Fluctuation-induced traffic congestion in heterogeneous networks

In studies of complex heterogeneous networks, particularly of the Internet, significant attention was paid to analyzing network failures caused by hardware faults or overload, where the network reaction was modeled as rerouting of traffic away from failed or congested elements. Here we model another type of the network reaction to congestion -- a sharp reduction of the input traffic rate through congested routes which occurs on much shorter time scales. We consider the onset of congestion in the Internet where local mismatch between demand and capacity results in traffic losses and show that it can be described as a phase transition characterized by strong non-Gaussian loss fluctuations at a mesoscopic time scale. The fluctuations, caused by noise in input traffic, are exacerbated by the heterogeneous nature of the network manifested in a scale-free load distribution. They result in the network strongly overreacting to the first signs of congestion by significantly reducing input traffic along the communication paths where congestion is utterly negligible.Comment: 4 pages, 3 figure

High-throughput genomic technology in research and clinical management of breast cancer. Molecular signatures of progression from benign epithelium to metastatic breast cancer

It is generally accepted that early detection of breast cancer has great impact on patient survival, emphasizing the importance of early diagnosis. In a widely recognized model of breast cancer development, tumor cells progress through chronological and well defined stages. However, the molecular basis of disease progression in breast cancer remains poorly understood. High-throughput molecular profiling techniques are excellent tools for the study of complex molecular alterations. By accurately mapping changes in the genome and subsequent biological/molecular pathways, the chances of finding potential novel treatment targets as well as intervention strategies are enhanced, and ultimately lives can be saved. This review provides a brief summary of recent progress in identifying molecular markers for invasiveness in early breast lesions

A new approach to deploy a self-adaptive distributed firewall

Distributed firewall systems emerged with the proposal of protecting individual hosts against attacks originating from inside the network. In these systems, firewall rules are centrally created, then distributed and enforced on all servers that compose the firewall, restricting which services will be available. However, this approach lacks protection against software vulnerabilities that can make network services vulnerable to attacks, since firewalls usually do not scan application protocols. In this sense, from the discovery of any vulnerability until the publication and application of patches there is an exposure window that should be reduced. In this context, this article presents Self-Adaptive Distributed Firewall (SADF). Our approach is based on monitoring hosts and using a vulnerability assessment system to detect vulnerable services, integrated with components capable of deciding and applying firewall rules on affected hosts. In this way, SADF can respond to vulnerabilities discovered in these hosts, helping to mitigate the risk of exploiting the vulnerability. Our system was evaluated in the context of a simulated network environment, where the results achieved demonstrate its viability

evaluation of advanced routing strategies with information theoretic complexity measures

Based on hierarchy and recursion (shortly, HR), recursive networking has evolved to become a possible architecture for the future Internet. In this paper, we advance the study of HR-based routing by means of the Gershenson-Fernandez information-theoretic framework, which provides four different complexity measures. Then, we introduce a novel and general approach for computing the information associated to a known or estimated routing table. Finally, we present simulation results regarding networks that are characterized by different topologies and routing strategies. In particular, we discuss some interesting facts we observed while comparing HR-based to traditional routing in terms of complexity measures

Acute Pancreatitis due to pH-Dependent Mesalazine That Occurred in the Course of Ulcerative Colitis

We report the case of a 26-year-old male who presented with acute pancreatitis during the course of treatment for pancolitic ulcerative colitis (UC) with a time-dependent mesalazine formulation, prednisolone and azathioprine (AZA). Despite a review of his clinical history and various tests, the cause of pancreatitis could not be determined. Since drug-induced pancreatitis was considered possible, administration of the time-dependent mesalazine preparation and AZA was discontinued, and conservative treatment for acute pancreatitis was performed. The pancreatitis promptly improved with these treatments, but drug lymphocyte stimulation test (DLST) for both the time-dependent mesalazine formulation and AZA was negative. A pH-dependent mesalazine formulation was given for maintenance therapy of UC. Subsequently, as the pancreatitis relapsed, drug-induced pancreatitis was strongly suspected. Administration of mesalazine was discontinued, and pancreatitis was smoothly in remission by conservative treatment. According to the positive DLST result for the pH-dependent mesalazine formulation and the clinical course, a diagnosis of pH-dependent mesalazine-induced pancreatitis due to this formulation was made. During the clinical course of UC, occurrence of drug-induced pancreatitis must always be considered

A hop-count based positioning algorithm for wireless ad-hoc networks

We propose a range-free localization algorithm for a wireless ad-hoc network utilizing the hop-count metric’s ability to indicate proximity to anchors (i.e., nodes with known positions). In traditional sense, hop-count generally means the number of intermediate routers a datagram has to go through between its source and the destination node. We analytically show that hop-count could be used to indicate proximity relative to an anchor node. Our proposed algorithm is computationally feasible for resource constrained wireless ad-hoc nodes, and gives reasonable accuracy. We perform both real experiments and simulations to evaluate the algorithm’s performance. Experimental results show that our algorithm outperforms similar proximity based algorithms utilizing received signal strength and expected transmission count. We also analyze the impact of various parameters like the number of anchor nodes, placements of anchor nodes and varying transmission powers of the nodes on the hop-count based localization algorithm’s performance through simulation

Elevated levels of Dickkopf-related protein 3 in seminal plasma of prostate cancer patients

<p>Abstract</p> <p>Background</p> <p>Expression of Dkk-3, a secreted putative tumor suppressor, is altered in age-related proliferative disorders of the human prostate. We now investigated the suitability of Dkk-3 as a diagnostic biomarker for prostate cancer (PCa) in seminal plasma (SP).</p> <p>Methods</p> <p>SP samples were obtained from 81 patients prior to TRUS-guided prostate biopsies on the basis of elevated serum prostate-specific antigen (PSA; > 4 ng/mL) levels and/or abnormal digital rectal examination. A sensitive indirect immunoenzymometric assay for Dkk-3 was developed and characterized in detail. SP Dkk-3 and PSA levels were determined and normalized to total SP protein. The diagnostic accuracies of single markers including serum PSA and multivariate models to discriminate patients with positive (N = 40) and negative (N = 41) biopsy findings were investigated.</p> <p>Results</p> <p>Biopsy-confirmed PCa showed significantly higher SP Dkk-3 levels (100.9 ± 12.3 vs. 69.2 ± 9.4 fmol/mg; <it>p </it>= 0.026). Diagnostic accuracy (AUC) of SP Dkk-3 levels (0.633) was enhanced in multivariate models by including serum PSA (model A; AUC 0.658) or both, serum and SP PSA levels (model B; AUC 0.710). In a subpopulation with clinical follow-up > 3 years post-biopsy to ensure veracity of negative biopsy status (positive biopsy N = 21; negative biopsy N = 25) AUCs for SP Dkk-3, model A and B increased to 0.667, 0.724 and 0.777, respectively.</p> <p>Conclusions</p> <p>In multivariate models to detect PCa, inclusion of SP Dkk-3 levels, which were significantly elevated in biopsy-confirmed PCa patients, improved the diagnostic performance compared with serum PSA only.</p

MT1-MMP regulates urothelial cell invasion via transcriptional regulation of Dickkopf-3

Membrane type-1 matrix metalloproteinase (MT1-MMP) is a zinc-binding endopeptidase, which plays a crucial role in tumour growth, invasion and metastasis. We have shown previously that MT1-MMP has higher expression levels in the human urothelial cell carcinoma (UCC) tissue. We show here that siRNA against MT1-MMP blocks invasion in UCC cell lines. Invasion is also blocked by broad-spectrum protease and MMP inhibitors including tissue inhibitor of metalloproteinase-1 and -2. Membrane type-1-MMP can also regulate transcription. We have used expression arrays to identify genes that are differentially transcribed when siRNA is used to suppress MT1-MMP expression. Upon MT1-MMP knockdown, Dickkopf-3 (DKK3) expression was highly upregulated. The stability of DKK3 mRNA was unaffected under these conditions, suggesting transcriptional regulation of DKK3 by MT1-MMP. Dickkopf-3 has been previously shown to inhibit invasion. We confirm that the overexpression of DKK3 leads to decreased invasive potential as well as delayed wound healing. We show for the first time that the effects of MT1-MMP on cell invasion are mediated in part through changes in DKK3 gene transcription

DNA methylation status of REIC/Dkk-3 gene in human malignancies

The REIC (reduced expression in immortalized cells)/Dkk-3 is down-regulated in various cancers and considered to be a tumor suppressor gene. REIC/Dkk-3 mRNA has two isoforms (type-a,b). REIC type-a mRNA has shown to be a major transcript in various cancer cells, and its promoter activity was much stronger than that of type-b. In this study, we examined the methylation status of REIC/Dkk-3 type-a in a broad range of human malignancies. We examined REIC/Dkk-3 type-a methylation in breast cancers, non-small-cell lung cancers, gastric cancers, colorectal cancers, and malignant pleural mesotheliomas using a quantitative combined bisulfite restriction analysis assay and bisulfate sequencing. REIC/Dkk-3 type-a and type-b expression was examined using reverse transcriptional PCR. The relationships between the methylation and clinicopathological factors were analyzed. The rate of REIC/Dkk-3 type-a methylation ranged from 26.2 to 50.0% in the various primary tumors that were examined. REIC/Dkk-3 type-a methylation in breast cancer cells was significantly heavier than that in the other cell lines that we tested. REIC/Dkk-3 type-a methylation was inversely correlated with REIC/Dkk-3 type-a expression. There was a correlation between REIC/Dkk-3 type-a and type-b mRNA expression. REIC/Dkk-3 type-a expression was restored in MDA-MB-231 cells using 5-aza-2'-deoxycytidine treatment. We found that estrogen receptor-positive breast cancers were significantly more common among the methylated group than among the non-methylated group. REIC/Dkk-3 type-a methylation was frequently detected in a broad range of cancers and appeared to play a key role in silencing REIC/Dkk-3 type-a expression in these malignancies

A multi-targeted approach to suppress tumor-promoting inflammation

Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-κB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes