Saddlepoint approximations to sensitivities of tail probabilities of random sums and comparisons with Monte Carlo estimators

This article proposes computing sensitivities of upper tail probabilities of random sums by the saddlepoint approximation. The considered sensitivity is the derivative of the upper tail probability with respect to the parameter of the summation index distribution. Random sums with Poisson or Geometric distributed summation indices and Gamma or Weibull distributed summands are considered. The score method with importance sampling is considered as an alternative approximation. Numerical studies show that the saddlepoint approximation and the method of score with importance sampling are very accurate. But the saddlepoint approximation is substantially faster than the score method with importance sampling. Thus, the suggested saddlepoint approximation can be conveniently used in various scientific problems.

The Moldable Debugger: A Framework for Developing Domain-Specific Debuggers

Debuggers are crucial tools for developing object-oriented software systems as they give developers direct access to the running systems. Nevertheless, traditional debuggers rely on generic mechanisms to explore and exhibit the execution stack and system state, while developers reason about and formulate domain-specific questions using concepts and abstractions from their application domains. This creates an abstraction gap between the debugging needs and the debugging support leading to an inefficient and error-prone debugging effort. To reduce this gap, we propose a framework for developing domain-specific debuggers called the Moldable Debugger. The Moldable Debugger is adapted to a domain by creating and combining domain-specific debugging operations with domain-specific debugging views, and adapts itself to a domain by selecting, at run time, appropriate debugging operations and views. We motivate the need for domain-specific debugging, identify a set of key requirements and show how our approach improves debugging by adapting the debugger to several domains.

Rasmussen's spectral sequences and the \germslN-concordance invariants

Combining known spectral sequences with a new spectral sequence relating reduced and unreduced slN-homology yields a relations hip between the Homflypt-homology of a knot and its slN-concordance invariants. As an application, some of the slN-concordance invariants are shown to be linearly independent.

Estimation and calibration of the water isotope differential diffusion length in ice core records

Palaeoclimatic information can be retrieved from the diffusion of the stable water isotope signal during firnification of snow. The diffusion length, a measure for the amount of diffusion a layer has experienced, depends on the firn temperature and the accumulation rate. We show that the estimation of the diffusion length using power spectral densities (PSDs) of the record of a single isotope species can be biased by uncertainties in spectral properties of the isotope signal prior to diffusion. By using a second water isotope and calculating the difference in diffusion lengths between the two isotopes, this problem is circumvented. We study the PSD method applied to two isotopes in detail and additionally present a new forward diffusion method for retrieving the differential diffusion length based on the Pearson correlation between the two isotope signals. The two methods are discussed and extensively tested on synthetic data which are generated in a Monte Carlo manner. We show that calibration of the PSD method with this synthetic data is necessary to be able to objectively determine the differential diffusion length. The correlation-based method proves to be a good alternative for the PSD method as it yields precision equal to or somewhat higher than the PSD method. The use of synthetic data also allows us to estimate the accuracy and precision of the two methods and to choose the best sampling strategy to obtain past temperatures with the required precision. In addition to application to synthetic data the two methods are tested on stable-isotope records from the EPICA (European Project for Ice Coring in Antarctica) ice core drilled in Dronning Maud Land, Antarctica, showing that reliable firn temperatures can be reconstructed with a typical uncertainty of 1.5 and 2 °C for the Holocene period and 2 and 2.5 °C for the last glacial period for the correlation and PSD method, respectively.

Practical domain-specific debuggers using the Moldable Debugger framework

Understanding the run-time behavior of software systems can be a challenging activity. Debuggers are an essential category of tools used for this purpose as they give developers direct access to the running systems. Nevertheless, traditional debuggers rely on generic mechanisms to introspect and interact with the running systems, while developers reason about and formulate domain-specific questions using concepts and abstractions from their application domains. This mismatch creates an abstraction gap between the debugging needs and the debugging support leading to an inefficient and error-prone debugging effort, as developers need to recover concrete domain concepts using generic mechanisms. To reduce this gap, and increase the efficiency of the debugging process, we propose a framework for developing domain-specific debuggers, called the Moldable Debugger, that enables debugging at the level of the application domain. The Moldable Debugger is adapted to a domain by creating and combining domain-specific debugging operations with domain-specific debugging views, and adapts itself to a domain by selecting, at run time, appropriate debugging operations and views. To ensure the proposed model has practical applicability (i.e., can be used in practice to build real debuggers), we discuss, from both a performance and usability point of view, three implementation strategies. We further motivate the need for domain-specific debugging, identify a set of key requirements and show how our approach improves debugging by adapting the debugger to several domains.

A Multiplex Real-Time PCR with High Resolution Melting Analysis for the Characterization of Antimicrobial Resistance in Neisseria gonorrhoeae.

Resistance to antibiotics used against Neisseria gonorrhoeae infections is a major public health concern. Antimicrobial resistance (AMR) testing relies on time-consuming culture-based methods. Development of rapid molecular tests for detecting AMR determinants could provide valuable tools for surveillance, epidemiological studies and to inform individual case management. We developed a fast (<1.5 hrs) SYBR-green based real-time PCR method with high resolution melting (HRM) analysis. One triplex and three duplex reactions included two sequences for N. gonorrhoeae identification and seven determinants of resistance to extended-spectrum cephalosporins (ESCs), azithromycin, ciprofloxacin, and spectinomycin. The method was validated by testing 39 previously fully-characterized N. gonorrhoeae strains, 19 commensal Neisseria spp., and an additional panel of 193 gonococcal isolates. Results were compared with culture-based AMR determination. The assay correctly identified N. gonorrhoeae and the presence or absence of the seven AMR determinants. There was some cross-reactivity with non-gonococcal Neisseria species and the detection limit was 10(3)-10(4) gDNA copies/reaction. Overall, the platform accurately detected resistance to ciprofloxacin (sensitivity and specificity, 100%), ceftriaxone (sensitivity 100%, specificity 90%), cefixime (sensitivity 92%, specificity 94%), azithromycin and spectinomycin (both sensitivity and specificity, 100%). In conclusion, our methodology accurately detects mutations generating resistance to antibiotics used to treat gonorrhea. Low assay sensitivity prevents direct diagnostic testing of clinical specimens but this method can be used to screen collections of gonococcal isolates for AMR more quickly than with current culture-based AMR testing.