The Enlightened Brain: Novel Imaging Methods Focus on Epileptic Networks at Multiple Scales

Epilepsy research is rapidly adopting novel fluorescence optical imaging methods to tackle unresolved questions on the cellular and circuit mechanisms of seizure generation and evolution. State of the art two-photon microscopy and wide-field fluorescence imaging can record the activity in epileptic networks at multiple scales, from neuronal microcircuits to brain-wide networks. These approaches exploit transgenic and viral technologies to target genetically encoded calcium and voltage sensitive indicators to subclasses of neurons, and achieve genetic specificity, spatial resolution and scalability that can complement electrophysiological recordings from awake animal models of epilepsy. Two-photon microscopy is well suited to study single neuron dynamics during interictal and ictal events, and highlight the differences between the activity of excitatory and inhibitory neuronal classes in the focus and propagation zone. In contrast, wide-field fluorescence imaging provides mesoscopic recordings from the entire cortical surface, necessary to investigate seizure propagation pathways, and how the unfolding of epileptic events depends on the topology of brain-wide functional connectivity. Answering these questions will inform pre-clinical studies attempting to suppress seizures with gene therapy, optogenetic or chemogenetic strategies. Dissecting which network nodes outside the seizure onset zone are important for seizure generation, propagation and termination can be used to optimize current and future evaluation methods to identify an optimal surgical strategy

Brazilian Bidens pilosa Linne´ yields fraction containing quercetin-derived flavonoid with free radical scavenger activity and hepatoprotective effects

Bidens pilosa is a plant used by Amazonian and Asian folks for some hepatopathies. The hydroethanol crude extract and three fractions were assessed for antioxidant and hepatoprotective effects. Higher levels of scavenger activity on the 1,1-diphenyl-2-picrylhydrazyl radical, inhibition of deoxyribose oxidation and lipid peroxidation in vitro were detected for the ethyl acetate fraction (IC50∼4.3-32.3 mg/ml) followed by the crude extract (IC50∼14.2-98.0 mg/ml). The ethyl acetate fraction, again followed by the crude extract, showed high contents of total soluble polyphenols (3.6±0.2 and 2.1±0.2 GAE/mg, respectively) and presence of a quercetin-derived flavonoid identified as quercetin 3,3′-dimethyl ether 7-Ο-β-D-glycopyranoside. Both products were assayed for hepatoprotector effects against CCl4-induced liver injury in mice. Markers of oxidative stress and hepatic injury were evaluated. The results showed that the 10-day pretreatments (15 mg/kg, p.o.) protected the livers against injury by blocking CCl4-induced lipid peroxidation and protein carbonylation and the DNA fragmentation was decreased (∼60%). The pretreatments avoided the loss of the plasma ferric reducing/antioxidant power and the elevation of serum transaminases and lactate dehydrogenase activities. The results suggest that the main constituents responsible for the hepatoprotective effects with free radical scavenger power associated are well extracted by performing fractionation with ethyl acetate. The findings support the Brazilian traditional use of this plant and justify further evaluations for the therapeutic efficacy and safety of the constituents of the ethyl acetate fraction to treat some liver diseases.Keywords: Bidens pilosa L.; hydroethanol maceration; ethyl acetate fractionation; free radical scavenger; hepatoprotection; CCl4 toxicit

A methodology to investigate heterogeneous oxidation of thermally aged cross-linked polyethylene by ToF-SIMS

Artificial ageing of polymeric insulation jackets is routinely performed in order to assess end-of-life material characteristics. Practical constraints including high temperatures/ short times ageing treatments lead to strong influence of diffusion-limited oxidation (DLO) resulting in unreliable life-time predictions. This study proposes a new experimental approach to the investigation of cable insulation ageing, exploiting analytical techniques capable of resolving chemistry at the length scale relevant for DLO (nano-microscale). When studying the potential effects of DLO using time of flight secondary ion mass spectrometry (ToF-SIMS) sample preparation becomes crucial. This paper presents the development of a methodology to generate suitable specimens to investigate the DLO effect using ToF-SIMS. A reference polymeric material has been thermally aged in various DLO conditions. Cross sections of aged samples were generated using three different methods. In order to assess the most suitable approach for this study, cross-section topography were scanned using a profilometer and the surface chemistry was investigated using ToF-SIMS together with multivariate analysis methods

Northeast Minnesota Flash Flood Disaster - Economic Development Impact Study

Duluth: ARDCARDC conducted a study to determine economic development impacts of the 2012 flood. ARDC collected information from all levels of government and held small group interviews to analyze gaps in data and identify lessons learned. Recommendations are paraphrased and summarized below. “A. Develop and Mobilize Micro Loans and Micro Grants for Disaster Response and Recovery. Micro loans and micro grants have been identified as a best practice for providing quick assistance to small businesses. The Northland Foundation’s Business Flood Recovery Fund has been cited as one of the most successful local response efforts following the 2012 floods. The program should be evaluated to learn how the region can keep the basic infrastructure of this program in place and how other groups can duplicate it or enhance it so that it can be remobilized even quicker in the aftermath of a future disaster. Micro loans should be explored as a source of assistance immediately following a disaster. Regional economic development funds, revolving loan funds and additional commercial lenders should examine their capacity and adopt disaster recovery lending programs that could be enacted immediately after future disasters. B. Maximize Planning and Zoning for Disaster Mitigation, Response, Recovery and Resiliency. 1. Land Use Planning: Decisions made before and after a disaster affect the resiliency and recovery of a community in the event of a disaster. Communities that integrate disaster resiliency into land use planning and development decisions can mitigate potential disaster impacts by: a. Integrating a hazard element into Comprehensive Plans, either as a stand-alone section or in discussion of other plan sections such as housing, infrastructure, and economic development. b. Assessing disaster vulnerability of sites in development plans. c. Encouraging development in less hazardous areas. d. Minimizing or mitigating vulnerable types of development in hazardous areas. e. Reducing disaster vulnerability through land use and zoning regulations. 2. Economic Development Planning. Recovery dictates long term success. The return of jobs, tourism, and capital investments are dependent on housing recovery, infrastructure restoration, environmental restoration, and social service provision. Communities should integrate disaster resiliency into economic development planning by: a. Assessing the unique needs and challenges for small businesses, large employers, economic diversification, and workforce/residents in the face of a disaster. b. Prioritizing economic development projects that are disaster resilient and fill a need in the post disaster community. c. Encouraging all physical projects to address disaster resiliency in the planning stage. 3. Infrastructure and Public Facilities: Restoration of infrastructure and public facilities is a prerequisite for recovery. Communities should prioritize long term infrastructure needs to take advantage of opportunity to upgrade, mitigate, or relocate infrastructure following a disaster. In the rush to rebuild, communities should be prepared to avoid repeating mistakes or missing opportunities to develop systems that will serve their residents and businesses better in the future. A disaster resiliency factor should be added to routine capital project planning. 4. Planning and Recovery Facilitation: To support community planning for and recovery from disasters, ARDC is available to work with communities on a project basis to: a. Offer a forum to convene diverse stakeholders and facilitate discussion and planning initiatives around the issues of economic resiliency and preparedness. b. Provide communities and businesses with regional demographic and economic data, hazard vulnerability and mitigation data, and disaster impact data. c. Establish familiarity with economic and community recovery funding sources and programs. d. Explore how ARDC’s revolving loan fund can be used to assist disaster impacted businesses. C. Improve information cataloging for long - term recovery and resiliency ARDC found that a lack of a one - stop portal for information on the evolving economic impact of the disaster is a challenge to long term planning and recovery efforts. A one - stop data repository may be best set up at the county and state levels. An up – to - date data repository can be useful for: • Developing and securing funding for recovery and resiliency programs and assessing the effectiveness of mitigation programs. (TIF districts, redevelopment programs, business continuity planning) • Establishing baseline to assess the long -term issues presented by future disasters in the region or elsewhere in the state. • Developing new local, regional, and state policies and programs. • Developing disaster profiles for use in community planning. • Developing tools and metrics for evaluating progress against set goals, objectives and milestones

Efficient assembly of very short oligonucleotides using T4 DNA Ligase

<p>Abstract</p> <p>Background</p> <p>In principle, a pre-constructed library of all possible short oligonucleotides could be used to construct many distinct gene sequences. In order to assess the feasibility of such an approach, we characterized T4 DNA Ligase activity on short oligonucleotide substrates and defined conditions suitable for assembly of a plurality of oligonucleotides.</p> <p>Findings</p> <p>Ligation by T4 DNA Ligase was found to be dependent on the formation of a double stranded DNA duplex of at least five base pairs surrounding the site of ligation. However, ligations could be performed effectively with overhangs smaller than five base pairs and oligonucleotides as small as octamers, in the presence of a second, complementary oligonucleotide. We demonstrate the feasibility of simultaneous oligonucleotide phosphorylation and ligation and, as a proof of principle for DNA synthesis through the assembly of short oligonucleotides, we performed a hierarchical ligation procedure whereby octamers were combined to construct a target 128-bp segment of the beta-actin gene.</p> <p>Conclusions</p> <p>Oligonucleotides as short as 8 nucleotides can be efficiently assembled using T4 DNA Ligase. Thus, the construction of synthetic genes, without the need for custom oligonucleotide synthesis, appears feasible.</p

an experience of urban transformation in multan pakistani punjab

This publication concerns studies, programmes and designs for the project Sustainable Social Economic and Environmental Revitalization in the historic core of Multan City in Pakistani Punjab developed by several Politecnico di Milano Departments and Fondazione Politecnico di Milano, an institution that cooperates with Politecnico di Milano in the research fields of architecture, engineering and industrial design. The activities are part of the Debt Swap Agreement signed in 2006 between the governments of Italy and Pakistan for development in the social sectors. Besides the extraordinarily valuable architecture of the Walled City of Multan and its dense and hard-working population, there is a physical and environmental condition that is extremely problematic and that may threaten the continuity of life in the historic part of a city, well known for being among the world's most ancient settlements. The social and cultural interest and the academic challenge of a new opportunity to deal with great traditions pushed the researchers to face the urgency and delicacy of a very complex theme. After the analysis, the surveys and the proposals, the Politecnico group completed the first operational phase reorganizing one of the main City Gate Place, building a new open pavilion and restoring a huge public building and the Gate. The last activity, planned and not yet implemented, refers to the Sarafa Bazaar Project, an integrated system for the urban arrangement through infrastructures systems as sewerage, public lighting and shading, new paving and conservation of historic building's facades

Evaluating people's perceptions of trust in a robot in a repeated interactions study

Funding Information: Acknowledgment. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 642667 (Safety Enables Cooperation in Uncertain Robotic Environments - SECURE). KD acknowledges funding from the Canada 150 Research Chairs Program. Publisher Copyright: © 2020, Springer Nature Switzerland AG This is a post-peer-review, pre-copyedit version of an article published of 'Rossi A., Dautenhahn K., Koay K.L., Walters M.L., Holthaus P. (2020) Evaluating People’s Perceptions of Trust in a Robot in a Repeated Interactions Study. In: Wagner A.R. et al. (eds) Social Robotics. ICSR 2020. Lecture Notes in Computer Science, vol 12483. Springer, Cham. https://doi.org/10.1007/978-3-030-62056-1_38'Trust has been established to be a key factor in fostering human-robot interactions. However, trust can change overtime according to different factors, including a breach of trust due to a robot’s error. In this exploratory study, we observed people’s interactions with a companion robot in a real house, adapted for human-robot interaction experimentation, over three weeks. The interactions happened in six scenarios in which a robot performed different tasks under two different conditions. Each condition included fourteen tasks performed by the robot, either correctly, or with errors with severe consequences on the first or last day of interaction. At the end of each experimental condition, participants were presented with an emergency scenario to evaluate their trust in the robot. We evaluated participants’ trust in the robot by observing their decision to trust the robot during the emergency scenario, and by collecting their views through questionnaires. We concluded that there is a correlation between the timing of an error with severe consequences performed by the robot and the corresponding loss of trust of the human in the robot. In particular, people’s trust is subjected to the initial mental formation

The management of bipolar mania: a national survey of baseline data from the EMBLEM study in Italy

<p>Abstract</p> <p>Background</p> <p>Although a number of studies have assessed the management of mania in routine clinical practice, no studies have so far evaluated the short- and long-term management and outcome of patients affected by bipolar mania in different European countries.</p> <p>The objective of the study is to present, in the context of a large multicenter survey (EMBLEM study), an overview of the baseline data on the acute management of a representative sample of manic bipolar patients treated in the Italian psychiatric hospital and community settings. EMBLEM is a 2-year observational longitudinal study that evaluates across 14 European countries the patterns of the drug prescribed in patients with bipolar mania, their socio-demographic and clinical features and the outcomes of the treatment.</p> <p>Methods</p> <p>The study consists of a 12-week acute phase and a ≤ 24-month maintenance phase. Bipolar patients were included into the study as in- or out-patients, if they initiated or changed, according to the decision of their psychiatrist, oral antipsychotics, anticonvulsants and/or lithium for the treatment of an episode of mania.</p> <p>Data concerning socio-demographic characteristics, psychiatric and medical history, severity of mania, prescribed medications, functional status and quality of life were collected at baseline and during the follow-up period.</p> <p>Results</p> <p>In Italy, 563 patients were recruited in 56 sites: 376 were outpatients and 187 inpatients. The mean age was 45.8 years. The mean CGI-BP was 4.4 (± 0.9) for overall score and mania, 1.9 (± 1.2) for depression and 2.6 (± 1.6) for hallucinations/delusions. The YMRS showed that 14.4% had a total score < 12, 25.1% ≥ 12 and < 20, and 60.5% ≥ 20. At entry, 75 patients (13.7%) were treatment-naïve, 186 (34.1%) were receiving a monotherapy (of which haloperidol [24.2%], valproate [16.7%] and lithium [14.5%] were the most frequently prescribed) while 285 (52.2%) a combined therapy (of which 8.0% were represented by haloperidol/lithium combinations). After a switch to an oral medication, 137 patients (24.8%) were prescribed a monotherapy while the rest (415, 75.2%) received a combination of drugs.</p> <p>Conclusion</p> <p>Data collected at baseline in the Italian cohort of the EMBLEM study represent a relevant source of information to start addressing the short and long-term therapeutic strategies for improving the clinical as well as the socio-economic outcomes of patients affected by bipolar mania. Although it's not an epidemiological investigation and has some limitations, the results show several interesting findings as a relatively late age of onset of bipolar disorder, a low rate of past suicide attempts, a low lifetime rate of alcohol abuse and drug addiction.</p

Organism-sediment interactions govern post-hypoxia recovery of ecosystem functioning

Hypoxia represents one of the major causes of biodiversity and ecosystem functioning loss for coastal waters. Since eutrophication-induced hypoxic events are becoming increasingly frequent and intense, understanding the response of ecosystems to hypoxia is of primary importance to understand and predict the stability of ecosystem functioning. Such ecological stability may greatly depend on the recovery patterns of communities and the return time of the system properties associated to these patterns. Here, we have examined how the reassembly of a benthic community contributed to the recovery of ecosystem functioning following experimentally-induced hypoxia in a tidal flat. We demonstrate that organism-sediment interactions that depend on organism size and relate to mobility traits and sediment reworking capacities are generally more important than recovering species richness to set the return time of the measured sediment processes and properties. Specifically, increasing macrofauna bioturbation potential during community reassembly significantly contributed to the recovery of sediment processes and properties such as denitrification, bedload sediment transport, primary production and deep pore water ammonium concentration. Such bioturbation potential was due to the replacement of the small-sized organisms that recolonised at early stages by large-sized bioturbating organisms, which had a disproportionately stronger influence on sediment. This study suggests that the complete recovery of organism-sediment interactions is a necessary condition for ecosystem functioning recovery, and that such process requires long periods after disturbance due to the slow growth of juveniles into adult stages involved in these interactions. Consequently, repeated episodes of disturbance at intervals smaller than the time needed for the system to fully recover organism-sediment interactions may greatly impair the resilience of ecosystem functioning.