bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulator's view on the scientific and regulatory challenges in new mobility outcomes & PROs
Authors: Schlosser-Weber Gabriele
Published: January 2018

The current focus from research based pharmaceutical companies is rather on cancer, not CNS. There are several reasons for this, e.g. problems with pre-clinical models, problems with dose-finding, large long-lasting trials, high failure rate, eventually leading to no return on investment. Are the regulatory requirements too high? Certainly not in Multiple Sclerosis, where we had 5 approvals since 2011 (Fingolimod, Fampridine, Teriflunomide, Alemtuzumab, Dimethylfumarate). In parallel we have worked on a new guideline for MS clinical trials, starting with a concept paper in 2011 followed by a large EMA workshop with all relevant stakeholders in 2013. The aim was "to make sure that in the revision of the MS guideline, the EMA can take the most up-to-date, state-of the-art scientific developments in MS into consideration, as well as the positions of experts in the field on the main topics in the guideline". The publication of the final guideline followed in Q2 in 2015 (http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2015/03/WC500185161.pdf). Among other things, we concluded that in the context of long-term outcomes the development of secondary progression is most important. Neither a relapse-based primary endpoint nor an MRI based endpoint can be accepted as a surrogate for disease progression. The EDSS as a rating scale for disability is widely used but has well-known deficiencies, e.g. considerable variability among assessors, that make the interpretation of clinical relevance difficult. However, MS specialists and regulators are familiar with EDSS and it is historically the most frequently used clinician assessment of neurologic impairment in MS clinical trials. Therefore it still will be important to use the EDSS, along with other candidate parameters, to assess true unremitting disability also in future trials to allow comparison among trials. Candidates for other parameters to assess disability are various short-time functional walking tests (e.g. T25-FW, 6MWT) and the MSWS12. Alternative tools to EDSS are currently being developed. Hereby it is important to apply functional assessments for measuring disability in MS. Specific recommendations are not given, but in general the requirements for new tools are that they are reliable, valid, sensitive to change over time, predictive value for disability progression, clinically meaningful and acceptable by the patient. EMA strongly encourages the development of new approaches and innovative methods. EMA intends to apply a flexible approach with regard to the acceptability of positive new endpoints, but a prerequisite is the scientific justification and adequate validation. Qualification procedures are recommended. Collaborative work will be necessary by academia, industry and regulators to develop criteria for appropriate use of PROs in studies, for instance to help assessing clinical relevance.
Trends in winter excess mortality in Mexico 1991 - 2008
Authors: González-Santiago Omar , Ramirez-Lara Evangelina , Gracia-Vásquez Sandra L. , Balderas-Rentería Isaias
Published: January 2018

Objective: Analyze the mortality by all causes in México during the Winter season. Methods: We extracted and tabulated data on monthly all-cause mortality in the general population from 1991 to 2008 from database INEGI. Coefficients of seasonal variation in mortality were calculated. Results: An increase of 15 % in mortality for general population during Winter was observed during the studied period. The more susceptible age groups were old people and children with an increase of winter deaths of 19 % and 11 % respectively. Months with low levels of mortality were April, October and September for children, adolescents and old people respectively. Conclusions: In Mexico winter months shown the highest levels of mortality. The increase in mortality is similar to some Mediterranean countries. More susceptible age groups correspond to child and old people. Months with low levels of mortality are different for each age group. In México it is necessary identify the main factors that contribute to low mortality among different months according age groups.
Simple cephalo-caudal patterns embedded in complex human interpersonal behavior
Authors: Manduva Valli Kiran
Published: January 2018

A novel model is presented to explain human social behavior. In recent years, a cephalo-caudal directionality to behavior has been reported in a few mammals including rodents, cattle and cats. This model shows how complex human behavior also follows this rule of cephalo-caudal directionality. The positions of the lower motor neurons mediating the specific acts in the cephalo-caudal neural axis are considered to be an important correlate of the act. The model consists of a primary layer, consisting of the orienting modules – eyes, head and body and a secondary layer consisting of the six transmitting channels – the eyes, facial expression, speech, upper limbs, lower limbs and the external genitalia. The model demonstrates through multiple examples that complex human behavior also follows a cephalo caudal directionality, both in the orienting modules as well as in the transmitting channels. In this paradigm, conciliatory and agonistic communications are examined as prototypes for analysis of more complex dominant and submissive behavior as well as psychiatric conditions such as mania and depression. The model is sensitive to the social context of behavior which is without precedent in the literature. Further, the concept of ‘mobility gradient’ is applied to human behavior to understand motor behavior in depression and mania and catatonic behavior. Finally, certain issues pertinent to difficulties of behavioral description and model building in human behavior are discussed. The model emphasizes the role of objective behavioral description paradigms that borrow from concepts in comparative psychology and animal behavior.
An optimization approach to detect differentially methylated regions from Whole Genome Bisulfite Sequencing data
Authors: Hesse Nina , Schröder Christopher , Rahmann Sven
Published: January 2018

Whole genome bisulfite sequencing (WGBS) is the current method of choice to obtain the methylation status of each single CpG dinucleotide in a genome. The typical analysis asks for regions that are differentially methylated (DMRs) between samples of two classes, such as different cell types. However, even with current low sequencing costs, many studies need to cope with few samples and medium coverage to stay within budget. We present a method to conservatively estimate the methylation difference between the two classes. Starting from a Bayesian paradigm, we formulate an optimization problem related to LASSO approaches. We present a dynamic programming approach to efficiently compute the optimal solution and its implementation diffmer. We discuss the dependency of the resulting DMRs on the free parameters of our approach and compare the results to those obtained by other DMR discovery tools (BSmooth and RADMeth). We showcase that our method discovers DMRs that are missed by the other tools.
Why did the UV-A-induced photoluminescent blue-green glow in trilobite eyes and exoskeletons not cause problems for trilobites?
Authors: Schoenemann Brigitte , Clarkson Euan N.K. , Horváth Gábor
Published: January 2018

The calcitic lenses in the eyes of Palaeozoic trilobites are unique in the animal kingdom, although the use of calcite would have conveyed great advantages for vision in aquatic systems. Calcite lenses are transparent, and due to their high refractive index they would facilitate the focusing of light. In some respects, however, calcite lenses bear evident disadvantages. Birefringence would cause double images at different depths, but this is not a problem for trilobites since the difference in the paths of the ordinary and extraordinary rays is less than the diameter of the receptor cells. Another point, not discussed hitherto, is that calcite fluoresces when illuminated with UV-A. Here we show experimentally that calcite lenses fluoresce, and we discuss why fluorescence does not diminish the optical quality of these lenses and the image formed by them. In the environments in which the trilobites lived, UV-A would not have been a relevant factor, and thus fluorescence would not have disturbed or confused their visual system. We also argue that whatever the reason was that calcite was never again used successfully in the visual systems of aquatic arthropods, it was not fluorescence.
Safe Hands: teaching innovation project to improve hand hygiene in health sciences.
Authors: Cambil-Martin Jacobo
Published: January 2018

Background: Since 2004, the World Alliance for Patient Safety brings proposing hand hygiene as the key measure of its international strategy in the fight against healthcare-associated infections. In Spain the Safe Hands Distinction of the Patient Safety Observatory recognizes the good practices on improving hand hygiene of the World Health Organization. Objectives: Apply the WHO multimodal strategy to improve hand hygiene at the Faculty of Health Sciences and maintain the culture of Patient Safety on hand hygiene by students and staff. Methods: A teaching innovation project called "Safe Hands" was developed in the Nursing Degree at the Faculty of Health Sciences of the University of Granada during the academic period 2013-2015. The tool "Guide to the Implementation of the WHO Multimodal Hand Hygiene Improvement Strategy" served to develop and plan the program to improve hand hygiene according to its five phases. In parallel, activities were implemented according to the three stages of the accreditation process "Safe Hands Distinction". Results: The Faculty of Health Sciences has become a dynamic secure environment that provides alcoholic gel for practice and training on hand hygiene, disseminates information and updated signage, reinforces the training of students and staff, and reinforces the quality assurance project. Study Limitations: It is necessary to complete the five years cycle of continuous improvement in quality of the WHO guide to establish an optimal strategy for improving hand hygiene. Conclusion: Safe Hands has launched the WHO multimodal strategy in an academic context. The Faculty of Health Sciences has got credited the Safe Hands Distinction, becoming the first Higher Education Center accredited in Spain to improve hand hygiene.
All the services large and micro: Revisiting industrial practices in services computing
Authors: Schermann Gerald , Cito Jürgen , Leitner Philipp
Published: January 2018

Services computing is both, an academic field of study looking back at close to 15 years of fundamental research, as well as a vibrant area of industrial software engineering. Industrial practice in this area is notorious for its ever-changing nature, with the state of the art changing almost on a yearly basis based on the ebb and flow of various hypes and trends. In this paper, we provide a look "across the wall" into industrial services computing. We conducted an empirical study based on the service ecosystem of 42 companies, and report, among other aspects, how service-to-service communication is implemented, how service discovery works in practice, what Quality-of-Service metrics practitioners are most interested in, and how services are deployed and hosted. We argue that not all assumptions that are typical in academic papers in the field are justified based on industrial practice, and conclude the paper with recommendations for future research that is more aligned with the services industry.
A Socratic epistemology for verbal emotional intelligence
Authors: Kazemzadeh Abe , Gibson James , Georgiou Panayiotis , Lee Sungbok , Narayanan Shrikanth
Published: January 2018

We describe and experimentally validate a question-asking framework for machine-learned linguistic knowledge about human emotions. Using the Socratic method as a theoretical inspiration, we develop an experimental method and computational model for computers to learn subjective information about emotions by playing emotion twenty questions (EMO20Q), a game of twenty questions limited to words denoting emotions. Using human-human EMO20Q data we bootstrap a sequential Bayesian model that drives a generalized pushdown automaton-based dialog agent that further learns from 300 human-computer dialogs collected on Amazon Mechanical Turk. The human-human EMO20Q dialogs show the capability of humans to use a large, rich, subjective vocabulary of emotion words. Training on successive batches of human-computer EMO20Q dialogs shows that the automated agent is able to learn from subsequent human-computer interactions. Our results show that the training procedure enables the agent to learn a large set of emotions words. The fully trained agent successfully completes EMO20Q at 67% of human performance and 30% better than the bootstrapped agent. Even when the agent fails to guess the human opponent's emotion word in the EMO20Q game, the agent's behavior of searching for knowledge makes it appear human-like, which enables the agent maintain user engagement and learn new, out-of-vocabulary words. These results lead us to conclude that the question-asking methodology and its implementation as a sequential Bayes pushdown automaton are a successful model for the cognitive abilities involved in learning, retrieving, and using emotion words by an automated agent in a dialog setting.
Accessing and applying molecular history
Authors: Stern Joshua G , Gaucher Eric A
Published: January 2018

Studying the evolutionary history of life’s molecules - DNA, RNA, and protein - reveals nature-based solutions to real-world problems. We discuss an approach to applied molecular evolution that is well-known within the field but may be unfamiliar to a wider audience. Using a case study at the intersection of molecular evolution and medicine, we introduce the fundamental concepts of orthology and paralogy. We also explain a practical entry point to molecular evolution named STORI: Selectable Taxon Ortholog Retrieval Iteratively. STORI is a machine learning algorithm designed to clear a bottleneck that researchers encounter when studying evolution.
Sampling designs matching species biology produce accurate and affordable abundance indices
Authors: Harris Grant , Farley Sean , Russell Gareth J , Butler Matthew J , Selinger Jeff
Published: January 2018

Wildlife biologists often use grid-based designs to sample animals and generate abundance estimates. Although sampling in grids is theoretically sound, in application, the method can be logistically difficult and expensive when sampling elusive species inhabiting extensive areas. These factors make it challenging to sample animals and meet the statistical assumption of all individuals having an equal probability of capture. Violating this assumption biases results. Does an alternative exist? Perhaps by sampling only where resources attract animals (i.e. targeted sampling), it would provide accurate abundance estimates more efficiently and affordably. However, biases from this approach would also arise if individuals have an unequal probability of capture, especially if some failed to visit the sampling area. Since most biological programs are resource limited, and acquiring abundance data drives many conservation and management applications, it becomes imperative to identify economical and informative sampling designs. Therefore, we evaluated abundance estimates generated from grid and targeted sampling designs using simulations based on geographic positioning system (GPS) data from 42 Alaskan brown bears (Ursus arctos). Migratory salmon drew brown bears from the wider landscape, concentrating them at anadromous streams. This provided a scenario for testing the targeted approach. Grid and targeted sampling varied by trap amount, location (traps placed randomly, systematically or by expert opinion), and traps stationary or moved between capture sessions. We began by identifying when to sample, and if bears had equal probability of capture. We compared abundance estimates against seven criteria: bias, precision, accuracy, effort, plus encounter rates, and probabilities of capture and recapture. One grid (49 km2 cells) and one targeted configuration provided the most accurate results. Both placed traps by expert opinion and moved traps between capture sessions, which raised capture probabilities. The grid design was least biased (-10.5%), but imprecise (CV 21.2%), and used most effort (16,100 trap-nights). The targeted configuration was more biased (-17.3%), but most precise (CV 12.3%), with least effort (7,000 trap-nights). Targeted sampling generated encounter rates four times higher, and capture and recapture probabilities 11% and 60% higher than grid sampling, in a sampling frame 88% smaller. Bears had unequal probability of capture with both sampling designs, partly because some bears never had traps available to sample them. Hence, grid and targeted sampling generated abundance indices, not estimates. Overall, targeted sampling provided the most accurate and affordable design to index abundance. Targeted sampling may offer an alternative method to index the abundance of other species inhabiting expansive and inaccessible landscapes elsewhere, provided their attraction to resource concentrations.
Screening level mixture risk assessment of pharmaceuticals in STP effluents
Authors: Backhaus Thomas , Karlsson Maja
Published: January 2018

We modeled the ecotoxicological risks of the pharmaceutical mixtures emitted from STP effluents into the environment. The classic mixture toxicity concept of Concentration Addition was used to calculate the total expected risk of the analytically determined mixtures, compare the expected impact of seven effluent streams and pinpoint the most sensitive group of species. The risk quotient of a single, randomly selected pharmaceutical is often more than a factor of 1 000 lower than the mixture risk, clearly indicating the need to systematically analyse the overall risk of all pharmaceuticals present. The MCR, which is the ratio between the most risky compound and the total mixture risk, varies between 1.2 and 4.2, depending on the actual scenario and species group under consideration. The mixture risk quotients, based on acute data and an assessment factor of 1 000, regularly exceed 1, indicating a potential risk for the environment, depending on the dilution in the recipient stream. The top 10 mixture components explain more than 95% of the mixture risk in all cases. A mixture toxicity assessment cannot go beyond the underlying single substance data. The lack of data on the chronic toxicity of most pharmaceuticals as well as the very few data available for in vivo fish toxicity has to be regarded as a major knowledge gap in this context. On the other hand, ignoring Independent Action or even using the sum of individual risk quotients as a rough approximation of Concentration Addition does not have a major impact on the final risk estimate.
Next generation cluster editing
Authors: Bellitto Thomas , Marschall Tobias , Schönhuth Alexander , Klau Gunnar W
Published: January 2018

Genomic structural variations play key roles in genetic diversity and disease. Despite recent advances in structural variation discovery, many variants are yet to be discovered. Midsize insertions and deletions pose particularly involved algorithmic challenges. The recent CLEVER algorithm addressed these challenges with a statistical model on cliques in a graph whose nodes are read alignments and whose edges arise from a statistical test on length and overlap of read alignments. However, the resulting read alignment clusters tend to be too small and are heavily overlapping, which leads to losses in recall performance rates. Here we present a model based on weighted cluster editing, which alleviates these issues: clusters are provably non-overlapping and tend to be larger. In order to render the inherent optimization problem tractable on all read alignments of a genome, we present a novel, principled heuristic, which runs in time linear in the length of the genome. The heuristic is based on an exact polynomial-time algorithm for weighted cluster editing in one-dimensional point graphs. We demonstrate that the new model improves recall rates achieved by CLEVER.
ProCS15: A DFT-based chemical shift predictor for backbone and Cβ atoms in proteins
Authors: Larsen Anders S , Bratholm Lars A , Christensen Anders S , Channir Maher Jan , Jensen Jan H.
Published: January 2018

We present ProCS15: A program that computes the isotropic chemical shielding values of backbone and C β atoms given a protein structure in less than a second. ProCS15 is based on around 2.35 million OPBE/6-31G(d,p)//PM6 calculations on tripeptides and small structural models of hydrogen-bonding. The ProCS15-predicted chemical shielding values are compared to experimentally measured chemical shifts for Ubiquitin and the third IgG-binding domain of Protein G through linear regression and yield RMSD values of up to 2.2, 0.7, and 4.8 ppm for carbon, hydrogen, and nitrogen atoms. These RMSD values are very similar to corresponding RMSD values computed using OPBE/6-31G(d,p) for the entire structure for each proteins. These maximum RMSD values can be reduced by using NMR-derived structural ensembles of Ubiquitin. For example, for the largest ensemble the largest RMSD values are 1.7, 0.5, and 3.5 ppm for carbon, hydrogen, and nitrogen. The corresponding RMSD values predicted by several empirical chemical shift predictors range between 0.7 - 1.1, 0.2 - 0.4, and 1.8 - 2.8 ppm for carbon, hydrogen, and nitrogen atoms, respectively.
A unifying theory to describe transmembrane transport derived from thermodynamic principles
Authors: Herrera-Valdez Marco A
Published: January 2018

Herrera-Valdez. A unifying theory of physiological transmembrane transport Cellular homeostasis involves transmembrane molecular transport that is, in turn, mediated by proteins that enable molecular transport along, or against the (electro) chemical gradient of the molecules being transported. Transmembrane transport has been modelled in many studies using many functional forms that were not always derived from the same assumptions. A generic formulation that describes transmembrane fluxes regardless of whether they are mediated by carrier proteins or by open channels is presented here. The functional form of the flux was obtained from basic thermodynamic principles. Further, taking a slightly different approach, the same generic formulation mentioned above can also be obtained from the Nernst-Planck equation for the case of channel- mediated electrodiffusion. The generic formulation can be regarded as the product of an amplitude term and a driving force term, both nonlinear functions of the transmembrane concentrations of the molecules and possibly the transmembrane potential. The former captures the characteristics of the membrane-spanning protein mediating the transport and the latter is a non-linear function of the transmembrane concentrations of the ions. The generic formulation explicitly shows that the basal rate at which ions cross the membrane is the main difference between currents mediated by pumps and channels. Electrogenic transmembrane fluxes can be converted to currents to construct models of membrane excitability in which all the transmembrane currents have the same functional form. The applicability of the generic derivations presented here is illustrated with models of excitability for neurones and pacemaker cardiocytes.
A unifying theory to describe transmembrane transport derived from thermodynamic principles
Authors: Herrera-Valdez Marco A
Published: January 2018

Herrera-Valdez. A unifying theory of physiological transmembrane transport Cellular homeostasis involves transmembrane molecular transport mediated by proteins that enable molecular transport along, or against the (electro) chemical gradient of the molecules being transported. Transmembrane transport has been modelled in many studies using many functional forms that were not always derived from the same assumptions. A generic formulation that describes transmembrane fluxes regardless of whether they are mediated by carrier proteins or by open channels is presented here. The functional form of the flux was obtained from basic thermodynamic principles. Further, taking a slightly different approach, the same generic formulation mentioned above can also be obtained from the Nernst-Planck equation for the case of channel- mediated electrodiffusion. The generic formulation can be regarded as the product of an amplitude term and a driving force term, both nonlinear functions of the transmembrane concentrations of the molecules and possibly the transmembrane potential. The former captures the characteristics of the membrane-spanning protein mediating the transport and the latter is a non-linear function of the transmembrane concentrations of the ions. The generic formulation explicitly shows that the basal rate at which ions cross the membrane is the main difference between currents mediated by pumps and channels. Electrogenic transmembrane fluxes can be converted to currents to construct models of membrane excitability in which all the transmembrane currents have the same functional form. The applicability of the generic derivations presented here is illustrated with models of excitability for neurones and pacemaker cardiocytes.
A unifying theory for physiological transmembrane transport derived from thermodynamic principles
Authors: Herrera-Valdez Marco A
Published: January 2018

Cellular homeostasis involves transmembrane molecular transport mediated by membrane-spanning proteins. Such proteins either carry the molecules across the membrane, or facilitate their diffusion. A generic formulation that describes transmembrane fluxes, derived from basic thermodynamic principles, and describing fluxes mediated by carrier proteins or by open channels using the same functional form is presented here. An alternative derivation from the Nernst-Planck equation that yields the same generic formulation can be obtained for the case of channel-mediated electrodiffusion. In general terms, the generic formulation is a product of an amplitude and a driving force. The amplitude models properties of the protein mediating the transport including basal rates of transport. The driving force term that depends non-linearly on the transmembrane concentrations of the molecules being transported, and possibly the transmembrane potential. The model applied for channel mediated currents is capable of displaying rectification. Further, an extension for channel gating derived en passage allows fitting of currents recorded in voltage-clamp without using powers for the gating variables. The generic formulation explicitly shows that the basal rate at which ions cross the membrane is the main macroscopic difference between currents mediated by carrier proteins and channels. Many functional forms that were not always derived from the same assumptions can be found in modelling studies of transmembrane transport, especially those studies focusing on the membrane potential of excitable cells. The derivations presented here unify the theory of biological transmembrane transport. Of particular interest, electrogenic transmembrane fluxes described with the general formulation can be converted to currents for the construction of models of membrane excitability; all based on the same assumptions and having the same functional form. The applicability of the generic derivations presented here is illustrated with models of excitability for neurones and pacemaker cardiocytes.
Marital disharmony in a couple's marriage and its psychological effects on their children during the HIV disclosure process in Kenya
Authors: Gachanja Grace
Published: January 2018

The aim of this research brief is to summarize a case report study that described an HIV-positive married couple’s poor disclosure experience of their illnesses to all their children in the household. It is important to communicate this couple’s HIV disclosure experience to healthcare professionals so that they are aware of the problems that can occur if married or cohabiting couples do not collaborate with each other during the disclosure process. The data presented in the case report study and in this research brief should be used to provide targeted counseling to HIV-positive parents or cohabiting couples considering disclosure to their children.
The experiences of HIV-positive and HIV-negative children after receiving disclosure of their own and their parents’ illnesses, respectively
Authors: Gachanja Grace
Published: January 2018

The aim of this research brief is to describe a study that sought to understand the post-disclosure experiences of HIV-positive and negative children after they received disclosure of their own and their parents’ illnesses, respectively. This is the first study from Sub-Saharan Africa (SSA) that describes the post-disclosure experiences of HIV-positive and negative children in one study. Prior studies in SSA have mostly centered on the post-disclosure experiences of HIV-positive children after receiving disclosure of their own illnesses, or HIV-positive mothers’ descriptions of the effect of maternal disclosure on their HIV-negative children.
Whale shark behaviors observed in northeastern Quintana Roo, Mexico.
Authors: de la Parra Rafael , Dove Alistair D.M. , Galván Beatriz
Published: January 2018

Background: Whale shark feeding aggregations in northeastern Quintana Roo (Yucatan Peninsula) between May and September are a natural phenomenon well known to local people for decades. Since 2001 we have observed these animals, first as tourists and then as part of formal research activities including conventional tagging, aerial survey and photographic identification. During this time we have made significant behavioral observations, other than previously described: passive and active feeding, banking as predatory response, tolerance even to be touched by people.

Methods: Observations were made primarily during snorkeling surveys of the wale shark aggregation between 2001 and 2013. Video documenting and photographic identifications were made using ECOCEAN and our own photographic catalogue of individual Quintana Roo animals. Data collected on each whale shark included its location, sex, total length estimation, tagging, photographs and behavioral observations. Over 1,340 hours were spent in documenting many conducts performed by whale sharks. Important to notice that these observations were made mostly around tourism activities, but many were made before or after tour operation, or on separate sub-aggregations, under SEMARNAT permission: SGPA/DGVS/10048/12 Results: 54,662 photographs were obtained during 366 observation days, plus 1,382 videos for over 315 minutes, on a decade of study and survey. Individual whale sharks in the QR aggregation have also been observed in Belize, Honduras and the Gulf of Mexico and some have visitation records exceeding 10 years. Occasionally, early spring ephemeral aggregations occur, perhaps in response to short term plankton blooms, these are composed by the same individual animals as revealed after photographic identification. These aggregations are mostly male and immature. Larger females seem to stay on the periphery of the aggregation or even form separate small groups. Smaller animals appear to be more curious of humans than ar e older animals. Many animals feed vertically and some are observed “coughing” and “mouth washing”. Vigorous tail-flapping and increased remora activity often precedes defecation, banking behavior may be social.

Conclusion: Prolonged observation shows that whale sharks have a more diverse behavioral repertoire than known previously and confirming observations made of aquarium-held animals, as well as their ability to synchronize their presence with high productivity occurrence. More detailed studies of group composition are definitely needed, as are functional studies of some of the other intriguing behaviors. Since whale shark behavior is often opportunistic and facultative, and depends on many factors to coincide, like specific weather and oceanic conditions, food concentration as well as anthropogenic influence, statistical analysis is beyond this study consideration. Do these events play a role in breeding opportunity?
Evaluation of the validity of the Psychology Experiment Building Language tests of vigilance, auditory memory, and decision making
Authors: Piper Brian , Mueller Shane T , Talebzadeh Sara , Ki Min Jung
Published: January 2018

Background. The Psychology Experimental Building Language (PEBL) http://pebl.sourceforge.net/ test battery is a popular application for neurobehavioral investigations. This study evaluated the correspondence between the PEBL and the non-PEBL versions of four executive function tests. Methods. In one cohort, young-adults (N = 44) completed both the Conner’s Continuous Performance Test (CCPT) and the PEBL CPT (PCPT) with the order counter-balanced. In a second cohort, participants (N = 47) completed a non-computerized (Wechsler) and a computerized (PEBL) Digit Span (WDS or PDS) both Forward and Backward. Participants also completed the Psychological Assessment Resources or the PEBL versions of the Iowa Gambling Task (PARIGT or PEBLIGT). Results. The between test correlations were moderately high (reaction time r = 0.78, omission errors r = 0.65, commission errors r = 0.66) on the CPT. DS Forward was significantly greater than DS Backward independent of the test modality. The total WDS score was moderately correlated with the PDS (r = 0.56). The PARIGT and the PEBLIGTs showed a very similar pattern for response times across blocks, development of preference for Advantageous over Disadvantageous Decks, and Deck selections. However, the amount of money earned (score – loan) was significantly higher in the PEBLIGT during the last Block. Conclusions. These findings are broadly supportive of the criterion validity of the PEBL measures of sustained attention, short-term memory, and decision making. Select differences between workalike versions of the same test highlight how detailed aspects of implementation may have more important consequences for computerized testing than has been previously acknowledged.
Designing Universal Chemical Markup (UCM) through the reusable methodology based on analyzing existing related formats
Authors: Mokrý Jan , Nič Miloslav
Published: January 2018

Background: In order to design concepts for a new general-purpose chemical format we analyzed the strengths and weaknesses of current formats for common chemical data. While the new format is discussed more in the next article, here we describe our software tools and two stage analysis procedure that supplied the necessary information for the development. The chemical formats analyzed in both stages were: CDX, CDXML, CML, CTfile and XDfile. In addition the following formats were included in the first stage only: CIF, InChI, NCBI ASN.1, NCBI XML, PDB, PDBx/mmCIF, PDBML, SMILES, SLN and Mol2. Results: A two stage analysis process devised for both XML (Extensible Markup Language) and non-XML formats enabled us to verify if and how potential advantages of XML are utilized in the widely used general-purpose chemical formats. In the first stage we accumulated information about analyzed formats and selected the formats with the most general-purpose chemical functionality for the second stage. During the second stage our set of software quality requirements was used to assess the benefits and issues of selected formats. Additionally, the detailed analysis of XML formats structure in the second stage helped us to identify concepts in those formats. Using these concepts we came up with the concise structure for a new chemical format, which is designed to provide precise built-in validation capabilities and aims to avoid the potential issues of analyzed formats. Conclusions: We believe our analysis methodology is potentially highly reusable and could be easily adapted even for domains outside the chemistry area. It is because the methodology and software tools will need only few changes, although analyzed formats and software quality requirements for a format will differ according to the given domain.
Universal Chemical Markup (UCM) - A new format for common chemical data
Authors: Mokrý Jan , Nič Miloslav
Published: January 2018

Background: We wish to introduce a new chemical format called UCM (Universal Chemical Markup). The format is based on XML (Extensible Markup Language) and its first version focuses on recording chemical structures and their properties. Results: UCM currently supports structures containing isotopes, ions and various types of bonding including delocalized bonds. Properties can be expressed by combining UCM with UnitsML (Units Markup Language). Using UnitsML one defines quantities with scientific units, and then refers to them in UCM when recording property values. Users can also add literature references with BibTeXML (BibTeX Markup Language) and annotate the recorded data using plain text or XHTML (Extensible Hypertext Markup Language) descriptions. In contrast to presently available general-purpose chemical formats, UCM offers built-in validation, which combines both grammar and pattern-based XML schema languages. Thus, all recorded data can be precisely validated by UCM schemas in standard XML validators. Conclusions: We developed the structure for UCM from scratch on the basis of an analysis described in our previous article. Starting from scratch allowed us to integrate BibTeXML, UnitsML and XHTML as well as chemical line notations and identifiers into UCM. It also helped us to avoid unnecessary redundant parts and create the implementation that aims to minimize ambiguity and is designed to be easily extensible in the future.
Metagenomic and satellite analyses of red snow in the Russian Arctic
Authors: Hisakawa Nao , Quistad Steven , Hester Eric R , Martynova Daria , Maughan Heather , Sala Enric , Gavrilo Maria , Rohwer Forest
Published: January 2018

Cryophilic algae thrive in liquid water within snow and ice in alpine and polar regions worldwide. Blooms of these algae lowers albedo (reflection of sunlight), thereby altering melting patterns (Kohshima et al. 1993; Lutz et al. 2014; Thomas & Duval 1995) . Here metagenomic DNA analysis and satellite imaging were used to investigate red snow in Franz Josef Land in the Russian Arctic. Franz Josef Land red snow metagenomes confirmed that the communities are composed of the autotroph Chlamydomonas nivalis that is supporting a complex viral and heterotrophic bacterial community. Comparisons with white snow communities from other sites suggest that snow and ice are initially colonized by fungal-dominated communities and then succeeded by the more complex C. nivalis-heterotroph red snow. Satellite image analysis showed that red snow covers up to 80% of the surface of snow and ice fields in Franz Josef Land and globally. Together these results show that C. nivalis supports a local food web that is on the rise as temperatures warm, with potential widespread impacts on alpine and polar environments worldwide.
Gastric Cancer Transcription Factors in Patient Reported Outcomes (GCTF-PRO) – Draft proposal
Authors: Lee Sonia
Published: January 2018

The GCTF-PRO seeks to examine the extent gastric cancer patients are tapping into new information particularly outside of conventional healthcare disclosures. Its significance is in assessing dimensions of QOL paradigms that frame statistical power using predictive methods. It seeks to embed evidence-based theories (perceptual and cognitive) to awareness levels in an attempt to bridge the biotechnological advances with prognostic/ diagnostic-related patient satisfactions. At present, it may complement existing GC QOL instruments and offer a novel approach on how cellular level prognoses could possibly correlate with QOL measures.
Were the necks of Apatosaurus and Brontosaurus adapted for combat?
Authors: Taylor Michael P , Wedel Mathew J , Naish Darren , Engh Brian
Published: January 2018

The apatosaurine sauropods — Apatosaurus, Brontosaurus and possibly others — resemble their diplodocine relatives, but are generally more robust. Apatosaur necks are much thicker than in other sauropods: cervical ribs and their supports are uniquely robust, and the ribs are strongly displaced ventrally. The diapophyseal and parapophyseal rami therefore project ventrolaterally, so that the neck would have been subtriangular in cross-section, not tubular.

Why did apatosaurines evolve necks that were apomorphically expensive to build, maintain, and operate? While sexual selection is not a convincing explanation for the evolution of sauropod necks in general, several features of apatosaurine necks suggest adaptation for combat:

1. Ventral displacement of cervical ribs improved the lever arms of the hypaxial muscles, strengthening ventral neck movements.

2. Ventrolaterally directed parapophyseal rami were oriented to resist ventral impacts.

3. The ventral trough between the cervical ribs provided soft-tissue protection for the trachea, oesophagus, and major blood vessels.

4. The ventrolateral processes on the cervical ribs may have been bony clubs, bearing thickened pads of connective tissue or keratinous knobs or spikes.

These adaptations suggest a style of combat in which the neck itself was crashed down or sideways into the opponent, rather than giraffe-style combat in which the head is the weapon. The closest extant analogue may be the elephant seal Mirounga: males fight by crashing their necks and anterior thoraxes together. As with apatosaurs, their cervical vertebrae are more robust than in relatives, and their ventral processes more pronounced; but enormous soft-tissue padding makes the analogy very inexact.
Trade-off Service Portfolio Planning – A Case Study on Mining the Android App Market
Authors: Nayebi Maleknaz , Ruhe Guenther
Published: January 2018

Service portfolio planning is the process of designing collections of services and deciding on their provision. The problem is highly information intensive, and most of the information required is hard to gather. In this paper, we present a solution approach based on the paradigm of Analytical Open Innovation (AOI). Open innovation is a cheap and low risk problem solving approach which relies on knowledge exchange with outside of company as a competitive advantage. Different forms of open innovation; crowd source, open source and outsource; facilitate the provider and consumer interactions and brings higher customer value. In our proposed AOI approach, open innovation is utilized for elicitation of services from web data, crowdsourcing the service value from potential customers and for the estimation of service implementation effort. For service evaluation, we apply the Kano theory of product development and customer satisfaction. Based on that and as the result from an optimization process, resource-optimized service portfolios are created that constitute trade-offs in balancing between gained value and effort needed. As a proof of concept, the proposed approach is illustrated via a case study project for the composition of Over the Top TV (OTT) services. The atomic services from 241 qualified apps were analyzed from the android app market. We demonstrate that the proposed approach is able to generate optimized trade-off solutions, composing better apps at each capacity level and achieving better customer satisfaction .The level of improvement in customer satisfaction varies between 16.5% and 95.3%.
Using experimental evolution and next-generation sequencing to teach bench and bioinformatic skills
Authors: Mikheyev Alexander S , Arora Jigyasa
Published: January 2018

Advances in sequencing technology have exponentially increased data-generating capabilities, and data analysis has now become the major hurdle in many research programs. As sequencing tools become more accessible and automated, experimental design and data analysis skills become the key factors in determining the success of a study. However, proper bioinformatic analysis also relies on a deep understanding of laboratory workflow, in order to prevent biases in the data. This is particularly true if commercial kits are used, as proprietary reagents frequently obfuscate underlying reactions and their conditions. Here we present a training module that seamlessly combines laboratory components (experimental evolution of T5 bacteriophage resistance by Escherichia coli, and library preparation), with bioinformatic analysis of the resulting data. Students conduct a simple genetic variant discovery experiment in the course of about a week. The module uses mature Illumina chemistry for both library preparation and sequencing, though it can be modified for use with any sequencing platform. Because most students do not use Linux, the bioinformatic pipeline is available inside a cross-platform virtual machine, simplifying software installation, and providing a non-threatening introduction to the command line. The analysis, which is made simpler by the fact that most resistance mutations occur in one gene, making them easier to find, emphasizes the potential pitfalls of using short-read data for mutational analysis, and explores biases inherent to the methodology. This module can fill an existing training gap in advanced undergraduate, or early graduate education, allowing student to experience first-hand design, execution, and analysis of next-generation sequencing experiments.
Screening for Alternaria brassicicola resistance in the Brassicaceae: Bio-assay optimization and confocal microscopy insights into the infection process
Authors: Nowakowska Marzena , Wrzesińska Małgorzata , Kamiński Piotr , Nowicki Marcin , Lichocka Małgorzata , Tartanus Michał , Kozik Elżbieta U
Published: January 2018

Heavy losses incited yearly by Alternaria brassicicola on the vegetable Brassicaceae – have prompted our search for sources of genetic resistance against the resultant disease, dark leaf spot. We optimized several parameters to test the performance of the plants under controlled conditions to this disease, including leaf age and position, inoculum concentration, and incubation temperature. Using these optimized conditions, we screened a collection of 38 Brassicaceae cultigens with two methods (detached leaf and seedlings). Our results show, that either method can be used for the A. brassicicola resistance breeding, while the plant’s genotype was crucial in determining its response to the pathogen. The bio-assays for Alternaria resistance were more effective than the field tests, and resulted in identification of two interspecific hybrids that might be used in breeding programs. Confocal microscopy analyses of the leaf samples provided novel insights into the pathogen mode of infection: Direct epidermal infection or stomatal attack were dependent on plants’ resistance against A. brassicicola. Further, the actin network of the host cells reorganized around the papillas deposited under the pathogen’s appressorium. Papilla composition is predicted to be important in determining the plant’s resistance.