Potentiality in Biology

We take the potentialities that are studied in the biological sciences (e.g., totipotency) to be an important subtype of biological dispositions. The goal of this paper is twofold: first, we want to provide a detailed understanding of what biological dispositions are. We claim that two features are essential for dispositions in biology: the importance of the manifestation process and the diversity of conditions that need to be satisfied for the disposition to be manifest. Second, we demonstrate that the concept of a disposition (or potentiality) is a very useful tool for the analysis of the explanatory practice in the biological sciences. On the one hand it allows an in-depth analysis of the nature and diversity of the conditions under which biological systems display specific behaviors. On the other hand the concept of a disposition may serve a unificatory role in the philosophy of the natural sciences since it captures not only the explanatory practice of biology, but of all natural sciences. Towards the end we will briefly come back to the notion of a potentiality in biology

Protein structure and phenotypic analysis of pathogenic and population missense variants in STXBP1

Background: Syntaxin-binding protein 1, encoded by STXBP1, is highly expressed in the brain and involved in fusing synaptic vesicles with the plasma membrane. Studies have shown that pathogenic loss-of-function variants in this gene result in various types of epilepsies, mostly beginning early in life. We were interested to model pathogenic missense variants on the protein structure to investigate the mechanism of pathogenicity and genotype–phenotype correlations. Methods: We report 11 patients with pathogenic de novo mutations in STXBP1 identified in the first 4293 trios of the Deciphering Developmental Disorder (DDD) study, including six missense variants. We analyzed the structural locations of the pathogenic missense variants from this study and the literature, as well as population missense variants extracted from Exome Aggregation Consortium (ExAC). Results: Pathogenic variants are significantly more likely to occur at highly conserved locations than population variants, and be buried inside the protein domain. Pathogenic mutations are also more likely to destabilize the domain structure compared with population variants, increasing the proportion of (partially) unfolded domains that are prone to aggregation or degradation. We were unable to detect any genotype–phenotype correlation, but unlike previously reported cases, most of the DDD patients with STXBP1 pathogenic variants did not present with very early-onset or severe epilepsy and encephalopathy, though all have developmental delay with intellectual disability and most display behavioral problems and suffered seizures in later childhood. Conclusion: Variants across STXBP1 that cause loss of function can result in severe intellectual disability with or without seizures, consistent with a haploinsufficiency mechanism. Pathogenic missense mutations act through destabilization of the protein domain, making it prone to aggregation or degradation. The presence or absence of early seizures may reflect ascertainment bias in the literature as well as the broad recruitment strategy of the DDD study

A model for orientation effects in electron‐transfer reactions

A method for solving the single‐particle Schrödinger equation with an oblate spheroidal potential of finite depth is presented. The wave functions are then used to calculate the matrix element T_BA which appears in theories of nonadiabatic electron transfer. The results illustrate the effects of mutual orientation and separation of the two centers on TBA. Trends in these results are discussed in terms of geometrical and nodal structure effects. Analytical expressions related to T_BA for states of spherical wells are presented and used to analyze the nodal structure effects for T_BA for the spheroidal wells

Elevated expression of artemis in human fibroblast cells is associated with cellular radiosensitivity and increased apoptosis

Copyright @ 2012 Nature Publishing GroupThis article has been made available through the Brunel Open Access Publishing Fund.Background: The objective of this study was to determine the molecular mechanism(s) responsible for cellular radiosensitivity in two human fibroblast cell lines 84BR and 175BR derived from two cancer patients. Methods: Clonogenic assays were performed following exposure to increasing doses of gamma radiation to confirm radiosensitivity. γ-H2AX foci assays were used to determine the efficiency of DNA double strand break (DSB) repair in cells. Quantitative-PCR (Q-PCR) established the expression levels of key DNA DSB repair proteins. Imaging flow cytometry using Annexin V-FITC was used to compare artemis expression and apoptosis in cells. Results: Clonogenic cellular hypersensitivity in the 84BR and 175BR cell lines was associated with a defect in DNA DSB repair measured by the γ-H2AX foci assay. Q-PCR analysis and imaging flow cytometry revealed a two-fold overexpression of the artemis DNA repair gene which was associated with an increased level of apoptosis in the cells before and after radiation exposure. Over-expression of normal artemis protein in a normal immortalised fibroblast cell line NB1-Tert resulted in increased radiosensitivity and apoptosis. Conclusion: We conclude elevated expression of artemis is associated with higher levels of DNA DSB, radiosensitivity and elevated apoptosis in two radio-hypersensitive cell lines. These data reveal a potentially novel mechanism responsible for radiosensitivity and show that increased artemis expression in cells can result in either radiation resistance or enhanced sensitivity.This work was supported in part by The Vidal Sassoon Foundation USA. This article is made available through the Brunel Open Access Publishing Fund

Tourists' perceptions of the free-roaming dog population in Samoa

A study was undertaken to establish how visiting tourists to Samoa perceived free-roaming dogs (Canis familiaris) and their management, additionally some factors that influence their perceptions were assessed. Questionnaires were administered to 281 tourists across Samoa over 5 weeks. Free-roaming dogs were seen by 98.2% (n = 269/274) of respondents, with 64.9% (n = 137/211) reporting that their presence had a negative effect on overall holiday experience. Respondents staying in the Apia (capital city) area were more likely to consider dogs a problem (p < 0.0001), and there was a significant association between whether the respondent owned a dog and if they thought dogs were a nuisance in Samoa (p < 0.003). Forty-four percent (20/89) of non-dog owners agreed that dogs were a nuisance compared to 22% (80/182) of dog owners. The majority felt that dogs required better control and management in Samoa (81%, n = 222) and that there were too many “stray” dogs (67.9%, n = 188). More respondents were negatively affected by the dogs’ presence (64.9%, 137/211), and felt that the dogs made their holiday worse, than respondents that felt the dogs’ presence improved their holiday experience (35.1%, 74/211). Most respondents stated that the dogs had a low impact (one to three; 68%, 187/275) on their stay in Samoa, whilst 24% (65/275) and 8% (23/275) stated they had a medium or high impact, respectively, on their stay. Respondents showed strong support for humane population management. Free-roaming dogs present a complex problem for Samoa and for its tourism industry in particular. The findings of this study further support the need for more discussion and action about the provision of veterinary services and population management for dogs in Samoa. It also provides information complementing an earlier study of the attitudes of local Samoans

Heat Treated NiP–SiC Composite Coatings: Elaboration and Tribocorrosion Behaviour in NaCl Solution

Tribocorrosion behaviour of heat-treated NiP and NiP–SiC composite coatings was investigated in a 0.6 M NaCl solution. The tribocorrosion tests were performed in a linear sliding tribometer with an electrochemical cell interface. It was analyzed the influence of SiC particles dispersion in the NiP matrix on current density developed, on coefficient of friction and on wear volume loss. The results showed that NiP–SiC composite coatings had a lower wear volume loss compared to NiP coatings. However, the incorporation of SiC particles into the metallic matrix affects the current density developed by the system during the tribocorrosion test. It was verified that not only the volume of co-deposited particles (SiC vol.%) but also the number of SiC particles per coating area unit (and consequently the SiC particles size) have made influence on the tribocorrosion behaviour of NiP–SiC composite coatings

Towards Physical Hybrid Systems

Some hybrid systems models are unsafe for mathematically correct but physically unrealistic reasons. For example, mathematical models can classify a system as being unsafe on a set that is too small to have physical importance. In particular, differences in measure zero sets in models of cyber-physical systems (CPS) have significant mathematical impact on the mathematical safety of these models even though differences on measure zero sets have no tangible physical effect in a real system. We develop the concept of "physical hybrid systems" (PHS) to help reunite mathematical models with physical reality. We modify a hybrid systems logic (differential temporal dynamic logic) by adding a first-class operator to elide distinctions on measure zero sets of time within CPS models. This approach facilitates modeling since it admits the verification of a wider class of models, including some physically realistic models that would otherwise be classified as mathematically unsafe. We also develop a proof calculus to help with the verification of PHS.Comment: CADE 201

ZnO:Co Diluted Magnetic Semiconductor or Hybrid Nanostructure for Spintronics?

We have studied the influence of intrinsic and extrinsic defects in the magnetic and electrical transport properties of Co-doped ZnO thin films. X ray absorption measurements show that Co substitute Zn in the ZnO structure and it is in the 2+ oxidation state. Magnetization (M) measurements show that doped samples are mainly paramagnetic. From M vs. H loops measured at 5 K we found that the values of the orbital L and spin S numbers are between 1 and 1.3 for L and S = 3/2, in agreement with the representative values for isolated Co 2+. The obtained negative values of the Curie-Weiss temperatures indicate the existence of antiferromagnetic interactions between transition metal atoms.Comment: To be published in Journal of Materials Scienc

Vertex importance extension of betweenness centrality algorithm

Variety of real-life structures can be simplified by a graph. Such simplification emphasizes the structure represented by vertices connected via edges. A common method for the analysis of the vertices importance in a network is betweenness centrality. The centrality is computed using the information about the shortest paths that exist in a graph. This approach puts the importance on the edges that connect the vertices. However, not all vertices are equal. Some of them might be more important than others or have more significant influence on the behavior of the network. Therefore, we introduce the modification of the betweenness centrality algorithm that takes into account the vertex importance. This approach allows the further refinement of the betweenness centrality score to fulfill the needs of the network better. We show this idea on an example of the real traffic network. We test the performance of the algorithm on the traffic network data from the city of Bratislava, Slovakia to prove that the inclusion of the modification does not hinder the original algorithm much. We also provide a visualization of the traffic network of the city of Ostrava, the Czech Republic to show the effect of the vertex importance adjustment. The algorithm was parallelized by MPI (http://www.mpi-forum.org/) and was tested on the supercomputer Salomon (https://docs.it4i.cz/) at IT4Innovations National Supercomputing Center, the Czech Republic.808726