Managing Vulnerabilities of Tactical Wireless RF Network Systems: A Case Study

Organisations and individuals benefit when wireless networks are protected. After assessing the risks associated with wireless technologies, organisations can reduce the risks by applying countermeasures to address specific threats and vulnerabilities. These countermeasures include management, operational and technical controls. While these countermeasures will not prevent all penetrations and adverse events, they can be effective in reducing many of the common risks associated with wireless RF networks. Among engineers dealing with different scaled and interconnected engineering systems, such as tactical wireless RF communication systems, there is a growing need for a means of analysing complex adaptive systems. We propose a methodology based on the systematic resolution of complex issues to manage the vulnerabilities of tactical wireless RF systems. There are is a need to assemble and balance the results of any successful measure, showing how well each solution meets the system’s objectives. The uncertain arguments used and other test results are combined using a form of mathematical theory for their analysis. Systems engineering thinking supports design decisions and enables decision‐makers to manage and assess the support for each solution. In these circumstances, complexity management arises from the many interacting and conflicting requirements of an increasing range of possible parameters. There may not be a single ‘right’ solution, only a satisfactory set of resolutions which this system helps to facilitate. Smart and innovative performance matrixes are introduced using a mathematical Bayesian network to manage, model, calculate and analyse all the potential vulnerability paths in wireless RF networks

Cell migration in paediatric glioma; characterisation and potential therapeutic targeting

Background: Paediatric high grade glioma (pHGG) and diffuse intrinsic pontine glioma (DIPG) are highly aggressive brain tumours. Their invasive phenotype contributes to their limited therapeutic response, and novel treatments that block brain tumour invasion are needed. Methods: Here, we examine the migratory characteristics and treatment effect of small molecule glycogen synthase kinase-3 inhibitors, lithium chloride (LiCl) and the indirubin derivative 6-bromoindirubin-oxime (BIO), previously shown to inhibit the migration of adult glioma cells, on two pHGG cell lines (SF188 and KNS42) and one patient-derived DIPG line (HSJD-DIPG-007) using 2D (transwell membrane, immunofluorescence, live cell imaging) and 3D (migration on nanofibre plates and spheroid invasion in collagen) assays. Results: All lines were migratory, but there were differences in morphology and migration rates. Both LiCl and BIO reduced migration and instigated cytoskeletal rearrangement of stress fibres and focal adhesions when viewed by immunofluorescence. In the presence of drugs, loss of polarity and differences in cellular movement were observed by live cell imaging. Conclusions: Ours is the first study to demonstrate that it is possible to pharmacologically target migration of paediatric glioma in vitro using LiCl and BIO, and we conclude that these agents and their derivatives warrant further preclinical investigation as potential anti-migratory therapeutics for these devastating tumours

Drug Resistance in Glioma Cells Induced by a Mesenchymal–Amoeboid Migratory Switch

Cancer cell invasion is a precondition for tumour metastasis and represents one of the most devastating characteristics of cancer. The development of drugs targeting cell migration, known as migrastatics, may improve the treatment of highly invasive tumours such as glioblastoma (GBM). In this study, investigations into the role of the cell adhesion protein Cellular communication network factor 1 (CCN1, also known as CYR61) in GBM cell migration uncovered a drug resistance mechanism adopted by cells when treated with the small molecule inhibitor CCG-1423. This inhibitor binds to importin α/β inhibiting the nuclear translocation of the transcriptional co-activator MKL1, thus preventing downstream effects including migration. Despite this reported role as an inhibitor of cell migration, we found that CCG-1423 treatment did not inhibit GBM cell migration. However, we could observe cells now migrating by mesenchymal–amoeboid transition (MAT). Furthermore, we present evidence that CCN1 plays a critical role in the progression of GBM with increased expression in higher-grade tumours and matched blood samples. These findings support a potential role for CCN1 as a biomarker for the monitoring and potentially early prediction of GBM recurrence, therefore as such could help to improve treatment of and increase survival rates of this devastating disease

Getting a Head Start: Diet, Sub-Adult Growth, and Associative Learning in a Seed-Eating Passerine

Developmental stress, and individual variation in response to it, can have important fitness consequences. Here we investigated the consequences of variable dietary protein on the duration of growth and associative learning abilities of zebra finches, Taeniopygia guttata, which are obligate graminivores. The high-protein conditions that zebra finches would experience in nature when half-ripe seed is available were mimicked by the use of egg protein to supplement mature seed, which is low in protein content. Growth rates and relative body proportions of males reared either on a low-protein diet (mature seed only) or a high-protein diet (seed plus egg) were determined from body size traits (mass, head width, and tarsus) measured at three developmental stages. Birds reared on the high-protein diet were larger in all size traits at all ages, but growth rates of size traits showed no treatment effects. Relative head size of birds reared on the two diets differed from age day 95 onward, with high-diet birds having larger heads in proportion to both tarsus length and body mass. High-diet birds mastered an associative learning task in fewer bouts than those reared on the low-protein diet. In both diet treatments, amount of sub-adult head growth varied directly, and sub-adult mass change varied inversely, with performance on the learning task. Results indicate that small differences in head growth during the sub-adult period can be associated with substantial differences in adult cognitive performance. Contrary to a previous report, we found no evidence for growth compensation among birds on the low-protein diet. These results have implications for the study of vertebrate cognition, developmental stress, and growth compensation

Seasonal cruise Q2 2021: Cruise Report

The spring season was the target for the Nansen Legacy cruise organized in late April and first half of May 2021 following the transect defined for this series of cruises to capture the variations of the year sampling physical, biological and chemical conditions in the ice and the sea. The transect went through both open water and ice. Seven process stations were visited (P1 through P7) together with smaller NLEG stations according to the program for the seasonal investigations. The first station (P1) was in open waters, while the remaining six main station had ice coverage of varying degree. Each of the process stations lasted 24 hours or more to allow a full diurnal cycle. Sampling included ice physics, ice samples, phytoplankton, zooplankton, marine chemistry and eco toxicology using acoustic, optical and robotics methods together with lab analyses of physical samples. Remote sensing data were also matched with in situ observations of both sea and ice conditions

Living with the Past: Nutritional Stress in Juvenile Males Has Immediate Effects on their Plumage Ornaments and on Adult Attractiveness in Zebra Finches

The environmental conditions individuals experience during early development are well known to have fundamental effects on a variety of fitness-relevant traits. Although it is evident that the earliest developmental stages have large effects on fitness, other developmental stages, such as the period when secondary sexual characters develop, might also exert a profound effect on fitness components. Here we show experimentally in male zebra finches, Taeniopygia guttata, that nutritional conditions during this later period have immediate effects on male plumage ornaments and on their attractiveness as adults. Males that had received high quality food during the second month of life, a period when secondary sexual characteristics develop, were significantly more attractive as adults in mate choice tests than siblings supplied with standard food during this period. Preferred males that had experienced better nutritional conditions had larger orange cheek patches when nutritional treatments ended than did unpreferred males. Sexual plumage ornaments of young males thus are honest indicators of nutritional conditions during this period. The mate choice tests with adult birds indicate that nutritional conditions during the period of song learning, brain and gonad development, and moult into adult plumage have persisting effects on male attractiveness. This suggests that the developmental period following nutritional dependence from the parents is just as important in affecting adult attractiveness as are much earlier developmental periods. These findings thus contribute to understanding the origin and consequences of environmentally determined fitness components

Seasonal cruise Q4 2019 : Cruise Report

This cruise was the second of in total four seasonal cruises with RV Kronprins Haakon in 2019/20 focusing on biology in the project Arven etter Nansen (AeN). This seasonal cruise was named Q4 (Q4= 4th quarter of the year) investigating in total 17 stations of the established AeN transect along 34 E in the Northern Barents Sea and adjacent Arctic Basin from 76 to 82°N (see Fig. 1 below). The cruise addressed objectives of the research foci in RF1 on Physical drivers, RF2 on Human drivers, RF3 on the living Barents Sea and RA-C Technology and method development, and collected a multitude of data along the Nansen Legacy transect which was ice covered except the southernmost station P1. In addition to in situ sampling, on board experiments were conducted to quantify biological processes, rates and interactions that will also be important feeds into modeling work and projections in RF4 The future Barents Sea. The cruise took a variety of continuous ship measurements (Weather station, EK80, EM203, ADCP, thermosalinograph, pCO2 underway) as well as station measurements such as CTD with water samples, biological sampling of the benthos (box corer, benthic trawl), water column (multinet, MIK net, macrozooplankton trawl and many other smaller nets) and sea ice (snow, ice cores, water just underneath sea ice). In addition, experimental work (respiration, grazing and egg production) was conducted in the ship’s laboratories. The chemistry team onboard measured oxygen, nutrients and pH from standard depths on most CTD stations and sea ice samples. The cruise started in Longyearbyen and ended in Tromsø (28.11.-17.12.2019). The sampling began at the deep (>3000 m) northernmost station of the transect, Stn. P7, and continued along the southward transect until station P1, in open water and Atlantic dominated water masses. During the expedition the Barents Sea was characterized by a relatively large sea ice cover with consolidated sea ice all the way from P7 to P2. The Polar Front was located just north of P1. All process stations were sampled (P7-P1) as well as two ice stations: one close to P7 ad one close to P5. At the southernmost station P1, stormy weather challenged sampling, but most tasks were in the end accomplished except of deploying the box corer, sediment trap and the AUV. These operations were considered too challenging due to strong drift and ship movement, and it was not safe to conduct small boat operations. Challenges with the box corer was also experienced at the deep station P7 due to technical issues. In the end, most work was accomplished despite challenging weather, sea ice conditions and some technical issues making this cruise successful in gaining new important knowledge about the Northern Barents Sea in the polar night season which is extremely poorly studied. The overall high biological activity and biomass at this time of the year, November-December, was surprising for most of us

GSK3β Regulates Differentiation and Growth Arrest in Glioblastoma

Cancers are driven by a population of cells with the stem cell properties of self-renewal and unlimited growth. As a subpopulation within the tumor mass, these cells are believed to constitute a tumor cell reservoir. Pathways controlling the renewal of normal stem cells are deregulated in cancer. The polycomb group gene Bmi1, which is required for neural stem cell self-renewal and also controls anti-oxidant defense in neurons, is upregulated in several cancers, including medulloblastoma. We have found that Bmi1 is consistently and highly expressed in GBM. Downregulation of Bmi1 by shRNAs induced a differentiation phenotype and reduced expression of the stem cell markers Sox2 and Nestin. Interestingly, expression of glycogen synthase kinase 3 beta (GSK3β), which was found to be consistently expressed in primary GBM, also declined. This suggests a functional link between Bmi1 and GSK3β. Interference with GSK3β activity by siRNA, the specific inhibitor SB216763, or lithium chloride (LiCl) induced tumor cell differentiation. In addition, tumor cell apoptosis was enhanced, the formation of neurospheres was impaired, and clonogenicity reduced in a dose-dependent manner. GBM cell lines consist mainly of CD133-negative (CD133-) cells. Interestingly, ex vivo cells from primary tumor biopsies allowed the identification of a CD133- subpopulation of cells that express stem cell markers and are depleted by inactivation of GSK3β. Drugs that inhibit GSK3, including the psychiatric drug LiCl, may deplete the GBM stem cell reservoir independently of CD133 status

Bcr/Abl Interferes with the Fanconi Anemia/BRCA Pathway: Implications in the Chromosomal Instability of Chronic Myeloid Leukemia Cells

Chronic myeloid leukemia (CML) is a malignant clonal disorder of the hematopoietic system caused by the expression of the BCR/ABL fusion oncogene. Although it is well known that CML cells are genetically unstable, the mechanisms accounting for this genomic instability are still poorly understood. Because the Fanconi anemia (FA) pathway is believed to control several mechanisms of DNA repair, we investigated whether this pathway was disrupted in CML cells. Our data show that CML cells have a defective capacity to generate FANCD2 nuclear foci, either in dividing cells or after DNA damage. Similarly, human cord blood CD34+ cells transduced with BCR/ABL retroviral vectors showed impaired FANCD2 foci formation, whereas FANCD2 monoubiquitination in these cells was unaffected. Soon after the transduction of CD34+ cells with BCR/ABL retroviral vectors a high proportion of cells with supernumerary centrosomes was observed. Similarly, BCR/ABL induced a high proportion of chromosomal abnormalities, while mediated a cell survival advantage after exposure to DNA cross-linking agents. Significantly, both the impaired formation of FANCD2 nuclear foci, and also the predisposition of BCR/ABL cells to develop centrosomal and chromosomal aberrations were reverted by the ectopic expression of BRCA1. Taken together, our data show for the first time a disruption of the FA/BRCA pathway in BCR/ABL cells, suggesting that this defective pathway should play an important role in the genomic instability of CML by the co-occurrence of centrosomal amplification and DNA repair deficiencies