591 research outputs found
Mentalising remotely: The AFNCCF’s adaptations to the coronavirus crisis
An overview of the work the approach taken by the Anna Freud National Centre for Children and Families in the rapid transition to remote working in response to the coronavirus lockdown. We outline some of the challenges of remote working and how we are seeking to mitigate them, informed by the over‐riding principle that individual relationships and the experiences of the child, young person and family must remain the central concern. The importance of maintaining a mentalising stance in remote working is discussed. We argue that a mentalising relationship which generates epistemic trust is possible in remote working, but this will require particular thought and effort on the part of the therapist. In particular, it is suggested that mentalising processes can be supported in remote working through, in the absence of the more implicit communications that are possible in face‐to‐face work, more explicit communications about mental states
Shift of the molecular bound state threshold in dense ultracold Fermi gases with Feshbach resonance
We consider a dense ultracold Fermi gas in the presence of a Feshbach
resonance. We investigate how the treshold for bound state formation, which is
just at the Feshbach resonance for a dilute gas, is modified due to the
presence of the Fermi sea. We make use of a preceding framework of handling
this many-body problem. We restrict ourselves to the simple case where the
chemical potential is negative, which allows us to cover in particular
the classical limit where the effect is seen to disappear. We show that, within
a simple approach where basically only the effect of Pauli exclusion is
included, the Fermi sea produces a large shift of the threshold, which is of
order of the width of the Feshbach resonance. This is in agreement with very
recent experimental findings.Comment: one reference adde
Proteostasis and the Regulation of Intra- and Extracellular Protein Aggregation by ATP-Independent Molecular Chaperones: Lens α-Crystallins and Milk Caseins
Conspectus: Molecular chaperone proteins perform a diversity of roles inside and outside the cell. One of the most important is the stabilization of misfolding proteins to prevent their aggregation, a process that is potentially detrimental to cell viability. Diseases such as Alzheimer\u27s, Parkinson\u27s, and cataract are characterized by the accumulation of protein aggregates. In vivo, many proteins are metastable and therefore under mild destabilizing conditions have an inherent tendency to misfold, aggregate, and hence lose functionality. As a result, protein levels are tightly regulated inside and outside the cell. Protein homeostasis, or proteostasis, describes the network of biological pathways that ensures the proteome remains folded and functional. Proteostasis is a major factor in maintaining cell, tissue, and organismal viability.
We have extensively investigated the structure and function of intra- and extracellular molecular chaperones that operate in an ATP-independent manner to stabilize proteins and prevent their misfolding and subsequent aggregation into amorphous particles or highly ordered amyloid fibrils. These types of chaperones are therefore crucial in maintaining proteostasis under normal and stress (e.g., elevated temperature) conditions. Despite their lack of sequence similarity, they exhibit many common features, i.e., extensive structural disorder, dynamism, malleability, heterogeneity, oligomerization, and similar mechanisms of chaperone action. In this Account, we concentrate on the chaperone roles of α-crystallins and caseins, the predominant proteins in the eye lens and milk, respectively. Intracellularly, the principal ATP-independent chaperones are the small heat-shock proteins (sHsps). In vivo, sHsps are the first line of defense in preventing intracellular protein aggregation. The lens proteins αA- and αB-crystallin are sHsps. They play a crucial role in maintaining solubility of the crystallins (including themselves) with age and hence in lens proteostasis and, ultimately, lens transparency. As there is little metabolic activity and no protein turnover in the lens, crystallins are very long lived proteins. Lens proteostasis is therefore very different to that in normal, metabolically active cells. Crystallins undergo extensive post-translational modification (PTM), including deamidation, racemization, phosphorylation, and truncation, which can alter their stability. Despite this, the lens remains transparent for tens of years, implying that lens proteostasis is intimately integrated with crystallin PTMs. Many PTMs do not significantly alter crystallin stability, solubility, and functionality, which thereby facilitates lens transparency. In the long term, however, extensive accumulation of crystallin PTMs leads to large-scale crystallin aggregation, lens opacification, and cataract formation. Extracellularly, various ATP-independent molecular chaperones exist that exhibit sHsp-like structural and functional features. For example, caseins, the major milk proteins, exhibit chaperone ability by inhibiting the amorphous and amyloid fibrillar aggregation of a diversity of destabilized proteins. Caseins maintain proteostasis within milk by preventing deleterious casein amyloid fibril formation via incorporation of thousands of individual caseins into an amorphous structure known as the casein micelle. Hundreds of nanoclusters of calcium phosphate are sequestered within each casein micelle through interactions with short, highly phosphorylated casein sequences. This results in a stable biofluid that contains a high concentration of potentially amyloidogenic caseins and concentrations of calcium and phosphate that can be far in excess of the solubility of calcium phosphate. Casein micelle formation therefore performs vital roles in neonatal nutrition and calcium homeostasis in the mammary gland
Superfluidity in the interior-gap states
We investigate superfluidity in the interior-gap states proposed by Liu and
Wilczek. At weak coupling, we find the {\em gapless} interior-gap state
unstable in physically accessible regimes of the parameter space, where the
superfluid density is shown to be always negative. We therefore conclude that
the spatially-uniform interior-gap phase is extremely unstable unless it is
fully gapped; in this case, however, the state is rather similar to
conventional BCS states.Comment: To appear in Physical Review
Degenerate fermion gas heating by hole creation
Loss processes that remove particles from an atom trap leave holes behind in
the single particle distribution if the trapped gas is a degenerate fermion
system. The appearance of holes increases the temperature and we show that the
heating is (i) significant if the initial temperature is well below the Fermi
temperature , and (ii) increases the temperature to
after half of the system's lifetime, regardless of the initial temperature. The
hole heating has important consequences for the prospect of observing
Cooper-pairing in atom traps.Comment: to be published in PR
Analysis of the population-level impact of co-administering ivermectin with albendazole or mebendazole for the control and elimination of Trichuris trichiura.
INTRODUCTION: Soil-transmitted helminth (STH) infections are predominately controlled by providing children with preventive chemotherapy with either albendazole or mebendazole. However, neither has a high efficacy against Trichuris trichiura. This low efficacy limits the overall effectiveness of the current STH control programmes against T. trichiura. It has been demonstrated that co-administering ivermectin with albendazole or mebendazole significantly increases the efficacy of current treatments, which may increase the overall effectiveness of control programmes. METHODS: Using a STH transmission mathematical model, we evaluated the potential impact of co-administering ivermectin with albendazole or mebendazole to treat T. trichiura within a preventive chemotherapy programme targeting children (2-15 year olds). We evaluated the impact in terms of reduction in prevalent infections, mean worm burden, and prevalence of heavy infections. RESULTS: Although the current treatment strategy reduced T. trichiura worm burden and prevalence of heavy infections, due to their poor efficacy the long term impact of preventive chemotherapy for children was smaller compared to the other STH. Co-administering ivermectin increased the projected impact of the preventive chemotherapy programme in terms of all three of the explored metrics, practically in high transmission settings. Furthermore, ivermectin co-administration greatly increased the feasibility of and timeframe for breaking transmission. CONCLUSIONS: Co-administering ivermectin notably increased the projected impact of preventive chemotherapy in high transmission settings and increased the feasibility for breaking transmission. This has important implications for control programmes, some of which may be shifting focus from morbidity control to interruption of transmission, and some of which may be logistically unable to provide preventive chemotherapy twice a year as recommended. However, the benefit of co-administering ivermectin is limited by the fact that 2-5 year olds are often ineligible to receive treatment
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