Introduction à la théorie de la viabilité

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

Large-scale association study identifies ICAM gene region as breast and prostate cancer susceptibility locus

We conducted a large-scale association study to identify genes that influence nonfamilial breast cancer risk using a collection of German cases and matched controls and >25,000 single nucleotide polymorphisms located within 16,000 genes. One of the candidate loci identified was located on chromosome 19p13.2 [odds ratio (OR) = 1.5, P = 0.001]. The effect was substantially stronger in the subset of cases with reported family history of breast cancer (OR = 3.4, P = 0.001). The finding was subsequently replicated in two independent collections (combined OR = 1.4, P < 0.001) and was also associated with predisposition to prostate cancer in an independent sample set of prostate cancer cases and matched controls (OR = 1.4, P = 0.002). High-density single nucleotide polymorphism mapping showed that the extent of association spans 20 kb and includes the intercellular adhesion molecule genes ICAM1, ICAM4, and ICAM5. Although genetic variants in ICAM5 showed the strongest association with disease status, ICAM1 is expressed at highest levels in normal and tumor breast tissue. A variant in ICAM5 was also associated with disease progression and prognosis. Because ICAMs are suitable targets for antibodies and small molecules, these findings may not only provide diagnostic and prognostic markers but also new therapeutic opportunities in breast and prostate cancer.

Efficiency comparison of Markov Chain Monte Carlo simulation with subset simulation (MCMC/ss) to standard Monte Carlo Simulation (sMC) for extreme event scenarios

Standard Monte Carlo (sMC) simulation models have been widely used in AEC industry research to address system uncertainties. Although the benefits of probabilistic simulation analyses over deterministic methods are well documented, the sMC simulation technique is quite sensitive to the probability distributions of the input variables. This phenomenon becomes highly pronounced when the region of interest within the joint probability distribution (a function of the input variables) is small. In such cases, the standard Monte Carlo approach is often impractical from a computational standpoint. In this paper, a comparative analysis of standard Monte Carlo simulation to Markov Chain Monte Carlo with subset simulation (MCMC/ss) is presented. The MCMC/ss technique constitutes a more complex simulation method (relative to sMC), wherein a structured sampling algorithm is employed in place of completely randomized sampling. Consequently, gains in computational efficiency can be made. The two simulation methods are compared via theoretical case studies.

Higher order universal one-way hash functions from the subset sum assumption

Universal One-Way Hash Functions (UOWHFs) may be used in place of collision-resistant functions in many public-key cryptographic applications. At Asiacrypt 2004, Hong, Preneel and Lee introduced the stronger security notion of higher order UOWHFs to allow construction of long-input UOWHFs using the Merkle-Damgård domain extender. However, they did not provide any provably secure constructions for higher order UOWHFs. We show that the subset sum hash function is a kth order Universal One-Way Hash Function (hashing n bits to m < n bits) under the Subset Sum assumption for k = O(log m). Therefore we strengthen a previous result of Impagliazzo and Naor, who showed that the subset sum hash function is a UOWHF under the Subset Sum assumption. We believe our result is of theoretical interest; as far as we are aware, it is the first example of a natural and computationally efficient UOWHF which is also a provably secure higher order UOWHF under the same well-known cryptographic assumption, whereas this assumption does not seem sufficient to prove its collision-resistance. A consequence of our result is that one can apply the Merkle-Damgård extender to the subset sum compression function with ‘extension factor’ k+1, while losing (at most) about k bits of UOWHF security relative to the UOWHF security of the compression function. The method also leads to a saving of up to m log(k+1) bits in key length relative to the Shoup XOR-Mask domain extender applied to the subset sum compression function.

The subset sum problem in Keno modelling

Aspects of Keno modelling throughout the Australian states of Queensland, New South Wales and Victoria are discussed: the trivial Heads or Tails and the more interesting Keno Bonus, which leads to consideration of the subset sum problem. The most intricate structure is where Heads or Tails and Keno Bonus are combined, and here, the issue of independence arises. Closed expressions for expected return to player are presented in each case.

Human CD141(+) (BDCA-3)(+) dendritic cells (DCs) represent a unique myeloid DC subset that cross-presents necrotic cell antigens

The characterization of human dendritic cell (DC) subsets is essential for the design of new vaccines. We report the first detailed functional analysis of the human CD141(+) DC subset. CD141(+) DCs are found in human lymph nodes, bone marrow, tonsil, and blood, and the latter proved to be the best source of highly purified cells for functional analysis. They are characterized by high expression of toll-like receptor 3, production of IL-12p70 and IFN-beta, and superior capacity to induce T helper 1 cell responses, when compared with the more commonly studied CD1c(+) DC subset. Polyinosine-polycytidylic acid (poly I:C)-activated CD141(+) DCs have a superior capacity to cross-present soluble protein antigen (Ag) to CD8(+) cytotoxic T lymphocytes than poly I:C-activated CD1c(+) DCs. Importantly, CD141(+) DCs, but not CD1c(+) DCs, were endowed with the capacity to cross-present viral Ag after their uptake of necrotic virus-infected cells. These findings establish the CD141(+) DC subset as an important functionally distinct human DC subtype with characteristics similar to those of the mouse CD8 alpha(+) DC subset. The data demonstrate a role for CD141(+) DCs in the induction of cytotoxic T lymphocyte responses and suggest that they may be the most relevant targets for vaccination against cancers, viruses, and other pathogens.

Mitochondrial membrane potential in a small subset of artemisinin-induced dormant plasmodium falciparum parasites in vitro

Artemisinin induced dormancy is a proposed mechanism for failures of mono-therapy and is linked with artemisinin resistance in Plasmodium falciparum. The biological characterization and dynamics of dormant parasites are not well understood. Here we report that following dihydroartemisinin (DHA) treatment in vitro, a small subset of morphologically dormant parasites was stained with rhodamine 123 (RH), a mitochondrial membrane potential (MMP) marker, and persisted to recovery. FACS sorted RH-positive parasites resumed growth at 10,000/well while RH-negative parasites failed to recover at 5 million/well. Furthermore, transcriptional activity for mitochondrial enzymes was only detected in RH-positive dormant parasites. Importantly, after treating dormant parasites with different concentrations of atovaquone, a mitochondrial inhibitor, the recovery of dormant parasites was delayed or stopped. This demonstrates that mitochondrial activity is critical for survival and regrowth of dormant parasites and that RH staining provides a means of identifying these parasites. These findings provide novel paths for studying and eradicating this dormant stage.

Interior view of the synagogue where David Dublon was cantor or rabbi; Dülmen, Germany Synagogues; Interior

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Interior view of the synagogue where David Dublon was cantor or rabbi with some of the children in the congregation; Dülmen, Germany Synagogues; Interior

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Official habits of Rabbi and Cantor Rabbis

Official habits of Rabbi and Cantor as introduced by the Beden Oberrat der Israeliten (Central Council of Jews) in 1843. The distinction of the Rabbi is expressed in his wearing a silk mantle over his wool coat and a white double collar, representing the tablets of Moses.

Dacomitinib versus erlotinib in patients with EGFR-mutated advanced nonsmall-cell lung cancer (NSCLC): Pooled subset analyses from two randomized trials

Background: The irreversible epidermal growth factor receptor (EGFR) inhibitors have demonstrated efficacy in NSCLC patients with activating EGFR mutations, but it is unknown if they are superior to the reversible inhibitors. Dacomitinib is an oral, small-molecule irreversible inhibitor of all enzymatically active HER family tyrosine kinases. Methods: The ARCHER 1009 (NCT01360554) and A7471028 (NCT00769067) studies randomized patients with locally advanced/metastatic NSCLC following progression with one or two prior chemotherapy regimens to dacomitinib or erlotinib. EGFR mutation testing was performed centrally on archived tumor samples. We pooled patients with exon 19 deletion and L858R EGFR mutations from both studies to compare the efficacy of dacomitinib to erlotinib. Results: One hundred twenty-one patients with any EGFR mutation were enrolled; 101 had activating mutations in exon 19 or 21. For patients with exon19/21 mutations, the median progression-free survival was 14.6 months [95% confidence interval (CI) 9.0–18.2] with dacomitinib and 9.6 months (95% CI 7.4–12.7) with erlotinib [unstratified hazard ratio (HR) 0.717 (95% CI 0.458–1.124), two-sided log-rank, P = 0.146]. The median survival was 26.6 months (95% CI 21.6–41.5) with dacomitinib versus 23.2 months (95% CI 16.0–31.8) with erlotinib [unstratified HR 0.737 (95% CI 0.431–1.259), two-sided log-rank, P = 0.265]. Dacomitinib was associated with a higher incidence of diarrhea and mucositis in both studies compared with erlotinib. Conclusions: Dacomitinib is an active agent with comparable efficacy to erlotinib in the EGFR mutated patients. The subgroup with exon 19 deletion had favorable outcomes with dacomitinib. An ongoing phase III study will compare dacomitinib to gefitinib in first-line therapy of patients with NSCLC harboring common activating EGFR mutations (ARCHER 1050; NCT01774721). Clinical trials number: ARCHER 1009 (NCT01360554) and A7471028 (NCT00769067).

On Guo and Nixon's Criterion for Feature Subset Selection: Assumptions, Implications,and Alternative Options

Guo and Nixon proposed a feature selection method based on maximizing I(x; Y),the multidimensional mutual information between feature vector x and class variable Y. Because computing I(x; Y) can be difficult in practice, Guo and Nixon proposed an approximation of I(x; Y) as the criterion for feature selection. We show that Guo and Nixon's criterion originates from approximating the joint probability distributions in I(x; Y) by second-order product distributions. We remark on the limitations of the approximation and discuss computationally attractive alternatives to compute I(x; Y).

On Training and Training Voids for Receive Antenna Subset Selection in Time-Varying Channels

Antenna selection (AS) provides most of the benefits of multiple-antenna systems at drastically reduced hardware costs. In receive AS, the receiver connects a dynamically selected subset of N available antennas to the L available RF chains. The "best" subset to be used for data reception is determined by means of channel estimates acquired using training sequences. Due to the nature of AS, the channel estimates at different antennas are obtained from different transmissions of the pilot sequence, and are, thus, outdated by different amounts in a time-varying channel. We show that a linear weighting of the estimates is optimum for the subset selection process, where the weights are related to the temporal correlation of the channel variations. When L is not an integer divisor of N, we highlight a new issue of "training voids", in which the last pilot transmission is not fully exploited by the receiver. We present a "void-filling" method for fully exploiting these voids, which essentially provides more accurate training for some antennas, and derive the optimal subset selection rule for any void-filling method. We also derive new closed-form equations for the performance of receive AS with optimal subset selection.

Training and Voids in Receive Antenna Subset Selection in Time-Varying Channels

Receive antenna selection (AS) provides many benefits of multiple-antenna systems at drastically reduced hardware costs. In it, the receiver connects a dynamically selected subset of N available antennas to the L available RF chains. Due to the nature of AS, the channel estimates at different antennas, which are required to determine the best subset for data reception, are obtained from different transmissions of the pilot sequence. Consequently, they are outdated by different amounts in a time-varying channel. We show that a linear weighting of the estimates is necessary and optimum for the subset selection process, where the weights are related to the temporal correlation of the channel variations. When L is not an integer divisor of N , we highlight a new issue of ``training voids'', in which the last pilot transmission is not fully exploited by the receiver. We then present new ``void-filling'' methods that exploit these voids and greatly improve the performance of AS. The optimal subset selection rules with void-filling, in which different antennas turn out to have different numbers of estimates, are also explicitly characterized. Closed-form equations for the symbol error probability with and without void-filling are also developed.