The Need For Judicial Restriction on the Use Of Drug Detecting Canines

The purpose of this comment is to examine these issues, outline the conflicting positions, and attempt to forecast the direction the courts may take in their effort to bring some harmony to this unsettled (and to some, unsettling) area of law. Few people would attempt to deny law enforcement officials the use of this highly effective and relatively unintrusive law enforcement tool. Yet there are those who fear that the unsettled questions concerning limits on the use of this tool may lead to serious abuse, and who raise the specter of unlimited government intrusion should this type of investigatory activity fall through the constitutional cracks and therefore be deemed exempt from judicial control

Comparison of Algorithms and Parameterisations for Infiltration into Organic-Covered Permafrost Soils

Infiltration into frozen and unfrozen soils is critical in hydrology, controlling active layer soil water dynamics and influencing runoff. Few Land Surface Models (LSMs) and Hydrological Models (HMs) have been developed, adapted or tested for frozen conditions and permafrost soils. Considering the vast geographical area influenced by freeze/thaw processes and permafrost, and the rapid environmental change observed worldwide in these regions, a need exists to improve models to better represent their hydrology. In this study, various infiltration algorithms and parameterisation methods, which are commonly employed in current LSMs and HMs were tested against detailed measurements at three sites in Canada’s discontinuous permafrost region with organic soil depths ranging from 0.02 to 3 m. Field data from two consecutive years were used to calibrate and evaluate the infiltration algorithms and parameterisations. Important conclusions include: (1) the single most important factor that controls the infiltration at permafrost sites is ground thaw depth, (2) differences among the simulated infiltration by different algorithms and parameterisations were only found when the ground was frozen or during the initial fast thawing stages, but not after ground thaw reaches a critical depth of 15 to 30 cm, (3) despite similarities in simulated total infiltration after ground thaw reaches the critical depth, the choice of algorithm influenced the distribution of water among the soil layers, and (4) the ice impedance factor for hydraulic conductivity, which is commonly used in LSMs and HMs, may not be necessary once the water potential driven frozen soil parameterisation is employed. Results from this work provide guidelines that can be directly implemented in LSMs and HMs to improve their application in organic covered permafrost soils

Wake bursting: a computational and experimental investigation for application to high-lift multielement airfoil design

High-lift aerodynamic flowfields are complex, and the potentially-adverse wake development associated with these high-lift systems is not fully understood. Thus, an exhaustive investigation including both experimental and computational efforts is needed to gain an increased understanding of the flowfield. Previous work indicates the strong off-the-surface adverse pressure gradients created by flaps may cause the main-element wake to "separate" in an aerodynamic phenomena known as wake bursting. Previous experimental research efforts to study wake bursting over a multielement airfoil are lacking a detailed study of the burst wakes in a wide range of spatial coordinates. In addition, no thorough comparison between the experimentally-captured data and computational simulations of a high-lift multielement airfoil has been performed. A variety of different experimental and computational tools can be used to study the burst-wake flowfield. These experimental techniques include the standard aerodynamic-performance and flow-visualization techniques in addition to complex wake survey methods. These wake surveys can be executed with one of a variety of probes to capture unsteady or steady data such as pressures or velocities. Because all desired flowfield parameters cannot be captured by one probe, results from different probes must be carefully analyzed and compared to other data such that a full understanding of the flowfield can be gained. Computational methods to study the burst-wake flowfield must adequately solve both the inviscid and viscous regions of the flowfield. Computations can be performed with low-order coupled viscous/inviscid program in addition to more-robust Navier-Stokes solvers, such as Reynolds-averaged Navier Stokes (RANS) programs. It is necessary to carefully compare the experimental and computational results such that the flowfield can be understood in greater detail. These comparisons will also yield insight into the effects of experimental testing environments and the weaknesses of computational solvers. Results for a three-element airfoil, consisting of a main element and a double-slotted flap, were determined using various experimental methods. Experimental results included aerodynamic polars, flow visualization, and wake surveys with both split-film and 7-hole probes. The split-film probe yielded two-dimensional unsteady velocity measurements while the 7-hole probe was use to capture time-averaged velocity vector, static pressure, and total pressure. The burst-wake region consisted of increased turbulence intensities and extremely-high turbulence production when compared to the flow outside of the wake. An increase in wake thickness with increasing downstream distance was captured from each probe, and the relationship between the wake thickness and freestream conditions was established. Low Reynolds numbers and increased angle of attack yielded the thickest wakes of all tested freestream conditions. In addition, flaps with extremely small gap sizes also yielded increased wake bursting than the large-gap airfoils. In general, minimal differences in the burst-wake flowfield were observed for small- or large-overhang simulations, and the results are found in the experiment. Two-dimensional computational results were captured for low-order and higher-order methods including both a panel code and a RANS program. In general, the RANS solver indicated larger and thicker wakes than the wakes predicted by the panel code or captured in the wake surveys. This result of larger and thicker wakes was found to be independent of the selected turbulence model. Further investigation suggested a large vortex resulted from the junction between the airfoil and the wind tunnel wall at both ends of the airfoil. These vortices introduced non-constant spanwise lift distributions for the multielement airfoil. When the effect of the vortices was considered, computational results matched the experimental data better than without the vortices, but differences still remained. These differences are attributed to difficulties in turbulence model development for computational simulations as well as limitations of the experimental probes (mainly resulting from finite probe size). Numerous different airfoils were designed such that the presence of the burst wakes was mitigated when compared to a baseline airfoil at a given value of lift for specific freestream conditions. These three airfoils were designed using different geometry constraints and different freestream conditions. Wake bursting was reduced by moving the transition point far downstream and applying a very weak pressure gradient on the forward portion of the suction surface. Increased aft loading, increased thickness in the upstream part of the airfoil, and careful control of the boundary layer yielded increased aerodynamic performance, including reduced drag and increased lift-to-drag ratio, due in large part to decreased wake bursting

Steps to Develop Early Warning Systems and Future Scenarios of Storm Wave-Driven Flooding Along Coral Reef-Lined Coasts

ABSTRACT: Tropical coral reef-lined coasts are exposed to storm wave-driven flooding. In the future, flood events during storms are expected to occur more frequently and to be more severe due to sea-level rise, changes in wind and weather patterns, and the deterioration of coral reefs. Hence, disaster managers and coastal planners are in urgent need of decision-support tools. In the short-term, these tools can be applied in Early Warning Systems (EWS) that can help to prepare for and respond to impending storm-driven flood events. In the long-term, future scenarios of flooding events enable coastal communities and managers to plan and implement adequate risk-reduction strategies. Modeling tools that are used in currently available coastal flood EWS and future scenarios have been developed for open-coast sandy shorelines, which have only limited applicability for coral reef-lined shorelines. The tools need to be able to predict local sea levels, offshore waves, as well as their nearshore transformation over the reefs, and translate this information to onshore flood levels. In addition, future scenarios require long-term projections of coral reef growth, reef composition, and shoreline change. To address these challenges, we have formed the UFORiC (Understanding Flooding of Reef-lined Coasts) working group that outlines its perspectives on data and model requirements to develop EWS for storms and scenarios specific to coral reef-lined coastlines. It reviews the state-of-the-art methods that can currently be incorporated in such systems and provides an outlook on future improvements as new data sources and enhanced methods become available

Responsible Aquaculture in 2050: Valuing Local Conditions and Human Innovations Will Be Key to Success

As aquaculture production expands, we must avoid mistakes made during increasing intensification of agriculture. Understanding environmental impacts and measures to mitigate them is important for designing responsible aquaculture production systems. There are four realistic goals that can make future aquaculture operations more sustainable and productive: (I) improvement of management practices to create more efficient and diverse systems at every production level; (2) emphasis on local decisionmaking, human capacity development, and collective action to generate productive aquaculture systems that fit into societal constraints and demands; (3) development of risk management efforts for all systems that reduce disease problems, eliminate antibiotic and drug abuse, and prevent exotic organism introduction into local waters; and (4) creation of systems to better identify more sustainably grown aquaculture products in the market and promote them to individual consumers. By 2050, seafood will be predominantly sourced through aquaculture, including not only finfish and invertebrates but also seaweeds.Keywords: Human capacity development, Best management practices, Responsible aquaculture, Integrated multitrophic aquaculture, Recirculating aquaculture system

Between-Monitor Differences in Step Counts Are Related to Body Size: Implications for Objective Physical Activity Measurement

The quantification of the relationships between walking and health requires that walking is measured accurately. We correlated different measures of step accumulation to body size, overall physical activity level, and glucose regulation.Participants were 25 men and 25 women American Indians without diabetes (Age: 20-34 years) in Phoenix, Arizona, USA. We assessed steps/day during 7 days of free living, simultaneously with three different monitors (Accusplit-AX120, MTI-ActiGraph, and Dynastream-AMP). We assessed total physical activity during free-living with doubly labeled water combined with resting metabolic rate measured by expired gas indirect calorimetry. Glucose tolerance was determined during an oral glucose tolerance test.Based on observed counts in the laboratory, the AMP was the most accurate device, followed by the MTI and the AX120, respectively. The estimated energy cost of 1000 steps per day was lower in the AX120 than the MTI or AMP. The correlation between AX120-assessed steps/day and waist circumference was significantly higher than the correlation between AMP steps and waist circumference. The difference in steps per day between the AX120 and both the AMP and the MTI were significantly related to waist circumference.Between-monitor differences in step counts influence the observed relationship between walking and obesity-related traits

Detection of a MicroRNA Signal in an In Vivo Expression Set of mRNAs

Background. microRNAs (miRNAs) are approximately 21 nucleotide non-coding transcripts capable of regulating gene expression. The most widely studied mechanism of regulation involves binding of a miRNA to the target mRNA. As a result, translation of the target mRNA is inhibited and the mRNA may be destabilized. The inhibitory effects of miRNAs have been linked to diverse cellular processes including malignant proliferation, apoptosis, development, differentiation, and metabolic processes. We asked whether endogenous fluctuations in a set of mRNA and miRNA profiles contain correlated changes that are statistically distinguishable from the many other fluctuations in the data set. Methodology/Principal Findings. RNA was extracted from 12 human primary brain tumor biopsies. These samples were used to determine genome-wide mRN

CNS-PNETs with C19MC amplification and/or LIN28 expression comprise a distinct histogenetic diagnostic and therapeutic entity

Amplification of the C19MC oncogenic miRNA cluster and high LIN28 expression has been linked to a distinctly aggressive group of cerebral CNS-PNETs (group 1 CNS-PNETs) arising in young children. In this study, we sought to evaluate the diagnostic specificity of C19MC and LIN28, and the clinical and biological spectra of C19MC amplified and/or LIN28+ CNS-PNETs. We interrogated 450 pediatric brain tumors using FISH and IHC analyses and demonstrate that C19MC alteration is restricted to a sub-group of CNS-PNETs with high LIN28 expression; however, LIN28 immunopositivity was not exclusive to CNS-PNETs but was also detected in a proportion of other malignant pediatric brain tumors including rhabdoid brain tumors and malignant gliomas. C19MC amplified/LIN28+ group 1 CNS-PNETs arose predominantly in children <4 years old; a majority arose in the cerebrum but 24 % (13/54) of tumors had extra-cerebral origins. Notably, group 1 CNS-PNETs encompassed several histologic classes including embryonal tumor with abundant neuropil and true rosettes (ETANTR), medulloepithelioma, ependymoblastoma and CNS-PNETs with variable differentiation. Strikingly, gene expression and methylation profiling analyses revealed a common molecular signature enriched for primitive neural features, high LIN28/LIN28B and DNMT3B expression for all group 1 CNS-PNETs regardless of location or tumor histology. Our collective findings suggest that current known histologic categories of CNS-PNETs which include ETANTRs, medulloepitheliomas, ependymoblastomas in various CNS locations, comprise a common molecular and diagnostic entity and identify inhibitors of the LIN28/let7/PI3K/mTOR axis and DNMT3B as promising therapeutics for this distinct histogenetic entity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00401-014-1291-1) contains supplementary material, which is available to authorized users

Systems Biology by the Rules: Hybrid Intelligent Systems for Pathway Modeling and Discovery

Background: Expert knowledge in journal articles is an important source of data for reconstructing biological pathways and creating new hypotheses. An important need for medical research is to integrate this data with high throughput sources to build useful models that span several scales. Researchers traditionally use mental models of pathways to integrate information and development new hypotheses. Unfortunately, the amount of information is often overwhelming and these are inadequate for predicting the dynamic response of complex pathways. Hierarchical computational models that allow exploration of semi-quantitative dynamics are useful systems biology tools for theoreticians, experimentalists and clinicians and may provide a means for cross-communication. Results: A novel approach for biological pathway modeling based on hybrid intelligent systems or soft computing technologies is presented here. Intelligent hybrid systems, which refers to several related computing methods such as fuzzy logic, neural nets, genetic algorithms, and statistical analysis, has become ubiquitous in engineering applications for complex control system modeling and design. Biological pathways may be considered to be complex control systems, which medicine tries to manipulate to achieve desired results. Thus, hybrid intelligent systems may provide a useful tool for modeling biological system dynamics and computational exploration of new drug targets. A new modeling approach based on these methods is presented in the context of hedgehog regulation of the cell cycle in granule cells. Code and input files can be found at the Bionet website: www.chip.ord/~wbosl/Software/Bionet. Conclusion: This paper presents the algorithmic methods needed for modeling complicated biochemical dynamics using rule-based models to represent expert knowledge in the context of cell cycle regulation and tumor growth. A notable feature of this modeling approach is that it allows biologists to build complex models from their knowledge base without the need to translate that knowledge into mathematical form. Dynamics on several levels, from molecular pathways to tissue growth, are seamlessly integrated. A number of common network motifs are examined and used to build a model of hedgehog regulation of the cell cycle in cerebellar neurons, which is believed to play a key role in the etiology of medulloblastoma, a devastating childhood brain cancer

WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma

TP53 mutations confer subgroup specific poor survival for children with medulloblastoma. We hypothesized that WNT activation which is associated with improved survival for such children abrogates TP53 related radioresistance and can be used to sensitize TP53 mutant tumors for radiation. We examined the subgroup-specific role of TP53 mutations in a cohort of 314 patients treated with radiation. TP53 wild-type or mutant human medulloblastoma cell-lines and normal neural stem cells were used to test radioresistance of TP53 mutations and the radiosensitizing effect of WNT activation on tumors and the developing brain. Children with WNT/TP53 mutant medulloblastoma had higher 5-year survival than those with SHH/TP53 mutant tumours (100% and 36.6% +/- 8.7%, respectively (p < 0.001)). Introduction of TP53 mutation into medulloblastoma cells induced radioresistance (survival fractions at 2Gy (SF2) of 89% +/- 2% vs. 57.4% +/- 1.8% (p < 0.01)). In contrast, beta-catenin mutation sensitized TP53 mutant cells to radiation (p < 0.05). Lithium, an activator of the WNT pathway, sensitized TP53 mutant medulloblastoma to radiation (SF2 of 43.5% +/- 1.5% in lithium treated cells vs. 56.6 +/- 3% (p < 0.01)) accompanied by increased number of.H2AX foci. Normal neural stem cells were protected from lithium induced radiation damage (SF2 of 33% +/- 8% for lithium treated cells vs. 27% +/- 3% for untreated controls (p = 0.05). Poor survival of patients with TP53 mutant medulloblastoma may be related to radiation resistance. Since constitutive activation of the WNT pathway by lithium sensitizes TP53 mutant medulloblastoma cells and protect normal neural stem cells from radiation, this oral drug may represent an attractive novel therapy for high-risk medulloblastomas.B.R.A.I.N Child Canada; Cancer Research UK; Brain Tumour Charity; Hungarian Brain Research Program [KTIA_13_NAP-A-V/3]; Janos Bolyai Scholarship of the Hungarian Academy of Sciences [TAMOP-4.2.2. A-11/1/KONV-2012-0025]; German Cancer Aid/Dr. Mildred Scheel Foundation for Cancer Research; Cure Childhood Cancer Foundation; St. Baldrick's Foundation; Southeastern Brain Tumor Foundation; Action Medical Research; [CZ.1.05/2.1.00/03.0101]; [CZ.1.07/2.3.00/20.0183