Open labware: 3-D printing your own lab equipment

The introduction of affordable, consumer-oriented 3-D printers is a milestone in the current “maker movement,” which has been heralded as the next industrial revolution. Combined with free and open sharing of detailed design blueprints and accessible development tools, rapid prototypes of complex products can now be assembled in one’s own garage—a game-changer reminiscent of the early days of personal computing. At the same time, 3-D printing has also allowed the scientific and engineering community to build the “little things” that help a lab get up and running much faster and easier than ever before

Oncogenic PIK3CA promotes cellular stemness in an allele dose-dependent manner

The PIK3CA gene, which encodes the p110α catalytic subunit of PI3 kinase (PI3K), is mutationally activated in cancer and in overgrowth disorders known as PIK3CA-related overgrowth spectrum (PROS). To determine the consequences of genetic PIK3CA activation in a developmental context of relevance to both PROS and cancer, we engineered isogenic human induced pluripotent stem cells (iPSCs) with heterozygous or homozygous knockin of PIK3CA H1047R While heterozygous iPSCs remained largely similar to wild-type cells, homozygosity for PIK3CA H1047R caused widespread, cancer-like transcriptional remodeling, partial loss of epithelial morphology, up-regulation of stemness markers, and impaired differentiation to all three germ layers in vitro and in vivo. Genetic analysis of PIK3CA-associated cancers revealed that 64% had multiple oncogenic PIK3CA copies (39%) or additional PI3K signaling pathway-activating "hits" (25%). This contrasts with the prevailing view that PIK3CA mutations occur heterozygously in cancer. Our findings suggest that a PI3K activity threshold determines pathological consequences of oncogenic PIK3CA activation and provide insight into the specific role of this pathway in human pluripotent stem cells

Reactivation of Fault Systems by Compartmentalized Hydrothermal Fluids in the Southern Andes Revealed by Magnetotelluric and Seismic Data

In active volcanic arcs such as the Andean volcanic mountain belt, magmatically‐sourced fluids are channelled through the brittle crust by faults and fracture networks. In the Andes, volcanoes, geothermal springs and major mineral deposits have a spatial and genetic relationship with NNE‐trending, margin‐parallel faults and margin‐oblique, NW‐trending Andean Transverse Faults (ATF). The Tinguiririca and Planchón‐Peteroa volcanoes in the Andean Southern Volcanic Zone (SVZ) demonstrate this relationship, as their spatially associated thermal springs show strike alignment to the NNE‐oriented El Fierro Thrust Fault System. We constrain the fault system architecture and its interaction with volcanically sourced hydrothermal fluids using a combined magnetotelluric (MT) and seismic survey that was deployed for 20 months. High conductivity zones are located along the axis of the active volcanic chain, delineating fluids and/or melt. A distinct WNW‐trending cluster of seismicity correlates with resistivity contrasts, considered to be a reactivated ATF. Seismicity occurs below 4 km, suggesting activity is limited to basement rocks, and the cessation of seismicity at 9 km delineates the local brittle‐ductile transition. As seismicity is not seen west of the El Fierro fault, we hypothesize that this structure plays a key role in compartmentalizing magmatically‐derived hydrothermal fluids to the east, where the fault zone acts as a barrier to cross‐fault fluid migration and channels fault‐parallel fluid flow to the surface from depth. Increases in fluid pressure above hydrostatic may facilitate reactivation. This site‐specific case study provides the first three‐dimensional seismic and magnetotelluric observations of the mechanics behind the reactivation of an ATF

Fibre Distribution and the Process-Property Dilemma

The options for the fibre reinforcement of polymer matrix composites cover a range from short-fibre chopped strand mat, through woven fabric to unidirectional pre-impregnated (prepreg) reinforcements. The modelling of such materials may be simplified by assumptions such as perfect regular packing of fibres and the total absence of fibre waviness. However, these and other features such as the crimp or waviness in woven fabrics make real materials more complex than the simplified models. Clustering of fibres creates fibre-rich and resin-rich volumes (FRV and RRV respectively) in the composites. Prior to impregnation, large RRV will be pore-space that can expedite the flow of resin in liquid composite moulding processes (especially resin transfer moulding (RTM) and resin infusion under flexible tooling (RIFT). In the composite, the clustering of fibres tends to reduce the mechanical properties. The use of image processing and analysis can permit micro-/meso-structural characterisation which may correlate to the respective properties. This chapter considers the quantification of microstructure images in the context of the process-property dilemma for woven carbon-fibre reinforced composites with the aim of increasing understanding of the balance between processability and mechanical performance

Feasibility study of an internally cooled bipolar applicator for RF coagulation of hepatic tissue: Experimental and computational study

Purpose: To study the capacity of an internally cooled radiofrequency (RF) bipolar applicator to create sufficiently deep thermal lesions in hepatic tissue. Materials and methods: Three complementary methodologies were employed to check the electrical and thermal behaviour of the applicator under test. The experimental studies were based on excised bovine (ex vivo study) and porcine liver (in vivo study) and the theoretical models were solved by means of the finite element method (FEM). Results: Experimental and computational results showed good agreement in terms of impedance progress and lesion depth (4 and 4.5 mm respectively for ex vivo conditions, and approximately 7 and 9 mm respectively for in vivo conditions), although the lesion widths were overestimated by the computer simulations. This could have been due to the method used to assess the thermal lesions; the experimental lesions were assessed by the white coagulation zone, whereas the tissue damage function was used to assess the computational lesions. Conclusions: The experimental results suggest that this applicator could create in vivo lesions to a depth of around 7mm. It was also observed that the thermal lesion is mainly confined to the area between both electrodes, which would allow lesion width to be controlled by selecting a specific applicator design. The comparison between the experimental and computational results suggests that the theoretical model could be usefully applied in further studies of the performance of this device. © 2012 Informa UK Ltd All rights reserved.This work received financial support from the Spanish Plan Nacional de I+D+I del Ministerio de Ciencia e Innovacion TEC2011-27133-C02-(01 and 02), from Universitat Politecnica de Valencia (INNOVA11-01-5502; and PAID-06-11 Ref. 1988). A. Gonzalez-Suarez is the recipient of grant VaLi+D (ACIF/2011/194) from the Generalitat Valenciana. The proof-reading of this paper was funded by the Universitat Politecnica de Valencia, Spain. The authors alone are responsible for the content and writing of the paper.González Suárez, A.; Trujillo Guillen, M.; Burdío Pinilla, F.; Andaluz Martínez, AM.; Berjano Zanón, E. (2012). Feasibility study of an internally cooled bipolar applicator for RF coagulation of hepatic tissue: Experimental and computational study. International Journal of Hyperthermia. 28(7):663-673. https://doi.org/10.3109/02656736.2012.716900S663673287Topp, S. A., McClurken, M., Lipson, D., Upadhya, G. A., Ritter, J. H., Linehan, D., & Strasberg, S. M. (2004). Saline-Linked Surface Radiofrequency Ablation. Annals of Surgery, 239(4), 518-527. doi:10.1097/01.sla.0000118927.83650.a4Gnerlich, J. L., Ritter, J. H., Linehan, D. C., Hawkins, W. G., & Strasberg, S. M. (2009). Saline-Linked Surface Radiofrequency Ablation. Annals of Surgery, 250(1), 96-102. doi:10.1097/sla.0b013e3181ae91afSakamoto, Y., Yamamoto, J., Kokudo, N., Seki, M., Kosuge, T., Yamaguchi, T., … Makuuchi, M. (2004). Bloodless liver resection using the Monopolar Floating Ball plus Ligasure diathermy: Preliminary results of 16 liver resections. World Journal of Surgery, 28(2), 166-172. doi:10.1007/s00268-003-7167-5Poon, R. T., Fan, S. T., & Wong, J. (2005). Liver resection using a saline-linked radiofrequency dissecting sealer for transection of the liver. Journal of the American College of Surgeons, 200(2), 308-313. doi:10.1016/j.jamcollsurg.2004.10.008EVERETT IV, T. H., LEE, K. W., WILSON, E. E., GUERRA, J. M., VAROSY, P. D., & OLGIN, J. E. (2008). Safety Profiles and Lesion Size of Different Radiofrequency Ablation Technologies: A Comparison of Large Tip, Open and Closed Irrigation Catheters. Journal of Cardiovascular Electrophysiology, 20(3), 325-335. doi:10.1111/j.1540-8167.2008.01305.xYokoyama, K., Nakagawa, H., Wittkampf, F. H. M., Pitha, J. V., Lazzara, R., & Jackman, W. M. (2006). Comparison of Electrode Cooling Between Internal and Open Irrigation in Radiofrequency Ablation Lesion Depth and Incidence of Thrombus and Steam Pop. Circulation, 113(1), 11-19. doi:10.1161/circulationaha.105.540062Demazumder, D., Mirotznik, M. S., & Schwartzman, D. (2001). Journal of Interventional Cardiac Electrophysiology, 5(4), 391-400. doi:10.1023/a:1013241927388Cooper, J. M., Sapp, J. L., Tedrow, U., Pellegrini, C. P., Robinson, D., Epstein, L. M., & Stevenson, W. G. (2004). Ablation with an internally irrigated radiofrequency catheter: Learning how to avoid steam pops. Heart Rhythm, 1(3), 329-333. doi:10.1016/j.hrthm.2004.04.019Burdío, F., Grande, L., Berjano, E., Martinez-Serrano, M., Poves, I., Burdío, J. M., … Güemes, A. (2010). A new single-instrument technique for parenchyma division and hemostasis in liver resection: a clinical feasibility study. The American Journal of Surgery, 200(6), e75-e80. doi:10.1016/j.amjsurg.2010.02.020Ríos, J. S., Zalabardo, J. M. S., Burdio, F., Berjano, E., Moros, M., Gonzalez, A., … Güemes, A. (2011). Single Instrument for Hemostatic Control in Laparoscopic Partial Nephrectomy in a Porcine Model Without Renal Vascular Clamping. Journal of Endourology, 25(6), 1005-1011. doi:10.1089/end.2010.0557Dorcaratto, D., Burdío, F., Fondevila, D., Andaluz, A., Poves, I., Martinez, M. A., … Grande, L. (2012). Laparoscopic Distal Pancreatectomy: Feasibility Study of Radiofrequency-Assisted Transection in a Porcine Model. Journal of Laparoendoscopic & Advanced Surgical Techniques, 22(3), 242-248. doi:10.1089/lap.2011.0417Zeh, A., Messer, J., Davis, J., Vasarhelyi, A., & Wohlrab, D. (2010). The Aquamantys System—An Alternative To Reduce Blood Loss in Primary Total Hip Arthroplasty? The Journal of Arthroplasty, 25(7), 1072-1077. doi:10.1016/j.arth.2009.10.008Sprunger, J., & Herrell, S. D. (2005). Partial Laparoscopic Nephrectomy Using Monopolar Saline-Coupled Radiofrequency Device: Animal Model and Tissue Effect Characterization. Journal of Endourology, 19(4), 513-519. doi:10.1089/end.2005.19.513Voeller, R. K., Zierer, A., Lall, S. C., Sakamoto, S., Schuessler, R. B., & Damiano, R. J. (2010). Efficacy of a novel bipolar radiofrequency ablation device on the beating heart for atrial fibrillation ablation: A long-term porcine study. The Journal of Thoracic and Cardiovascular Surgery, 140(1), 203-208. doi:10.1016/j.jtcvs.2009.06.034Pai, M., Spalding, D., Jiao, L., & Habib, N. (2012). Use of Bipolar Radiofrequency in Parenchymal Transection of the Liver, Pancreas and Kidney. Digestive Surgery, 29(1), 43-47. doi:10.1159/000335732Berjano, E. J. (2006). BioMedical Engineering OnLine, 5(1), 24. doi:10.1186/1475-925x-5-24Tungjitkusolmun, S., Staelin, S. T., Haemmerich, D., Jang-Zern Tsai, Hong Cao, Webster, J. G., … Vorperian, V. R. (2002). Three-dimensional finite-element analyses for radio-frequency hepatic tumor ablation. IEEE Transactions on Biomedical Engineering, 49(1), 3-9. doi:10.1109/10.972834Doss, J. D. (1982). Calculation of electric fields in conductive media. Medical Physics, 9(4), 566-573. doi:10.1118/1.595107Abraham, J. P., & Sparrow, E. M. (2007). A thermal-ablation bioheat model including liquid-to-vapor phase change, pressure- and necrosis-dependent perfusion, and moisture-dependent properties. International Journal of Heat and Mass Transfer, 50(13-14), 2537-2544. doi:10.1016/j.ijheatmasstransfer.2006.11.045Jo, B., & Aksan, A. (2010). Prediction of the extent of thermal damage in the cornea during conductive keratoplasty. Journal of Thermal Biology, 35(4), 167-174. doi:10.1016/j.jtherbio.2010.02.004Pearce, J., Panescu, D., & Thomsen, S. (2005). Simulation of diopter changes in radio frequency conductive keratoplasty in the cornea. Modelling in Medicine and Biology VI. doi:10.2495/bio050451Yang, D., Converse, M. C., Mahvi, D. M., & Webster, J. G. (2007). Expanding the Bioheat Equation to Include Tissue Internal Water Evaporation During Heating. IEEE Transactions on Biomedical Engineering, 54(8), 1382-1388. doi:10.1109/tbme.2007.890740Zhao, G., Zhang, H.-F., Guo, X.-J., Luo, D.-W., & Gao, D.-Y. (2007). Effect of blood flow and metabolism on multidimensional heat transfer during cryosurgery. Medical Engineering & Physics, 29(2), 205-215. doi:10.1016/j.medengphy.2006.03.005Pätz T, Körger T, Preusser T, Simulation of radiofrequency ablation including water evaporation. In: IFMBE Proceedings of the World Congress on Medical Physics and Biomedical Engineering 25/IV, 2009, 1287–1290Berjano, E. J., Burdío, F., Navarro, A. C., Burdío, J. M., Güemes, A., Aldana, O., … Gregorio, M. A. de. (2006). Improved perfusion system for bipolar radiofrequency ablation of liver: preliminary findings from a computer modeling study. Physiological Measurement, 27(10), N55-N66. doi:10.1088/0967-3334/27/10/n03Burdío, F., Berjano, E. J., Navarro, A., Burdío, J. M., Grande, L., Gonzalez, A., … Lequerica, J. L. (2009). Research and development of a new RF-assisted device for bloodless rapid transection of the liver: Computational modeling and in vivo experiments. BioMedical Engineering OnLine, 8(1), 6. doi:10.1186/1475-925x-8-6Chang, I. A., & Nguyen, U. D. (2004). BioMedical Engineering OnLine, 3(1), 27. doi:10.1186/1475-925x-3-27Beop-Min Kim, Jacques, S. L., Rastegar, S., Thomsen, S., & Motamedi, M. (1996). Nonlinear finite-element analysis of the role of dynamic changes in blood perfusion and optical properties in laser coagulation of tissue. IEEE Journal of Selected Topics in Quantum Electronics, 2(4), 922-933. doi:10.1109/2944.577317Panescu, D., Whayne, J. G., Fleischman, S. D., Mirotznik, M. S., Swanson, D. K., & Webster, J. G. (1995). Three-dimensional finite element analysis of current density and temperature distributions during radio-frequency ablation. IEEE Transactions on Biomedical Engineering, 42(9), 879-890. doi:10.1109/10.412649González-Suárez A, Alba J, Trujillo M, Berjano E, Experimental and theoretical study of an internally cooled bipolar electrode for RF coagulation of biological tissues. Conf Proc IEEE Eng Med Biol Soc 2011;6878–6881Rosenberg, A. G. (2007). Reducing Blood Loss in Total Joint Surgery With a Saline-Coupled Bipolar Sealing Technology. The Journal of Arthroplasty, 22(4), 82-85. doi:10.1016/j.arth.2007.02.018PETERSEN, H. H., ROMAN-GONZALEZ, J., JOHNSON, S. B., HASTRUP SVENDSEN, J., HAUNSO, S., & PACKER, D. L. (2004). Mechanisms for Enlarging Lesion Size During Irrigated Tip Radiofrequency Ablation:. Is There a Virtual Electrode Effect? Journal of Interventional Cardiology, 17(3), 171-177. doi:10.1111/j.1540-8183.2004.09879.

CD209 in inflammatory bowel disease: a case-control study in the Spanish population

<p>Abstract</p> <p>Background</p> <p>The etiology of Ulcerative Colitis (UC) and Crohn's Disease (CD), considered together as Inflammatory Bowel Diseases (IBD), involves environmental and genetic factors. Although some genes are already known, the genetics underlying these diseases is complex and new candidates are continuously emerging. The <it>CD209 </it>gene is located in a region linked previously to IBD and a <it>CD209 </it>functional polymorphism (rs4804803) has been associated to other inflammatory conditions. Our aim was to study the potential involvement of this <it>CD209 </it>variant in IBD susceptibility.</p> <p>Methods</p> <p>We performed a case-control study with 515 CD patients, 497 UC patients and 731 healthy controls, all of them white Spaniards. Samples were typed for the <it>CD209 </it>single nucleotide polymorphism (SNP) rs4804803 by TaqMan technology. Frequency comparisons were performed using χ²tests.</p> <p>Results</p> <p>No association between <it>CD209 </it>and UC or CD was observed initially. However, stratification of UC patients by <it>HLA-DR3 </it>status, a strong protective allele, showed that carriage of the <it>CD209</it>_G allele could increase susceptibility in the subgroup of <it>HLA-DR3</it>-positive individuals (p = 0.03 OR = 1.77 95% CI 1.04–3.02, <it>vs. </it>controls).</p> <p>Conclusion</p> <p>A functional variant in the <it>CD209 </it>gene, rs4804803, does not seem to be influencing Crohn's disease susceptibility. However, it could be involved in the etiology or pathology of Ulcerative Colitis in <it>HLA-DR3</it>-positive individuals but further studies are necessary.</p

Exploring the science–policy interface on climate change: The role of the IPCC in informing local decision-making in the UK

Building on the Intergovernmental Panel on Climate Change’s (IPCC) review of how to make its Assessment Reports (ARs) more accessible in the future, the research reported here assesses the extent to which the ARs are a useful tool through which scientific advice informs local decision-making on climate change in the United Kingdom. Results from interviews with local policy representatives and three workshops with UK academics, practitioners and local decision makers are presented. Drawing on these data, we outline three key recommendations made by participants on how the IPCC ARs can be better utilized as a form of scientific advice to inform local decision-making on climate change. First, to provide more succinct summaries of the reports paying close attention to the language, content, clarity, context and length of these summaries; second, to better target and frame the reports from a local perspective to maximize engagement with local stakeholders; and third, to work with local decision makers to better understand how scientific advice on climate change is being incorporated in local decision-making. By adopting these, the IPCC would facilitate local decision-making on climate change and provide a systematic review of how its reports are being used locally. We discuss implications of these recommendations and their relevance to the wider debate within and outside the IPCC as to the most effective way the IPCC can more effectively tailor its products to user needs without endangering the robustness of its scientific findings. This article is published as part of a collection on scientific advice to government

Search for sterile neutrino mixing in the MINOS long-baseline experiment

A search for depletion of the combined flux of active neutrino species over a 735 km baseline is reported using neutral-current interaction data recorded by the MINOS detectors in the NuMI neutrino beam. Such a depletion is not expected according to conventional interpretations of neutrino oscillation data involving the three known neutrino flavors. A depletion would be a signature of oscillations or decay to postulated noninteracting sterile neutrinos, scenarios not ruled out by existing data. From an exposure of 3.18×1020 protons on target in which neutrinos of energies between ~500¿¿MeV and 120 GeV are produced predominantly as ¿µ, the visible energy spectrum of candidate neutral-current reactions in the MINOS far detector is reconstructed. Comparison of this spectrum to that inferred from a similarly selected near-detector sample shows that of the portion of the ¿µ flux observed to disappear in charged-current interaction data, the fraction that could be converting to a sterile state is less than 52% at 90% confidence level (C.L.). The hypothesis that active neutrinos mix with a single sterile neutrino via oscillations is tested by fitting the data to various models. In the particular four-neutrino models considered, the mixing angles ¿24 and ¿34 are constrained to be less than 11° and 56° at 90% C.L., respectively. The possibility that active neutrinos may decay to sterile neutrinos is also investigated. Pure neutrino decay without oscillations is ruled out at 5.4 standard deviations. For the scenario in which active neutrinos decay into sterile states concurrently with neutrino oscillations, a lower limit is established for the neutrino decay lifetime t3/m3&gt;2.1×10-12¿¿s/eV at 90% C.L

Habitat and Scale Shape the Demographic Fate of the Keystone Sea Urchin Paracentrotus lividus in Mediterranean Macrophyte Communities

Demographic processes exert different degrees of control as individuals grow, and in species that span several habitats and spatial scales, this can influence our ability to predict their population at a particular life-history stage given the previous life stage. In particular, when keystone species are involved, this relative coupling between demographic stages can have significant implications for the functioning of ecosystems. We examined benthic and pelagic abundances of the sea urchin Paracentrotus lividus in order to: 1) understand the main life-history bottlenecks by observing the degree of coupling between demographic stages; and 2) explore the processes driving these linkages. P. lividus is the dominant invertebrate herbivore in the Mediterranean Sea, and has been repeatedly observed to overgraze shallow beds of the seagrass Posidonia oceanica and rocky macroalgal communities. We used a hierarchical sampling design at different spatial scales (100 s, 10 s and <1 km) and habitats (seagrass and rocky macroalgae) to describe the spatial patterns in the abundance of different demographic stages (larvae, settlers, recruits and adults). Our results indicate that large-scale factors (potentially currents, nutrients, temperature, etc.) determine larval availability and settlement in the pelagic stages of urchin life history. In rocky macroalgal habitats, benthic processes (like predation) acting at large or medium scales drive adult abundances. In contrast, adult numbers in seagrass meadows are most likely influenced by factors like local migration (from adjoining rocky habitats) functioning at much smaller scales. The complexity of spatial and habitat-dependent processes shaping urchin populations demands a multiplicity of approaches when addressing habitat conservation actions, yet such actions are currently mostly aimed at managing predation processes and fish numbers. We argue that a more holistic ecosystem management also needs to incorporate the landscape and habitat-quality level processes (eutrophication, fragmentation, etc.) that together regulate the populations of this keystone herbivore

Sex disparities in attitudes towards intimate partner violence against women in sub-Saharan Africa: a socio-ecological analysis

<p>Abstract</p> <p>Background</p> <p>Attitudes towards intimate partner violence against women (IPVAW) has been suggested as one of the prominent predictor of IPVAW. In this study, we take a step back from individual-level variables and examine relationship between societal-level measures and sex differences in attitudes towards IPVAW.</p> <p>Methods</p> <p>We used meta-analytic procedure to synthesize the results of most recent data sets available from Demographic and Health Survey (DHS) of 17 countries in sub-Saharan Africa conducted between 2003 and 2007. Pooled odds ratio (OR) and 95% confidence intervals (CI) were computed for all countries. Test of heterogeneity, sensitivity analysis, and meta-regression were also carried out.</p> <p>Results</p> <p>Women were twice as likely to justify wife beating than men (pooled OR = 1.97; 95% CI 1.53- 2.53) with statistically significant heterogeneity. The magnitude in sex disparities in attitudes towards IPVAW increased with increasing percentage of men practicing polygamy in each country. Furthermore, magnitude in sex disparities in attitudes towards IPVAW decreased monotonically with increasing adult male and female literacy rate, gender development index, gross domestic product and human development index.</p> <p>Conclusion</p> <p>This meta-analysis has provided evidence that women were more likely to justify IPVAW than men in sub-Saharan Africa. Our results revealed that country's socio-economic factors may be associated with sex differential in attitudes towards IPVAW.</p