Character Selection During Interactive Taxonomic Identification: “Best Characters”

Software interfaces for interactive multiple-entry taxonomic identification (polyclaves) sometimes provide a “best character” or “separation” coefficient, to guide the user to choose a character that could most effectively reduce the number of identification steps required. The coefficient could be particularly helpful when difficult or expensive tasks are needed for forensic identification, and in very large databases, uses that appear likely to increase in importance. Several current systems also provide tools to develop taxonomies or single-entry identification keys, with a variety of coefficients that are appropriate to that purpose. For the identification task, however, information theory neatly applies, and provides the most appropriate coefficient. To our knowledge, Delta-Intkey is the only currently available system that uses a coefficient related to information theory, and it is currently being reimplemented, which may allow for improvement. We describe two improvements to the algorithm used by Delta-Intkey. The first improves transparency as the number of remaining taxa decreases, by normalizing the range of the coefficient to [0,1]. The second concerns numeric ranges, which require consistent treatment of sub-intervals and their end-points. A stand-alone Bestchar program for categorical data is provided, in the Python and R languages. The source code is freely available and dedicated to the Public Domain

Biologically Inspired Feedback Design for Drosophila Flight

We use a biologically motivated model of the Drosophila's flight mechanics and sensor processing to design a feedback control scheme to regulate forward flight. The model used for insect flight is the grand unified fly (GUF) [3] simulation consisting of rigid body kinematics, aerodynamic forces and moments, sensory systems, and a 3D environment model. We seek to design a control algorithm that will convert the sensory signals into proper wing beat commands to regulate forward flight. Modulating the wing beat frequency and mean stroke angle produces changes in the flight envelope. The sensory signals consist of estimates of rotational velocity from the haltere organs and translational velocity estimates from visual elementary motion detectors (EMD's) and matched retinal velocity filters. The controller is designed based on a longitudinal model of the flight dynamics. Feedforward commands are generated based on a desired forward velocity. The dynamics are linearized around this operating point and a feedback controller designed to correct deviations from the operating point. The control algorithm is implemented in the GUF simulator and achieves the desired tracking of the forward reference velocities and exhibits biologically realistic responses

Inhibition of RNA polymerase II transcription in human cells by synthetic DNA-binding ligands

Sequence-specific DNA-binding small molecules that can permeate human cells potentially could regulate transcription of specific genes. Multiple cellular DNA-binding transcription factors are required by HIV type 1 for RNA synthesis. Two pyrrole-imidazole polyamides were designed to bind DNA sequences immediately adjacent to binding sites for the transcription factors Ets-l, lymphoid-enhancer binding factor 1, and TATA-box binding protein. These synthetic ligands specifically inhibit DNA-binding of each transcription factor and HIV type 1 transcription in cell-free assays. When used in combination, the polyamides inhibit virus replication by >99% in isolated human peripheral blood lymphocytes, with no detectable cell toxicity, The ability of small molecules to target predetermined DNA sequences located within RNA polymerase II promoters suggests a general approach for regulation of gene expression, as well as a mechanism for the inhibition of viral replication

Using Decision Analysis to Improve Malaria Control Policy Making

Malaria and other vector-borne diseases represent a significant and growing burden in many tropical countries. Successfully addressing these threats will require policies that expand access to and use of existing control methods, such as insecticide-treated bed nets (ITNs) and artemesinin combination therapies (ACTs) for malaria, while weighing the costs and benefits of alternative approaches over time. This paper argues that decision analysis provides a valuable framework for formulating such policies and combating the emergence and re-emergence of malaria and other diseases. We outline five challenges that policy makers and practitioners face in the struggle against malaria, and demonstrate how decision analysis can help to address and overcome these challenges. A prototype decision analysis framework for malaria control in Tanzania is presented, highlighting the key components that a decision support tool should include. Developing and applying such a framework can promote stronger and more effective linkages between research and policy, ultimately helping to reduce the burden of malaria and other vector-borne diseases

Fluctuating Motor Forces Bend Growing Microtubules

Despite their rigidity, microtubules in living cells bend significantly during polymerization resulting in greater curvature than can be explained by thermal forces alone. However, the source of the non-thermal forces that bend growing microtubules remains obscure. We analyzed the motion of microtubule tips in NIH-3T3 fibroblasts expressing EGFP-EB1, a fluorescent +TIP protein that specifically binds to the growing ends of microtubules. We found that dynein inhibition significantly reduced the deviation of the growing tip from its initial trajectory. Inhibiting myosin modestly reduced tip fluctuations, while simultaneous myosin and dynein inhibition caused no further decrease in fluctuations compared to dynein inhibition alone. Our results can be interpreted with a model in which dynein linkages play a key role in generating and transmitting fluctuating forces that bend growing microtubules.National Institutes of Health (U.S.) (NIH GM102486)National Science Foundation (U.S.) (NSF CMMI 0954302, NSF CMMI 0927945, and NSF CTS-0505929

Actomyosin Pulls to Advance the Nucleus in a Migrating Tissue Cell

AbstractThe cytoskeletal forces involved in translocating the nucleus in a migrating tissue cell remain unresolved. Previous studies have variously implicated actomyosin-generated pushing or pulling forces on the nucleus, as well as pulling by nucleus-bound microtubule motors. We found that the nucleus in an isolated migrating cell can move forward without any trailing-edge detachment. When a new lamellipodium was triggered with photoactivation of Rac1, the nucleus moved toward the new lamellipodium. This forward motion required both nuclear-cytoskeletal linkages and myosin activity. Apical or basal actomyosin bundles were found not to translate with the nucleus. Although microtubules dampen fluctuations in nuclear position, they are not required for forward translocation of the nucleus during cell migration. Trailing-edge detachment and pulling with a microneedle produced motion and deformation of the nucleus suggestive of a mechanical coupling between the nucleus and the trailing edge. Significantly, decoupling the nucleus from the cytoskeleton with KASH overexpression greatly decreased the frequency of trailing-edge detachment. Collectively, these results explain how the nucleus is moved in a crawling fibroblast and raise the possibility that forces could be transmitted from the front to the back of the cell through the nucleus

Vision as a compensatory mechanism for disturbance rejection in upwind flight

Recent experimental results demonstrate that flies possess a robust tendency to orient towards the frontally-centered focus of the visual motion field that typically occurs during upwind flight. We present a closed loop flight model, with a control algorithm based on feedback of the location of the visual focus of contraction, which is affected by changes in wind direction. The feasibility of visually guided upwind orientation is demonstrated with a model derived from current understanding of the biomechanics and sensorimotor computation of insects. The matched filter approach used to model the visual system computations compares extremely well with open-loop experimental data

Apples and pears? A comparison of two sources of national lung cancer audit data in England

In 2014, the method of data collection from NHS trusts in England for the National Lung Cancer Audit (NLCA) was changed from a bespoke dataset called LUCADA (Lung Cancer Data). Under the new contract, data are submitted via the Cancer Outcome and Service Dataset (COSD) system and linked additional cancer registry datasets. In 2014, trusts were given opportunity to submit LUCADA data as well as registry data. 132 NHS trusts submitted LUCADA data, and all 151 trusts submitted COSD data. This transitional year therefore provided the opportunity to compare both datasets for data completeness and reliability. We linked the two datasets at the patient level to assess the completeness of key patient and treatment variables. We also assessed the interdata agreement of these variables using Cohen’s kappa statistic, κ. We identified 26 001 patients in both datasets. Overall, the recording of sex, age, performance status and stage had more than 90% agreement between datasets, but there were more patients with missing performance status in the registry dataset. Although levels of agreement for surgery, chemotherapy and external-beam radiotherapy were high between datasets, the new COSD system identified more instances of active treatment. There seems to be a high agreement of data between the datasets, and the findings suggest that the registry dataset coupled with COSD provides a richer dataset than LUCADA. However, it lagged behind LUCADA in performance status recording, which needs to improve over time

Direct force probe reveals the mechanics of nuclear homeostasis in the mammalian cell

How cells maintain nuclear shape and position against various intracellular and extracellular forces is not well understood, although defects in nuclear mechanical homeostasis are associated with a variety of human diseases. We estimated the force required to displace and deform the nucleus in adherent living cells with a technique to locally pull the nuclear surface. A minimum pulling force of a few nanonewtons--far greater than typical intracellular motor forces--was required to significantly displace and deform the nucleus. Upon force removal, the original shape and position were restored quickly within a few seconds. This stiff, elastic response required the presence of vimentin, lamin A/C, and SUN (Sad1p, UNC-84)-domain protein linkages, but not F-actin or microtubules. Although F-actin and microtubules are known to exert mechanical forces on the nuclear surface through molecular motor activity, we conclude that the intermediate filament networks maintain nuclear mechanical homeostasis against localized forces

A general theorem on angular-momentum changes due to potential vorticity mixing and on potential-energy changes due to buoyancy mixing

An initial zonally symmetric quasigeostrophic potential-vorticity (PV) distribution q_i(y) is subjected to complete or partial mixing within some finite zone |y| < L, where y is latitude. The change in M, the total absolute angular momentum, between the initial and any later time is considered. For standard quasigeostrophic shallow-water beta-channel dynamics it is proved that, for any q_i(y) such that dq_i/dy > 0 throughout |y| < L, the change in M is always negative. This theorem holds even when "mixing" is understood in the most general possible sense. Arbitrary stirring or advective rearrangement is included, combined to an arbitrary extent with spatially inhomogeneous diffusion. The theorem holds whether or not the PV distribution is zonally symmetric at the later time. The same theorem governs Boussinesq potential-energy changes due to buoyancy mixing in the vertical. For the standard quasigeostrophic beta-channel dynamics to be valid the Rossby deformation length L_D >> \epsilon L where \epsilon is the Rossby number; when L_D = \infty the theorem applies not only to the beta-channel, but also to a single barotropic layer on the full sphere, as considered in the recent work of Dunkerton and Scott on "PV staircases". It follows that the M-conserving PV reconfigurations studied by those authors must involve processes describable as PV unmixing, or anti-diffusion, in the sense of time-reversed diffusion. Ordinary jet self-sharpening and jet-core acceleration do not, by contrast, require unmixing, as is shown here by detailed analysis. Mixing in the jet flanks suffices. The theorem extends to multiple layers and continuous stratification. A corollary is a new nonlinear stability theorem for shear flows.Comment: 14 pages, 4 figures; Final version, accepted by J. Atmos. Sci, in pres