A stitch in time: Efficient computation of genomic DNA melting bubbles

Background: It is of biological interest to make genome-wide predictions of the locations of DNA melting bubbles using statistical mechanics models. Computationally, this poses the challenge that a generic search through all combinations of bubble starts and ends is quadratic. Results: An efficient algorithm is described, which shows that the time complexity of the task is O(NlogN) rather than quadratic. The algorithm exploits that bubble lengths may be limited, but without a prior assumption of a maximal bubble length. No approximations, such as windowing, have been introduced to reduce the time complexity. More than just finding the bubbles, the algorithm produces a stitch profile, which is a probabilistic graphical model of bubbles and helical regions. The algorithm applies a probability peak finding method based on a hierarchical analysis of the energy barriers in the Poland-Scheraga model. Conclusions: Exact and fast computation of genomic stitch profiles is thus feasible. Sequences of several megabases have been computed, only limited by computer memory. Possible applications are the genome-wide comparisons of bubbles with promotors, TSS, viral integration sites, and other melting-related regions.Comment: 16 pages, 10 figure

Electrochemically Generated Acid and Its Containment to 100 Micron Reaction Areas for the Production of DNA Microarrays

An addressable electrode array was used for the production of acid at sufficient concentration to allow deprotection of the dimethoxytrityl (DMT) protecting group from an overlaying substrate bound to a porous reaction layer. Containment of the generated acid to an active electrode of 100 micron diameter was achieved by the presence of an organic base. This procedure was then used for the production of a DNA array, in which synthesis was directed by the electrochemical removal of the DMT group during synthesis. The product array was found to have a detection sensitivity to as low as 0.5 pM DNA in a complex background sample

Capturing the essence of folding and functions of biomolecules using Coarse-Grained Models

The distances over which biological molecules and their complexes can function range from a few nanometres, in the case of folded structures, to millimetres, for example during chromosome organization. Describing phenomena that cover such diverse length, and also time scales, requires models that capture the underlying physics for the particular length scale of interest. Theoretical ideas, in particular, concepts from polymer physics, have guided the development of coarse-grained models to study folding of DNA, RNA, and proteins. More recently, such models and their variants have been applied to the functions of biological nanomachines. Simulations using coarse-grained models are now poised to address a wide range of problems in biology.Comment: 37 pages, 8 figure

Protocol-Inspired Hardware Testing

The relevance of protocol conformance testing techniques to hardware testing is discussed. It is shown that the ioconf (input-output conformance) approach used in protocol testing can be applied to generate tests for a synchronous hardware design using its formal specification. The generated tests are automatically applied to a circuit by a VHDL testbench, thus giving confidence that the hardware design meets its high-level formal specification. Case studies illustrate how the ideas can be applied to standard hardware verification benchmarks such as the Single Pulser and Black-Jack Dealer

Bioethical and medico-legal implications of withdrawing artificial nutrition and hydration from adults in critical care

The withdrawal of artificial nutrition and hydration or other life-sustaining treatments is a clinical decision, made in ICUs or in other settings, involving patients suffering from serious and irreversible diseases or impaired consciousness. Such clinical decisions must be made in the best interests of the patient, and must respect the wishes previously expressed by patients, laid down in their wills, in advance directives or in information passed on by relatives or legally appointed health-care agents, and in observance of common bioethical and legal rules in individual nations. Intensivists who are expert in the management of lifesustaining treatments are also involved in deciding when to withdraw futile therapies and instigate end-of-life care procedures for dying patients, with the sole aim of providing comfort and ensuring that suffering is not prolonged unnecessaril

Thermoregulation and fluid balance during a 30-km march in 60-versus 80-year-old subjects

The presence of impaired thermoregulatory and fluid balance responses to exercise in older individuals is well established. To improve our understanding on thermoregulation and fluid balance during exercise in older individuals, we compared thermoregulatory and fluid balance responses between sexagenarians and octogenarians during prolonged exercise. Forty sexagenarians (60 ± 1 year) and 36 octogenarians (81 ± 2 year) volunteered to participate in a 30-km march at a self-selected pace. Intestinal temperature (T in) and heart rate were recorded every 5 km. Subjects reported fluid intake, while urine output was measured and sweat rate was calculated. Octogenarians demonstrated a lower baseline T in and a larger exercise-induced increase in T in compared to sexagenarians (1.2 ± 0.5 °C versus 0.7 ± 0.4 °C, p  0.05). These results suggest that thermoregulatory responses deteriorate with advancing age, while fluid balance is regulated appropriately during a 30-km walking march under moderate ambient conditions

Optimal-Foraging Predator Favors Commensalistic Batesian Mimicry

BACKGROUND:Mimicry, in which one prey species (the Mimic) imitates the aposematic signals of another prey (the Model) to deceive their predators, has attracted the general interest of evolutionary biologists. Predator psychology, especially how the predator learns and forgets, has recently been recognized as an important factor in a predator-prey system. This idea is supported by both theoretical and experimental evidence, but is also the source of a good deal of controversy because of its novel prediction that in a Model/Mimic relationship even a moderately unpalatable Mimic increases the risk of the Model (quasi-Batesian mimicry). METHODOLOGY/PRINCIPAL FINDINGS:We developed a psychology-based Monte Carlo model simulation of mimicry that incorporates a "Pavlovian" predator that practices an optimal foraging strategy, and examined how various ecological and psychological factors affect the relationships between a Model prey species and its Mimic. The behavior of the predator in our model is consistent with that reported by experimental studies, but our simulation's predictions differed markedly from those of previous models of mimicry because a more abundant Mimic did not increase the predation risk of the Model when alternative prey were abundant. Moreover, a quasi-Batesian relationship emerges only when no or very few alternative prey items were available. Therefore, the availability of alternative prey rather than the precise method of predator learning critically determines the relationship between Model and Mimic. Moreover, the predation risk to the Model and Mimic is determined by the absolute density of the Model rather than by its density relative to that of the Mimic. CONCLUSIONS/SIGNIFICANCE:Although these predictions are counterintuitive, they can explain various kinds of data that have been offered in support of competitive theories. Our model results suggest that to understand mimicry in nature it is important to consider the likely presence of alternative prey and the possibility that predation pressure is not constant

Estimating the Magnitude and Direction of Altered Arbovirus Transmission Due to Viral Phenotype

Vectorial capacity is a measure of the transmission potential of a vector borne pathogen within a susceptible population. Vector competence, a component of the vectorial capacity equation, is the ability of an arthropod to transmit an infectious agent following exposure to that agent. Comparisons of arbovirus strain-specific vector competence estimates have been used to support observed or hypothesized differences in transmission capability. Typically, such comparisons are made at a single time point during the extrinsic incubation period, the time in days it takes for the virus to replicate and disseminate to the salivary glands. However, vectorial capacity includes crucial parameters needed to effectively evaluate transmission capability, though often this is based on the discrete vector competence values. Utilization of the rate of change of vector competence over a range of days gives a more accurate measurement of the transmission potential. Accordingly, we investigated the rate of change in vector competence of dengue virus in Aedes aegypti mosquitoes and the resulting vectorial capacity curves. The areas under the curves represent the effective vector competence and the cumulative transmission potentials of arboviruses within a population of mosquitoes. We used the calculated area under the curve for each virus strain and the corresponding variance estimates to test for differences in cumulative transmission potentials between strains of dengue virus based on our dynamic model. To further characterize differences between dengue strains, we devised a displacement index interpreted as the capability of a newly introduced strain to displace the established, dominant circulating strain. The displacement index can be used to better understand the transmission dynamics in systems where multiple strains/serotypes circulate or even multiple arbovirus species. The use of a rate of a rate of change based model of vectorial capacity and the informative calculations of the displacement index will lead to better measurements of the differences in transmission potential of arboviruses

How university’s activities support the development of students’ entrepreneurial abilities: case of Slovenia and Croatia

The paper reports how the offered university activities support the development of students’ entrepreneurship abilities. Data were collected from 306 students from Slovenian and 609 students from Croatian universities. The study reduces the gap between theoretical researches about the academic entrepreneurship education and individual empirical studies about the student’s estimation of the offered academic activities for development of their entrepreneurial abilities. The empirical research revealed differences in Slovenian and Croatian students’ perception about (a) needed academic activities and (b) significance of the offered university activities, for the development of their entrepreneurial abilities. Additionally, the results reveal that the impact of students’ gender and study level on their perception about the importance of the offered academic activities is not significant for most of the considered activities. The main practical implication is focused on further improvement of universities’ entrepreneurship education programs through selection and utilization of activities which can fill in the recognized gaps between the students’ needed and the offered academic activities for the development of students’ entrepreneurial abilities