ABC–CDE: Toward Approximate Bayesian Computation With Complex High-Dimensional Data and Limited Simulations

Approximate Bayesian computation (ABC) is typically used when the likelihood is either unavailable or intractable but where data can be simulated under different parameter settings using a forward model. Despite the recent interest in ABC, high-dimensional data and costly simulations still remain a bottleneck in some applications. There is also no consensus as to how to best assess the performance of such methods without knowing the true posterior. We show how a nonparametric conditional density estimation (CDE) framework, which we refer to as ABC–CDE, help address three nontrivial challenges in ABC: (i) how to efficiently estimate the posterior distribution with limited simulations and different types of data, (ii) how to tune and compare the performance of ABC and related methods in estimating the posterior itself, rather than just certain properties of the density, and (iii) how to efficiently choose among a large set of summary statistics based on a CDE surrogate loss. We provide theoretical and empirical evidence that justify ABC–CDE procedures that directly estimate and assess the posterior based on an initial ABC sample, and we describe settings where standard ABC and regression-based approaches are inadequate. Supplemental materials for this article are available online.     

Effects of novel taxanes SB-T-1213 and IDN5109 on tubulin polymerization and mitosis

SB-T-1213 and IDN5109 are semisynthetic, orally available taxanes that are up to 400-fold more active than paclitaxel against drug-resistant cells. IDN5109 is in clinical trials. We investigated the primary target for SB-T-1213 and IDN5109 and whether the compounds interact with microtubules differently than paclitaxel. Unlike paclitaxel, at 1-10 microM both novel taxanes initiate microtubule polymerization in vitro with no lag. They enhance polymerization equally or more potently than paclitaxel. SB-T-1213 induces unusual microtubules with attached extra protofilaments or open sheets, and IDN5109 induces large protofilamentous sheets. Both inhibit HeLa cell proliferation, block mitosis at the metaphase/anaphase transition, bundle microtubules at high drug concentrations, and induce abnormal metaphase spindles and apoptosis. They target microtubules but alter their polymerization and structure differently than paclitaxel. These differences may play a role in their enhanced cytotoxicity and efficacy.     

Multiple reactivity of freund's “methyl isothiocyanate sulfide” in cycloaddition-elimination reactions

4-Methyl-5-methylimino-1,2,4-dithiazolidine-3-thione ( l )and 2,4-dimethyl-1,2,4-thiadiazolidine-3,5-dithione ( 2 ) are interconvertible in acetone at 50°. They react with ketenes and electrophilic acetylenes to give the thiazole derivatives 6 and 7 after elimination of methyl isothiocyanate or carbon disulfide. Electrophilic isothiocyanates and phenylsulfonyl isocyanate transform the C = S function of 1 in an imine function ( 8 ), and a similar transformation of the thiourea C = S function of 2 is observed on reaction with phenylsulfonyl isocyanate, giving 9 .     

Advances in capillary electrophoretically mediated microanalysis

Recent developments in the use of capillary electrophoretic techniques for the in-line study of enzyme reactions and derivatization protocols are reviewed. The article is divided into two parts: (i) in-line enzyme reactions and (ii) in-line derivatization. The first part introduces electrophoretically mediated microanalysis (EMMA) and discusses and illustrates the different modes of EMMA. A literature overview is provided, starting from 1996, and the investigated enzymes are classified into two tables based on the mode of engagement (i.e., continuous or transient) of the developed EMMA-based assay. The second part starts with an introduction of the procedures and the nomenclature used in the area of in-line derivatization protocols based on EMMA. Reported derivatization procedures are discussed and classified in tables, according to the functional group that is derivatized.     

Inhibition study of angiotensin converting enzyme by capillary electrophoresis after enzymatic reaction at capillary inlet

Capillary electrophoresis was used to study the inhibition of angiotensin-converting enzyme (ACE) by different inhibitors. Reaction occurred at the capillary inlet during a predetermined waiting period, followed by the electrophoretic separation of the reaction compounds. ACE activity was determined by the quantification of the reaction product, hippuric acid, at 230 nm. The technique was used to study the potency of five different inhibitors (captopril, lisinopril, perindoprilat, quinaprilat and benazeprilat). During a kinetic study, the Ki value of captopril was estimated to be 55.4 +/- 8.8 nM, a value consistent with previously reported values.     

Brain weight differences associated with induced focal microgyria

Background  

Disrupting neural migration with bilateral focal freezing necrosis on postnatal day 1 (P1) results in the formation of 4-layered microgyria. This developmental injury triggers a pervasive neural reorganization, which is evident at the electrophysiological, behavioral, and anatomical levels. In this experiment, we investigated changes in brain weight as an index of global disruption of neural systems caused by focal damage to the developing cortical plate.     

Efficient Protection in MPλS Networks Using Backup Trees: Part One—Concepts and Heuristics

Multi-protocol lambda switching (MPS) has recently been applied in the optical network control plane to provide fast lightpath provisioning. As an increasing amount of traffic is carried in optical transport networks (OTNs), single network failures can affect a vast amount of traffic, making lightpath protection crucial. Therefore, shared backup tree (BT) lightpath protection is a promising paradigm in MPS networks due to its ability of fast recovery and its efficiency in consumed resources. A shared BT is used to protect a group of working lightpaths towards the same destination. From the working lightpaths in such a group, only one affected lightpath at a time can be recovered using the BT. The main problem is how to group and route the working paths (WPs) and how to route the BTs, in such a way that the capacity resources used by the WPs and the BTs are minimized. In Part One of this study (presented in this paper), we propose three approaches to cope with this problem. The first approach is a purely integer linear programming (ILP) based method. The second one is a combination of ILP and a heuristic technique. The last one is a purely heuristic approach. In this paper, these approaches are theoretically compared. In Part Two [1] of this study, several simulations are carried out in order to compare these approaches in terms of performance and computing effort. The experimental results are in line with the theoretical expectations.     

Linear Discrepancy and Weak Discrepancy of Partially Ordered Sets

The linear discrepancy of a partially ordered set P=(X,) is the least integer k for which there exists an injection f: XZ satisfying (i) if xy then f(x)<f(y) and (ii) if xy then |f(x)–f(y)|k. This concept is closely related to the weak discrepancy of P studied previously. We prove a number of properties of linear and weak discrepancies and relate them to other poset parameters. Both parameters have applications in ranking the elements of a partially ordered set so that the difference in rank of incomparable elements is minimized.     

Mathematics in Context: Measurement,Packaging and Caring for Our Environment

The purpose of this article is to present illustrative examples which will help teachers and teacher educators combine mathematics and science through the activities which involve higher order thinking and worthwhile tasks. Packaging provides an important and meaningful context for exploring important mathematics and an important environmental issue.