944 research outputs found
Tumor-Targeted Quantum Dots Can Help Surgeons Find Tumor Boundaries
No full textDespite surgical advances and recent progress in adjuvant therapies, the prognosis for patients with malignant brain tumors such as glioblastoma multiforme has remained poor, and the neurological deterioration suffered by most patients as a consequence of tumor progression is dramatic and severe. In addition, malignant brain tumors have > 95% recurrence close to the primary site of initial resection. Unfortunately, standard imaging techniques do not permit the intraoperative identification of individual or small clusters of residual tumor cells, precluding their selective removal while sparing the surrounding normal brain tissue. In this report, we show that quantum dots (QDs) coupled to epidermal growth factor (EGF) or anti-EGF receptor receptor (EGFR, Her1) specifically and sensitively label glial tumor cells in cell culture, glioma mouse models, and human brain-tumor biopsies. A clear demarcation between brain and tumor tissue at the macroscopic as well as the cellular level is provided by the fluorescence emission of the QDs
Specific visualization of glioma cells in living low-grade tumor tissue.
No full textBackgroundThe current therapy of malignant gliomas is based on surgical resection, radio-chemotherapy and chemotherapy. Recent retrospective case-series have highlighted the significance of the extent of resection as a prognostic factor predicting the course of the disease. Complete resection in low-grade gliomas that show no MRI-enhanced images are especially difficult. The aim in this study was to develop a robust, specific, new fluorescent probe for glioma cells that is easy to apply to live tumor biopsies and could identify tumor cells from normal brain cells at all levels of magnification.Methodology/principal findingsIn this investigation we employed brightly fluorescent, photostable quantum dots (QDs) to specifically target epidermal growth factor receptor (EGFR) that is upregulated in many gliomas. Living glioma and normal cells or tissue biopsies were incubated with QDs coupled to EGF and/or monoclonal antibodies against EGFR for 30 minutes, washed and imaged. The data include results from cell-culture, animal model and ex vivo human tumor biopsies of both low-grade and high-grade gliomas and show high probe specificity. Tumor cells could be visualized from the macroscopic to single cell level with contrast ratios as high as 1000: 1 compared to normal brain tissue.Conclusions/significanceThe ability of the targeted probes to clearly distinguish tumor cells in low-grade tumor biopsies, where no enhanced MRI image was obtained, demonstrates the great potential of the method. We propose that future application of specifically targeted fluorescent particles during surgery could allow intraoperative guidance for the removal of residual tumor cells from the resection cavity and thus increase patient survival
Improving Anycast with Measurements
No full textSince the first Distributed Denial-of-Service (DDoS) attacks were launched, the strength of such attacks has been steadily increasing, from a few megabits per second to well into the terabit/s range. The damage that these attacks cause, mostly in terms of financial cost, has prompted researchers and operators alike to investigate and implement mitigation strategies. Examples of such strategies include local filtering appliances, Border Gateway Protocol (BGP)-based blackholing and outsourced mitigation in the form of cloud-based DDoS protection providers.
Some of these strategies are more suited towards high bandwidth DDoS attacks than others. For example, using a local filtering appliance means that all the attack traffic will still pass through the owner's network. This inherently limits the maximum capacity of such a device to the bandwidth that is available. BGP Blackholing does not have such limitations, but can, as a side-effect, cause service disruptions to end-users. A different strategy, that has not attracted much attention in academia, is based on anycast.
Anycast is a technique that allows operators to replicate their service across different physical locations, while keeping that service addressable with just a single IP-address. It relies on the BGP to effectively load balance users. In practice, it is combined with other mitigation strategies to allow those to scale up. Operators can use anycast to scale their mitigation capacity horizontally.
Because anycast relies on BGP, and therefore in essence on the Internet itself, it can be difficult for network engineers to fine tune this balancing behavior. In this thesis, we show that that is indeed the case through two different case studies. In the first, we focus on an anycast service during normal operations, namely the Google Public DNS, and show that the routing within this service is far from optimal, for example in terms of distance between the client and the server. In the second case study, we observe the root DNS, while it is under attack, and show that even though in aggregate the bandwidth available to this service exceeds the attack we observed, clients still experienced service degradation. This degradation was caused due to the fact that some sites of the anycast service received a much higher share of traffic than others.
In order for operators to improve their anycast networks, and optimize it in terms of resilience against DDoS attacks, a method to assess the actual state of such a network is required. Existing methodologies typically rely on external vantage points, such as those provided by RIPE Atlas, and are therefore limited in scale, and inherently biased in terms of distribution. We propose a new measurement methodology, named Verfploeter, to assess the characteristics of anycast networks in terms of client to Point-of-Presence (PoP) mapping, i.e. the anycast catchment. This method does not rely on external vantage points, is free of bias and offers a much higher resolution than any previous method. We validated this methodology by deploying it on a testbed that was locally developed, as well as on the B root DNS. We showed that the increased \textit{resolution} of this methodology improved our ability to assess the impact of changes in the network configuration, when compared to previous methodologies.
As final validation we implement Verfploeter on Cloudflare's global-scale anycast Content Delivery Network (CDN), which has almost 200 global Points-of-Presence and an aggregate bandwidth of 30 Tbit/s. Through three real-world use cases, we demonstrate the benefits of our methodology: Firstly, we show that changes that occur when withdrawing routes from certain PoPs can be accurately mapped, and that in certain cases the effect of taking down a combination of PoPs can be calculated from individual measurements. Secondly, we show that Verfploeter largely reinstates the ping to its former glory, showing how it can be used to troubleshoot network connectivity issues in an anycast context. Thirdly, we demonstrate how accurate anycast catchment maps offer operators a new and highly accurate tool to identify and filter spoofed traffic.
Where possible, we make datasets collected over the course of the research in this thesis available as open access data. The two best (open) dataset awards that were awarded for these datasets confirm that they are a valued contribution.
In summary, we have investigated two large anycast services and have shown that their deployments are not optimal. We developed a novel measurement methodology, that is free of bias and is able to obtain highly accurate anycast catchment mappings. By implementing this methodology and deploying it on a global-scale anycast network we show that our method adds significant value to the fast-growing anycast CDN industry and enables new ways of detecting, filtering and mitigating DDoS attacks
Carbohydrate utilization and metabolism is highly differentiated in Agaricus bisporus
No full textBackground: Agaricus bisporus is commercially grown on compost, in which the available carbon sources consist mainly of plant-derived polysaccharides that are built out of various different constituent monosaccharides. The major constituent monosaccharides of these polysaccharides are glucose, xylose, and arabinose, while smaller amounts of galactose, glucuronic acid, rhamnose and mannose are also present.
Results: In this study, genes encoding putative enzymes from carbon metabolism were identified and their expression was studied in different growth stages of A. bisporus. We correlated the expression of genes encoding plant and fungal polysaccharide modifying enzymes identified in the A. bisporus genome to the soluble carbohydrates and the composition of mycelium grown compost, casing layer and fruiting bodies.
Conclusions: The compost grown vegetative mycelium of A. bisporus consumes a wide variety of monosaccharides. However, in fruiting bodies only hexose catabolism occurs, and no accumulation of other sugars was observed. This suggests that only hexoses or their conversion products are transported from the vegetative mycelium to the fruiting body, while the other sugars likely provide energy for growth and maintenance of the vegetative mycelium. Clear correlations were found between expression of the genes and composition of carbohydrates. Genes encoding plant cell wall polysaccharide degrading enzymes were mainly expressed in compost-grown mycelium, and largely absent in fruiting bodies. In contrast, genes encoding fungal cell wall polysaccharide modifying enzymes were expressed in both fruiting bodies and vegetative mycelium, but different gene sets were expressed in these samples
Trafficking and endocytosis of BRI1 and SERK receptors
No full textTo be able to react on environmental changes, plants use receptors on their cell membranes. Receptors in the plasma membrane catch signals via their extracellular domain and transduce these to other proteins. The receptors studied in this thesis are part of the brassinosteroid signaling pathway in Arabidopsis. The main receptor BRI1 binds brassinosteroids (BRs), upon which dimerization with the co-receptors SERK3 and SERK1 takes place. Receptors are removed from the plasma membrane to end up in small vesicles, the endosomes. From endosomes, either signaling or degradation of the receptors takes place. The interaction between the SERK1 receptor and the CDC48A protein might be based on the mediation of degradation of mis-folded SERK1 proteins from the ER (endoplasmic reticulum) in the proteasome, in a quality control-like fashion. The co-receptors SERK1 and SERK3 are required for BR signaling, that takes place from the endosomes and not or less from BR signaling from the plasma membrane. <br/
Balancing stress and recovery in sports
No full textTo reach elite level in sports, athletes have to start their intensive and time-consuming training at an early stage. The road to the top is a stressful one, not only due to the physiological stress of training, but also caused by psychological and social stress. In order to improve performance athletes continuously challenge their personal boundaries. This may lead to a local or general overload of the human body that results into injuries, illnesses and overtraining. Overtraining is characterized by an unexplained decrement in sport-specific performance and is often coupled with symptoms such as increased fatigue, poor concentration, disturbed mood, and altered eating and sleeping patterns. Full recovery may take months to years. Monitoring stress and recovery may help to optimize performance and prevent a local or general overload. Clinical measurements showed that mood state and hormonal responses to a double maximal exercise protocol provided valuable information to confirm the diagnosis of overtraining.
Quality management for integrated contracts; can the client improve it?:the role of a public client in the contractor's quality management
No full textAnycast and its potential for DDoS mitigation
No full textIP anycast is widely being used to distribute essential Internet services, such as DNS, across the globe. One of the main reasons for doing so is to increase the redundancy of the service and reduce the impacts of the growing threat of DDoS attacks. IP anycast can be further used to mitigate DDoS attacks by confining the attack traffic to certain areas. This might cause the targeted service to become unavailable only to a fraction of its users. In this PhD research we aim at investigating how IP anycast can be optimized both statically and dynamically to support the mitigation of DDoS attacks
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