140 research outputs found
A Micro-Payment Scheme Encouraging Collaboration in Multi-Hop Cellular Networks
We propose a micro-payment scheme for multi-hop cellular networks that encourages collaboration in packet forwarding by letting users benefit from relaying others` packets. At the same time as proposing mechanisms for detecting and rewarding collaboration, we introduce appropriate mechanisms for detecting and punishing various forms of abuse. We show that the resulting scheme -- which is exceptionally light-weight -- makes collaboration rational and cheating undesirable
Complementary and Alternative Medicine for Chronic Prostatitis/Chronic Pelvic Pain Syndrome
To discuss challenges concerning treatment for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and review complementary and alternative medical (CAM) therapies being evaluated for this condition, we performed a comprehensive search of articles published from 1990–2005 using the PubMed, Medline databases. Data from the articles were abstracted and pooled by subject. Keywords cross-searched with CP/CPPS included: complementary, alternative, integrative, therapies, interventions, nutrition, antioxidants, herbs, supplements, biofeedback and acupuncture. Listed articles with no abstracts were not included. Various CAM therapies for CP/CPPS exist including biofeedback, acupuncture, hyperthermia and electrostimulation. Additionally, a variety of in vitro and in vivo studies testing herbal and nutritional supplements were found. Saw palmetto, cernilton and quercetin were the most frequently tested supplements for CP/CPPS. Although many CAM therapies demonstrate positive preliminary observations as prospective treatments for CP/CPPS, further exploratory studies including more randomized, controlled trials are necessary for significant validation as treatment options for this complex disorder
Secure Vehicular Communication Systems: Implementation, Performance, and Research Challenges
Vehicular Communication (VC) systems are on the verge of practical
deployment. Nonetheless, their security and privacy protection is one of the
problems that have been addressed only recently. In order to show the
feasibility of secure VC, certain implementations are required. In [1] we
discuss the design of a VC security system that has emerged as a result of the
European SeVeCom project. In this second paper, we discuss various issues
related to the implementation and deployment aspects of secure VC systems.
Moreover, we provide an outlook on open security research issues that will
arise as VC systems develop from today's simple prototypes to full-fledged
systems
Collaborative Location Privacy with Rational Users
Recent smartphones incorporate embedded GPS devices that enable users to obtain geographic information about their surroundings by providing a location-based service (LBS) with their current coordinates. However, LBS providers collect a significant amount of data from mobile users and could be tempted to misuse it, by compromising a customer's location privacy (her ability to control the information about her past and present location). Many solutions to mitigate this privacy threat focus on changing both the architecture of location-based systems and the business models of LBS providers. MobiCrowd does not introduce changes to the existing business practices of LBS providers, rather it requires mobile devices to communicate wirelessly in a peer-to-peer fashion. To lessen the privacy loss, users seeking geographic information try to obtain this data by querying neighboring nodes, instead of connecting to the LBS. However, such a solution will only function if users are willing to share regional data obtained from the LBS provider. We model this collaborative location-data sharing problem with rational agents following threshold strategies. Initially, we study agent cooperation by using pure game theory and then by combining game theory with an epidemic model that is enhanced to support threshold strategies to address a complex multi-agent scenario. From our game-theoretic analysis, we derive cooperative and non-cooperative Nash equilibria and the optimal threshold that maximizes agents' expected utility
Computing Nash Equilibrium in Wireless Ad Hoc Networks: A Simulation-Based Approach
This paper studies the problem of computing Nash equilibrium in wireless
networks modeled by Weighted Timed Automata. Such formalism comes together with
a logic that can be used to describe complex features such as timed energy
constraints. Our contribution is a method for solving this problem using
Statistical Model Checking. The method has been implemented in UPPAAL model
checker and has been applied to the analysis of Aloha CSMA/CD and IEEE 802.15.4
CSMA/CA protocols.Comment: In Proceedings IWIGP 2012, arXiv:1202.422
Delineation of prognostic biomarkers in prostate cancer
Prostate cancer is the most frequently diagnosed cancer in American men(1,2). Screening for prostate-specific antigen (PSA) has led to earlier detection of prostate cancer(3), but elevated serum PSA levels may be present in non-malignant conditions such as benign prostatic hyperlasia (BPH). Characterization of gene-expression profiles that molecularly distinguish prostatic neoplasms may identify genes involved in prostate carcinogenesis, elucidate clinical biomarkers, and lead to an improved classification of prostate cancer(4-6). Using microarrays of complementary DNA, we examined gene-expression profiles of more than 50 normal and neoplastic prostate specimens and three common prostate-cancer cell lines. Signature expression profiles of normal adjacent prostate (NAP), BPH, localized prostate cancer, and metastatic, hormone-refractory prostate cancer were determined. Here we establish many associations between genes and prostate cancer. We assessed two of these genes-hepsin, a transmembrane serine protease, and pim-1, a serine/threonine kinase-at the protein level using tissue microarrays consisting of over 700 clinically stratified prostate-cancer specimens. Expression of hepsin and pim-1 proteins was significantly correlated with measures of clinical outcome. Thus, the integration of cDNA microarray, high-density tissue microarray, and linked clinical and pathology data is a powerful approach to molecular profiling of human cancer.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62849/1/412822a0.pd
Alzheimer's risk variants in the clusterin gene are associated with alternative splicing
Genetic variation in CLU encoding clusterin has been associated with Alzheimer's disease (AD) through replicated genome-wide studies, but the underlying mechanisms remain unknown. Following earlier reports that tightly regulated CLU alternative transcripts have different functions, we tested CLU single-nucleotide polymorphisms (SNPs), including those associated with AD for quantitative effects on individual alternative transcripts. In 190 temporal lobe samples without pathology, we found that the risk allele of the AD-associated SNP rs9331888 increases the relative abundance of transcript NM_203339 (P=4.3 × 10−12). Using an independent set of 115 AD and control samples, we replicated this result (P=0.0014) and further observed that multiple CLU transcripts are at higher levels in AD compared with controls. The AD SNP rs9331888 is located in the first exon of NM_203339 and therefore, it is a functional candidate for the observed effects. We tested this hypothesis by in vitro dual luciferase assays using SK-N-SH cells and mouse primary cortical neurons and found allelic effects on enhancer function, consistent with our results on post-mortem human brain. These results suggest a biological mechanism for the genetic association of CLU with AD risk and indicate that rs9331888 is one of the functional DNA variants underlying this association
Multimodal Biomarkers That Predict the Presence of Gleason Pattern 4: Potential Impact for Active Surveillance
AbstractPurpose:Latent grade group ≥2 prostate cancer can impact the performance of active surveillance protocols. To date, molecular biomarkers for active surveillance have relied solely on RNA or protein. We trained and independently validated multimodal (mRNA abundance, DNA methylation, and/or DNA copy number) biomarkers that more accurately separate grade group 1 from grade group ≥2 cancers.Materials and Methods:Low- and intermediate-risk prostate cancer patients were assigned to training (n=333) and validation (n=202) cohorts. We profiled the abundance of 342 mRNAs, 100 DNA copy number alteration loci, and 14 hypermethylation sites at 2 locations per tumor. Using the training cohort with cross-validation, we evaluated methods for training classifiers of pathological grade group ≥2 in centrally reviewed radical prostatectomies. We trained 2 distinct classifiers, PRONTO-e and PRONTO-m, and validated them in an independent radical prostatectomy cohort.Results:PRONTO-e comprises 353 mRNA and copy number alteration features. PRONTO-m includes 94 clinical, mRNAs, copy number alterations, and methylation features at 14 and 12 loci, respectively. In independent validation, PRONTO-e and PRONTO-m predicted grade group ≥2 with respective true-positive rates of 0.81 and 0.76, and false-positive rates of 0.43 and 0.26. Both classifiers were resistant to sampling error and identified more upgrading cases than a well-validated presurgical risk calculator, CAPRA (Cancer of the Prostate Risk Assessment; P < .001).Conclusions:Two grade group classifiers with superior accuracy were developed by incorporating RNA and DNA features and validated in an independent cohort. Upon further validation in biopsy samples, classifiers with these performance characteristics could refine selection of men for active surveillance, extending their treatment-free survival and intervals between surveillance.Active surveillance (AS) is recommended for men with low- and favorable intermediate–risk prostate cancer.1 Compared to AS for low-risk men, AS for intermediate-risk men would likely benefit from more intensive surveillance to stave off disease progression. Despite increased use of advanced imaging tools, risk calculators, and molecular biomarkers, a third or more of men initially classified as low risk actually have intermediate or higher risk, heralded by subsequent detection of occult Gleason pattern 4.2,3 Strategies to identify such men have limited accuracy. They include attention to traditional risk factors such as age, tumor size and extent, and PSA level, measured by tests such as digital rectal examination, multiparametric (mp) MRI, and biopsy and blood analyses. Despite its increasing use in prostate cancer risk assessment, expert prostate mpMRI is a limited resource with low (circa 59%) sensitivity for intermediate-risk cases.4 A biomarker that more accurately distinguishes between grade group (GG) 1 and GG ≥2 could be helpful in deintensifying AS for men with truly low-risk cancers.Several commercially available and guideline-approved tests use gene (mRNA or protein) expression levels in prostate cancer biopsies to detect adverse pathology (AP; ie, GG ≥3 or nonorgan-confined disease) in the subsequent prostatectomy. However, no existing molecular test has been adopted in current guidelines as standard of care to distinguish between GG1 and GG ≥2 cancers.1,5,6 Despite indications that such tests could be useful,6,7 uptake has been limited, perhaps because of low accuracy, which in turn may derive from limitations in the number and types of molecular features included in each test. Since cardinal molecular features of early prostate carcinogenesis include not only altered gene expression but also DNA methylation events and copy number alterations (CNAs),8-10 we hypothesized that tests combining these features could provide superior performance in separating low-grade (GG1) cancers from their higher-grade (GG ≥2) counterparts.The personalized risk stratification for patients with early prostate cancer (PRONTO) program is a pan-Canadian effort that aims to develop a GG classifier to stratify risk in prostate cancer and achieve technical and clinical validation in statistically powered cohorts. Here, we report the development of 2 candidate classifiers comprising different types of molecular features. These classifiers, developed and independently validated, achieve superior performance by integrating tumor mRNA abundance, DNA copy number, and/or DNA methylation profiles. We demonstrate that these classifiers could add value above and beyond routinely captured clinical data and are remarkably resistant to sampling error. We discuss how adoption of classifiers with these attributes has the potential to improve current AS approaches without increasing patient morbidity. By identifying men at increased risk of occult GG ≥2 cancer, surveillance biopsies could be taken earlier to confirm the presence and extent of Gleason pattern 4 cancer. By confirming GG1 cancers, such biomarkers could identify men for whom it would be safe to forgo MRI or increase the intervals between surveillance biopsies, reducing burdens on health care systems and patients
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