Innate immune response to Salmonella typhimurium, a model enteric pathogen

The innate immune system provides the first line of defense against invading microorganisms by inducing a variety of inflammatory and antimicrobial responses. These responses are particularly important in the gastrointestinal tract, where the needs for efficient nutrient uptake and host defense collide. Many pathogens have evolved to specifically colonize the intestine, causing millions of cases of enteric infections a year. A paradigm of an enteric pathogen is Salmonella enterica, a gram-negative bacterium that causes a wide range of gastrointestinal and systemic diseases. Infections with Salmonella enterica serovar Typhimurium (S. typhimurium) lead to an acute intestinal inflammation in human and animal hosts, as a result of the bacterium invading the mucosa. A distinctive feature of Salmonella is that it has not only adapted to survive in a strong inflammatory environment, but it also uses this adaptation as a strategy to gain a growth advantage over the intestinal microbiota. We will use the model organism S. typhimurium to discuss the innate immune mechanisms employed by the mammalian gastrointestinal system and how the pathogen responds and subverts these mechanisms. In particular, we focus on the recognition of extra- and intra-cellular Salmonellae by germline-encoded pattern recognition receptors of the TLR and NLR families, and how Salmonella might profit from the activation of these receptors

Linkless octree using multi-level perfect hashing

The standard C/C++ implementation of a spatial partitioning data structure, such as octree and quadtree, is often inefficient in terms of storage requirements particularly when the memory overhead for maintaining parent-to-child pointers is significant with respect to the amount of actual data in each tree node. In this work, we present a novel data structure that implements uniform spatial partitioning without storing explicit parent-to-child pointer links. Our linkless tree encodes the storage locations of subdivided nodes using perfect hashing while retaining important properties of uniform spatial partitioning trees, such as coarse-to-fine hierarchical representation, efficient storage usage, and efficient random accessibility. We demonstrate the performance of our linkless trees using image compression and path planning examples.postprin

In vivo analysis of fracture toughness of thyroid gland tumors

BackgroundHuman solid tumors that are hard or firm on physical palpation are likely to be cancerous, a clinical maxim that has been successfully applied to cancer screening programs, such as breast self-examination. However, the biological relevance or prognostic significance of tumor hardness remains poorly understood. Here we present a fracture mechanics based in vivo approach for characterizing the fracture toughness of biological tissue of human thyroid gland tumors.MethodsIn a prospective study, 609 solid thyroid gland tumors were percutaneously probed using standard 25 gauge fine needles, their tissue toughness ranked on the basis of the nature and strength of the haptic force feedback cues, and subjected to standard fine needle biopsy. The tumors' toughness rankings and final cytological diagnoses were combined and analyzed. The interpreting cytopathologist was blinded to the tumors' toughness rankings.ResultsOur data showed that cancerous and noncancerous tumors displayed remarkable haptically distinguishable differences in their material toughness.ConclusionThe qualitative method described here, though subject to some operator bias, identifies a previously unreported in vivo approach to classify fracture toughness of a solid tumor that can be correlated with malignancy, and paves the way for the development of a mechanical device that can accurately quantify the tissue toughness of a human tumor

Random attractors for degenerate stochastic partial differential equations

We prove the existence of random attractors for a large class of degenerate stochastic partial differential equations (SPDE) perturbed by joint additive Wiener noise and real, linear multiplicative Brownian noise, assuming only the standard assumptions of the variational approach to SPDE with compact embeddings in the associated Gelfand triple. This allows spatially much rougher noise than in known results. The approach is based on a construction of strictly stationary solutions to related strongly monotone SPDE. Applications include stochastic generalized porous media equations, stochastic generalized degenerate p-Laplace equations and stochastic reaction diffusion equations. For perturbed, degenerate p-Laplace equations we prove that the deterministic, infinite dimensional attractor collapses to a single random point if enough noise is added.Comment: 34 pages; The final publication is available at http://link.springer.com/article/10.1007%2Fs10884-013-9294-

Asian Society of Gynecologic Oncology International Workshop 2014

published_or_final_versio

CCL5 regulation of mucosal chlamydial immunity and infection

<p>Abstract</p> <p>Background</p> <p>Following genital chlamydial infection, an early T helper type 1 (Th1)-associated immune response precedes the activation and recruitment of specific Th1 cells bearing distinct chemokine receptors, subsequently leading to the clearance of <it>Chlamydia</it>. We have shown that CCR5, a receptor for CCL5, is crucial for protective chlamydial immunity. Our laboratory and others have also demonstrated that CCL5 deficiencies found in man and animals can increase the susceptibility and progression of infectious diseases by modulating mucosal immunity. These findings suggest the CCR5-CCL5 axis is necessary for optimal chlamydial immunity. We hypothesized CCL5 is required for protective humoral and cellular immunity against <it>Chlamydia</it>.</p> <p>Results</p> <p>The present study revealed that CCR5 and CCL5 mRNAs are elevated in the spleen, iliac lymph nodes (ILNs), and genital mucosa following <it>Chlamydia muriduram </it>challenge. Antibody (Ab)-mediated inhibition of CCL5 during genital chlamydial infection suppressed humoral and Th1 > Th2 cellular responses by splenic-, ILN-, and genital mucosa-derived lymphocytes. Antigen (Ag)-specific proliferative responses of CD4⁺T cells from spleen, ILNs, and genital organs also declined after CCL5 inhibition.</p> <p>Conclusion</p> <p>The suppression of these responses correlated with delayed clearance of <it>C. muriduram</it>, which indicate chlamydial immunity is mediated by Th1 immune responses driven in part by CCL5. Taken together with other studies, the data show that CCL5 mediates the temporal recruitment and activation of leukocytes to mitigate chlamydial infection through enhancing adaptive mucosal humoral and cellular immunity.</p

Histone deacetylase regulates high mobility group A2-targeting microRNAs in human cord blood-derived multipotent stem cell aging

Cellular senescence involves a reduction in adult stem cell self-renewal, and epigenetic regulation of gene expression is one of the main underlying mechanisms. Here, we observed that the cellular senescence of human umbilical cord blood-derived multipotent stem cells (hUCB-MSCs) caused by inhibition of histone deacetylase (HDAC) activity leads to down-regulation of high mobility group A2 (HMGA2) and, on the contrary, to up-regulation of p16INK4A, p21CIP1/WAF1 and p27KIP1. We found that let-7a1, let-7d, let-7f1, miR-23a, miR-26a and miR-30a were increased during replicative and HDAC inhibitor-mediated senescence of hUCB-MSCs by microRNA microarray and real-time quantitative PCR. Furthermore, the configurations of chromatins beading on these miRNAs were prone to transcriptional activation during HDAC inhibitor-mediated senescence. We confirmed that miR-23a, miR-26a and miR-30a inhibit HMGA2 to accelerate the progress of senescence. These findings suggest that HDACs may play important roles in cellular senescence by regulating the expression of miRNAs that target HMGA2 through histone modification

Personalization for unobtrusive service interaction

Increasingly, mobile devices play a key role in the communication between users and the services embedded in their environment. With ever greater number of services added to our surroundings, there is a need to personalize services according to the user needs and environmental context avoiding service behavior from becoming overwhelming. In order to prevent this information overload, we present a method for the development of mobile services that can be personalized in terms of obtrusiveness (the degree in which each service intrudes the user's mind) according to the user needs and preferences. That is, services can be developed to provide their functionality at different obtrusiveness levels depending on the user by minimizing the duplication of efforts. On the one hand, we provide mechanisms for describing the obtrusiveness degree required for a service. On the other hand, we make use of Feature Modeling techniques in order to define the obtrusiveness level adaptation in a declarative manner. An experiment was conducted in order to put in practice the proposal and evaluate the user acceptance for the personalization capabilities provided by our approach. © Springer-Verlag London Limited 2011.This work has been developed with the support of MICINN under the project EVERYWARE TIN2010-18011 and co-financed with ERDF, in the grants program FPU.Gil Pascual, M.; Giner Blasco, P.; Pelechano Ferragud, V. (2012). Personalization for unobtrusive service interaction. Personal and Ubiquitous Computing. 16(5):543-561. https://doi.org/10.1007/s00779-011-0414-0S543561165Abrams M, Phanouriou C, Batongbacal AL, Williams SM, Shuster JE (1999) Uiml: an appliance-independent xml user interface language. In: WWW ’99. Elsevier, North-Holland, pp 1695–1708Ballagas R, Borchers J, Rohs M, Sheridan JG (2006) The smart phone: a ubiquitous input device. IEEE Pervas Comput 5(1):70Balme L, Demeure A, Barralon N, Coutaz J, Calvary G (2004) Cameleon-rt: a software architecture reference model for distributed, migratable, and plastic user interfaces. In: EUSAI, pp 291–302Benavides D, Cortés RA, Trinidad P (2005) Automated reasoning on feature models. In: LNCS, advanced information systems engineering: 17th international conference, CAiSE 2005 3520, pp 491–503Blomquist A, Arvola M (2002) Personas in action: ethnography in an interaction design team. In: Proceedings of NordiCHI ’02. ACM, New York, NY, pp 197–200Bright A, Kay J, Ler D, Ngo K, Niu W, Nuguid A (2005) Adaptively recommending museum tours. In: Nick Ryan Tullio Salmon Cinotti GR (ed) Proceedings of workshop on smart environments and their applications to cultural heritage. Archaeolingua, pp 29–32Brown DM (2010) Communicating design: developing web site documentation for design and planning, 2nd edn. New Riders Press, USACalvary G, Coutaz J, Thevenin D, Limbourg Q, Bouillon L, Vanderdonckt J (2003) A unifying reference framework for multi-target user interfaces. Interact Comput 15(3):289–308Cetina C, Giner P, Fons J, Pelechano V (2009) Autonomic computing through reuse of variability models at runtime: the case of smart homes. Computer 42(10):37–43Chatfield C, Carmichael D, Hexel R, Kay J, Kummerfeld B (2005) Personalisation in intelligent environments: managing the information flow. In: OZCHI ’05. Computer-human interaction special interest group of Australia, pp 1–10Clerckx T, Winters F, Coninx K (2005) Tool support for designing context-sensitive user interfaces using a model-based approach. In: TAMODIA ’05: Proceedings of the 4th international workshop on Task models and diagrams. ACM Press, New York, pp 11–18Czarnecki K, Helsen S, Eisenecker U (2004) Staged configuration using feature models. In: Proceedings of SPLCDuarte C, Carriço L (2006) A conceptual framework for developing adaptive multimodal applications. In: Proceedings of IUI ’06. ACM, New York, pp 132–139Evans (2003) Domain-driven design: tacking complexity In the heart of software. Addison-Wesley Longman Publishing Co., Inc., BostonsFavre JM (2004) Foundations of model (Driven) (Reverse) engineering: models—Episode I: stories of the fidus papyrus and of the solarus. In: Bezivin J, Heckel R (eds) Language engineering for model-driven software development, no. 04101, Dagstuhl seminar proceedings. Dagstuhl, GermanyFischer G (2001) User modeling in human–computer interaction. User Model User-Adap Inter 11(1–2):65–86Gibbs WW (2005) Considerate computing. Scientific American 292(1):54–61Giner P, Cetina C, Fons J, Pelechano V (2010) Developing mobile workflow support in the internet of things. IEEE Pervas Comput 9(2):18–26Giner P, Cetina C, Fons J, Pelechano V (2011) Implicit interaction design for pervasive workflows. Pers Ubiquit Comput 1–10Gulliksen J, Goransson B, Boivie I, Blomkvist S, Persson J, Cajander A (2003) Key principles for user-centred systems design. Behav Inform Technol 22:397–409Hinckley K, Horvitz E (2001) Toward more sensitive mobile phones. In: Proceedings of the UIST ’01. ACM, New York, pp 191–192Ho J, Intille SS (2005) Using context-aware computing to reduce the perceived burden of interruptions from mobile devices. In: Proceedings of CHI ’05. ACM, New York, pp 909–918Horvitz E, Kadie C, Paek T, Hovel D (2003) Models of attention in computing and communication: from principles to applications. Commun ACM 46(3):52–59Ju W, Leifer L (2008) The design of implicit interactions: making interactive systems less obnoxious. Des Issues 24(3):72–84Lewis JR (1995) Ibm computer usability satisfaction questionnaires: psychometric evaluation and instructions for use. Int J Hum-Comput Interact 7(1):57–78Limbourg Q, Vanderdonckt J, Michotte B, Bouillon L, López-Jaquero V (2004) Usixml: a language supporting multi-path development of user interfaces. In: EHCI/DS-VIS, pp 200–220Mao JY, Vredenburg K, Smith PW, Carey T (2001) User-centered design methods in practice: a survey of the state of the art. In: CASCON ’01. IBM Press, New York, p 12McCrickard DS, Chewar CM (2003) Attuning notification design to user goals and attention costs. Commun ACM 46:67–72Mori G, Paternò F, Santoro C (2002) Ctte: support for developing and analyzing task models for interactive system design. IEEE Trans Softw Eng 28(8):797–813Mori G, Paternò F, Santoro C (2004) Design and development of multidevice user interfaces through multiple logical descriptions. IEEE Trans Softw Eng 30(8):507–520Myers B, Hudson SE, Pausch R (2000) Past, present, and future of user interface software tools. ACM Trans Comput-Hum Interact 7(1):3–28OMG (2006) Business process modeling notation (BPMN) specification. OMG Final Adopted SpecificationPaternò F, Santoro C (2003) A unified method for designing interactive systems adaptable to mobile and stationary platforms. Interact Comput 15(3):349–366Puerta A, Eisenstein J (2002) Ximl: a common representation for interaction data. In: Proceedings of IUI ’02. ACM, New York, pp 214–215Ramchurn SD, Deitch B, Thompson MK, Roure DCD, Jennings NR, Luck M (2004) Minimising intrusiveness in pervasive computing environments using multi-agent negotiation. In: First international conference on mobile and ubiquitous systems, pp 364–372Rumbaugh J, Jacobson I, Booch G (1998) The unified modeling language reference manual. Addison-Wesley, LondonSchobbens PY, Heymans P, Trigaux JC, Bontemps Y (2007) Generic semantics of feature diagrams. Comput Networks 51(2):456–479Serral E, Pérez F, Valderas P, Pelechano V (2010) An end-user tool for adapting smart environment automation to user behaviour at runtime. In: Proceedings of UCAmI ’10Streefkerk JW, van Esch-Bussemakers MP, Neerincx MA (2006) Designing personal attentive user interfaces in the mobile public safety domain. Comput Hum Behav 22:749–770Tedre M (2008) What should be automated? Interactions 15(5):47–49Unger R, Chandler C (2009) A project guide to UX design: for user experience designers in the field or in the making. New Riders Publishing, Thousand OaksVan den Bergh J, Coninx K. Using uml 2.0 and profiles for modelling context-sensitive user interfaces. In: Proceedings of the MDDAUI2005 CEUR workshopVastenburg MH, Keyson DV, de Ridder H (2008) Considerate home notification systems: a field study of acceptability of notifications in the home. Pers Ubiquit Comput 12(8):555–566Vertegaal R (2003) Attentive user interfaces. Commun ACM 46(3):30–33Weiser M, Brown JS (1997) The coming age of calm technology, pp 75–85Weld DS, Anderson C, Domingos P, Etzioni O, Gajos K, Lau T, Wolf S (2003) Automatically personalizing user interfaces. In: IJCAI ’03, pp 1613–161