbative treatment of the interaction of a classical, multiple-mode electromagnetic field with a quantum system. This quantum system may correspond to a many-electron, bound atomic system and a single continuum electron. However, including pseudo-states in the expansion of the many-electron atomic wave function can provide a representation of multiple continuum electrons. The 'dressed' many-electron atomic states thereby obtained can be used in a realistic non-perturbative evaluation of the transition probabilities for an extensive class of atomic collision and radiation processes in the presence of intense electromagnetic fields. In order to incorporate environmental relaxation and decoherence phenomena, we propose to utilize the ordinary Hilbert-space (Hamiltonian) R-matrix-Floquet method as a starting-point for a Liouville-space (reduced-density-operator) formulation. To illustrate how the Liouville-space R-matrix-Floquet formulation can be implemented for coherent atomic radiative processes, we discuss applications to electromagnetically induced transparency, as well as to related pump–probe optical phenomena, and also to the unified description of radiative and dielectronic recombination in electron–ion beam interactions and high-temperature plasmas
PRS1 A COMPARISON OF CLINICAL PROFILES, MEDICATION USE AND SYMPTOMOLOGY IN ASTHMA PATIENTS PRESCRIBED LOW/MODERATE DOSE FLUTICASONE PROPIONATE/SALMETEROL OR MODERATE/HIGH DOSE FLUTICASONE PROPIONATE
Nutrition Strategies for Triathlon
Contemporary sports nutrition guidelines recommend that each athlete develop a personalised, periodised and practical approach to eating that allows him or her to train hard, recover and adapt optimally, stay free of illness and injury and compete at their best at peak races. Competitive triathletes undertake a heavy training programme to prepare for three different sports while undertaking races varying in duration from 20 min to 10 h. The everyday diet should be adequate in energy availability, provide CHO in varying amounts and timing around workouts according to the benefits of training with low or high CHO availability and spread high-quality protein over the day to maximise the adaptive response to each session. Race nutrition requires a targeted and well-practised plan that maintains fuel and hydration goals over the duration of the specific event, according to the opportunities provided by the race and other challenges, such as a hot environment. Supplements and sports foods can make a small contribution to a sports nutrition plan, when medical supplements are used under supervision to prevent/treat nutrient deficiencies (e.g. iron or vitamin D) or when sports foods provide a convenient source of nutrients when it is impractical to eat whole foods. Finally, a few evidence-based performance supplements may contribute to optimal race performance when used according to best practice protocols to suit the triathlete’s goals and individual responsiveness
The central image of a gravitationally lensed quasar
A galaxy can act as a gravitational lens, producing multiple images of a
background object. Theory predicts there should be an odd number of images but,
paradoxically, almost all observed lenses have 2 or 4 images. The missing image
should be faint and appear near the galaxy's center. These ``central images''
have long been sought as probes of galactic cores too distant to resolve with
ordinary observations. There are five candidates, but in one case the third
image is not necessarily a central image, and in the others, the central
component might be a foreground source rather than a lensed image. Here we
report the most secure identification of a central image, based on radio
observations of PMN J1632-0033, one of the latter candidates. Lens models
incorporating the central image show that the mass of the lens galaxy's central
black hole is less than 2 x 10^8 M_sun, and the galaxy's surface density at the
location of the central image is more than 20,000 M_sun per square parsec, in
agreement with expectations based on observations of galaxies hundreds of times
closer to the Earth.Comment: Nature, in press [7 pp, 2 figs]. Standard media embargo applies
before publicatio
Continuation for thin film hydrodynamics and related scalar problems
This chapter illustrates how to apply continuation techniques in the analysis
of a particular class of nonlinear kinetic equations that describe the time
evolution through transport equations for a single scalar field like a
densities or interface profiles of various types. We first systematically
introduce these equations as gradient dynamics combining mass-conserving and
nonmass-conserving fluxes followed by a discussion of nonvariational amendmends
and a brief introduction to their analysis by numerical continuation. The
approach is first applied to a number of common examples of variational
equations, namely, Allen-Cahn- and Cahn-Hilliard-type equations including
certain thin-film equations for partially wetting liquids on homogeneous and
heterogeneous substrates as well as Swift-Hohenberg and Phase-Field-Crystal
equations. Second we consider nonvariational examples as the
Kuramoto-Sivashinsky equation, convective Allen-Cahn and Cahn-Hilliard
equations and thin-film equations describing stationary sliding drops and a
transversal front instability in a dip-coating. Through the different examples
we illustrate how to employ the numerical tools provided by the packages
auto07p and pde2path to determine steady, stationary and time-periodic
solutions in one and two dimensions and the resulting bifurcation diagrams. The
incorporation of boundary conditions and integral side conditions is also
discussed as well as problem-specific implementation issues
Caveolin-1 Influences Vascular Protease Activity and Is a Potential Stabilizing Factor in Human Atherosclerotic Disease
Caveolin-1 (Cav-1) is a regulatory protein of the arterial wall, but its role in human atherosclerosis remains unknown. We have studied the relationships between Cav-1 abundance, atherosclerotic plaque characteristics and clinical manisfestations of atherosclerotic disease.We determined Cav-1 expression by western blotting in atherosclerotic plaques harvested from 378 subjects that underwent carotid endarterectomy. Cav-1 levels were significantly lower in carotid plaques than non-atherosclerotic vascular specimens. Low Cav-1 expression was associated with features of plaque instability such as large lipid core, thrombus formation, macrophage infiltration, high IL-6, IL-8 levels and elevated MMP-9 activity. Clinically, a down-regulation of Cav-1 was observed in plaques obtained from men, patients with a history of myocardial infarction and restenotic lesions. Cav-1 levels above the median were associated with absence of new vascular events within 30 days after surgery [0% vs. 4%] and a trend towards lower incidence of new cardiovascular events during longer follow-up. Consistent with these clinical data, Cav-1 null mice revealed elevated intimal hyperplasia response following arterial injury that was significantly attenuated after MMP inhibition. Recombinant peptides mimicking Cav-1 scaffolding domain (Cavtratin) reduced gelatinase activity in cultured porcine arteries and impaired MMP-9 activity and COX-2 in LPS-challenged macrophages. Administration of Cavtratin strongly impaired flow-induced expansive remodeling in mice.This is the first study that identifies Cav-1 as a novel potential stabilizing factor in human atherosclerosis. Our findings support the hypothesis that local down-regulation of Cav-1 in atherosclerotic lesions contributes to plaque formation and/or instability accelerating the occurrence of adverse clinical outcomes. Therefore, given the large number of patients studied, we believe that Cav-1 may be considered as a novel target in the prevention of human atherosclerotic disease and the loss of Cav-1 may be a novel biomarker of vulnerable plaque with prognostic value
Financial crises and the attainment of the SDGs: an adjusted multidimensional poverty approach
This paper analyses the impact of financial crises on the Sustainable Development Goal of eradicating poverty. To do so, we develop an adjusted Multidimensional Poverty Framework (MPF) that includes 15 indicators that span across key poverty aspects related to income, basic needs, health, education and the environment. We then use an econometric model that allows us to examine the impact of financial crises on these indicators in 150 countries over the period 1980–2015. Our analysis produces new estimates on the impact of financial crises on poverty’s multiple social, economic and environmental aspects and equally important captures dynamic linkages between these aspects. Thus, we offer a better understanding of the potential impact of current debt dynamics on Multidimensional Poverty and demonstrate the need to move beyond the boundaries of SDG1, if we are to meet the target of eradicating poverty. Our results indicate that the current financial distress experienced by many low-income countries may reverse the progress that has been made hitherto in reducing poverty. We find that financial crises are associated with an approximately 10% increase of extreme poor in low-income countries. The impact is even stronger in some other poverty aspects. For instance, crises are associated with an average decrease of government spending in education by 17.72% in low-income countries. The dynamic linkages between most of the Multidimensional Poverty indicators, warn of a negative domino effect on a number of SDGs related to poverty, if there is a financial crisis shock. To pre-empt such a domino effect, the specific SDG target 17.4 on attaining long-term debt sustainability through coordinated policies plays a key role and requires urgent attention by the international community
Recommended from our members
Towards controlled terminology for reporting germline cancer susceptibility variants: an ENIGMA report.
The vocabulary currently used to describe genetic variants and their consequences reflects many years of studying and discovering monogenic disease with high penetrance. With the recent rapid expansion of genetic testing brought about by wide availability of high-throughput massively parallel sequencing platforms, accurate variant interpretation has become a major issue. The vocabulary used to describe single genetic variants in silico, in vitro, in vivo and as a contributor to human disease uses terms in common, but the meaning is not necessarily shared across all these contexts. In the setting of cancer genetic tests, the added dimension of using data from genetic sequencing of tumour DNA to direct treatment is an additional source of confusion to those who are not experienced in cancer genetics. The language used to describe variants identified in cancer susceptibility genetic testing typically still reflects an outdated paradigm of Mendelian inheritance with dichotomous outcomes. Cancer is a common disease with complex genetic architecture; an improved lexicon is required to better communicate among scientists, clinicians and patients, the risks and implications of genetic variants detected. This review arises from a recognition of, and discussion about, inconsistencies in vocabulary usage by members of the ENIGMA international multidisciplinary consortium focused on variant classification in breast-ovarian cancer susceptibility genes. It sets out the vocabulary commonly used in genetic variant interpretation and reporting, and suggests a framework for a common vocabulary that may facilitate understanding and clarity in clinical reporting of germline genetic tests for cancer susceptibility
- …