scholarly journals Anomalous Laterally Stressed Kinetically Trapped DNA Surface Conformations

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Valery V. Prokhorov ◽  
Nikolay A. Barinov ◽  
Kirill A. Prusakov ◽  
Evgeniy V. Dubrovin ◽  
Maxim D. Frank-Kamenetskii ◽  
...  
Keyword(s):  
Electrostatic Interaction ◽  
Mechanical Response ◽  
Persistence Length ◽  
Strong Impact ◽  
List Type ◽  
Surface Charges ◽  
Monomolecular Films ◽  
Chain Approximation ◽  
The Impact ◽  
Positively Charged

Highlights DNA kinking is inevitable for the highly anisotropic 1D–1D electrostatic interaction with the one-dimensionally periodically charged surface. The double helical structure of the DNA kinetically trapped on positively charged monomolecular films comprising the lamellar templates is strongly laterally stressed and extremely perturbed at the nanometer scale. The DNA kinetic trapping is not a smooth 3D—> 2D conformational flattening but is a complex nonlinear in-plane mechanical response (bending, tensile and unzipping) driven by the physics beyond the scope of the applicability of the linear worm-like chain approximation. Abstract Up to now, the DNA molecule adsorbed on a surface was believed to always preserve its native structure. This belief implies a negligible contribution of lateral surface forces during and after DNA adsorption although their impact has never been elucidated. High-resolution atomic force microscopy was used to observe that stiff DNA molecules kinetically trapped on monomolecular films comprising one-dimensional periodically charged lamellar templates as a single layer or as a sublayer are oversaturated by sharp discontinuous kinks and can also be locally melted and supercoiled. We argue that kink/anti-kink pairs are induced by an overcritical lateral bending stress (> 30 pNnm) inevitable for the highly anisotropic 1D-1D electrostatic interaction of DNA and underlying rows of positive surface charges. In addition, the unexpected kink-inducing mechanical instability in the shape of the template-directed DNA confined between the positively charged lamellar sides is observed indicating the strong impact of helicity. The previously reported anomalously low values of the persistence length of the surface-adsorbed DNA are explained by the impact of the surface-induced low-scale bending. The sites of the local melting and supercoiling are convincingly introduced as other lateral stress-induced structural DNA anomalies by establishing a link with DNA high-force mechanics. The results open up the study in the completely unexplored area of the principally anomalous kinetically trapped DNA surface conformations in which the DNA local mechanical response to the surface-induced spatially modulated lateral electrostatic stress is essentially nonlinear. The underlying rich and complex in-plane nonlinear physics acts at the nanoscale beyond the scope of applicability of the worm-like chain approximation.

When Do Psychopathic Traits Affect Cooperative Behavior?: An Iterated Prisoner's Dilemma Experimental Study

2020 ◽  
Author(s):  
M Testori ◽  
M Kempf ◽  
RB Hoyle ◽  
Hedwig Eisenbarth
Keyword(s):  
Prisoner's Dilemma ◽  
Cooperative Behavior ◽  
Prisoner’S Dilemma ◽  
Selection Procedure ◽  
Psychopathic Traits ◽  
Strong Impact ◽  
Iterated Prisoner's Dilemma ◽  
Human Decision ◽  
The Impact ◽  
Iterated Prisoner’S Dilemma

© 2019 Hogrefe Publishing. Personality traits have been long recognized to have a strong impact on human decision-making. In this study, a sample of 314 participants took part in an online game to investigate the impact of psychopathic traits on cooperative behavior in an iterated Prisoner's dilemma game. We found that disinhibition decreased the maintenance of cooperation in successive plays, but had no effect on moving toward cooperation after a previous defection or on the overall level of cooperation over rounds. Furthermore, our results underline the crucial importance of a good model selection procedure, showing how a poor choice of statistical model can provide misleading results.

The Impact of Economic Crisis on Tourism Industry: A Bangladesh Perspective

2016 ◽  
Vol 2 (1) ◽  
Author(s):  
Md. Ziaul Haque
Keyword(s):  
Economic Crisis ◽  
Tourism Industry ◽  
Political Crisis ◽  
Strong Impact ◽  
Negative Consequences ◽  
Policy Makers ◽  
Tourism Product ◽  
International Tourist ◽  
Sustained Recovery ◽  
The Impact

The tourism sector is experiencing numerous challenges as a result of the global economic crisis. After a significant contraction in 2009, tourism rebounded strongly  in  2010  and  in  2011  the  international  tourist  arrivals  and  receipts  are projected to increase substantially. The Tourism industry is expected to show a sustained recovery in 2012. The crisis has particularly strong impact and slightly negative consequences in Bangladesh. The country is undergoing a political crisis, as well, and it seems that the forthcoming elections may be the only solution for the restoration of stability and social peace.  In addition, tourism can be the driving force behind Bangladesh economic recovery. However, for its achievement the country’s policy makers should take several measures towards restructuring and improving the sector. These measures include: enhancement of alternative forms of tourism; environmental protection; creation of quality infrastructure; and boost of competitiveness through a tourism product that offers value for money

The Impact Of Economic Crisis On Tourism Industry: A Bangladesh Perspective

2015 ◽  
Vol 1 (1) ◽  
pp. 15
Author(s):  
Md. Ziaul Haque
Keyword(s):  
Economic Crisis ◽  
Tourism Industry ◽  
Political Crisis ◽  
Strong Impact ◽  
Negative Consequences ◽  
Policy Makers ◽  
Tourism Product ◽  
International Tourist ◽  
Sustained Recovery ◽  
The Impact

The tourism sector is experiencing numerous challenges as a result of the global economic crisis. After a significant contraction in 2009, tourism rebounded strongly  in  2010  and  in  2011  the  international  tourist  arrivals  and  receipts  are projected to increase substantially. The Tourism industry is expected to show a sustained recovery in 2012. The crisis has particularly strong impact and slightly negative consequences in Bangladesh. The country is undergoing a political crisis, as well, and it seems that the forthcoming elections may be the only solution for the restoration of stability and social peace.  In addition, tourism can be the driving force behind Bangladesh economic recovery. However, for its achievement the country’s policy makers should take several measures towards restructuring and improving the sector. These measures include: enhancement of alternative forms of tourism; environmental protection; creation of quality infrastructure; and boost of competitiveness through a tourism product that offers value for money

Studies on Related ms Magnitude Rate Models in Triangular Wave Unloading Section of Calcium Medium-Fine Sandstone

2010 ◽  
Vol 152-153 ◽  
pp. 164-170
Author(s):  
Jie Liu ◽  
Jian Lin Li ◽  
Ying Xia Li ◽  
Shan Shan Yang ◽  
Ji Fang Zhou ◽  
...  
Keyword(s):  
Mechanical Response ◽  
Strain Curve ◽  
Experimental System ◽  
Constant Term ◽  
Lag Time ◽  
Vertical Force ◽  
Time Segment ◽  
Triangular Wave ◽  
Apparent Modulus ◽  
The Impact

Specific to the improvement in the present research of mechanical response under cyclic loading, this paper, taking the calcareous middle- coarse sandstone as the research subject and the RMT-150C experimental system in which data is recoded by ms magnitude as the platform, develops several related models concerning the unloading rate of triangle waves. The unloading process is divided into lag time segment and non-lag time segment, with criterions and related parameters provided as well. The term apparent elastic modulus is defined. The test data analysis shows that there exist a linear relationship between the apparent modulus and instant vertical force before load damage in non-lag time segment. On the preceding basis, a rate-dependent model of triangular wave un-installation section in non-lag time segment is established. Due to the inability of the loading equipment to accurately input the triangle wave, the average loading rate is amended and a constant term is added into it. The model is proved to be reliable, as the predicted value of the deformation rate and the stress strain curve coincides with measured value. At the same time, the impact of the lag time is pointed out quantitatively and a predication model of lag time segment is set up.

scholarly journals Surface charge modulation of rifampicin-loaded PLA nanoparticles to improve antibiotic delivery in Staphylococcus aureus biofilms

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
David Da Costa ◽  
Chloé Exbrayat-Héritier ◽  
Basile Rambaud ◽  
Simon Megy ◽  
Raphaël Terreux ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Surface Charge ◽  
Treatment Efficacy ◽  
Particle Migration ◽  
Bacterial Biofilm ◽  
Poly Lactic Acid ◽  
Retention Capacity ◽  
The Impact ◽  
Positively Charged ◽  
Antibiotic Delivery

Abstract Background After the golden age of antibiotic discovery, bacterial infections still represent a major challenge for public health worldwide. The biofilm mode of growth is mostly responsible for chronic infections that current therapeutics fail to cure and it is well-established that novel strategies must be investigated. Particulate drug delivery systems are considered as a promising strategy to face issues related to antibiotic treatments in a biofilm context. Particularly, poly-lactic acid (PLA) nanoparticles present a great interest due to their ability to migrate into biofilms thanks to their submicronic size. However, questions still remain unresolved about their mode of action in biofilms depending on their surface properties. In the current study, we have investigated the impact of their surface charge, firstly on their behavior within a bacterial biofilm, and secondly on the antibiotic delivery and the treatment efficacy. Results Rifampicin-loaded PLA nanoparticles were synthetized by nanoprecipitation and characterized. A high and superficial loading of rifampicin, confirmed by an in silico simulation, enabled to deliver effective antibiotic doses with a two-phase release, appropriate for biofilm-associated treatments. These nanoparticles were functionalized with poly-l-lysine, a cationic peptide, by surface coating inducing charge reversal without altering the other physicochemical properties of these particles. Positively charged nanoparticles were able to interact stronger than negative ones with Staphylococcus aureus, under planktonic and biofilm modes of growth, leading to a slowed particle migration in the biofilm thickness and to an improved retention of these cationic particles in biofilms. While rifampicin was totally ineffective in biofilms after washing, the increased retention capacity of poly-l-lysine-coated rifampicin-loaded PLA nanoparticles has been associated with a better antibiotic efficacy than uncoated negatively charged ones. Conclusions Correlating the carrier retention capacity in biofilms with the treatment efficacy, positively charged rifampicin-loaded PLA nanoparticles are therefore proposed as an adapted and promising approach to improve antibiotic delivery in S. aureus biofilms.

scholarly journals Using Satellite Data for CBRN (Chemical, Biological, Radiological, and Nuclear) Threat Detection, Monitoring, and Modelling

2021 ◽  
Author(s):  
Gary Sutlieff ◽  
Lucy Berthoud ◽  
Mark Stinchcombe
Keyword(s):  
Satellite Data ◽  
Meteorological Data ◽  
Atmospheric Composition ◽  
Chemical Detection ◽  
List Type ◽  
Data Types ◽  
Wide Range ◽  
Future Technologies ◽  
The Impact ◽  
Near Future

Abstract CBRN (Chemical, Biological, Radiological, and Nuclear) threats are becoming more prevalent, as more entities gain access to modern weapons and industrial technologies and chemicals. This has produced a need for improvements to modelling, detection, and monitoring of these events. While there are currently no dedicated satellites for CBRN purposes, there are a wide range of possibilities for satellite data to contribute to this field, from atmospheric composition and chemical detection to cloud cover, land mapping, and surface property measurements. This study looks at currently available satellite data, including meteorological data such as wind and cloud profiles, surface properties like temperature and humidity, chemical detection, and sounding. Results of this survey revealed several gaps in the available data, particularly concerning biological and radiological detection. The results also suggest that publicly available satellite data largely does not meet the requirements of spatial resolution, coverage, and latency that CBRN detection requires, outside of providing terrain use and building height data for constructing models. Lastly, the study evaluates upcoming instruments, platforms, and satellite technologies to gauge the impact these developments will have in the near future. Improvements in spatial and temporal resolution as well as latency are already becoming possible, and new instruments will fill in the gaps in detection by imaging a wider range of chemicals and other agents and by collecting new data types. This study shows that with developments coming within the next decade, satellites should begin to provide valuable augmentations to CBRN event detection and monitoring. Article Highlights There is a wide range of existing satellite data in fields that are of interest to CBRN detection and monitoring. The data is mostly of insufficient quality (resolution or latency) for the demanding requirements of CBRN modelling for incident control. Future technologies and platforms will improve resolution and latency, making satellite data more viable in the CBRN management field

Cost of Dementia and Its Correlation With Dependence

2016 ◽  
Vol 28 (8) ◽  
pp. 1448-1464 ◽  
Author(s):  
Örjan Åkerborg ◽  
Andrea Lang ◽  
Anders Wimo ◽  
Anders Sköldunger ◽  
Laura Fratiglioni ◽  
...  
Keyword(s):  
Cognitive Ability ◽  
Resource Utilization ◽  
Annual Cost ◽  
Neuropsychiatric Symptoms ◽  
Dementia Care ◽  
Cost Of Care ◽  
Path Model ◽  
National Study ◽  
Strong Impact ◽  
The Impact

Objective: To estimate the cost of dementia care and its relation to dependence. Method: Disease severity and health care resource utilization was retrieved from the Swedish National Study on Aging and Care. Informal care was assessed with the Resource Utilization in Dementia instrument. A path model investigates the relationship between annual cost of care and dependence, cognitive ability, functioning, neuropsychiatric symptoms, and comorbidities. Results: Average annual cost among patients diagnosed with dementia was €43,259, primarily incurred by accommodation. Resource use, that is, institutional care, community care, and accommodation, and corresponding costs increased significantly by increasing dependency. Path analysis showed that cognitive ability, functioning, and neuropsychiatric symptoms were significantly correlated with dependence, which in turn had a strong impact on annual cost. Discussion: This study confirms that cost of dementia care increases with dependence and that the impact of other disease indicators is mainly mediated by dependence.

scholarly journals Does agricultural intensification cause tipping points in ecosystem services?

2021 ◽  
Author(s):  
Stephen C. L. Watson ◽  
Adrian C. Newton ◽  
Lucy E. Ridding ◽  
Paul M. Evans ◽  
Steven Brand ◽  
...  
Keyword(s):  
Ecosystem Services ◽  
Agricultural Intensification ◽  
Spatial Dynamics ◽  
Policy Option ◽  
List Type ◽  
Tipping Points ◽  
Software Models ◽  
Non Linear ◽  
Study Interval ◽  
The Impact

Abstract Context Agricultural intensification is being widely pursued as a policy option to improve food security and human development. Yet, there is a need to understand the impact of agricultural intensification on the provision of multiple ecosystem services, and to evaluate the possible occurrence of tipping points. Objectives To quantify and assess the long-term spatial dynamics of ecosystem service (ES) provision in a landscape undergoing agricultural intensification at four time points 1930, 1950, 1980 and 2015. Determine if thresholds or tipping points in ES provision may have occurred and if there are any detectable impacts on economic development and employment. Methods We used the InVEST suite of software models together with a time series of historical land cover maps and an Input–Output model to evaluate these dynamics over an 85-year period in the county of Dorset, southern England. Results Results indicated that trends in ES were often non-linear, highlighting the potential for abrupt changes in ES provision to occur in response to slight changes in underlying drivers. Despite the fluctuations in provision of different ES, overall economic activity increased almost linearly during the study interval, in line with the increase in agricultural productivity. Conclusions Such non-linear thresholds in ES will need to be avoided in the future by approaches aiming to deliver sustainable agricultural intensification. A number of positive feedback mechanisms are identified that suggest these thresholds could be considered as tipping points. However, further research into these feedbacks is required to fully determine the occurrence of tipping points in agricultural systems.

128 Development of an M1-polarized, non-viral chimeric antigen receptor macrophage (CAR-M) platform for cancer immunotherapy

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A141-A141
Author(s):  
Yumi Ohtani ◽  
Kayleigh Ross ◽  
Aditya Dandekar ◽  
Rashid Gabbasov ◽  
Michael Klichinsky
Keyword(s):  
Cancer Immunotherapy ◽  
Chimeric Antigen Receptor ◽  
Scale Up ◽  
Antigen Receptor ◽  
Innate Immune ◽  
List Type ◽  
M1 Phenotype ◽  
The Impact ◽  
Anti Tumor Activity ◽  
Immunosuppressive Factors

BackgroundWe have previously developed CAR-M as a novel cell therapy approach for the treatment of solid tumors.1 CAR-M have the potential to overcome key challenges that cell therapies face in the solid tumor setting – tumor infiltration, immunosuppression, lymphocyte exclusion – and can induce epitope spreading to overcome target antigen heterogeneity. While macrophages transduced with the adenoviral vector Ad5f35 (Ad CAR-M) traffic to tumors, provide robust anti-tumor activity, and recruit and activate T cells, we sought to identify a robust non-viral method of macrophage engineering in order to reduce the cost of goods, manufacturing complexity, and potential immunogenicity associated with viral vectors.MethodsAs innate immune cells, macrophages detect exogenous nucleic acids and respond with inflammatory and apoptotic programs. Thus, we sought to identify a means of mRNA delivery that avoids recognition by innate immune sensors. We screened a broad panel of mRNA encoding an anti-HER2 CAR comprising multiplexed 5’Cap and base modifications using an optimized and scalable electroporation approach and evaluated the impact of interferon-β priming on CAR-M phenotype and function.ResultsWe identified the optimal multiplexed mRNA modifications that led to maximal macrophage viability, transfection efficiency, intensity of CAR expression, and duration of expression. Non-viral HER2 CAR-M phagocytosed and killed human HER2+ tumor cells. Unlike Ad CAR-M, mRNA CAR-M were not skewed toward an M1 state by mRNA electroporation. Priming non-viral CAR-M with IFN-β induced a durable M1 phenotype, as shown by stable upregulation of numerous M1 markers and pathways. IFN-β priming significantly enhanced the anti-tumor activity of CAR but not control macrophages. IFN-β primed mRNA CAR-M were resistant to M2 conversion, maintaining an M1 phenotype despite challenge with various immunosuppressive factors, and converted bystander M2 macrophages toward M1. Interestingly, priming mRNA CAR-M with IFN-β significantly enhanced the persistence of CAR expression, overcoming the known issue of rapid mRNA turnover. RNA-seq analysis revealed that IFN-β priming affected pathways involved in increasing translation and decreasing RNA degradation in human macrophages.ConclusionsWe have established a novel, optimized non-viral CAR-M platform based on chemically modified mRNA and IFN-β priming. IFN-β priming induced a durable M1 phenotype, improved CAR expression, improved CAR persistence, led to enhanced anti-tumor function, and rendered resistance to immunosuppressive factors. This novel platform is amenable to scale-up, GMP manufacturing, and represents an advance in the development of CAR-M.ReferenceKlichinsky M, Ruella M, Shestova O, et al. Human chimeric antigen receptor macrophages for cancer immunotherapy. Nat Biotechnol 2020;38(8):947–953.

scholarly journals Research on the impact of ship traffic flow on the restricted channel segment of the middle Yangtze River based on traffic wave theory

2021 ◽  
Vol 3 (8) ◽  
Author(s):  
Ting Liu ◽  
Gabriel Lodewijks
Keyword(s):  
Traffic Flow ◽  
Flow Rate ◽  
Flow Simulation ◽  
Wave Theory ◽  
Flow Density ◽  
List Type ◽  
Ship Traffic ◽  
Traffic Wave ◽  
The Impact ◽  
Channel Segment

Abstract Abstract On the basis of the influence of dry season on ship traffic flow, the gathering and dissipating process of ship traffic flow was researched with Greenshields linear flow—density relationship model, the intrinsic relationship between the ship traffic congestion state and traffic wave in the unclosed restricted channel segment was emphatically explored when the ship traffic flow in a tributary channel inflows, and the influence law of multiple traffic waves on the ship traffic flow characteristics in unclosed restricted segment is revealed. On this basis, the expressions of traffic wave speed and direction, dissipation time of queued ships and the number of ships affected were provided, and combined with Monte Carlo method, the ship traffic flow simulation model in the restricted channel segment was built. The simulation results show that in closed restricted channel segment the dissipation time of ships queued is mainly related to the ship traffic flow rate of segments A and C, and the total number of ships affected to the ship traffic flow rate of segment A. And in unclosed restricted channel segment, the dissipation time and the total number of ships affected are also determined by the meeting time of the traffic waves in addition to the ship traffic flow rate of segments. The research results can provide the theoretical support for further studying the ship traffic flow in unclosed restricted channel segment with multiple tributaries Article Highlights The inflow of tributaries' ship traffic flows has an obvious impact on the traffic conditions in the unenclosed restricted channel segment. The interaction and influence between multiple ship traffic waves and the mechanism of generating new traffic waves are explained. The expression of both dissipation time of queued ships and the total number of ships affected in the closed and unclosed restricted channel segment are given.

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