Linear regression for calibration lines revisited: weighting schemes for bioanalytical methods

When the assumption of homoscedasticity is not met for analytical data, a simple and effective way to counteract the greater influence of the greater concentrations on the fitted regression line is to use weighted least squares linear regression (WLSLR). The purpose of the present paper is to stress the relevance of weighting schemes for linear regression analysis and to show how this approach can be useful in the bioanalytical field. The steps to be taken in the study of the linear calibration approach are described. The application of weighting schemes was shown by using a high-performance liquid chromatography method for the determination of lamotrigine in biological fluids as a practical example. By using the WLSLR, the accuracy of the analytical method was improved at the lower end of the calibration curve. Bioanalytical methods data analysis was improved by using the WLSLR procedure.     

Inducements revisited

The paper defends the permissibility of paying inducements to research subjects against objections not covered in an earlier paper in Bioethics. The objections are that inducements would cause inequity, crowd out research, and undesirably commercialize the researcher-subject relationship. The paper shows how these objections presuppose implausible factual and/or normative claims. The final position reached is a qualified defence of freedom of contract which not only supports the permissibility of inducements but also offers guidance to ethics committees in dealing with practical problems that might arise if inducements are offered.     

Coadaptation revisited

During the four decades or more since Dobzhansky introduced the term "coadaptation" to refer to the commonly observed selective superiority of inversion heterozygotes in populations of Drosophila pseudoobscura, the definition of the term has evolved, as have views concerning the rapidity with which coadaptation might occur. Indeed, the paucity of demonstrated instances of linkage disequilibrium in natural populations has led many to dismiss coadaptation as a factor in evolutionary change. The present article reviews the reasons why coadaptation (and the equivalent expression, "integration of gene pools") was proposed as a phenomenon occurring in local (or experimental) populations, offers supporting data obtained through a reanalysis of data on irradiated populations of D. melanogaster, and concludes that sound evidence supports coadaptation as a factor in the genetic change of populations.     

Pursuit-deterrence revisited

Pursuit-deterrent signals - signals used by prey that apparently convince predators not to pursue them - were discovered 15 years ago, but their existence continues to rest on shaky empirical evidence. First, pursuit-deterrent signals are usually inferred by eliminating competing hypotheses rather than testing predictions derived from the pursuit-deterrent hypothesis directly. Second, the strength of selection pressures maintaining such signals in prey populations are unknown because behavioral ecologists infrequently observe natural predation attempts. Third, the nature of information passing between prey and predators is open to misinterpretation because measures are rarely taken to separate signals that advertise perception of the predator from those that advertise perception and the prey's condition.     

Lysosomes revisited

The first international symposium on lysosomes [1] was held in 1963 at the Ciba Foundation, under the chairmanship of Danielli and with the participation of a prestigious membership. It is interesting to compare our present understanding of the properties and functions of lysosomes with what was known 20 years ago.     

Dyslexia revisited

Summary Specific developmental dyslexia, a condition characterized by reduced reading, spelling, and writing abilities combined with normal intellectual capacity, has challenged geneticists and environmentalists. Although most of the strikingly controversial results can be traced to differences concerning diagnostic decision-making, there are many hints of a genetic contribution. Twin studies and extensive pedigree analysis substantiate this view, but it is too early to infer a definite mode of inheritance from the available data.     

Bayer revisited

Bayer accuses me of wrongly claiming that he holds a negative thesis about the role that the liberal emphasis on privacy rights has had on AIDS public health policy. In his reply to my review essay, he denies holding such a thesis and, moreover, makes the stronger claim that his position is sympathetic to liberalism, or at least to some versions of it. Although I appreciate Bayer's efforts to clarify his views about liberalism and a "culture of restraint and responsibility", it is clear to me that our differences are related not to a misunderstanding on my part, but to a fundamental disagreement concerning what liberalism as a political philosophy is, and what public policy implications it entails in the case of AIDS....     

Superbubbles revisited

Background

Superbubbles are distinctive subgraphs in direct graphs that play an important role in assembly algorithms for high-throughput sequencing (HTS) data. Their practical importance derives from the fact they are connected to their host graph by a single entrance and a single exit vertex, thus allowing them to be handled independently. Efficient algorithms for the enumeration of superbubbles are therefore of important for the processing of HTS data. Superbubbles can be identified within the strongly connected components of the input digraph after transforming them into directed acyclic graphs. The algorithm by Sung et al. (IEEE ACM Trans Comput Biol Bioinform 12:770–777, 2015) achieves this task in \(\mathcal {O}(m~log(m))\)-time. The extraction of superbubbles from the transformed components was later improved to by Brankovic et al. (Theor Comput Sci 609:374–383, 2016) resulting in an overall \(\mathcal {O}(m+n)\)-time algorithm.

Results

A re-analysis of the mathematical structure of superbubbles showed that the construction of auxiliary DAGs from the strongly connected components in the work of Sung et al. missed some details that can lead to the reporting of false positive superbubbles. We propose an alternative, even simpler auxiliary graph that solved the problem and retains the linear running time for general digraph. Furthermore, we describe a simpler, space-efficient \(\mathcal {O}(m+n)\)-time algorithm for detecting superbubbles in DAGs that uses only simple data structures.

Implementation

We present a reference implementation of the algorithm that accepts many commonly used formats for the input graph and provides convenient access to the improved algorithm. https://github.com/Fabianexe/Superbubble.

     

Spermatogenesis revisited

Summary This ultrastructural study confirms and extends the light microscope findings of Bryan (1971) concerning the presence and developmental fate of multinucleate spermatids. Four main classes of cells: uninucleate-individual, uninucleate-conjoined, multinucleate-conjoined, and multinucleate-individual, were identified along with a few instances of more complex syncytial organizations. When the respective nuclei in a given multinucleate are far enough apart, each develops autonomously but in synchrony with its neighbors. When nuclei are intimately associated, the normal pattern of spermiogenesis may be altered, giving rise to highly bizarre spermatozoa. Commonly, a single Golgi complex serves a pair of nuclei and gives rise to a T-shaped acrosome which binds the nuclei together. During the ensuing nuclear elongation phase, such units are invested by a single manchette. Pairs of axonemes within a common plasma membrane have also been encountered. These ultrastructural findings indicate that multinucleate spermatids are true components (not artifacts) of the seminiferous epithelium of normal animals. The presence of such cells and the unusual developmental consequences which can arise as a result of the multinucleate state must be taken into account when evaluating the course of spermatogenesis in cases of mutation- or chemically-induced infertility.These studies have been supported by funds from The Office of General Research, The University of Georgia.