Loom: Query-aware Partitioning of Online Graphs

As with general graph processing systems, partitioning data over a cluster of machines improves the scalability of graph database management systems. However, these systems will incur additional network cost during the execution of a query workload, due to inter-partition traversals. Workload-agnostic partitioning algorithms typically minimise the likelihood of any edge crossing partition boundaries. However, these partitioners are sub-optimal with respect to many workloads, especially queries, which may require more frequent traversal of specific subsets of inter-partition edges. Furthermore, they largely unsuited to operating incrementally on dynamic, growing graphs. We present a new graph partitioning algorithm, Loom, that operates on a stream of graph updates and continuously allocates the new vertices and edges to partitions, taking into account a query workload of graph pattern expressions along with their relative frequencies. First we capture the most common patterns of edge traversals which occur when executing queries. We then compare sub-graphs, which present themselves incrementally in the graph update stream, against these common patterns. Finally we attempt to allocate each match to single partitions, reducing the number of inter-partition edges within frequently traversed sub-graphs and improving average query performance. Loom is extensively evaluated over several large test graphs with realistic query workloads and various orderings of the graph updates. We demonstrate that, given a workload, our prototype produces partitionings of significantly better quality than existing streaming graph partitioning algorithms Fennel and LDG

Bacterial outer-membrane vesicles promote Vγ9Vδ2 T cell oncolytic activity

BACKGROUND: Increasing evidence suggests the immune activation elicited by bacterial outer-membrane vesicles (OMVs) can initiate a potent anti-tumor immunity, facilitating the recognition and destruction of malignant cells. At present the pathways underlying this response remain poorly understood, though a role for innate-like cells such as γδ T cells has been suggested. METHODS: Peripheral blood mononuclear cells (PBMCs) from healthy donors were co-cultured with E. coli MG1655 Δpal ΔlpxM OMVs and corresponding immune activation studied by cell marker expression and cytokine production. OMV-activated γδ T cells were co-cultured with cancer cell lines to determine cytotoxicity. RESULTS: The vesicles induced a broad inflammatory response with γδ T cells observed as the predominant cell type to proliferate post-OMV challenge. Notably, the majority of γδ T cells were of the Vγ9Vδ2 type, known to respond to both bacterial metabolites and stress markers present on tumor cells. We observed robust cytolytic activity of Vγ9Vδ2 T cells against both breast and leukaemia cell lines (SkBr3 and Nalm6 respectively) after OMV-mediated expansion. CONCLUSIONS: Our findings identify for the first time, that OMV-challenge stimulates the expansion of Vγ9Vδ2 T cells which subsequently present anti-tumor capabilities. We propose that OMV-mediated immune activation leverages the anti-microbial/anti-tumor capacity of Vγ9Vδ2 T cells, an axis amenable for improved future therapeutics

Social cognition in multiple sclerosis:A systematic review and meta-analysis

Objective: To quantify the magnitude of deficits in theory of mind (ToM) and facial emotion recognition among patients with multiple sclerosis (MS) relative to healthy controls. Methods: An electronic database search of Ovid MEDLINE, PsycINFO, and Embase was conducted from inception to April 1, 2016. Eligible studies were original research articles published in peer-reviewed journals that examined ToM or facial emotion recognition among patients with a diagnosis of MS and a healthy control comparison group. Data were independently extracted by 2 authors. Effect sizes were calculated using Hedges g. Results: Twenty-one eligible studies were identified assessing ToM (12 studies) and/or facial emotion recognition (13 studies) among 722 patients with MS and 635 controls. Deficits in both ToM (g -0.71, 95% confidence interval [CI] -0.88 to -0.55, p < 0.001) and facial emotion recognition (g -0.64, 95% CI -0.81 to -0.47, p < 0.001) were identified among patients with MS relative to healthy controls. The largest deficits were observed for visual ToM tasks and for the recognition of negative facial emotional expressions. Older age predicted larger emotion recognition deficits. Other cognitive domains were inconsistently associated with social cognitive performance. Conclusions: Social cognitive deficits are an overlooked but potentially important aspect of cognitive impairment in MS with potential prognostic significance for social functioning and quality of life. Further research is required to clarify the longitudinal course of social cognitive dysfunction, its association with MS disease characteristics and neurocognitive impairment, and the MS-specific neurologic damage underlying these deficits

Bilateral symmetry breaking in a nonlinear Fabry-Perot cavity exhibiting optical tristability

We show the existence of a region in the parameter space that defines the field dynamics in a Fabry-Perot cylindrical cavity, where three output stable stationary states of the light are possible for a given localized incident field. Two of these states do not preserve the bilateral (i.e. left-right) symmetry of the entire system. These broken-symmetry states are the high-transmission nonlinear modes of the system. We also discuss how to excite these states.Comment: 5 pages, 5 figure

Mis-regulation of Zn and Mn homeostasis is a key phenotype of Cu stress in Streptococcus pyogenes.

All bacteria possess homeostastic mechanisms that control the availability of micronutrient metals within the cell. Cross-talks between different metal homeostasis pathways within the same bacterial organism have been reported widely. In addition, there have been previous suggestions that some metal uptake transporters can promote adventitious uptake of the wrong metal. This work describes the cross-talk between Cu and the Zn and Mn homeostasis pathways in Group A Streptococcus (GAS). Using a ∆copA mutant strain that lacks the primary Cu efflux pump and thus traps excess Cu in the cytoplasm, we show that growth in the presence of supplemental Cu promotes downregulation of genes that contribute to Zn or Mn uptake. This effect is not associated with changes in cellular Zn or Mn levels. Co-supplementation of the culture medium with Zn or, to a lesser extent, Mn alleviates key Cu stress phenotypes, namely bacterial growth and secretion of the fermentation end-product lactate. However, neither co-supplemental Zn nor Mn influences cellular Cu levels or Cu availability in Cu-stressed cells. In addition, we provide evidence that the Zn or Mn uptake transporters in GAS do not promote Cu uptake. Together, the results from this study strengthen and extend our previous proposal that mis-regulation of Zn and Mn homeostasis is a key phenotype of Cu stress in GAS. [Abstract copyright: © The Author(s) 2023. Published by Oxford University Press.

Stable solitons in coupled Ginzburg-Landau equations describing Bose-Einstein condensates and nonlinear optical waveguides and cavities

We introduce a model of a two-core system, based on an equation of the Ginzburg-Landau (GL) type, coupled to another GL equation, which may be linear or nonlinear. One core is active, featuring intrinsic linear gain, while the other one is lossy. The difference from previously studied models involving a pair of linearly coupled active and passive cores is that the stabilization of the system is provided not by a linear diffusion-like term, but rather by a cubic or quintic dissipative term in the active core. Physical realizations of the models include systems from nonlinear optics (semiconductor waveguides or optical cavities), and a double-cigar-shaped Bose-Einstein condensate with a negative scattering length, in which the active ``cigar'' is an atom laser. The replacement of the diffusion term by the nonlinear loss is principally important, as diffusion does not occur in these physical media, while nonlinear loss is possible. A stability region for solitary pulses is found in the system's parameter space by means of direct simulations. One border of the region is also found in an analytical form by means of a perturbation theory. Moving pulses are studied too. It is concluded that collisions between them are completely elastic, provided that the relative velocity is not too small. The pulses withstand multiple tunneling through potential barriers. Robust quantum-rachet regimes of motion of the pulse in a time-periodic asymmetric potential are found as well.Comment: 14 pages, 7 figure

Somatic Mutation Screening Using Archival Formalin-Fixed, Paraffin-Embedded Tissues by Fluidigm Multiplex PCR and Illumina Sequencing.

High-throughput somatic mutation screening using FFPE tissues is a major challenge because of a lack of established methods and validated variant calling algorithms. We aimed to develop a targeted sequencing protocol by Fluidigm multiplex PCR and Illumina sequencing and to establish a companion variant calling algorithm. The experimental protocol and variant calling algorithm were first developed and optimized against a series of somatic mutations (147 substitutions, 12 indels ranging from 1 to 33 bp) in seven genes, previously detected by Sanger sequencing of DNA from 163 FFPE lymphoma biopsy specimens. The optimized experimental protocol and variant calling algorithm were further ascertained in two separate experiments by including the seven genes as a part of larger gene panels (22 or 13 genes) using FFPE and high-molecular-weight lymphoma DNAs, respectively. We found that most false-positive variants were due to DNA degradation, deamination, and Taq polymerase errors, but they were nonreproducible and could be efficiently eliminated by duplicate experiments. A small fraction of false-positive variants appeared in duplicate, but they were at low alternative allele frequencies and could be separated from mutations when appropriate threshold value was used. In conclusion, we established a robust practical approach for high-throughput mutation screening using archival FFPE tissues.The research was supported by grants [LLR10006, LLR13006] from Leukaemia & Lymphoma Research, U.K. and Kay Kendal Leukaemia Fund. SM is a PhD student supported by Medical Research Council, Department of Pathology, University of Cambridge, and Addenbrooke’s Charitable Trust. LEI is a PhD student supported by the Pathological Society of UK & Ireland. XX was supported by a visiting fellowship from the China Scholarship Council, Ministry of Education, P.R. China. NG was supported by a Kay Kendal Leukaemia Fund [KKL649] and an Addenbrooke’s Charitable Trust fellowship.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.jmoldx.2015.04.008 This article is permanently embargoed in this repository. However, the full text is freely available in PubMed Central 6 months via http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4597275

Gendered endings: Narratives of male and female suicides in the South African Lowveld

This is the author's accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/s11013-012-9258-y. Copyright @ Springer Science+Business Media, LLC 2012.Durkheim’s classical theory of suicide rates being a negative index of social solidarity downplays the salience of gendered concerns in suicide. But gendered inequalities have had a negative impact: worldwide significantly more men than women perpetrate fatal suicides. Drawing on narratives of 52 fatal suicides in Bushbuckridge, South Africa, this article suggests that Bourdieu’s concepts of ‘symbolic violence’ and ‘masculine domination’ provide a more appropriate framework for understanding this paradox. I show that the thwarting of investments in dominant masculine positions have been the major precursor to suicides by men. Men tended to take their own lives as a means of escape. By contrast, women perpetrated suicide to protest against the miserable consequences of being dominated by men. However, contra the assumption of Bourdieu’s concept of ‘habitus’, the narrators of suicide stories did reflect critically upon gender constructs