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.     

Statistic Complexity: Combining Kolmogorov Complexity with an Ensemble Approach

Background

The evaluation of the complexity of an observed object is an old but outstanding problem. In this paper we are tying on this problem introducing a measure called statistic complexity.

Methodology/Principal Findings

This complexity measure is different to all other measures in the following senses. First, it is a bivariate measure that compares two objects, corresponding to pattern generating processes, on the basis of the normalized compression distance with each other. Second, it provides the quantification of an error that could have been encountered by comparing samples of finite size from the underlying processes. Hence, the statistic complexity provides a statistical quantification of the statement ‘ is similarly complex as ’.

Conclusions

The presented approach, ultimately, transforms the classic problem of assessing the complexity of an object into the realm of statistics. This may open a wider applicability of this complexity measure to diverse application areas.     

Complexity by Subtraction

The eye and brain: standard thinking is that these devices are both complex and functional. They are complex in the sense of having many different types of parts, and functional in the sense of having capacities that promote survival and reproduction. Standard thinking says that the evolution of complex functionality proceeds by the addition of new parts, and that this build-up of complexity is driven by selection, by the functional advantages of complex design. The standard thinking could be right, even in general. But alternatives have not been much discussed or investigated, and the possibility remains open that other routes may not only exist but may be the norm. Our purpose here is to introduce a new route to functional complexity, a route in which complexity starts high, rising perhaps on account of the spontaneous tendency for parts to differentiate. Then, driven by selection for effective and efficient function, complexity decreases over time. Eventually, the result is a system that is highly functional and retains considerable residual complexity, enough to impress us. We try to raise this alternative route to the level of plausibility as a general mechanism in evolution by describing two cases, one from a computational model and one from the history of life.     

Reducing GWAS Complexity

Genome-wide association studies (GWAS) have revealed numerous genomic 'hits' associated with complex phenotypes. In most cases these hits, along with surrogate genetic variation as measure by numerous single nucleotide polymorphisms (SNPs) that are in linkage disequilibrium, are not in coding genes making assignment of functionality or causality intractable. Here we propose that fine-mapping along with the matching of risk SNPs at chromatin biofeatures lessen this complexity by reducing the number of candidate functional/causal SNPs. For example, we show here that only on average 2 SNPs per prostate cancer risk locus are likely candidates for functionality/causality; we further propose that this manageable number should be taken forward in mechanistic studies. The candidate SNPs can be looked up for each prostate cancer risk region in 2 recent publications in 2015^1,2 Han Y, Hazelett DJ, Wiklund F, Schumacher FR, Stram DO, Berndt SI, Wang Z, Rand KA, Hoover RN, Machiela MJ, et al. Integration of Multiethnic Fine-mapping and Genomic Annotation to Prioritize Candidate Functional SNPs at Prostate Cancer Susceptibility Regions. Hum Mol Genet 2015; 24(19):5603–18. Amin Al Olama A, Dadaev T, Hazelett DJ, Li Q, Leongamornlert D, Saunders EJ, Stephens S, Cieza-Borrella C, Whitmore I, Benlloch Garcia S, et al. Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans. Hum Mol Genet 2015; 24(19):5589–602.  from our groups.     

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.     

Spermatogenesis revisited

Summary Gametogenesis is normal through meiosis and the earliest phases of spermiogenesis in male-sterile mice homozygous for the recessive, pleiotropic, mutation hpy (hydrocephalic-polydactyl). However, structurally complete sperm flagella were not encountered. Instead, partially assembled axonemal structures and/or poorly organized aggregates of other tail components (mitochondria, outer coarse fibers) were seen at the posterior poles of nuclei in older spermatids. The ultrastructure of centrioles in spermatids was normal, but that of axonemes associated with them was not. These findings suggest that the observed flagella dysgenesis results from defects in assembly rather than from defective intiation centers. Released gametes usually consisted of distorted nuclei and associated acrosome enclosed in a relatively close fitting plasma membrane. Perturbations of sperm head development were also encountered; they included extreme nuclear elongation, and distortion of the acrosome and underlying nuclear material by inpushings of finger-like processes of Sertoli cells. It is believed that sperm head anomalies are secondary consequences of the mutant condition. The findings support the view that the hpy locus represents one of a number of genes primarily involved in the mediation of flagella development.Aided by a grant from The National Foundation-March of DimesA preliminary account of some of the findings was presented elsewhere (Bryan, 1976)The author wishes to express his thanks to Mrs. Charla Danforth and Mr. James Barrows for capable technical assistance, to Dr. Walter J. Humphreys, Director, The Central Electron Microscope Laboratory, University of Georgia, for use of the facility, and to Dr. Willard F. Hollander, Iowa State University, for original breeding stock and helpful discussions