The expression pattern of MUC1 (EMA) is related to tumour characteristics and clinical outcome of invasive ductal breast carcinoma

Aims: To clarify MUC1 patterns in invasive ductal breast carcinoma and to relate them to clinicopathological parameters, coexpression of other biological markers and prognosis. Methods and results: Samples from 243 consecutive patients with primary ductal carcinoma were incorporated into tissue microarrays (TMAs). Slides were stained for MUC1, oestrogen receptor (ER), progesterone receptor (PR), Her2/neu, p53 and cyclin D1. Apical membrane MUC1 expression was associated with smaller tumours (P = 0.001), lower tumour grades (P < 0.001), PR positivity (P = 0.003) and increased overall survival (OS; P = 0.030). Diffuse cytoplasmic MUC1 expression was associated with cyclin D1 positivity (P = 0.009) and increased relapse-free survival (RFS; P = 0.034). Negativity for MUC1 was associated with ER negativity (P = 0.004), PR negativity (P = 0.001) and cyclin D1 negativity (P = 0.009). In stepwise multivariate analysis MUC1 negativity was an independent predictor of both RFS [hazard ratio (HR) 3.5, 95% confidence interval (CI) 1.5, 8.5; P = 0.005] and OS (HR 14.7, 9 5% Cl 4.9, 44. 1; P < 0.001). Conclusions: The expression pattern of MUC1 in invasive ductal breast carcinoma is related to tumour characteristics and clinical outcome. In addition, negative MUC1 expression is an independent risk factor for poor RFS and OS, besides 'classical' prognostic indicators

Work relations and the multiple dimensions of the work-life boundary: Hairstyling at home

This article proposes a multidimensional approach to analysis of the work-life boundary and examines the affects of particular social and organizational relations on the preservation or porous-ness of different dimensions. In line with Nippert-Eng (1996), it is suggested that different dimensions of the boundary are reinforced or weakened by different social and organizational pressures. Analysis describes a specific type of multidimensional breaching – instances when work is taken outside of the worksite (spatial breaching) and is carried out outside of work-time (temporal breaching). Empirical research was conducted among hairstylists working in salons and barbershops in a city in the North of England. Because of the nature of the tasks involved in hairstyling – that the skills involved are widely exchangeable and so may be employed in extra-work environments and temporalities – hairstylists provide a nice site for investigating the circumstances when this does (or does not) occur. Data collection involved a comprehensive self-completion survey of salons and barbershops in the city (response rate: 40%; N=132) and semi-structured interviews with 70 stylists working in 52 salons or barbershops. Findings demonstrate that work relations (hairstylists’ structural relations of production – whether a worker is an owner-proprietor, chair-renter, on-commission stylist, basic-only stylist, or trainee) are critical in determining both workers’ ability and desire to resist the seepage of work into their social lives as well as the particular dimensions of the boundary that are breached. This is because work relations affect the relative importance of four identified motivations for taking work out of the salon (income production; training; inter-personal reciprocity rooted in social relations; and inter-personal reciprocity rooted in the workplace)

Entanglement-free Heisenberg-limited phase estimation

Measurement underpins all quantitative science. A key example is the measurement of optical phase, used in length metrology and many other applications. Advances in precision measurement have consistently led to important scientific discoveries. At the fundamental level, measurement precision is limited by the number N of quantum resources (such as photons) that are used. Standard measurement schemes, using each resource independently, lead to a phase uncertainty that scales as 1/sqrt(N) - known as the standard quantum limit. However, it has long been conjectured that it should be possible to achieve a precision limited only by the Heisenberg uncertainty principle, dramatically improving the scaling to 1/N. It is commonly thought that achieving this improvement requires the use of exotic quantum entangled states, such as the NOON state. These states are extremely difficult to generate. Measurement schemes with counted photons or ions have been performed with N <= 6, but few have surpassed the standard quantum limit and none have shown Heisenberg-limited scaling. Here we demonstrate experimentally a Heisenberg-limited phase estimation procedure. We replace entangled input states with multiple applications of the phase shift on unentangled single-photon states. We generalize Kitaev's phase estimation algorithm using adaptive measurement theory to achieve a standard deviation scaling at the Heisenberg limit. For the largest number of resources used (N = 378), we estimate an unknown phase with a variance more than 10 dB below the standard quantum limit; achieving this variance would require more than 4,000 resources using standard interferometry. Our results represent a drastic reduction in the complexity of achieving quantum-enhanced measurement precision.Comment: Published in Nature. This is the final versio

On strongly chordal graphs that are not leaf powers

A common task in phylogenetics is to find an evolutionary tree representing proximity relationships between species. This motivates the notion of leaf powers: a graph G = (V, E) is a leaf power if there exist a tree T on leafset V and a threshold k such that uv is an edge if and only if the distance between u and v in T is at most k. Characterizing leaf powers is a challenging open problem, along with determining the complexity of their recognition. This is in part due to the fact that few graphs are known to not be leaf powers, as such graphs are difficult to construct. Recently, Nevries and Rosenke asked if leaf powers could be characterized by strong chordality and a finite set of forbidden subgraphs. In this paper, we provide a negative answer to this question, by exhibiting an infinite family \G of (minimal) strongly chordal graphs that are not leaf powers. During the process, we establish a connection between leaf powers, alternating cycles and quartet compatibility. We also show that deciding if a chordal graph is \G-free is NP-complete, which may provide insight on the complexity of the leaf power recognition problem

Unexpected features of branched flow through high-mobility two-dimensional electron gases

GaAs-based two-dimensional electron gases (2DEGs) show a wealth of remarkable electronic states, and serve as the basis for fast transistors, research on electrons in nanostructures, and prototypes of quantum-computing schemes. All these uses depend on the extremely low levels of disorder in GaAs 2DEGs, with low-temperature mean free paths ranging from microns to hundreds of microns. Here we study how disorder affects the spatial structure of electron transport by imaging electron flow in three different GaAs/AlGaAs 2DEGs, whose mobilities range over an order of magnitude. As expected, electrons flow along narrow branches that we find remain straight over a distance roughly proportional to the mean free path. We also observe two unanticipated phenomena in high-mobility samples. In our highest-mobility sample we observe an almost complete absence of sharp impurity or defect scattering, indicated by the complete suppression of quantum coherent interference fringes. Also, branched flow through the chaotic potential of a high-mobility sample remains stable to significant changes to the initial conditions of injected electrons.Comment: 22 pages, 4 figures, 1 tabl

Healthcare students’ perceptions about their role, confidence and competence to deliver brief public health interventions and advice

Background Public health improvement has long been an important focus for the United Kingdom Department of Health. The Allied Health Professions (AHP) Federation has 84,000 members, such a large number of AHP professionals should play a role in public health initiatives, but it is not clear if they or the AHP students who will be the future healthcare workforce feel themselves equipped to do so. Our aim was to understand the perceptions of AHP students about their role in delivering public health advice. Methods AHP students were recruited in one teaching university from different departments. Participants were final year AHP students who had completed all clinical placements related to their course. All students were emailed an invitation to participate, and those interested were asked to contact the researchers to participate in one of several focus groups. Data were recorded, transcribed, and analysed using framework analysis by two independent researchers. Results Nineteen students were recruited and participated in four focus groups. The main themes produced by the data analysis were: understanding of public health issues, perceptions of their role in this, challenges and opportunities to develop a public health role, and preparation for a public health role. Conclusions AHP students felt that they had a role in public health advice-giving, but barriers to providing this advice included their own lack of confidence and knowledge, time, and the environment of the clinical placement. They considered that there should be more teaching on public health issues, and that these should feature in both the curriculum and on clinical placement

Interferon regulatory factor 8-deficiency determines massive neutrophil recruitment but T cell defect in fast growing granulomas during tuberculosis

Following Mycobacterium tuberculosis (Mtb) infection, immune cell recruitment in lungs is pivotal in establishing protective immunity through granuloma formation and neogenesis of lymphoid structures (LS). Interferon regulatory factor-8 (IRF-8) plays an important role in host defense against Mtb, although the mechanisms driving anti-mycobacterial immunity remain unclear. In this study, IRF-8 deficient mice (IRF-8−/−) were aerogenously infected with a low-dose Mtb Erdman virulent strain and the course of infection was compared with that induced in wild-type (WT-B6) counterparts. Tuberculosis (TB) progression was examined in both groups using pathological, microbiological and immunological parameters. Following Mtb exposure, the bacterial load in lungs and spleens progressed comparably in the two groups for two weeks, after which IRF-8−/− mice developed a fatal acute TB whereas in WT-B6 the disease reached a chronic stage. In lungs of IRF-8−/−, uncontrolled growth of pulmonary granulomas and impaired development of LS were observed, associated with unbalanced homeostatic chemokines, progressive loss of infiltrating T lymphocytes and massive prevalence of neutrophils at late infection stages. Our data define IRF-8 as an essential factor for the maintenance of proper immune cell recruitment in granulomas and LS required to restrain Mtb infection. Moreover, IRF-8−/− mice, relying on a common human and mouse genetic mutation linked to susceptibility/severity of mycobacterial diseases, represent a valuable model of acute TB for comparative studies with chronically-infected congenic WT-B6 for dissecting protective and pathological immune reactions

Gauge-theoretic invariants for topological insulators: A bridge between Berry, Wess-Zumino, and Fu-Kane-Mele

We establish a connection between two recently-proposed approaches to the understanding of the geometric origin of the Fu-Kane-Mele invariant $\mathrm{FKM} \in \mathbb{Z}_2$, arising in the context of 2-dimensional time-reversal symmetric topological insulators. On the one hand, the $\mathbb{Z}_2$ invariant can be formulated in terms of the Berry connection and the Berry curvature of the Bloch bundle of occupied states over the Brillouin torus. On the other, using techniques from the theory of bundle gerbes it is possible to provide an expression for $\mathrm{FKM}$ containing the square root of the Wess-Zumino amplitude for a certain $U(N)$-valued field over the Brillouin torus. We link the two formulas by showing directly the equality between the above mentioned Wess-Zumino amplitude and the Berry phase, as well as between their square roots. An essential tool of independent interest is an equivariant version of the adjoint Polyakov-Wiegmann formula for fields $\mathbb{T}^2 \to U(N)$, of which we provide a proof employing only basic homotopy theory and circumventing the language of bundle gerbes.Comment: 23 pages, 1 figure. To appear in Letters in Mathematical Physic

Scans for signatures of selection in Russian cattle breed genomes reveal new candidate genes for environmental adaptation and acclimation

Domestication and selective breeding has resulted in over 1000 extant cattle breeds. Many of these breeds do not excel in important traits but are adapted to local environments. These adaptations are a valuable source of genetic material for efforts to improve commercial breeds. As a step toward this goal we identified candidate regions to be under selection in genomes of nine Russian native cattle breeds adapted to survive in harsh climates. After comparing our data to other breeds of European and Asian origins we found known and novel candidate genes that could potentially be related to domestication, economically important traits and environmental adaptations in cattle. The Russian cattle breed genomes contained regions under putative selection with genes that may be related to adaptations to harsh environments (e.g., AQP5, RAD50, and RETREG1). We found genomic signatures of selective sweeps near key genes related to economically important traits, such as the milk production (e.g., DGAT1, ABCG2), growth (e.g., XKR4), and reproduction (e.g., CSF2). Our data point to candidate genes which should be included in future studies attempting to identify genes to improve the extant breeds and facilitate generation of commercial breeds that fit better into the environments of Russia and other countries with similar climates

The importance of identity-by-state information for the accuracy of genomic selection

<p>Abstract</p> <p>Background</p> <p>It is commonly assumed that prediction of genome-wide breeding values in genomic selection is achieved by capitalizing on linkage disequilibrium between markers and QTL but also on genetic relationships. Here, we investigated the reliability of predicting genome-wide breeding values based on population-wide linkage disequilibrium information, based on identity-by-descent relationships within the known pedigree, and to what extent linkage disequilibrium information improves predictions based on identity-by-descent genomic relationship information.</p> <p>Methods</p> <p>The study was performed on milk, fat, and protein yield, using genotype data on 35 706 SNP and deregressed proofs of 1086 Italian Brown Swiss bulls. Genome-wide breeding values were predicted using a genomic identity-by-state relationship matrix and a genomic identity-by-descent relationship matrix (averaged over all marker loci). The identity-by-descent matrix was calculated by linkage analysis using one to five generations of pedigree data.</p> <p>Results</p> <p>We showed that genome-wide breeding values prediction based only on identity-by-descent genomic relationships within the known pedigree was as or more reliable than that based on identity-by-state, which implicitly also accounts for genomic relationships that occurred before the known pedigree. Furthermore, combining the two matrices did not improve the prediction compared to using identity-by-descent alone. Including different numbers of generations in the pedigree showed that most of the information in genome-wide breeding values prediction comes from animals with known common ancestors less than four generations back in the pedigree.</p> <p>Conclusions</p> <p>Our results show that, in pedigreed breeding populations, the accuracy of genome-wide breeding values obtained by identity-by-descent relationships was not improved by identity-by-state information. Although, in principle, genomic selection based on identity-by-state does not require pedigree data, it does use the available pedigree structure. Our findings may explain why the prediction equations derived for one breed may not predict accurate genome-wide breeding values when applied to other breeds, since family structures differ among breeds.</p