138 research outputs found

    PRM60 Assessing Relative Clinical Value Across Tumor Types in Metastatic Disease

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    Effects of time window size and placement on the structure of aggregated networks

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    Complex networks are often constructed by aggregating empirical data over time, such that a link represents the existence of interactions between the endpoint nodes and the link weight represents the intensity of such interactions within the aggregation time window. The resulting networks are then often considered static. More often than not, the aggregation time window is dictated by the availability of data, and the effects of its length on the resulting networks are rarely considered. Here, we address this question by studying the structural features of networks emerging from aggregating empirical data over different time intervals, focussing on networks derived from time-stamped, anonymized mobile telephone call records. Our results show that short aggregation intervals yield networks where strong links associated with dense clusters dominate; the seeds of such clusters or communities become already visible for intervals of around one week. The degree and weight distributions are seen to become stationary around a few days and a few weeks, respectively. An aggregation interval of around 30 days results in the stablest similar networks when consecutive windows are compared. For longer intervals, the effects of weak or random links become increasingly stronger, and the average degree of the network keeps growing even for intervals up to 180 days. The placement of the time window is also seen to affect the outcome: for short windows, different behavioural patterns play a role during weekends and weekdays, and for longer windows it is seen that networks aggregated during holiday periods are significantly different.Comment: 19 pages, 11 figure

    ACQR: Acoustic Quick Response Codes for Content Sharing on Low End Phones with No Internet Connectivity.

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    ABSTRACT In this paper we introduce Acoustic Quick Response codes to facilitate sharing between Interactive Voice Response (IVR) service users. IVRs are telephone-based, and similar to the world wide web in many aspects, but currently lack support for content sharing. Our approach uses 'audio codes' to let people share their call positions, and allows callers to hold their normal (low-end) handsets together to synchronise. The technique uses remote generation and recognition of audio codes to ensure that sharing is possible on any type of phone without the need for textual literacy or an internet connection. We begin by exploring existing user needs for sharing, then evaluate the technical robustness of our audio-based design. We demonstrate the value of the approach for voice service users over several separate studies-including an eight-month extended field deployment-then conclude with a discussion of future possibilities for such scenarios

    Bringing LTL Model Checking to Biologists

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    The BioModelAnalyzer (BMA) is a web based tool for the development of discrete models of biological systems. Through a graphical user interface, it allows rapid development of complex models of gene and protein interaction networks and stability analysis without requiring users to be proficient computer programmers. Whilst stability is a useful specification for testing many systems, testing temporal specifications in BMA presently requires the user to perform simulations. Here we describe the LTL module, which includes a graphical and natural language interfaces to testing LTL queries. The graphical interface allows for graphical construction of the queries and presents results visually in keeping with the current style of BMA. The Natural language interface complements the graphical interface by allowing a gentler introduction to formal logic and exposing educational resources

    Differential cargo mobilisation within Weibel-Palade bodies after transient fusion with the plasma membrane.

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    Inflammatory chemokines can be selectively released from Weibel-Palade bodies (WPBs) during kiss-and-run exocytosis. Such selectivity may arise from molecular size filtering by the fusion pore, however differential intra-WPB cargo re-mobilisation following fusion-induced structural changes within the WPB may also contribute to this process. To determine whether WPB cargo molecules are differentially re-mobilised, we applied FRAP to residual post-fusion WPB structures formed after transient exocytosis in which some or all of the fluorescent cargo was retained. Transient fusion resulted in WPB collapse from a rod to a spheroid shape accompanied by substantial swelling (>2 times by surface area) and membrane mixing between the WPB and plasma membranes. Post-fusion WPBs supported cumulative WPB exocytosis. To quantify diffusion inside rounded organelles we developed a method of FRAP analysis based on image moments. FRAP analysis showed that von Willebrand factor-EGFP (VWF-EGFP) and the VWF-propolypeptide-EGFP (Pro-EGFP) were immobile in post-fusion WPBs. Because Eotaxin-3-EGFP and ssEGFP (small soluble cargo proteins) were largely depleted from post-fusion WPBs, we studied these molecules in cells preincubated in the weak base NH4Cl which caused WPB alkalinisation and rounding similar to that produced by plasma membrane fusion. In these cells we found a dramatic increase in mobilities of Eotaxin-3-EGFP and ssEGFP that exceeded the resolution of our method (∟ 2.4 ¾m2/s mean). In contrast, the membrane mobilities of EGFP-CD63 and EGFP-Rab27A in post-fusion WPBs were unchanged, while P-selectin-EGFP acquired mobility. Our data suggest that selective re-mobilisation of chemokines during transient fusion contributes to selective chemokine secretion during transient WPB exocytosis. Selective secretion provides a mechanism to regulate intravascular inflammatory processes with reduced risk of thrombosis

    Multichannel social signatures and persistent features of ego networks

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    The structure of egocentric networks reflects the way people balance their need for strong, emotionally intense relationships and a diversity of weaker ties. Egocentric network structure can be quantified with ’social signatures’, which describe how people distribute their communication effort across the members (alters) of their personal networks. Social signatures based on call data have indicated that people mostly communicate with a few close alters; they also have persistent, distinct signatures. To examine if these results hold for other channels of communication, here we compare social signatures built from call and text message data, and develop a way of constructing mixed social signatures using both channels. We observe that all types of signatures display persistent individual differences that remain stable despite the turnover in individual alters. We also show that call, text, and mixed signatures resemble one another both at the population level and at the level of individuals. The consistency of social signatures across individuals for different channels of communication is surprising because the choice of channel appears to be alter-specific with no clear overall pattern, and ego networks constructed from calls and texts overlap only partially in terms of alters. These results demonstrate individuals vary in how they allocate their communication effort across their personal networks and this variation is persistent over time and across different channels of communication

    Biomaterial Scaffolds as Pre‐metastatic Niche Mimics Systemically Alter the Primary Tumor and Tumor Microenvironment

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    Primary tumor (PT) immune cells and pre‐metastatic niche (PMN) sites are critical to metastasis. Recently, synthetic biomaterial scaffolds used as PMN mimics are shown to capture both immune and metastatic tumor cells. Herein, studies are performed to investigate whether the scaffold‐mediated redirection of immune and tumor cells would alter the primary tumor microenvironment (TME). Transcriptomic analysis of PT cells from scaffold‐implanted and mock‐surgery mice identifies differentially regulated pathways relevant to invasion and metastasis progression. Transcriptomic differences are hypothesized to result from scaffold‐mediated modulations of immune cell trafficking and phenotype in the TME. Culturing tumor cells with conditioned media generated from PT immune cells of scaffold‐implanted mice decrease invasion in vitro more than two‐fold relative to mock surgery controls and reduce activity of invasion‐promoting transcription factors. Secretomic characterization of the conditioned media delineates interactions between immune cells in the TME and tumor cells, showing an increase in the pan‐metastasis inhibitor decorin and a concomitant decrease in invasion‐promoting chemokine (C‐C motif) ligand 2 (CCL2) in scaffold‐implanted mice. Flow cytometric and transcriptomic profiling of PT immune cells identify phenotypically distinct tumor‐associated macrophages (TAMs) in scaffold‐implanted mice, which may contribute to an invasion‐suppressive TME. Taken together, this study demonstrates biomaterial scaffolds systemically influence metastatic progression through manipulation of the TME.Biomaterial implants that mimic the pre‐metastatic niche are shown to redirect immune and tumor cell populations in vivo. However, the systemic effects of pre‐metastatic niche mimics on metastasis progression have yet to be characterized. In this work, synthetic biomaterial implants were shown to systemically alter the primary tumor and the tumor microenvironment to promote an invasion‐suppressive phenotype.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144244/1/adhm201700903-sup-0001-S1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144244/2/adhm201700903_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144244/3/adhm201700903.pd

    Lesson from the Stoichiometry Determination of the Cohesin Complex: A Short Protease Mediated Elution Increases the Recovery from Cross-Linked Antibody-Conjugated Beads

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    Affinity purification of proteins using antibodies coupled to beads and subsequent mass spectrometric analysis has become a standard technique for the identification of protein complexes. With the recent transfer of the isotope dilution mass spectrometry principle (IDMS) to the field of proteomics, quantitative analysesssuch as the stoichiometry determination of protein complexesshave become achievable. Traditionally proteins were eluted from antibody-conjugated beads using glycine at low pH or using diluted acids such as HCl, TFA, or FA, but elution was often found to be incomplete. Using the cohesin complex and the anaphase promoting complex/cyclosome (APC/C) as examples, we show that a short 15-60 min predigestion with a protease such as LysC (modified on-bead digest termed protease elution) increases the elution efficiency 2- to 3-fold compared to standard acid elution protocols. While longer incubation periodssas performed in standard on-bead digestionsled to partial proteolysis of the cross-linked antibodies, no or only insignificant cleavage was observed after 15-60 min protease mediated elution. Using the protease elution method, we successfully determined the stoichiometry of the cohesin complex by absolute quantification of the four core subunits using LC-SRM analysis and 19 reference peptides generated with the EtEP strategy. Protease elution was 3-fold more efficient compared to HCl elution, but measurements using both elution techniques are in agreement with

    Genes for the Major Structural Components of Thermotogales Species’ Togas Revealed by Proteomic and Evolutionary Analyses of OmpA and OmpB Homologs

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    The unifying structural characteristic of members of the bacterial order Thermotogales is their toga, an unusual cell envelope that includes a loose-fitting sheath around each cell. Only two toga-associated structural proteins have been purified and characterized in Thermotoga maritima: the anchor protein OmpA1 (or Ompι) and the porin OmpB (or Ompβ). The gene encoding OmpA1 (ompA1) was cloned and sequenced and later assigned to TM0477 in the genome sequence, but because no peptide sequence was available for OmpB, its gene (ompB) was not annotated. We identified six porin candidates in the genome sequence of T. maritima. Of these candidates, only one, encoded by TM0476, has all the characteristics reported for OmpB and characteristics expected of a porin including predominant β-sheet structure, a carboxy terminus porin anchoring motif, and a porin-specific amino acid composition. We highly enriched a toga fraction of cells for OmpB by sucrose gradient centrifugation and hydroxyapatite chromatography and analyzed it by LC/MS/MS. We found that the only porin candidate that it contained was the TM0476 product. This cell fraction also had β-sheet character as determined by circular dichroism, consistent with its enrichment for OmpB. We conclude that TM0476 encodes OmpB. A phylogenetic analysis of OmpB found orthologs encoded in syntenic locations in the genomes of all but two Thermotogales species. Those without orthologs have putative isofunctional genes in their place. Phylogenetic analyses of OmpA1 revealed that each species of the Thermotogales has one or two OmpA homologs. T. maritima has two OmpA homologs, encoded by ompA1 (TM0477) and ompA2 (TM1729), both of which were found in the toga protein-enriched cell extracts. These annotations of the genes encoding toga structural proteins will guide future examinations of the structure and function of this unusual lineage-defining cell sheath

    Continuous and transparent multimodal authentication: reviewing the state of the art

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    Individuals, businesses and governments undertake an ever-growing range of activities online and via various Internet-enabled digital devices. Unfortunately, these activities, services, information and devices are the targets of cybercrimes. Verifying the user legitimacy to use/access a digital device or service has become of the utmost importance. Authentication is the frontline countermeasure of ensuring only the authorized user is granted access; however, it has historically suffered from a range of issues related to the security and usability of the approaches. They are also still mostly functioning at the point of entry and those performing sort of re-authentication executing it in an intrusive manner. Thus, it is apparent that a more innovative, convenient and secure user authentication solution is vital. This paper reviews the authentication methods along with the current use of authentication technologies, aiming at developing a current state-of-the-art and identifying the open problems to be tackled and available solutions to be adopted. It also investigates whether these authentication technologies have the capability to fill the gap between high security and user satisfaction. This is followed by a literature review of the existing research on continuous and transparent multimodal authentication. It concludes that providing users with adequate protection and convenience requires innovative robust authentication mechanisms to be utilized in a universal level. Ultimately, a potential federated biometric authentication solution is presented; however it needs to be developed and extensively evaluated, thus operating in a transparent, continuous and user-friendly manner
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