Biological Systems from an Engineer’s Point of View

Mathematical modeling of the processes that pattern embryonic development (often called biological pattern formation) has a long and rich history [1,2]. These models proposed sets of hypothetical interactions, which, upon analysis, were shown to be capable of generating patterns reminiscent of those seen in the biological world, such as stripes, spots, or graded properties. Pattern formation models typically demonstrated the sufficiency of given classes of mechanisms to create patterns that mimicked a particular biological pattern or interaction. In the best cases, the models were able to make testable predictions [3], permitting them to be experimentally challenged, to be revised, and to stimulate yet more experimental tests (see review in [4]). In many other cases, however, the impact of the modeling efforts was mitigated by limitations in computer power and biochemical data. In addition, perhaps the most limiting factor was the mindset of many modelers, using Occam’s razor arguments to make the proposed models as simple as possible, which often generated intriguing patterns, but those patterns lacked the robustness exhibited by the biological system. In hindsight, one could argue that a greater attention to engineering principles would have focused attention on these shortcomings, including potential failure modes, and would have led to more complex, but more robust, models. Thus, despite a few successful cases in which modeling and experimentation worked in concert, modeling fell out of vogue as a means to motivate decisive test experiments. The recent explosion of molecular genetic, genomic, and proteomic data—as well as of quantitative imaging studies of biological tissues—has changed matters dramatically, replacing a previous dearth of molecular details with a wealth of data that are difficult to fully comprehend. This flood of new data has been accompanied by a new influx of physical scientists into biology, including engineers, physicists, and applied mathematicians [5–7]. These individuals bring with them the mindset, methodologies, and mathematical toolboxes common to their own fields, which are proving to be appropriate for analysis of biological systems. However, due to inherent complexity, biological systems seem to be like nothing previously encountered in the physical sciences. Thus, biological systems offer cutting edge problems for most scientific and engineering-related disciplines. It is therefore no wonder that there might seem to be a “bandwagon” of new biology-related research programs in departments that have traditionally focused on nonliving systems. Modeling biological interactions as dynamical systems (i.e., systems of variables changing in time) allows investigation of systems-level topics such as the robustness of patterning mechanisms, the role of feedback, and the self-regulation of size. The use of tools from engineering and applied mathematics, such as sensitivity analysis and control theory, is becoming more commonplace in biology. In addition to giving biologists some new terminology for describing their systems, such analyses are extremely useful in pointing to missing data and in testing the validity of a proposed mechanism. A paper in this issue of PLoS Biology clearly and honestly applies analytical tools to the authors’ research and obtains insights that would have been difficult if not impossible by other means [8]

Observations of Outflowing UV Absorbers in NGC 4051 with the Cosmic Origins Spectrograph

We present new Hubble Space Telescope (HST)/Cosmic Origins Spectrograph observations of the Narrow-Line Seyfert 1 galaxy NGC 4051. These data were obtained as part of a coordinated observing program including X-ray observations with the Chandra/High Energy Transmission Grating (HETG) Spectrometer and Suzaku. We detected nine kinematic components of UV absorption, which were previously identified using the HST/Space Telescope Imaging Spectrograph. None of the absorption components showed evidence for changes in column density or profile within the \sim 10 yr between the STIS and COS observations, which we interpret as evidence of 1) saturation, for the stronger components, or 2) very low densities, i.e., n_H < 1 cm^-3, for the weaker components. After applying a +200 km s^-1 offset to the HETG spectrum, we found that the radial velocities of the UV absorbers lay within the O VII profile. Based on photoionization models, we suggest that, while UV components 2, 5 and 7 produce significant O VII absorption, the bulk of the X-ray absorption detected in the HETG analysis occurs in more highly ionized gas. Moreover, the mass loss rate is dominated by high ionization gas which lacks a significant UV footprint.Comment: 41 pages, 10 Figures; accepted for publication in the Astrophysical Journa

Cost-effectiveness of community versus hospital eye service follow-up for patients with quiescent treated age-related macular degeneration alongside the ECHoES randomised trial

Objectives To assess the cost-effectiveness of optometrist-led follow-up monitoring reviews for patients with quiescent neovascular age-related macular degeneration (nAMD) in community settings (including high street opticians) compared with ophthalmologist-led reviews in hospitals. Design A model based cost-effectiveness analysis with a 4-week time horizon, based on a ‘virtual’ non-inferiority randomised trial designed to emulate a parallel group design. Setting A virtual internet-based clinical assessment, conducted at community optometry practices, and hospital ophthalmology clinics. Participants Ophthalmologists with experience in the age-related macular degeneration service; fully qualified optometrists not participating in nAMD shared care schemes. Interventions The participating optometrists and ophthalmologists classified lesions from vignettes and were asked to judge whether any retreatment was required. Vignettes comprised clinical information, colour fundus photographs and optical coherence tomography images. Participants’ classifications were validated against experts’ classifications (reference standard). Resource use and cost information were attributed to these retreatment decisions. Main Outcome Measures Correct classification of whether further treatment is needed, compared with a reference standard. Results The mean cost per assessment, including the subsequent care pathway, was £411 for optometrists and £397 for ophthalmologists: a cost difference of £13 (95% CI: -£18, £45). Optometrists were non-inferior to ophthalmologists with respect to the overall percentage of lesions correctly assessed (difference: -1.0%; 95% CI: -4.5%, 2.5%). Conclusions In the base case analysis, the slightly larger number of incorrect retreatment decisions by optometrists led to marginally and non-significantly higher costs. Sensitivity analyses that reflected different practices across eye hospitals indicate that shared care pathways between optometrists and ophthalmologists can be identified which may reduce demands on scant hospital resources, although in light of the uncertainty around differences in outcome and cost it remains unclear whether the differences between the two care pathways are significant in economic terms. </p

Formal total syntheses of classic natural product target molecules via palladium-catalyzed enantioselective alkylation

Pd-catalyzed enantioselective alkylation in conjunction with further synthetic elaboration enables the formal total syntheses of a number of “classic” natural product target molecules. This publication highlights recent methods for setting quaternary and tetrasubstituted tertiary carbon stereocenters to address the synthetic hurdles encountered over many decades across multiple compound classes spanning carbohydrate derivatives, terpenes, and alkaloids. These enantioselective methods will impact both academic and industrial settings, where the synthesis of stereogenic quaternary carbons is a continuing challenge

An experimental study of the near wake of a two-dimensional hypersonic blunt body with mass addition

An experimental investigation of the steady, laminar near-wake flow field of a two-dimensional, adiabatic, circular cylinder with surface mass transfer has been made at a free-stream Mach number of 6.0. The pressure and mass-concentration fields associated with the transfer of argon, nitrogen or helium into the near wake were studied for mass transfer from the forward stagnation region, and from the base. For sufficiently low mass transfer rates from the base, for which a recirculating zone exists, the entire near-wake flow field correlates with the momentum flux, not the mass flux, of the injectant, and the mass-concentration field is determined by counter-current diffusion into the reversed flow. For mass addition from the forward stagnation region, the pressure field is undisturbed and the mass-concentration field is nearly uniform in the region of reversed flow. The axial decay of argon mass concentration in the intermediate wake, downstream of the neck, is explained with the aid of an integral solution in the incompressible plane, from which the location of the virtual origin for the asymptotic far-wake solution has been derived as one result

First Steps towards Underdominant Genetic Transformation of Insect Populations

The idea of introducing genetic modifications into wild populations of insects to stop them from spreading diseases is more than 40 years old. Synthetic disease refractory genes have been successfully generated for mosquito vectors of dengue fever and human malaria. Equally important is the development of population transformation systems to drive and maintain disease refractory genes at high frequency in populations. We demonstrate an underdominant population transformation system in Drosophila melanogaster that has the property of being both spatially self-limiting and reversible to the original genetic state. Both population transformation and its reversal can be largely achieved within as few as 5 generations. The described genetic construct {Ud} is composed of two genes; (1) a UAS-RpL14.dsRNA targeting RNAi to a haploinsufficient gene RpL14 and (2) an RNAi insensitive RpL14 rescue. In this proof-of-principle system the UAS-RpL14.dsRNA knock-down gene is placed under the control of an Actin5c-GAL4 driver located on a different chromosome to the {Ud} insert. This configuration would not be effective in wild populations without incorporating the Actin5c-GAL4 driver as part of the {Ud} construct (or replacing the UAS promoter with an appropriate direct promoter). It is however anticipated that the approach that underlies this underdominant system could potentially be applied to a number of species. Figure

Improving access to emergent spinal care through knowledge translation : an ethnographic study

Background: For patients and family members, access to timely specialty medical care for emergent spinal conditions is a significant stressor to an already serious condition. Timing to surgical care for emergent spinal conditions such as spinal trauma is an important predictor of outcome. However, few studies have explored ethnographically the views of surgeons and other key stakeholders on issues related to patient access and care for emergent spine conditions. The primary study objective was to determine the challenges to the provision of timely care as well as to identify areas of opportunities to enhance care delivery. Methods: An ethnographic study of key administrative and clinical care providers involved in the triage and care of patients referred through CritiCall Ontario was undertaken utilizing standard methods of qualitative inquiry. This comprised 21 interviews with people involved in varying capacities with the provision of emergent spinal care, as well as qualitative observations on an orthopaedic/neurosurgical ward, in operating theatres, and at CritiCall Ontario’s call centre. Results: Several themes were identified and organized into categories that range from inter-professional collaboration through to issues of hospital-level resources and the role of relationships between hospitals and external organizations at the provincial level. Underlying many of these issues is the nature of the medically complex emergent spine patient and the scientific evidentiary base upon which best practice care is delivered. Through the implementation of knowledge translation strategies facilitated from this research, a reduction of patient transfers out of province was observed in the one-year period following program implementation. Conclusions: Our findings suggest that competing priorities at both the hospital and provincial level create challenges in the delivery of spinal care. Key stakeholders recognized spinal care as aligning with multiple priorities such as emergent/critical care, medical through surgical, acute through rehabilitative, disease-based (i.e. trauma, cancer), and wait times initiatives. However, despite newly implemented strategies, there continues to be increasing trends over time in the number of spinal CritiCall Ontario referrals. This reinforces the need for ongoing inter-professional efforts in care delivery that take into account the institutional contexts that may constrain individual or team efforts

Measurements of neutrino oscillation in appearance and disappearance channels by the T2K experiment with 6.6 x 10(20) protons on target

111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee comments111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee comments111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee commentsWe thank the J-PARC staff for superb accelerator performance and the CERN NA61/SHINE Collaboration for providing valuable particle production data. We acknowledge the support of MEXT, Japan; NSERC, NRC, and CFI, Canada; CEA and CNRS/IN2P3, France; DFG, Germany; INFN, Italy; National Science Centre (NCN), Poland; RSF, RFBR and MES, Russia; MINECO and ERDF funds, Spain; SNSF and SER, Switzerland; STFC, UK; and the U. S. Deparment of Energy, USA. We also thank CERN for the UA1/NOMAD magnet, DESY for the HERA-B magnet mover system, NII for SINET4, the WestGrid and SciNet consortia in Compute Canada, GridPP, UK, and the Emerald High Performance Computing facility in the Centre for Innovation, UK. In addition, participation of individual researchers and institutions has been further supported by funds from ERC (FP7), EU; JSPS, Japan; Royal Society, UK; and DOE Early Career program, USA

Online interprofessional education facilitation : a scoping review

<p><b>Introduction:</b> The use of online media to deliver interprofessional education (IPE) is becoming more prevalent across health professions education settings. Facilitation of IPE activities is known to be critical to the effective delivery of IPE, however, specifics about the nature of online IPE facilitation remains unclear.</p> <p><b>Aim:</b> To explore the health professions education literature to understand the extent, range and nature of research on online IPE facilitation.</p> <p><b>Methods:</b> Scoping review methodology was used to guide a search of four electronic databases for relevant papers. Of the 2095 abstracts initially identified, after screening of both abstracts and full-text papers, 10 studies were selected for inclusion in this review. Following abstraction of key information from each study, a thematic analysis was undertaken.</p> <p><b>Results:</b> Three key themes emerged to describe the nature of the IPE facilitation literature: (1) types of online IPE facilitation contributions, (2) the experience of online IPE facilitation and (3) personal outcomes of online IPE facilitation. These IPE facilitation themes were particularly focused on facilitation of interprofessional student teams on an asynchronous basis.</p> <p><b>Discussion:</b> While the included studies provide some insight into the nature of online IPE facilitation, future research is needed to better understand facilitator contributions, and the facilitation experience and associated outcomes, both relating to synchronous and asynchronous online environments.</p

Measurement of the electron neutrino charged-current interaction rate on water with the T2K ND280 pi(0) detector

10 pages, 6 figures, Submitted to PRDhttp://journals.aps.org/prd/abstract/10.1103/PhysRevD.91.112010© 2015 American Physical Society11 pages, 6 figures, as accepted to PRD11 pages, 6 figures, as accepted to PRD11 pages, 6 figures, as accepted to PR