Journal Staff

The advancement of mobile clients and applications makes it possible for people to always stayconnected, sending and receiving data constantly. The nature of the 3G technology widelyused, however, causes a high battery drain in cellular phones and because of that a lot of toolsfor measuring mobile phones energy consumption has been developed. In this report we lookinto the trace-driven tool EnergyBox and find out how we can use it to estimate the energyconsumption of 3G transmissions for an application we’ve developed ourselves. We beginwith identifying the types of traffic our application generates and identify which parts of itmake up our applications background traffic. Different combinations of the identified traffictypes are looked into in order to decide which ones that need to be present in the packet tracesfor an estimation of our applications energy footprint for 3G transmission. Further, answersare sought to how long the time span should be for which the packet traces are collected andhow many of them are needed in order to draw a conclusion about our application’s energyfootprint. We conclude that all traffic types responsible for our application’s backgroundtraffic need to be present in the analyzed packet traces, and data suggests that collectingmore than 10 one minute packet traces does not improve accuracy significantly (less than1%). Without user interaction, our application generates traffic, which transmitted over 3G,drains as much as an average of 930mW, meaning that a Samsung Galaxy S4 battery with acapacity of 9.88Wh would last for a maximum of 10 hours and 30 minutes (excluding otherenergy consuming sources inside the handset)

Binding Affinities of Factor Xa Inhibitors Estimated by Thermodynamic Integration and MM/GBSA.

We present free energy estimates of nine 3-amidinobenzyl-1H-indole-2-carboxamide inhibitors of factor Xa. Using alchemical thermodynamic integration (TI) calculations, we estimate the difference in binding free energies with high accuracy and precision, except for mutations involving one of the amidinobenzyl rings. Crystal studies show that the inhibitors may bind in two distinct conformations, and using TI, we show that the two conformations give a similar binding affinity. Furthermore, we show that we can reduce the computational demand, while still retaining a high accuracy and precision, by using fewer integration points and shorter protein-ligand simulations. Finally, we have compared the TI results to those obtained with the simpler MM/GBSA method (molecular-mechanics with generalized Born surface-area solvation). MM/GBSA gives better results for the mutations that involve a change of net charge, but if a precision similar to that of the TI method is required, the MM/GBSA method is actually slightly more expensive. Thus, we have shown that TI could be a valuable tool in drug design

Setting the Pace: New Insights into Central Pattern Generator Interactions in Box Jellyfish Swimming

Central Pattern Generators (CPGs) produce rhythmic behaviour across all animal phyla. Cnidarians, which have a radially symmetric nervous system and pacemaker centres in multiples of four, provide an interesting comparison to bilaterian animals for studying the coordination between CPGs. The box jellyfish Tripedalia cystophora is remarkable among cnidarians due to its most elaborate visual system. Together with their ability to actively swim and steer, they use their visual system for multiple types of behaviour. The four swim CPGs are directly regulated by visual input. In this study, we addressed the question of how the four pacemaker centres of this radial symmetric cnidarian interact. We based our investigation on high speed camera observations of the timing of swim pulses of tethered animals (Tripedalia cystophora) with one or four rhopalia, under different simple light regimes. Additionally, we developed a numerical model of pacemaker interactions based on the inter pulse interval distribution of animals with one rhopalium. We showed that the model with fully resetting coupling and hyperpolarization of the pacemaker potential below baseline fitted the experimental data best. Moreover, the model of four swim pacemakers alone underscored the proportion of long inter pulse intervals (IPIs) considerably. Both in terms of the long IPIs as well as the overall swim pulse distribution, the simulation of two CPGs provided a better fit than that of four. We therefore suggest additional sources of pacemaker control than just visual input. We provide guidelines for future research on the physiological linkage of the cubozoan CPGs and show the insight from bilaterian CPG research, which show that pacemakers have to be studied in their bodily and nervous environment to capture all their functional features, are also manifest in cnidarians

Treatment with Anti-HER2 Chimeric Antigen Receptor Tumor-Infiltrating Lymphocytes (CAR-TILs) Is Safe and Associated with Antitumor Efficacy in Mice and Companion Dogs

Patients with metastatic melanoma have a historically poor prognosis, but recent advances in treatment options, including targeted therapy and immunotherapy, have drastically improved the outcomes for some of these patients. However, not all patients respond to available treatments, and around 50% of patients with metastatic cutaneous melanoma and almost all patients with metastases of uveal melanoma die of their disease. Thus, there is a need for novel treatment strategies for patients with melanoma that do not benefit from the available therapies. Chimeric antigen receptor-expressing T (CAR-T) cells are largely unexplored in melanoma. Traditionally, CAR-T cells have been produced by transducing blood-derived T cells with a virus expressing CAR. However, tumor-infiltrating lymphocytes (TILs) can also be engineered to express CAR, and such CAR-TILs could be dual-targeting. To this end, tumor samples and autologous TILs from metastasized human uveal and cutaneous melanoma were expanded in vitro and transduced with a lentiviral vector encoding an anti-HER2 CAR construct. When infused into patient-derived xenograft (PDX) mouse models carrying autologous tumors, CAR-TILs were able to eradicate melanoma, even in the absence of antigen presentation by HLA. To advance this concept to the clinic and assess its safety in an immune-competent and human-patient-like setting, we treated four companion dogs with autologous anti-HER2 CAR-TILs. We found that these cells were tolerable and showed signs of anti-tumor activity. Taken together, CAR-TIL therapy is a promising avenue for broadening the tumor-targeting capacity of TILs in patients with checkpoint immunotherapy-resistant melanoma

Aligning integrated assessment modelling with socio-technical transition insights: an application to low-carbon energy scenario analysis in Europe

In this study, we present and apply an interdisciplinary approach that systematically draws qualitative insights from socio-technical transition studies to develop new quantitative scenarios for integrated assessment modelling. We identify the transition narrative as an analytical bridge between socio-technical transition studies and integrated assessment modelling. Conceptual interaction is realised through the development of two contrasting transition narratives on the role of actors in meeting the European Unions' 80% greenhouse gas emission reduction objective for 2050. The first transition narrative outlines how large-scale innovation trajectories are driven by incumbent actors, whereas the second transition narrative assumes more ‘alternative’ strategies by new entrants with strong opposition to large-scale technologies. We use the multi-level perspective to draw out plausible storylines on actor positioning and momentum of change for several technological and social niche-innovations in both transition narratives. These storylines are then translated into quantitative scenarios for integrated assessment modelling. Although both developed transition pathways align with the European Union's low-carbon objective for 2050, we find that each pathway depicts a substantial departure from systems that are known to date. Future research could focus on further systematic (joint) development of operational links between the two analytical approaches, as well as work on improved representation of demand-oriented solutions in techno-economic modelling

Affinity proteomics reveals elevated muscle proteins in plasma of children with cerebral malaria

Systemic inflammation and sequestration of parasitized erythrocytes are central processes in the pathophysiology of severe Plasmodium falciparum childhood malaria. However, it is still not understood why some children are more at risks to develop malaria complications than others. To identify human proteins in plasma related to childhood malaria syndromes, multiplex antibody suspension bead arrays were employed. Out of the 1,015 proteins analyzed in plasma from more than 700 children, 41 differed between malaria infected children and community controls, whereas 13 discriminated uncomplicated malaria from severe malaria syndromes. Markers of oxidative stress were found related to severe malaria anemia while markers of endothelial activation, platelet adhesion and muscular damage were identified in relation to children with cerebral malaria. These findings suggest the presence of generalized vascular inflammation, vascular wall modulations, activation of endothelium and unbalanced glucose metabolism in severe malaria. The increased levels of specific muscle proteins in plasma implicate potential muscle damage and microvasculature lesions during the course of cerebral malaria