Extracellular cell stress (heat shock) proteins - immune responses and disease: an overview

Extracellular cell stress proteins are highly conserved phylogenetically and have been shown to act as powerful signalling agonists and receptors for selected ligands in several different settings. They also act as immunostimulatory ‘danger signals’ for the innate and adaptive immune systems. Other studies have shown that cell stress proteins and the induction of immune reactivity to self-cell stress proteins can attenuate disease processes. Some proteins (e.g. Hsp60, Hsp70, gp96) exhibit both inflammatory and anti-inflammatory properties, depending on the context in which they encounter responding immune cells. The burgeoning literature reporting the presence of stress proteins in a range of biological fluids in healthy individuals/non-diseased settings, the association of extracellular stress protein levels with a plethora of clinical and pathological conditions and the selective expression of a membrane form of Hsp70 on cancer cells now supports the concept that extracellular cell stress proteins are involved in maintaining/regulating organismal homeostasis and in disease processes and phenotype. Cell stress proteins, therefore, form a biologically complex extracellular cell stress protein network having diverse biological, homeostatic and immunomodulatory properties, the understanding of which offers exciting opportunities for delivering novel approaches to predict, identify, diagnose, manage and treat disease

On renormalization group flows and the a-theorem in 6d

We study the extension of the approach to the a-theorem of Komargodski and Schwimmer to quantum field theories in d=6 spacetime dimensions. The dilaton effective action is obtained up to 6th order in derivatives. The anomaly flow a_UV - a_IR is the coefficient of the 6-derivative Euler anomaly term in this action. It then appears at order p^6 in the low energy limit of n-point scattering amplitudes of the dilaton for n > 3. The detailed structure with the correct anomaly coefficient is confirmed by direct calculation in two examples: (i) the case of explicitly broken conformal symmetry is illustrated by the free massive scalar field, and (ii) the case of spontaneously broken conformal symmetry is demonstrated by the (2,0) theory on the Coulomb branch. In the latter example, the dilaton is a dynamical field so 4-derivative terms in the action also affect n-point amplitudes at order p^6. The calculation in the (2,0) theory is done by analyzing an M5-brane probe in AdS_7 x S^4. Given the confirmation in two distinct models, we attempt to use dispersion relations to prove that the anomaly flow is positive in general. Unfortunately the 4-point matrix element of the Euler anomaly is proportional to stu and vanishes for forward scattering. Thus the optical theorem cannot be applied to show positivity. Instead the anomaly flow is given by a dispersion sum rule in which the integrand does not have definite sign. It may be possible to base a proof of the a-theorem on the analyticity and unitarity properties of the 6-point function, but our preliminary study reveals some difficulties.Comment: 41 pages, 5 figure

Cancer mortality in 13 to 29-year-olds in England and Wales, 1981–2005

We examined cancer mortality at ages 13–29 years in England and Wales between 1981 and 2005, a total of 20 026 deaths over approximately 303 million person-years (mpy) at risk by sex, age group and time period. Overall, the mortality rate was 65.6 per mpy. Malignant neoplasms of the central nervous system showed the highest rate (8.5), followed by myeloid and monocytic leukaemia (6.6), lymphoid leukaemia (6.4), malignant bone tumours (5.4) and non-Hodgkin's lymphoma (5.2). These groups together accounted for almost 50% of all cancer deaths. The mortality rate for males (72.4) was 23% higher than for females (58.6) (P-value <0.0001). Males showed significantly higher mortality rates than females in almost all diagnostic groups, in general, mortality increasing with age (P-value <0.0001). There were significant decreases in mortality over time, the annual percentage change between 1981 and 2005 being minus 1.86 (95% confidence interval −2.09 to −1.62). Cancer groups with the highest mortality differed from those with the highest incidence

An Elementary Quantum Network of Single Atoms in Optical Cavities

Quantum networks are distributed quantum many-body systems with tailored topology and controlled information exchange. They are the backbone of distributed quantum computing architectures and quantum communication. Here we present a prototype of such a quantum network based on single atoms embedded in optical cavities. We show that atom-cavity systems form universal nodes capable of sending, receiving, storing and releasing photonic quantum information. Quantum connectivity between nodes is achieved in the conceptually most fundamental way: by the coherent exchange of a single photon. We demonstrate the faithful transfer of an atomic quantum state and the creation of entanglement between two identical nodes in independent laboratories. The created nonlocal state is manipulated by local qubit rotation. This efficient cavity-based approach to quantum networking is particularly promising as it offers a clear perspective for scalability, thus paving the way towards large-scale quantum networks and their applications.Comment: 8 pages, 5 figure

How managers can build trust in strategic alliances: a meta-analysis on the central trust-building mechanisms

Trust is an important driver of superior alliance performance. Alliance managers are influential in this regard because trust requires active involvement, commitment and the dedicated support of the key actors involved in the strategic alliance. Despite the importance of trust for explaining alliance performance, little effort has been made to systematically investigate the mechanisms that managers can use to purposefully create trust in strategic alliances. We use Parkhe’s (1998b) theoretical framework to derive nine hypotheses that distinguish between process-based, characteristic-based and institutional-based trust-building mechanisms. Our meta-analysis of 64 empirical studies shows that trust is strongly related to alliance performance. Process-based mechanisms are more important for building trust than characteristic- and institutional-based mechanisms. The effects of prior ties and asset specificity are not as strong as expected and the impact of safeguards on trust is not well understood. Overall, theoretical trust research has outpaced empirical research by far and promising opportunities for future empirical research exist

Suppression of the ATP-binding cassette transporter ABCC4 impairs neuroblastoma tumour growth and sensitises to irinotecan in vivo

The ATP-binding cassette transporter ABCC4 (multidrug resistance protein 4, MRP4) mRNA level is a strong predictor of poor clinical outcome in neuroblastoma which may relate to its export of endogenous signalling molecules and chemotherapeutic agents. We sought to determine whether ABCC4 contributes to development, growth and drug response in neuroblastoma in vivo. In neuroblastoma patients, high ABCC4 protein levels were associated with reduced overall survival. Inducible knockdown of ABCC4 strongly inhibited the growth of human neuroblastoma cells in vitro and impaired the growth of neuroblastoma xenografts. Loss of Abcc4 in the Th-MYCN transgenic neuroblastoma mouse model did not impact tumour formation; however, Abcc4-null neuroblastomas were strongly sensitised to the ABCC4 substrate drug irinotecan. Our findings demonstrate a role for ABCC4 in neuroblastoma cell proliferation and chemoresistance and provide rationale for a strategy where inhibition of ABCC4 should both attenuate the growth of neuroblastoma and sensitise tumours to ABCC4 chemotherapeutic substrates

CHIMPS: Physical properties of molecular clumps across the inner Galaxy

The latest generation of high-angular-resolution unbiased Galactic plane surveys in molecular-gas tracers are enabling the interiors of molecular clouds to be studied across a range of environments. The CO Heterodyne Inner MilkyWay Plane Survey (CHIMPS) simultaneously mapped a sector of the inner Galactic plane, within 27:8 . 46:2 and jbj 0: 5, in 13CO (3-2) and C18O (3-2) at an angular resolution of 15 arcsec. The combination of the CHIMPS data with 12CO (3-2) data from the CO High Resolution Survey (COHRS) has enabled us to perform a voxel-by-voxel local-thermodynamic-equilibrium (LTE) analysis, determining the excitation temperature, optical depth, and column density of 13CO at each; b; v position. Distances to discrete sources identified by FELLWALKER in the 13CO (3-2) emission maps were determined, allowing the calculation of numerous physical properties of the sources, and we present the first source catalogues in this paper.We find that, in terms of size and density, the CHIMPS sources represent an intermediate population between large-scale molecular clouds identified by CO and dense clumps seen in thermal dust continuum emission, and therefore represent the bulk transition from the diffuse to the dense phase of molecular gas.We do not find any significant systematic variations in the masses, column densities, virial parameters, mean excitation temperature, or the turbulent pressure over the range of Galactocentric distance probed, but we do find a shallow increase in the mean volume density with increasing Galactocentric distance. We find that inter-arm clumps have significantly narrower linewidths, and lower virial parameters and excitation temperatures than clumps located in spiral arms. When considering the most reliable distance-limited subsamples, the largest variations occur on the clump-to-clump scale, echoing similar recent studies that suggest that the star-forming process is largely insensitive to the Galactic-scale environment, at least within the inner disc

Системный анализ процесса затвердевания литых заготовок разной массы и назначения

Выявлены особенности пространственно-временной эволюции температурных полей в процессе затвердевания разных заготовок (слитков и отливок) для повышения их качества.Виявлено особливості просторово-часової еволюції температурних полів в процесі тверднення різних заготовок (зливків та виливків) для підвищення їх якості.It is revealed the peculiarities of distance-time evolution of the temperature fields in solidification process different billets (ingots and casts) for raise them quality

The role of secretory leukocyte proteinase inhibitor and elafin (elastase-specific inhibitor/skin-derived antileukoprotease) as alarm antiproteinases in inflammatory lung disease

Secretory leukocyte proteinase inhibitor and elafin are two low-molecular-mass elastase inhibitors that are mainly synthesized locally at mucosal sites. It is thought that their physicochemical properties allow them to efficiently inhibit target enzymes, such as neutrophil elastase, released into the interstitium. Historically, in the lung, these inhibitors were first purified from secretions of patients with chronic obstructive pulmonary disease and cystic fibrosis. This suggested that they might be important in controlling excessive neutrophil elastase release in these pathologies. They are upregulated by 'alarm signals' such as bacterial lipopolysaccharides, and cytokines such as interleukin-1 and tumor necrosis factor and have been shown to be active against Gram-positive and Gram-negative bacteria, so that they have joined the growing list of antimicrobial 'defensin-like' peptides produced by the lung. Their site of synthesis and presumed functions make them very attractive candidates as potential therapeutic agents under conditions in which the excessive release of elastase by neutrophils might be detrimental. Because of its natural tropism for the lung, the use of adenovirus-mediated gene transfer is extremely promising in such applications