Overlay Network Creation and Maintenance with Selfish Users

Overlay networks have been used for adding and enhancing functionality to the end-users without requiring modifications in the Internet core mechanisms. Overlay networks have been used for a variety of popular applications including routing, file sharing, content distribution, and server deployment. Previous work has focused on devising practical neighbor selection heuristics under the assumption that users conform to a specific wiring protocol. This is not a valid assumption in highly decentralized systems like overlay networks. Overlay users may act selfishly and deviate from the default wiring protocols by utilizing knowledge they have about the network when selecting neighbors to improve the performance they receive from the overlay. This thesis goes against the conventional thinking that overlay users conform to a specific protocol. The contributions of this thesis are threefold. It provides a systematic evaluation of the design space of selfish neighbor selection strategies in real overlays, evaluates the performance of overlay networks that consist of users that select their neighbors selfishly, and examines the implications of selfish neighbor and server selection to overlay protocol design and service provisioning respectively. This thesis develops a game-theoretic framework that provides a unified approach to modeling Selfish Neighbor Selection (SNS) wiring procedures on behalf of selfish users. The model is general, and takes into consideration costs reflecting network latency and user preference profiles, the inherent directionality in overlay maintenance protocols, and connectivity constraints imposed on the system designer. Within this framework the notion of user’s "best response" wiring strategy is formalized as a k-median problem on asymmetric distance and is used to obtain overlay structures in which no node can re-wire to improve the performance it receives from the overlay. Evaluation results presented in this thesis indicate that selfish users can reap substantial performance benefits when connecting to overlay networks composed of non-selfish users. In addition, in overlays that are dominated by selfish users, the resulting stable wirings are optimized to such great extent that even non-selfish newcomers can extract near-optimal performance through naïve wiring strategies. To capitalize on the performance advantages of optimal neighbor selection strategies and the emergent global wirings that result, this thesis presents EGOIST: an SNS-inspired overlay network creation and maintenance routing system. Through an extensive measurement study on the deployed prototype, results presented in this thesis show that EGOIST’s neighbor selection primitives outperform existing heuristics on a variety of performance metrics, including delay, available bandwidth, and node utilization. Moreover, these results demonstrate that EGOIST is competitive with an optimal but unscalable full-mesh approach, remains highly effective under significant churn, is robust to cheating, and incurs minimal overheads. This thesis also studies selfish neighbor selection strategies for swarming applications. The main focus is on n-way broadcast applications where each of n overlay user wants to push its own distinct file to all other destinations as well as download their respective data files. Results presented in this thesis demonstrate that the performance of our swarming protocol for n-way broadcast on top of overlays of selfish users is far superior than the performance on top of existing overlays. In the context of service provisioning, this thesis examines the use of distributed approaches that enable a provider to determine the number and location of servers for optimal delivery of content or services to its selfish end-users. To leverage recent advances in virtualization technologies, this thesis develops and evaluates a distributed protocol to migrate servers based on end-users demand and only on local topological knowledge. Results under a range of network topologies and workloads suggest that the performance of the distributed deployment is comparable to that of the optimal but unscalable centralized deployment.

Is a Detector Only Good for Detection?

A common design of an object recognition system has two steps, a detection step followed by a foreground within-class classification step. For example, consider face detection by a boosted cascade of detectors followed by face ID recognition via one-vs-all (OVA) classifiers. Another example is human detection followed by pose recognition. Although the detection step can be quite fast, the foreground within-class classification process can be slow and becomes a bottleneck. In this work, we formulate a filter-and-refine scheme, where the binary outputs of the weak classifiers in a boosted detector are used to identify a small number of candidate foreground state hypotheses quickly via Hamming distance or weighted Hamming distance. The approach is evaluated in three applications: face recognition on the FRGC V2 data set, hand shape detection and parameter estimation on a hand data set and vehicle detection and view angle estimation on a multi-view vehicle data set. On all data sets, our approach has comparable accuracy and is at least five times faster than the brute force approach.

Godwin, Fénelon, and the disappearing teacher

The connection between Godwin and Fénelon has traditionally been restricted to the famous and controversial moment in the first edition of Political Justice (1793) in which Godwin presents an example of the interdependence of rationality and ethical action. This paper argues, however, that Fénelon, and particularly his political and educational treatise Telemachus (1699), plays a significant role in a number of Godwin's subsequent fictional works. Employing Telemachus to explore the theories of education presented by Godwin in the various editions of Political Justice and The Enquirer (1797), this paper explores the manner in which Godwin's version of the Enlightenment transcendence of pedagogical power comes up against its limits. Reading this issue in relation to Godwin's argument, in ‘Of Choice in Reading’, that literature remains outside of socio-ethical corruption, three of Godwin's major novels are shown to demonstrate that Telemachus provides the chance for meta-textual moments in which the appeal to reason (the reader's rational capacity or ‘private judgement’) is at once reflected upon and produced. Reading educational theories and problems into Godwin's major fiction in this fashion helps to clarify aspects of the Godwinian (or ‘Jacobin’) novel.

Towards enhanced divine-human-earth relations: a Christian-Buddhist contribution

The central claim of the dissertation is that lesser known and somewhat neglected, yet influential thinkers, within classical religious traditions have something worthwhile to contribute to the kind of ethos we should adopt in the face of the world’s various environmental crises. Moreover an exploration of such perspectives is best done in dialogue, particularly between Eastern and Western thought. I examine this claim primarily through a dialogue between the Christian philosopher John Scottus Eriugena and the Japanese Buddhist philosopher Kūkai (Kōbō Daishi). This dialogue, framed by the triad of divine-human-earth relations, primarily emphasises the oneness of all reality, and it finds expression in Eriugena’s concept of natura or phusis and Kūkai’s central teaching that the phenomenal world is the cosmic Buddha Dainichi. By highlighting this focus, I contribute to the existing academic field of ecology and religion on the subject of holism. However, I go beyond the materialist focus that generally marks such ecological holism within that field, offering instead a more metaphysical approach. This is indicated through my use of the concept of ‘immanental transcendence’ to describe Eriugena’s and Kūkai’s dynamic, numinous and mysterious notion of reality, as well as my exploration of Eriugena’s concept of theophany and Kūkai’s notion of kaji. I further explore how both philosophers highlight the human role in the process of reaching enlightenment—understood as attaining union with the whole. In that regard, I note significant differences in their positions: in particular, I note that Kūkai’s emphasis on bodily practices contrasts with Eriugena’s more conceptual approach. Finally to bolster my claim, I examine some ecologically oriented understandings of contemporary phenomenological approaches found particularly in the work of Jean-Luc Marion and to a lesser extent Merleau-Ponty, arguing that these reflect notions of reality and of the human role similar to those of the medieval philosophers.

Colony sex ratios vary with breeding structure but not relatedness asymmetry in the facultatively polygynous ant Pheidole pallidula

We investigated sex allocation in a Mediterranean population of the facultatively polygynous (multiple queen per colony) ant Pheidole pallidula. This species shows a strong split sex ratio, with most colonies producing almost exclusively a single-sex brood. Our genetic (microsatellite) analyses reveal that P. pallidula has an unusual breeding system, with colonies being headed by a single or a few unrelated queens. As expected in such a breeding system, our results show no variation in relatedness asymmetry between monogynous (single queen per colony) and polygynous colonies. Nevertheless, sex allocation was tightly associated with the breeding structure, with monogynous colonies producing a male-biased brood and polygynous colonies almost only females. In addition, sex allocation was closely correlated with colony total sexual productivity. Overall, our data show that when colonies become more productive (and presumably larger) they shift from monogyny to polygyny and from male production to female production, a pattern that has never been reported in social insects.

Interleukin 10 reduces the incidence of pancreatitis after therapeutic endoscopic retrograde cholangiopancreatography.

BACKGROUND & AIMS: Prophylactic administration of interleukin (IL)-10 decreases the severity of experimental pancreatitis. Prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis in humans is a unique model to study the potential role of IL-10 in this setting. METHODS: In a single-center, double-blind, randomized, placebo-controlled study, the effect of a single injection of 4 microg/kg (group 1) or 20 microg/kg (group 2) IL-10 was compared with that of placebo (group 0), all administered 30 minutes before therapeutic ERCP. The primary endpoint was the effect of IL-10 on serum levels of amylases and lipases measured 4, 24, and 48 hours after ERCP. The secondary objective was to evaluate changes in plasma cytokines (IL-6, IL-8, tumor necrosis factor) at the same time points and the incidence of acute pancreatitis in the 3 groups. Subjects undergoing a first therapeutic ERCP were eligible for inclusion. RESULTS: A total of 144 patients were included. Seven were excluded based on intention to treat (n = 1) or per protocol (n = 6). Forty-five, 48, and 44 patients remained in groups 0, 1, and 2, respectively. The 3 groups were comparable for age, sex, underlying disease, indication for treatment, type of treatment, and plasma levels of C-reactive protein (CRP), cytokines, and hydrolases at baseline. No significant difference was observed in CRP, cytokine, and hydrolase plasma levels after ERCP. Forty-three patients developed hyperhydrolasemia (18 in group 0, 14 in group 1, and 11 in group 2; P = 0.297), and 19 patients developed acute clinical pancreatitis (11 in group 0, 5 in group 1, 3 in group 2; P = 0.038). Two severe cases were observed in the placebo group. No mortality related to ERCP was observed. Logistic regression identified 3 independent risk factors for post-therapeutic ERCP pancreatitis: IL-10 administration (odds ratio [OR], 0.46; 95% confidence interval [95% CI], 0.22-0.96; P = 0.039), pancreatic sphincterotomy (OR, 5.04; 95% CI, 1.53-16.61; P = 0.008), and acinarization (OR, 8.19; 95% CI, 1.83-36.57; P = 0.006). CONCLUSIONS: A single intravenous dose of IL-10, given 30 minutes before the start of the procedure, independently reduces the incidence of post-therapeutic ERCP pancreatitis.

Endogenous interleukin-10 modulates fibrosis and regeneration in experimental chronic pancreatitis.

Interleukin (IL)-10, a potent anti-inflammatory cytokine, limits the severity of acute pancreatitis and downregulates transforming growth factor (TGF)-beta release by inflammatory cells on stimulation. Proinflammatory mediators, reactive oxygen species, and TGF-beta can activate pancreatic stellate cells and their synthesis of collagen I and III. This study evaluates the role of endogenous IL-10 in the modulation of the regeneration phase following acute pancreatitis and in the development of pancreatic fibrosis. IL-10 knockout (KO) mice and their C57BL/6 controls were submitted to repeated courses (3/wk, during 6 wk, followed by 1 wk of recovery) of cerulein-induced acute pancreatitis. TGF-beta(1) release was measured on plasma, and its pancreatic expression was assessed by quantitative RT-PCR and immunohistochemistry. Intrapancreatic IL-10 gene expression was assessed by semiquantitative RT-PCR, and intrapancreatic collagen content was assessed by picrosirius staining. Activated stellate cells were detected by immunohistochemistry. S phase intrapancreatic cells were marked using tritiated thymidine labeling. After repeated acute pancreatitis, IL-10 KO mice had more severe histological lesions and fibrosis (intrapancreatic collagen content) than controls. TGF-beta(1) plasma levels, intrapancreatic transcription, and expression by ductal and interstitial cells, as well as the number of activated stellate cells, were significantly higher. IL-10 KO mice disclosed significantly fewer acinar cells in S phase, whereas the opposite was observed for pseudotubular cells. Endogenous IL-10 controls the regeneration phase and limits the severity of fibrosis and glandular atrophy induced by repeated episodes of acute pancreatitis in mice.

A randomised phase II study of two different schedules of pegylated liposomal doxorubicin in metastatic breast cancer (EORTC-10993).

One hundred and sixteen women with measurable metastatic breast cancer participated in a randomised phase II study of single agent liposomal pegylated doxorubicin (Caelyx) given either as a 60 mg/m2 every 6 weeks (ARM A) or 50 mg/m2 every 4 weeks (ARM B) schedule. Patients were over 65 years of age or, if younger, had refused or been unsuitable for standard anthracyclines. The aims of the study were to evaluate toxicity and dose delivery with the two schedules and obtain further information on the response rate of liposomal pegylated doxorubicin as a single agent in anthracycline nai ve advanced breast cancer. Twenty-six patients had received prior adjuvant chemotherapy (including an anthracycline in 10). Sixteen had received non-anthracycline-based first-line chemotherapy for advanced disease. One hundred and eleven patients were evaluable for toxicity and 106 for response. The delivered dose intensity (DI) was 9.8 mg/m2 (95% CI, 7.2-10.4) with 37 (69%) achieving a DI of >90% on ARM A and 11.9 mg/m2 (95% CI, 7.5-12.8) with 37 (65%) achieving a DI of >90% on ARM B. The adverse event profiles of the two schedules were distinctly different. Mucositis was more common with the every 6 weeks regimen (35% CTC grade 3/4 in ARM A, 14% in ARM B) but palmar plantar erythrodysesthesia (PPE) was more frequent with the every 4 weeks regimen (2% CTC grade 3/4 in ARM A, 16% in ARM B). Confirmed objective partial responses by RECIST criteria were seen with both schedules; 15/51 (29%) on ARM A and 17/56 (31%) on ARM B. Liposomal pegylated doxorubicin showed significant activity in advanced breast cancer with a generally favourable side-effect profile. The high frequency of stomatitis seen with 6 weekly treatment makes this the less preferred of the two schedules tested.

Mature results of a randomized phase II multicenter study of exemestane versus tamoxifen as first-line hormone therapy for postmenopausal women with metastatic breast cancer.

BACKGROUND: Women with hormone-responsive metastatic breast cancer (MBC) may respond to or have stable disease with a number of hormone therapies. We explored the efficacy and safety of the steroidal aromatase inactivator exemestane as first-line hormonal therapy in MBC in postmenopausal women. PATIENTS AND METHODS: Patients with measurable disease were eligible if they had received no prior hormone therapy for metastatic disease and had hormone receptor positive disease or hormone receptor unknown disease with a long disease-free interval from adjuvant therapy. They were randomized to tamoxifen 20 mg/day or exemestane 25 mg/day in this open-label study. RESULTS: Blinded independently reviewed response rates for exemestane and tamoxifen were 41% and 17%, respectively. Fifty-seven per cent of exemestane- and 42% of tamoxifen-treated patients experienced clinical benefit, defined as complete or partial response, or disease stabilization lasting at least 6 months. There was a low incidence of severe flushing, sweating, nausea and edema in women who received exemestane. One exemestane-treated patient had a pulmonary embolism with grade 4 dyspnea. CONCLUSIONS: Exemestane is well tolerated and active in the first-line treatment of hormone-responsive MBC. An ongoing EORTC phase III trial is comparing the efficacy, measuring time-to-disease progression, of exemestane and tamoxifen.

Promising results with exemestane in the first-line treatment of metastatic breast cancer: a randomized phase II EORTC trial with a tamoxifen control.

Because tamoxifen (TAM), a nonsteroidal antiestrogen, is routinely used in the adjuvant setting, other hormone therapies are needed as alternatives for first-line treatment of metastatic breast cancer (MBC). Currently, exemestane (EXE) and other antiaromatase agents are indicated for use in patients who experience failure of TAM. In this multicenter, randomized, open-label, TAM-controlled (20 mg/day), phase II trial, we examined the activity and tolerability of EXE 25 mg/day for the first-line treatment of MBC in postmenopausal women. Exemestane was well tolerated and demonstrated substantial first-line antitumor activity based on intent-to-treat analysis of peer-reviewed responses. In the EXE arm, values for complete, partial, and objective response, clinical benefit, and time to tumor progression (TTP) exceeded those reported for TAM although no statistical comparison was made. Based on these encouraging results, a phase III trial will compare EXE and TAM.

The effect of exemestane on serum lipid profile in postmenopausal women with metastatic breast cancer: a companion study to EORTC Trial 10951, 'Randomized phase II study in first line hormonal treatment for metastatic breast cancer with exemestane or tamoxifen in postmenopausal patients'.

BACKGROUND: The impact of aromatase inhibitors (AIs) on non-cancer-related outcomes, which are known to be affected by oestrogens, has become increasingly important in postmenopausal women with hormone-dependent breast cancer. So far, data related to the effect of AIs on lipid profile in postmenopausal women is scarce. This study, as a companion substudy of an EORTC phase II trial (10951), evaluated the impact of exemestane, a steroidal aromatase inactivator, on the lipid profile of postmenopausal metastatic breast cancer (MBC) patients. PATIENTS AND METHODS: The EORTC trial 10951 randomised 122 postmenopausal breast cancer patients to exemestane (E) 25 mg (n = 62) or tamoxifen (T) 20 mg (n = 60) once daily as a first-line treatment in the metastatic setting. Exemestane showed promising results in all the primary efficacy end points of the trial (response rate, clinical benefit rate and response duration), and it was well tolerated with low incidence of serious toxicity. As a secondary end point of this phase II trial, serum triglycerides (TRG), high-density lipoprotein cholesterol (HDL), total cholesterol (TC), lipoprotein a (Lip a), and apolipoproteins (Apo) B and A1 were measured at baseline and while on therapy (at 8, 24 and 48 weeks) to assess the impact of exemestane and tamoxifen on serum lipid profiles. Of the 122 randomised patients, those who had baseline and at least one other lipid assessment are included in the present analysis. The patients who received concomitant drugs that could affect lipid profile are included only if these drugs were administered throughout the study treatment. Increase or decrease in lipid parameters within 20% of baseline were considered as non-significant and thus unchanged. RESULTS: Seventy-two patients (36 in both arms) were included in the statistical analysis. The majority of patients had abnormal TC and normal TRG, HDL, Apo A1, Apo B and Lip a levels at baseline. Neither exemestane nor tamoxifen had adverse effects on TC, HDL, Apo A1, Apo B or Lip a levels at 8, 24 and 48 weeks of treatment. Exemestane and tamoxifen had opposite effects on TRG levels: exemestane lowered while tamoxifen increased TRG levels over time. There were too few patients with normal baseline TC and abnormal TRG, HDL, Apo A1, Apo B and Lip a levels to allow for assessment of E's impact on these subsets. The atherogenic risk determined by Apo A1:Apo B and TC:HDL ratios remained unchanged throughout the treatment period in both the E and T arms. CONCLUSIONS: Overall, exemestane has no detrimental effect on cholesterol levels and the atherogenic indices, which are well-known risk factors for coronary artery disease. In addition, it has a beneficial effect on TRG levels. These data, coupled with E's excellent efficacy and tolerability, support further exploration of its potential in the metastatic, adjuvant and chemopreventive setting.

A binding site for the cyclic adenosine 3',5'-monophosphate-response element-binding protein as a regulatory element in the grp78 promoter.

The 78-kDa glucose-regulated protein (GRP78) is ubiquitously expressed in many cell types. Its promoter contains multiple protein-binding sites and functional elements. In this study we examined a high affinity protein-binding site spanning bp -198 to -180 of the rat grp78 promoter, using nuclear extracts from both B-lymphoid and HeLa cells. This region contains a sequence TGACGTGA which, with the exception of one base, is identical to the cAMP-response element (CRE). Site-directed mutagenesis reveals that this sequence functions as a major basal level regulatory element in hamster fibroblast cells and is also necessary to maintain high promoter activity under stress-induced conditions. By gel mobility shift analysis, we detect two specific protein complexes. The major specific complex I, while immunologically distinct from the 42-kDa CRE-binding protein (CREB), binds most strongly to the grp site, but also exhibits affinity for the CRE consensus sequence. As such, complex I may consist of other members of the CREB/activating transcription factor protein family. The minor specific complex II consists of CREB or a protein antigenically related to it. A nonspecific complex III consists of the Ku autoantigen, an abundant 70- to 80-kDa protein complex in HeLa nuclear extracts. By cotransfection experiments, we demonstrate that in F9 teratocarcinoma cells, the grp78 promoter can be transactivated by the phosphorylated CREB or when the CREB-transfected cells are treated with the calcium ionophore A23187. The differential regulation of the grp78 gene by cAMP in specific cell types and tissues is discussed.

Urinary lipoarabinomannan as predictor for the tuberculosis immune reconstitution inflammatory syndrome

info:eu-repo/semantics/published

The reminiscence bump in the temporal distribution of the best football players of all time: Pelé, Cruijff or Maradona?

The reminiscence bump is the tendency to recall more autobiographical memories from adolescence and early adulthood than from adjacent lifetime periods. In this online study, the robustness of the reminiscence bump was examined by looking at participants' judgements about the quality of football players. Dutch participants (N = 619) were asked who they thought the five best players of all time were. The participants could select the names from a list or enter the names when their favourite players were not on the list. Johan Cruijff, Pelé, and Diego Maradona were the three most often mentioned players. Participants frequently named football players who reached the midpoint of their career when the participants were adolescents (mode = 17). The results indicate that the reminiscence bump can also be identified outside the autobiographical memory domain.

Association of Common Genetic Polymorphisms with Melanoma Patient IL-12p40 Blood Levels, Risk, and Outcomes.

Recent investigation has identified association of IL-12p40 blood levels with melanoma recurrence and patient survival. No studies have investigated associations of single-nucleotide polymorphisms (SNPs) with melanoma patient IL-12p40 blood levels or their potential contributions to melanoma susceptibility or patient outcome. In the current study, 818,237 SNPs were available for 1,804 melanoma cases and 1,026 controls. IL-12p40 blood levels were assessed among 573 cases (discovery), 249 cases (case validation), and 299 controls (control validation). SNPs were evaluated for association with log[IL-12p40] levels in the discovery data set and replicated in two validation data sets, and significant SNPs were assessed for association with melanoma susceptibility and patient outcomes. The most significant SNP associated with log[IL-12p40] was in the IL-12B gene region (rs6897260, combined P=9.26 × 10(-38)); this single variant explained 13.1% of variability in log[IL-12p40]. The most significant SNP in EBF1 was rs6895454 (combined P=2.24 × 10(-9)). A marker in IL12B was associated with melanoma susceptibility (rs3213119, multivariate P=0.0499; OR=1.50, 95% CI 1.00-2.24), whereas a marker in EBF1 was associated with melanoma-specific survival in advanced-stage patients (rs10515789, multivariate P=0.02; HR=1.93, 95% CI 1.11-3.35). Both EBF1 and IL12B strongly regulate IL-12p40 blood levels, and IL-12p40 polymorphisms may contribute to melanoma susceptibility and influence patient outcome.