In vitro selection of RNA aptamers against a composite small molecule-protein surface

A particularly challenging problem in chemical biology entails developing systems for modulating the activity of RNA using small molecules. One promising new approach towards this problem exploits the phenomenon of ‘surface borrowing,’ in which the small molecule is presented to the RNA in complex with a protein, thereby expanding the overall surface area available for interaction with RNA. To extend the utility of surface borrowing to include potential applications in synthetic biology, we set out to create an ‘orthogonal’ RNA-targeting system, one in which all components are foreign to the cell. Here we report the identification of small RNA modules selected in vitro to bind a surface-engineered protein, but only when the two macromolecules are bound to a synthetic bifunctional small molecule

“After a finding of Noncompliance, What?!”

Treaties have long been the cornerstones of international relations. They can be seen as one of the sole mechanisms to formalize agreements between sovereign states. In principle, these agreements are legally binding. In practice, the result is less certain. Issues ranging from the how the country views itself on the international stage to the specific treaty terms and enforcement mechanisms can all effect prospects for compliance. What is certain is the disruption and uncertainty that noncompliance causes. If not addressed, a treaty’s utility will eventually erode to the point where the agreement has no force. Other countries would also perceive little value in treaty ratification if compliance cannot be sufficiently verified. This report focuses on current issues of noncompliance with Russia, Syria, Iran, and North. Korea. Key themes arise across these cases and point to specific factors that impact treaty compliance. The report distills these key themes into general and case-specific recommendations for bringing a country back from noncompliance

Microbiome and infectivity studies reveal complex polyspecies tree disease in Acute Oak Decline

Decline-diseases are complex and becoming increasingly problematic to tree health globally. Acute Oak Decline (AOD) is characterized by necrotic stem lesions and galleries of the bark-boring beetle, Agrilus biguttatus, and represents a serious threat to oak. Although multiple novel bacterial species and Agrilus galleries are associated with AOD lesions, the causative agent(s) are unknown. The AOD pathosystem therefore provides an ideal model for a systems-based research approach to address our hypothesis that AOD lesions are caused by a polymicrobial complex. Here we show that three bacterial species, Brenneria goodwinii, Gibbsiella quercinecans and Rahnella victoriana, are consistently abundant in the lesion microbiome and possess virulence genes used by canonical phytopathogens that are expressed in AOD lesions. Individual and polyspecies inoculations on oak logs and trees demonstrated that B. goodwinii and G. quercinecans cause tissue necrosis and, in combination with A. biguttatus, produce the diagnostic symptoms of AOD. We have proved a polybacterial cause of AOD lesions, providing new insights into polymicrobial interactions and tree disease. This work presents a novel conceptual and methodological template for adapting Koch’s postulates to address the role of microbial communities in disease

Beyond the Hype: A Real-World Evaluation of the Impact and Cost of Machine Learning-Based Malware Detection

There is a lack of scientific testing of commercially available malware detectors, especially those that boast accurate classification of never-before-seen (i.e., zero-day) files using machine learning (ML). The result is that the efficacy and gaps among the available approaches are opaque, inhibiting end users from making informed network security decisions and researchers from targeting gaps in current detectors. In this paper, we present a scientific evaluation of four market-leading malware detection tools to assist an organization with two primary questions: (Q1) To what extent do ML-based tools accurately classify never-before-seen files without sacrificing detection ability on known files? (Q2) Is it worth purchasing a network-level malware detector to complement host-based detection? We tested each tool against 3,536 total files (2,554 or 72% malicious, 982 or 28% benign) including over 400 zero-day malware, and tested with a variety of file types and protocols for delivery. We present statistical results on detection time and accuracy, consider complementary analysis (using multiple tools together), and provide two novel applications of a recent cost-benefit evaluation procedure by Iannaconne & Bridges that incorporates all the above metrics into a single quantifiable cost. While the ML-based tools are more effective at detecting zero-day files and executables, the signature-based tool may still be an overall better option. Both network-based tools provide substantial (simulated) savings when paired with either host tool, yet both show poor detection rates on protocols other than HTTP or SMTP. Our results show that all four tools have near-perfect precision but alarmingly low recall, especially on file types other than executables and office files -- 37% of malware tested, including all polyglot files, were undetected.Comment: Includes Actionable Takeaways for SOC

Immunosenescence in wild animals:Meta-analysis and outlook

Immunosenescence, the decline in immune defense with age, is an important mortality source in elderly humans but little is known of immunosenescence in wild animals. We systematically reviewed and meta-analysed evidence for age-related changes in immunity in captive and free-living populations of wild species (321 effect sizes in 62 studies across 44 species of mammals, birds and reptiles). As in humans, senescence was more evident in adaptive (acquired) than innate immune functions. Declines were evident for cell function (antibody response), the relative abundance of naive immune cells and an in vivo measure of overall immune responsiveness (local response to phytohaemagglutinin injection). Inflammatory markers increased with age, similar to chronic inflammation associated with human immunosenescence. Comparisons across taxa and captive vs free-living animals were difficult due to lack of overlap in parameters and species measured. Most studies are cross-sectional, which yields biased estimates of age-effects when immune function co-varies with survival. We therefore suggest longitudinal sampling approaches, and highlight techniques from human cohort studies that can be incorporated into ecological research. We also identify avenues to address predictions from evolutionary theory and the contribution of immunosenescence to age-related increases in disease susceptibility and mortality

Pilot study of Lokomat versus manual-assisted treadmill training for locomotor recovery post-stroke

<p>Abstract</p> <p>Background</p> <p>While manually-assisted body-weight supported treadmill training (BWSTT) has revealed improved locomotor function in persons with post-stroke hemiparesis, outcomes are inconsistent and it is very labor intensive. Thus an alternate treatment approach is desirable. Objectives of this pilot study were to: 1) compare the efficacy of body-weight supported treadmill training (BWSTT) combined with the Lokomat robotic gait orthosis versus manually-assisted BWSTT for locomotor training post-stroke, and 2) assess effects of fast versus slow treadmill training speed.</p> <p>Methods</p> <p>Sixteen volunteers with chronic hemiparetic gait (0.62 ± 0.30 m/s) post-stroke were randomly allocated to Lokomat (n = 8) or manual-BWSTT (n = 8) 3×/wk for 4 weeks. Groups were also stratified by fast (mean 0.92 ± 0.15 m/s) or slow (0.58 ± 0.12 m/s) training speeds. The primary outcomes were self-selected overground walking speed and paretic step length ratio. Secondary outcomes included: fast overground walking speed, 6-minute walk test, and a battery of clinical measures.</p> <p>Results</p> <p>No significant differences in primary outcomes were revealed between Lokomat and manual groups as a result of training. However, within the Lokomat group, self-selected walk speed, paretic step length ratio, and four of the six secondary measures improved (<it>p </it>= 0.04–0.05, effect sizes = 0.19–0.60). Within the manual group, only balance scores improved (<it>p </it>= 0.02, effect size = 0.57). Group differences between fast and slow training groups were not revealed (<it>p </it>≥ 0.28).</p> <p>Conclusion</p> <p>Results suggest that Lokomat training may have advantages over manual-BWSTT following a modest intervention dose in chronic hemiparetic persons and further, that our training speeds produce similar gait improvements. Suggestions for a larger randomized controlled trial with optimal study parameters are provided.</p

Probabilistic Daily ILI Syndromic Surveillance with a Spatio-Temporal Bayesian Hierarchical Model

BACKGROUND: For daily syndromic surveillance to be effective, an efficient and sensible algorithm would be expected to detect aberrations in influenza illness, and alert public health workers prior to any impending epidemic. This detection or alert surely contains uncertainty, and thus should be evaluated with a proper probabilistic measure. However, traditional monitoring mechanisms simply provide a binary alert, failing to adequately address this uncertainty. METHODS AND FINDINGS: Based on the Bayesian posterior probability of influenza-like illness (ILI) visits, the intensity of outbreak can be directly assessed. The numbers of daily emergency room ILI visits at five community hospitals in Taipei City during 2006-2007 were collected and fitted with a Bayesian hierarchical model containing meteorological factors such as temperature and vapor pressure, spatial interaction with conditional autoregressive structure, weekend and holiday effects, seasonality factors, and previous ILI visits. The proposed algorithm recommends an alert for action if the posterior probability is larger than 70%. External data from January to February of 2008 were retained for validation. The decision rule detects successfully the peak in the validation period. When comparing the posterior probability evaluation with the modified Cusum method, results show that the proposed method is able to detect the signals 1-2 days prior to the rise of ILI visits. CONCLUSIONS: This Bayesian hierarchical model not only constitutes a dynamic surveillance system but also constructs a stochastic evaluation of the need to call for alert. The monitoring mechanism provides earlier detection as well as a complementary tool for current surveillance programs

Biodegradable Thermosensitive Hydrogel for SAHA and DDP Delivery: Therapeutic Effects on Oral Squamous Cell Carcinoma Xenografts

Background: OSCC is one of the most common malignancies and numerous clinical agents currently applied in combinative chemotherapy. Here we reported a novel therapeutic strategy, SAHA and DDP-loaded PECE (SAHA-DDP/PECE), can improve the therapeutic effects of intratumorally chemotherapy on OSCC cell xenografts. Objective/Purpose: The objective of this study was to evaluate the therapeutic efficacy of the SAHA-DDP/PECE in situ controlled drug delivery system on OSCC cell xenografts. Methods: A biodegradable and thermosensitive hydrogel was successfully developed to load SAHA and DDP. Tumorbeared mice were intratumorally administered with SAHA-DDP/PECE at 50 mg/kg (SAHA) +2 mg/kg (DDP) in 100 ul PECE hydrogel every two weeks, SAHA-DDP at 50 mg/kg(SAHA) +2 mg/kg(DDP) in NS, 2 mg/kg DDP solution, 50 mg/kg SAHA solution, equal volume of PECE hydrogel, or equal volume of NS on the same schedule, respectively. The antineoplastic actions of SAHA and DDP alone and in combination were evaluated using the determination of tumor volume, immunohistochemistry, western blot, and TUNEL analysis. Results: The hydrogel system was a free-flowing sol at 10uC, become gel at body temperature, and could sustain more than 14 days in situ. SAHA-DDP/PECE was subsequently injected into tumor OSCC tumor-beared mice. The results demonstrated that such a strategy as this allows the carrier system to show a sustained release of SAHA and DDP in vivo, and coul

Crop Updates - 2003 Pulses

This session covers fifty one papers from different authors 2002 PULSE INDUSTRY HIGHLIGHTS CONTRIBUTORS BACKGROUND 2002 REGIONAL ROUNDUP 1.Northern Agricultural Region, M. Harries, Department of Agriculture 2.Central agricultural Region, R. French and I. Pritchard, Department of Agriculture 3.Great Southern and Lakes, R. Beermier, N. Poulish and S. White, Department of Agriculture 4.Esperance Mallee, M. Seymour, Department of Agriculture PULSE PRODUCTION ECONOMY AND GENETIC IMPROVEMENT 5.Faba Bean, P. White, Department of Agriculture 6.Germplasm evaluation, P. White, T. Pope, M. Harries and M. Seymour, Department of Agriculture 7.Row spacing and sowing rate, M. Seymour, Department of Agriculture 8.Tolerance to post emergent herbicides, M. Seymour, M. Harries, R. Beermier, M. Blyth and L. Young, Department of Agriculture 9.Investigation of environmental staining and storage discolouration, N. Abbas1,2, J. Plummer1, P. White3, D. Harris4 and K. Siddique1,2, 1Plant Biology, The University of Western Australia, 2CLIMA, The University of Western Australia, 3Department of Agriculture, 4Chemistry Centre of Western Australia. Desi chickpea 10.Breeding highlights, T. Khan1,2 and K. Siddique2 1Department of Agriculture, 2CLIMA, The University of Western Australia 11. Variety evaluation, T. Khan and K. Regan, Department of Agriculture 12. Residual effect of chickpea row spacing and sowing rate on wheat yield, G. Riethmuller and B. MacLeod, Department of Agriculture 13. Genotype x environmental interaction studies to help explain adaptation, J. Berger1, N. Turner1,2, K. Siddique1, 1CLIMA, The University of Western Australia, 2CSIRO Plant Industry 14. Genetic characterisation of wild relatives, F. Shan and H. Clarke, CLIMA, The University of Western Australia 15. Tolerance to chilling at flowering, H. Clarke, CLIMA, The University of Western Australia 16. Kabuli chickpea, K. Regan, Department of Agriculture 17. Premium quality varieties for the Ord River Irrigation Area, K. Siddique1, K. Regan2 and P. Smith2 1CLIMA, The University of Western Australia, 2Department of Agriculture 18. Development of aschochyta resistant varieties for Australia, K. Siddique1, K. Regan2 and M. Baker2 1CLIMA, University of Western Australia, 2Department of Agriculture Field pea 19. Breeding highlights, T. Khan and B. French, Department of Agriculture 20. Variety evaluation, T. Khan, Department of Agriculture 21. Specialty types for the high rainfall regions, P. White and T. Khan, Department of Agriculture 22. Are new varieties more sensitive to delayed sowing than Dundale? R. French, M. Seymour and R. Beermier, Department of Agriculture 23. Does the size of sown seed affect seed size and yield at harvest? R. Beermier and N. Poulish, Department of Agriculture 24. Tolerance to post emergent herbicides, H. Dhammu, T. Piper and D. Nicholson, Department of Agriculture 25. Lentil, K. Regan, Department of Agriculture 26. Variety evaluation, K. Regan and M. Harries, Department of Agriculture 27. Interstate evaluation of advanced breeding lines, K. Regan1 and M. Materne2 1Department of Agriculture, 2Victorian Institute for Dryland Agriculture, Agriculture Victoria 28. Timing of harvest for the best seed yield, M. Harries and M. Blyth, Department of Agriculture 29. Tolerance to post emergent herbicides, M. Harries and D. Nicholson, Department of Agriculture, H. Dhammu, T. Piper and L. Young, Department of Agriculture 30. Row spacing and stubble, G. Riethmuller, Department of Agriculture Pulse species 31. High value pulses for the high rainfall areas, N. Poulish1, P. White1,2 and K. Siddique1,2 , 1Department of Agriculture, 2CLIMA, The University of Western Australia 32. Alternative Rhizobium inoculant carrier technologies, J. Howieson and R. Yates, Centre for Rhizobium Studies (CRS), Murdoch University 33. Time of harvest to improve seed yield and quality of pulses, G. Riethmuller and R. French, Department of Agriculture 34. Phosphorus and zinc responses in pulses, S. Loss1, Z. Rengel2, B. Bowden3, M. Bolland3 and K. Siddique4 , 1Wesfarmers CSBP, 2Soil Science and Plant Nutrition, The University of Western Australia, 3Department of Agriculture, 4CLIMA, The University of Western Australia 35. Robust protocols for doubled haploid production in field pea and chickpea, J. Croser and K. Siddique, CLIMA, The University of Western Australia DEMONSTRATION OF PULSES IN THE FARMING SYSTEM 36. Field pea and lentil on clayed sandplain, M. Seymour, Department of Agriculture 37. Field pea variety demonstration, M. Harries and M. Blyth, Department of Agriculture 38. The benefit of field peas compared to lupins, R. Beermier, Department of Agriculture DISEASE AND PEST MANAGEMENT 39. Ascochyta blight of chickpea, B. MacLeod, Department of Agriculture 40. Management of chickpeas with improved ascochyta resistance, B. Macleod, A. Harrod, M. Harries and M. Blyth, Department of Agriculture 41. Chlorothalonil provides the most effective control, B. Macleod, A. Harrod, M. Harries and M. Blyth, Department of Agriculture 42. Importance of early sprays and value of seed dressing (post emergence), B. Macleod and A. Harrod, Department of Agriculture 43. A windborne stage of ascochyta blight in WA, J. Galloway and B. MacLeod, Department of Agriculture Ascochyta disease of pulses 44. Geographic location effects ascochyta spore maturation on pulse stubble, J. Galloway and B. MacLeod, Department of Agriculture Blackspot of field pea 45. Rapid recurrent selection to improve resistance to black spot, C. Beeck1, J. Wroth1, W. Cowling1 and T. Khan2, 1Plant Science, The University of Western Australia, 2Department of Agriculture 46. Survival of blackspot on old field pea stubble, J. Galloway and B. MacLeod, Department of Agriculture 47. Blackspot spores mature earlier in the southern regions, M. Salam, J. Galloway, A. Diggle and B. MacLeod, Department of Agriculture Viruses in pulses 48. Early insecticide application suppresses spread of Beet Western Yellows virus in field pea, R. Jones, B. Coutts and L. Smith, Department of Agriculture, and CLIMA, The University of Western Australia Insect pests and nematodes 49. Incorporation of pea weevil resistance from Pisum fulvum into field pea, O. Byrne1 and D. Hardie2, 1CLIMA, The University of Western Australia 2Department of Agriculture 50. Resistance to Helicoverpa in wild species of chickpea, J. Ridsdill-Smith1, H. Sharma2 and K. Mann1, 1CSIRO Entomology, Western Australia, 2 ICRISAT, Hyderabad, India 51. Relative hosting ability of field pea genotypes to root lesion nematode, S. Kelly, S. Sharma, H. Hunter and V. Vanstone, Department of Agriculture ACKNOWLEDGEMENTS APPENDIX I: Publications by Pulse Productivity Project Staff 2002 APPENDIX II: Summary of previous results APPENDIX III: List of common acronym