bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of Ifosfamide-Cisplatin-Etoposide (ICE) Chemotherapy for a CNS Germinoma in a Child With Down Syndrome
Authors: Nodomi Seishiro , Umeda Katsutsugu , Ueno Hiroo , Saida Satoshi , Hiramatsu Hidefumi , Funaki Takeshi , Arakawa Yoshiki , Mizowaki Takashi , Adachi Souichi , Heike Toshio
Published: November 2016

Intracranial germ cell tumor is sometimes associated with Down syndrome; however, no optimal treatment has been developed due to the high risk of recurrence and treatment-related mortality. Here, we report on a patient with an intracranial germinoma in the bilateral basal ganglia. The patient received 3 courses of ifosfamide-cisplatin-etoposide in combination with whole-brain irradiation (24 Gy), with no serious complications. The patient is alive and disease free 16 months after the initial diagnosis. This regimen is a feasible treatment for intracranial germ cell tumor associated with Down syndrome, although careful attention must be paid to the increased risk for severe infection.
Early Lymphocyte Recovery and Outcome in Osteosarcoma
Authors: Lee Lynn , Fei Lin , Pope Jennifer , Wagner Lars M.
Published: November 2016

Background:

Early lymphocyte recovery following chemotherapy has been associated with improved outcome in many cancers, including in one small study of osteosarcoma patients.

Materials and Methods:

To confirm this finding, we retrospectively reviewed data from 53 patients with newly diagnosed osteosarcoma who had blood counts on day 14 (±1 d) following the first cycle of cisplatin and doxorubicin.

Results:

The median absolute lymphocyte count (ALC) 14 days after starting the first cycle of chemotherapy (ALC-14) was 1990 cells/μL (range: 600 to 6470). For 32 patients with an ALC-14≥1800 cells/μL, the 5-year progression-free survival (PFS) was 69%, compared with 33% for patients with an ALC-14 of <1800 cell/μL (P=0.036). In multivariable analysis of factors including age, sex, metastatic disease, and favorable histologic response to induction chemotherapy, ALC-14 was significantly associated with PFS (P=0.0081) and overall survival (P=0.0131). The use of ALC-14 appears to further stratify PFS and overall survival among patients when grouped by histologic response.

Conclusions:

We confirmed that early lymphocyte recovery was associated with outcome in pediatric osteosarcoma. Although presumably reflecting immune-mediated tumor control, the precise mechanism for this is unclear. Further study of peripheral blood lymphocyte subpopulations in prospectively treated patients is underway.
Central Nervous System Symptoms Due to Transient Methemoglobinemia in a Child With G6PD Deficiency
Authors: Sharma Shreya , Srinivasaraghavan Rangan , Krishnamurthy Sriram
Published: November 2016

The authors herein report a 5-year-old child who presented with massive hemolysis, irritability, and cyanosis. The final diagnosis was glucose-6-phosphate dehydrogenase deficiency with associated central nervous system symptoms probably because of concomitantly acquired methemoglobinemia following oxidant drug exposure. The associated acute-onset anemia would have contributed to the development of cerebral anoxia–related seizures and encephalopathy.
The Differential Diagnosis Between Natural Death and Homicide, an Everlasting Challenge for the Forensic Pathologist
Authors: di Luca Alessandro , de Matteis Valentino , Marcelli Antonio , Polacco Matteo , Pascali Vincenzo L. , Oliva Antonio
Published: November 2016

Most of the work performed by the forensic expert is to find proof for different plausible hypotheses that may be used in a trial to serve justice purposes when the “identity” of a case is already unveiled. Yet the previous phase of the investigation is also of great importance, and sometimes (like in the presented case), it represents the core element of the entire investigation. The appropriate determination of the differential diagnosis between a natural death and a death of forensic interest (ie, homicide) is the first and crucial step in the classification of a case. This article analyzes the case of the body of a man found lying on the border of a country road with his wrists tied up with rope and the resulting investigation performed by the medicolegal forensic expert. In the end, as more specific examinations where performed aimed to find the truth, the final conclusions excluded a violent death and confirmed that the cause of the death was an acute myocardial infarction.
High-grade Neuroendocrine Carcinoma of the Lung With Carcinoid Morphology
Authors: Quinn Anne Marie , Chaturvedi Anshuman , Nonaka Daisuke
Published: November 2016

Twelve lung neuroendocrine tumors with morphologic features of carcinoid tumors but with mitotic count >10/2 mm2 are reported. There were 7 males and 5 females, with age ranging from 56 to 78 years. Four cases were from never-smokers. All tumors showed architectural and cytomorphologic features of carcinoid tumor, including organoid nesting, insular, trabecular, or acinar growth, and tumor cells with low nucleocytoplasmic ratio, abundant cytoplasm, ovoid to round nuclei, and salt and pepper chromatin. Angulated or confluent nesting, insular or lobular growth pattern was also seen. Nuclear irregularities and anisonucleosis were focally present. Mitotic count ranged from 11 to 61/2 mm2. Punctate-type necrosis was present in 8 tumors. Anaplastic cytology, large infarct-type necrosis, desmoplasia, or marked inflammatory infiltrate was not found in any of the tumors. One tumor occurred in the background of diffuse idiopathic pulmonary neuroendocrine hyperplasia. All tumors were treated by resection, and all but 1 patient subsequently developed metastasis, and 7 died of the tumor. For metastatic tumors, 4 patients were treated by platinum-based chemotherapy with no apparent response, whereas 3 other patients were treated by combined capecitabine and temozolomide—novel chemotherapy for well-differentiated neuroendocrine tumor/carcinoid tumor—2 of them responded. This subset of tumor would be classified as large cell neuroendocrine carcinoma according to the current WHO classification scheme, but their clinical and pathologic features appear to have more in common with the carcinoid tumor group than large cell neuroendocrine carcinoma, therefore, identification of this subset may be relevant for further therapeutic management.
Successful Treatment of Brachial Plexopathy Due to Herpes Zoster Infection With Intravenous Immunoglobulin
Authors: Sáenz-Farret Michel , Sandoval-Rodríguez Valeria , Paz-Navarro Claudia Esther , Zúñiga-Ramírez Carlos
Published: November 2016

Objective

The aim of this study was to report the case of a male patient with Parkinson disease who developed brachial plexopathy (BP) due to varicella-zoster virus, which was successfully treated with human immunoglobulin.

Method

We report the case of a 75-year-old male subject with a diagnosis of Parkinson disease who came to our hospital complaining of pain, skin lesions, and strength loss in his right arm during the past 2 months. Physical examination revealed vesicular rash compatible with varicella-zoster virus lesions. Nerve conduction studies and magnetic resonance imaging of the brachial plexus showed inflammatory changes at that level. A trial with oral valacyclovir followed by intravenous methylprednisolone bolus was administered without further response. However, human intravenous immunoglobulin resulted in complete recovery of the symptoms.

Conclusions

Human immunoglobulin is effective in BP due to zoster infection and must be considered if standard treatment fails. To the best of our knowledge, this is the first report of BP associated to zoster infection successfully treated with intravenous immunoglobulin.
Effects of sea ice cover on satellite-detected primary production in the Arctic Ocean
Authors: Kahru Mati , Lee Zhongping , Mitchell B. Greg , Nevison Cynthia D.
Published: November 2016

The influence of decreasing Arctic sea ice on net primary production (NPP) in the Arctic Ocean has been considered in multiple publications but is not well constrained owing to the potentially large errors in satellite algorithms. In particular, the Arctic Ocean is rich in coloured dissolved organic matter (CDOM) that interferes in the detection of chlorophyll
a
concentration of the standard algorithm, which is the primary input to NPP models. We used the quasi-analytic algorithm (Lee
et al
. 2002
Appl. Opti.
41
, 5755−5772. (
doi:10.1364/AO.41.005755
)) that separates absorption by phytoplankton from absorption by CDOM and detrital matter. We merged satellite data from multiple satellite sensors and created a 19 year time series (1997–2015) of NPP. During this period, both the estimated annual total and the summer monthly maximum pan-Arctic NPP increased by about 47%. Positive monthly anomalies in NPP are highly correlated with positive anomalies in open water area during the summer months. Following the earlier ice retreat, the start of the high-productivity season has become earlier, e.g. at a mean rate of −3.0 d yr
−1
in the northern Barents Sea, and the length of the high-productivity period has increased from 15 days in 1998 to 62 days in 2015. While in some areas, the termination of the productive season has been extended, owing to delayed ice formation, the termination has also become earlier in other areas, likely owing to limited nutrients.
Bridging the gap: parkour athletes provide new insights into locomotion energetics of arboreal apes
Authors: Halsey Lewis G. , Coward Samuel R. L. , Thorpe Susannah K. S.
Published: November 2016

The tree canopy is an energetically challenging environment to traverse. Along with compliant vegetation, gaps in the canopy can prove energetically costly if they force a route-extending detour. Arboreal apes exhibit diverse locomotion strategies, including for gap crossing. Which one they employ in any given scenario may be influenced by the energy costs to do so, which are affected by the details of the immediate environment in combination with their body size. Measuring energetics of arboreal apes is not tractable; thus our knowledge in this area is limited. We devised a novel, custom-made experimental set-up to record the energy expenditure of parkour athletes tree-swaying, jumping and vertical climbing. The latter strategy was vastly more expensive, indicating that when energy economy is the focus arboreal apes will prioritize routes that limit height changes. Whether tree-swaying or jumping was most economical for the athletes depended upon interactions between tree stiffness, the distance to cross, number of tree-sways required and their own mass. Updated analysis of previous interspecific correlations suggests that whether the relative costs to vertical climb are size-invariant across primate species is complicated by details of the climbing context.
Zebrafish embryonic development is induced by carp sperm
Authors: Delomas Thomas A. , Dabrowski Konrad
Published: November 2016

Haploid gynogenetic screens increase the efficiency of forward genetic screens and linkage analysis in fish. Typically, UV-irradiated zebrafish sperm is used to activate zebrafish oocytes for haploid screens. We describe the use of UV-irradiated common carp sperm to activate haploid gynogenetic zebrafish development. Carp × zebrafish hybrids are shown to have a characteristic set of features during embryonic development and exhibit functional development of several tissues (muscle, heart and nervous system). Hybrids become inviable past the embryonic stages. This technique eliminates the possibility of incompletely irradiated zebrafish spermatozoa contaminating haploid progenies. While developing this protocol, one unique zebrafish female was identified which, upon insemination with UV-irradiated carp spermatozoa, repeatedly displayed spontaneous diploidization of the maternal chromosomes in her offspring.
Daylight saving time can decrease the frequency of wildlife–vehicle collisions
Authors: Ellis William A. , FitzGibbon Sean I. , Barth Benjamin J. , Niehaus Amanda C. , David Gwendolyn K. , Taylor Brendan D. , Matsushige Helena , Melzer Alistair , Bercovitch Fred B. , Carrick Frank , Jones Darryl N. , Dexter Cathryn , Gillett Amber , Predavec Martin , Lunney Dan , Wilson Robbie S.
Published: November 2016

Daylight saving time (DST) could reduce collisions with wildlife by changing the timing of commuter traffic relative to the behaviour of nocturnal animals. To test this idea, we tracked wild koalas (
Phascolarctos cinereus
) in southeast Queensland, where koalas have declined by 80% in the last 20 years, and compared their movements with traffic patterns along roads where they are often killed. Using a simple model, we found that DST could decrease collisions with koalas by 8% on weekdays and 11% at weekends, simply by shifting the timing of traffic relative to darkness. Wildlife conservation and road safety should become part of the debate on DST.
(In)validating experimentally derived knowledge about influenza A defective interfering particles
Authors: Liao Laura E. , Iwami Shingo , Beauchemin Catherine A. A.
Published: November 2016

A defective interfering particle (DIP) in the context of influenza A virus is a virion with a significantly shortened RNA segment substituting one of eight full-length parent RNA segments, such that it is preferentially amplified. Hence, a cell co-infected with DIPs will produce mainly DIPs, suppressing infectious virus yields and affecting infection kinetics. Unfortunately, the quantification of DIPs contained in a sample is difficult because they are indistinguishable from standard virus (STV). Using a mathematical model, we investigated the standard experimental method for counting DIPs based on the reduction in STV yield (Bellett & Cooper, 1959,
Journal of General Microbiology
21
, 498–509 (
doi:10.1099/00221287-21-3-498
)). We found the method is valid for counting DIPs provided that: (i) an STV-infected cell's co-infection window is approximately half its eclipse phase (it blocks infection by other virions before it begins producing progeny virions), (ii) a cell co-infected by STV and DIP produces less than 1 STV per 1000 DIPs and (iii) a high MOI of STV stock (more than 4 PFU per cell) is added to perform the assay. Prior work makes no mention of these criteria such that the method has been applied incorrectly in several publications discussed herein. We determined influenza A virus meets these criteria, making the method suitable for counting influenza A DIPs.
Elongated magnetite nanoparticle formation from a solid ferrous precursor in a magnetotactic bacterium
Authors: Baumgartner Jens , Menguy Nicolas , Gonzalez Teresa Perez , Morin Guillaume , Widdrat Marc , Faivre Damien
Published: November 2016

Magnetotactic bacteria are aquatic microorganisms that intracellularly mineralize ferrimagnetic nanoparticles enabling the cells to align with the geomagnetic field. The bacteria produce a magnetic mineral of species-specific phase (magnetite Fe(II)Fe(III)
2
O
4
or greigite Fe(II)Fe(III)
2
S
4
), size, morphology and particle assembly. Several species produce crystals of unusual elongated particle shapes, which break the symmetry of the thermodynamically favoured isometric morphology. Such morphologies are thought to affect domain size and orientation of the internal magnetization. Therefore, they are interesting study objects to develop new synthetic strategies for the morphological control of nanoparticles. We investigate the formation of such irregularly shaped nanomagnets in the species
Desulfovibrio magneticus
RS-1. In contrast to previously described organisms, this bacterium accumulates iron predominantly as Fe(II) rather than Fe(III) consistent with an alternative oxidative biomineralization route. Further, using high-resolution electron microscopy, we observe an epitaxial relationship between precursor and the final mineral phase supporting the notion of a solid-state transformation pathway. The precursor is likely a green rust previously thought to convert to magnetite only by dissolution and re-precipitation. Our findings represent a novel observation in the interconversion of iron (oxyhydr)oxide materials and suggest that solid-state growth processes could be required to produce irregularly shaped, elongated magnetite nanocrystals.
Inferring animal social networks and leadership: applications for passive monitoring arrays
Authors: Jacoby David M. P. , Papastamatiou Yannis P. , Freeman Robin
Published: November 2016

Analyses of animal social networks have frequently benefited from techniques derived from other disciplines. Recently, machine learning algorithms have been adopted to infer social associations from time-series data gathered using remote, telemetry systems situated at provisioning sites. We adapt and modify existing inference methods to reveal the underlying social structure of wide-ranging marine predators moving through spatial arrays of passive acoustic receivers. From six months of tracking data for grey reef sharks (
Carcharhinus amblyrhynchos
) at Palmyra atoll in the Pacific Ocean, we demonstrate that some individuals emerge as leaders within the population and that this behavioural coordination is predicted by both sex and the duration of co-occurrences between conspecifics. In doing so, we provide the first evidence of long-term, spatially extensive social processes in wild sharks. To achieve these results, we interrogate simulated and real tracking data with the explicit purpose of drawing attention to the key considerations in the use and interpretation of inference methods and their impact on resultant social structure. We provide a modified translation of the GMMEvents method for R, including new analyses quantifying the directionality and duration of social events with the aim of encouraging the careful use of these methods more widely in less tractable social animal systems but where passive telemetry is already widespread.
Computer aided chemical design: using quantum chemical calculations to predict properties of a series of halochromic guaiazulene derivatives
Authors: Woodward Adam W. , Ghazvini Zadeh Ebrahim H. , Bondar Mykhailo V. , Belfield Kevin D.
Published: November 2016

With the scientific community becoming increasingly aware of the need for greener products and methodologies, the optimization of synthetic design is of greater importance. Building on experimental data collected from a synthesized guaiazulene derivative, a series of analogous structures were investigated with time-dependent density functional theory (TD-DFT) methods in an effort to identify a compound with desirable photophysical properties. This
in silico
analysis may eliminate the need to synthesize numerous materials that, when investigated, do not possess viable characteristics. The synthesis of several computationally investigated structures revealed discrepancies in the calculation results. Further refined computational study of the molecules yielded results closer to those observed experimentally and helps set the stage for computationally guided design of organic photonic materials. Three novel derivatives were synthesized from guaiazulene, a naturally occurring chromophore, exhibiting distinct halochromic behaviour, which may have potential in a switchable optoelectronic system or combined with a photoacid generator for data storage. The protonated forms were readily excitable via two-photon absorption.
Chemical antipredator defence is linked to higher extinction risk
Authors: Arbuckle Kevin
Published: November 2016

Many attributes of species may be linked to contemporary extinction risk, though some such traits remain untested despite suggestions that they may be important. Here, I test whether a trait associated with higher background extinction rates, chemical antipredator defence, is also associated with current extinction risk, using amphibians as a model system—a group facing global population declines. I find that chemically defended species are approximately 60% more likely to be threatened than species without chemical defence, although the severity of the contemporary extinction risk may not relate to chemical defence. The results confirm that background and contemporary extinction rates can be predicted from the same traits, at least in certain cases. This suggests that associations between extinction risk and phenotypic traits can be temporally stable over long periods. The results also provide novel insights into the relevance of antipredator defences for species subject to conservation concerns.
Indications for influence of artificial (man-made) activity on radon signals, in simulation experiments
Authors: Steinitz G. , Kotlarsky P. , Piatibratova O.
Published: November 2016

Radon (Rn-222; a radioactive noble gas) is characterized by large temporal variations that differ significantly from variations of (i) other trace elements in geogas (noble gases); (ii) variation patterns of other dynamic geophysical systems (atmospheric, tidal). Consensus exists that there is no simple and straightforward understanding of the phenomena and its behaviour. This lacuna in the understanding of the underlying principles hampers the development of applications—such as radon as a proxy of processes in the seismogenic context. Using results from field investigations and simulation experiments the GSI suggested that an unidentified extraterrestrial component, probably in solar radiation, drives periodic radon signals in the diurnal and annual frequency bands. Recent findings from experimental investigations shed additional perspectives allowing a new evaluation of the issue. Particular transient signals, measured with alpha and gamma detectors, are interpreted to reflect the influence of artificial activity. Criteria are (i) signals lasting several hours that occur around midday on workdays (Sunday–Thursday); (ii) signals composed of a train of around 10 strong pulses, each lasting less than 15 min, occurring within several hours once a week, from Wednesday afternoon/evening to Thursday morning. A first interpretation is that an unidentified artificial activity of some sort (industrial?) generates and emits an unidentified agent that reaches enhanced confined mode experiments at the GSI laboratory, which respond to the incoming agent in the form of radon signals. Developing the capability of identification of such an earth-bound source generating an influencing agent is a key step towards understanding of external influence on radioactivity of radon.
Neotropical wrens learn new duet rules as adults
Authors: Rivera-Cáceres Karla D. , Quirós-Guerrero Esmeralda , Araya-Salas Marcelo , Searcy William A.
Published: November 2016

Although song development in songbirds has been much studied as an analogue of language development in humans, the development of vocal interaction rules has been relatively neglected in both groups. Duetting avian species provide an ideal model to address the acquisition of interaction rules as duet structure involves time and pattern-specific relationships among the vocalizations from different individuals. In this study, we address the development of the most striking properties of duets: the specific answering rules that individuals use to link their own phrase types to those of their partners (duet codes) and precise temporal coordination. By performing two removal experiments in canebrake wrens (
Cantorchilus zeledoni
), we show that individuals use a fixed phrase repertoire to create new phrase pairings when they acquire a new partner. Furthermore, immediately after pairing, individuals perform duets with poor coordination and poor duet code adherence, but both aspects improve with time. These results indicate that individuals need a learning period to be able to perform well-coordinated duets that follow a consistent duet code. We conclude that both duet coordination and duet code adherence are honest indicators of pair-bond duration.
Zika and Chikungunya virus co-infection in a traveller returning from Colombia, 2016: virus isolation and genetic analysis
Authors: Cherabuddi Kartikeya , Iovine Nicole M. , Shah Kairav , White Sarah K. , Paisie Taylor , Salemi Marco , Morris Jr J. Glenn , Lednicky John A.
Published: November 2016

Introduction:

Zika
virus (ZIKV) and Chikungunya
virus (CHIKV) can share the same mosquito vector, and co-infections by these viruses can occur in humans. While infections with these viruses share commonalities, CHIKV is unique in causing arthritis and arthralgias that may persist for a year or more. These infections are commonly diagnosed by RT–PCR-based methods during the acute phase of infection. Even with the high specificity and sensitivity characteristic of PCR, false negatives can occur, highlighting the need for additional diagnostic methods for confirmation.

Case presentation:

On her return to the USA, a traveller to Colombia, South America developed an illness consistent with Zika, Chikungunya and/or Dengue. RT-PCR of her samples was positive only for ZIKV. However, arthralgias persisted for months, raising concerns about co-infection with CHIKV or Mayaro viruses. Cell cultures inoculated with her original clinical samples demonstrated two types of cytopathic effects, and both ZIKV and CHIKV were identified in the supernatants. On phylogenetic analyses, both viruses were found to be related to strains found in Colombia.

Conclusion:

These findings highlight the need to consider CHIKV co-infection in patients with prolonged rheumatological symptoms after diagnosis with ZIKV, and the usefulness of cell culture as an amplification step for low-viremia blood and other samples.
The natural selection of metabolism explains curvature in fossil body mass evolution
Authors: Witting Lars
Published: November 2016

The natural selection of metabolism and mass can explain inter-specific allometries from prokaryotes to mammals (Witting 2017a), with exponents that depend on the selected metabolism and the spatial dimensionality (2D/3D) of intra-specific behaviour. The predicted 2D-exponent for total metabolism increases from 3/4 to 7/4 when the fraction of the inter-specific body mass variation that follows from primary variation in metabolism increases from zero to one.

A 7/4 exponent for mammals has not been reported from inter-specific comparisons, but I detect the full range of allometries for evolution in the fossil record. There are no fossil data for allometric correlations between metabolism and mass, but I estimate life history allometries from the allometryfor the rate of evolutionin mass (w) in physical time (t).

Theexponent describes the curvature of body mass evolution, with predicted values being: 3/2 (2D) for within niche evolution in small horses over 54 million years. 5/4 (2D) and 9/8 (3D) for across niche evolution of maximum mass in four mammalian clades. 3/4 (2D) for fast evolution in large horses, and maximum mass in trunked and terrestrial mammals. 1 for maximum mass across major life-forms during 3.5 billion years of evolution along a metabolic bound.
Rooting density differentiates wheat genotypes through Bayesian modeling
Authors: Wasson Anton P. , Chiu Grace S. , Zwart Alexander B. , Binns Timothy R.
Published: November 2016

Wheat pre-breeders use soil coring and core-break counts to phenotype root architecture traits, with data collected on rooting density for hundreds of genotypes in small increments of depth. The measured densities are both large datasets and highly variable even within the same genotype, hence, any rigorous, comprehensive statistical analysis of such complex field data would be technically challenging. Traditionally, most attributes of the field data are therefore discarded in favor of simple numerical summary descriptors which retain much of the high variability exhibited by the raw data. This poses practical challenges: although plant scientists have established that root traits do drive resource capture in crops, traits that are more randomly (rather than genetically) determined are difficult to breed for. In this paper we develop a Bayesian hierarchical nonlinear modeling approach that utilizes the complete field data for wheat genotypes to fit anidealizedrelative intensity function for the root distribution over depth. Our approach was used to determineheritability: how much of the variation between field samples was purely random versus being mechanistically driven by the plant genetics? Based on the genotypic intensity functions, the overall heritability estimate was 0.62 (95% Bayesian confidence interval was 0.52 to 0.71). Despite root count profiles that were statistically very noisy, our Bayesian analysis led to denoised profiles which exhibited rigorously discernible phenotypic traits. The profile-specific traits could be representative of a genotype and thus can be used as a quantitative tool to associate phenotypic traits with specific genotypes.
Scalable parameter estimation for genome-scale biochemical reaction networks
Authors: Fröhlich Fabian , Kaltenbacher Barbara , Theis Fabian J. , Hasenauer Jan
Published: November 2016

Mechanistic mathematical modeling of biochemical reaction networks using ordinary differential equation (ODE) models has improved our understanding of small-and medium-scale biological processes. While the same should in principle hold for large-and genome-scale processes, the computational methods for the analysis of ODE models which describe hundreds or thousands of biochemical species and reactions are missing so far. While individual simulations are feasible, the inference of the model parameters from experimental data is computationally too intensive. In this manuscript, we evaluate adjoint sensitivity analysis for parameter estimation in large scale biochemical reaction networks. We present the approach for time-discrete measurement and compare it to state-of-the-art methods used in systems and computational biology. Our comparison reveals a significantly improved computational efficiency and a superior scalability of adjoint sensitivity analysis. The computational complexity is effectively independent of the number of parameters, enabling the analysis of large-and genome-scale models. Our study of a comprehensive kinetic model of ErbB signaling shows that parameter estimation using adjoint sensitivity analysis requires a fraction of the computation time of established methods. The proposed method will facilitate mechanistic modeling of genome-scale cellular processes, as required in the age of omics.

Author Summary

In this manuscript, we introduce a scalable method for parameter estimation for genome-scale biochemical reaction networks. Mechanistic models for genome-scale biochemical reaction networks describe the behavior of thousands of chemical species using thousands of parameters. Standard methods for parameter estimation are usually computationally intractable at these scales. Adjoint sensitivity based approaches have been suggested to have superior scalability but any rigorous evaluation is lacking. We implement a toolbox for adjoint sensitivity analysis for biochemical reaction network which also supports the import of SBML models. We show by means of a set of benchmark models that adjoint sensitivity based approaches unequivocally outperform standard approaches for large-scale models and that the achieved speedup increases with respect to both the number of parameters and the number of chemical species in the model. This demonstrates the applicability of adjoint sensitivity based approaches to parameter estimation for genome-scale mechanistic model. The MATLAB toolbox implementing the developed methods is available fromhttp://ICB-DCM.github.io/AMICI/.
Predicting gene expression level inE. colifrom mRNA sequence information
Authors: Zhao Linlin , Abedpour Nima , Blum Christopher , Kolkhof Petra , Beller Mathias , Kollmann Markus , Capriotti Emidio
Published: November 2016

Motivation

The accurate characterization of the translational mechanism is crucial for enhancing our understanding of the relationship between genotype and phenotype. In particular, predicting the impact of the genetic variants on gene expression will allow to optimize specific pathways and functions for engineering new biological systems. In this context, the development of accurate methods for predicting translation efficiency from the nucleotide sequence is a key challenge in computational biology.

Methods

In this work we presentPGExpress, a binary classifier to discriminate between mRNA sequences with low and high translation efficiency inE.coli.PGExpressalgorithm takes as input 12 features corresponding to RNA folding and anti-Shine-Dalgarno hybridization free energies. The method was trained on a set of 1,772 sequence variants (WT-High) of 137 essentialE.coligenes. For each gene, we considered 13 sequence variants of the first 33 nucleotides encoding for the same amino acids followed by the superfolder GFP. Each gene variant is represented sequence blocks that include the Ribosome Binding Site (RBS), the first 33 nucleotides of the coding region (C33), the remaining part of the coding region (CC), and their combinations.

Results

Our logistic regression-based tool (PGExpress) was trained using a 20-fold gene-based cross-validation procedure on the WT-High dataset. In this testPGExpressachieved an overall accuracy of 74%, a Matthews correlation coefficient 0.49 and an Area Under the Receiver Operating Characteristic Curve (AUC) of 0.81. Tested on 3 sets of sequences with different Ribosome Binding Sites,PGExpressreaches similar AUC. Finally, we validated our method by performing in-house experiments on five newly generated mRNA sequence variants. The predictions of the expression level of the new variants are in agreement with our experimental results inE.coli.

Availability

http://folding.biofold.org/pgexpress

Contact

markus.kollmann@hhu.de,emidio.capriotti@unibo.it
Development of a multivariate clinical prediction model for the diagnosis of mild stroke/TIA in physician first-contact patient settings
Authors: Bibok Maximilian B. , Penn Andrew M. , Lesperance Mary L. , Stat P. , Votova Kristine , Balshaw Robert
Published: November 2016

OBJECTIVE

To develop a clinical prediction model for diagnosing mild stroke/transient ischemic attack (TIA) in first-contact patient settings. DESIGN: Retrospective study design utilizing logistic regression modeling of patient clinical symptoms collected from patient chart histories and referral data. SETTING: Regional fast-track TIA clinic on Vancouver Island, Canada, accepting referrals from emergency departments (ED) and general practice (GP). PARTICIPANTS: Model development: 4187 ED and GP referred patients from 2008–2011 who were assessed at the TIA clinic. Temporal hold-out validation: 1953 ED and GP referred patients from 2012–2013 assessed at the same clinic. OUTCOMES: Diagnosis of mild stroke/TIA by clinic neurologists. RESULTS: 123 candidate predictors were assessed using univariate feature selection for inclusion in the model, and culminated in the selection of 50 clinical features. Post-hoc investigation of the selected predictors revealed 12 clinically relevant interaction terms. Model performance on the temporal hold-out validation set achieved a sensitivity/specificity of 71.8% / 72.8% using the ROC01 cutpoint (≥ 0.662), and an AUC of 79.9% (95% CI, 77.9%–81.9%). In comparison, the ABCD2 score (≥ 4) achieved a sensitivity/specificity of 70.4% / 54.5% and an AUC of 67.5% (95% CI, 65.2%–69.9%). The logistic regression model demonstrated good calibration on the hold-out set (β0= −0.257); βlinear= 1.047).

CONCLUSIONS

The developed diagnostic model performs better than the ABCD2 score at diagnosing mild stroke/TIA on the basis of clinical symptoms. The model has the potential to replace the use of the prognostic ABCD2 score in diagnostic medical contexts in which the ABCD2 score is currently used, such as patient triage.
The right pick: structural basis of snRNA selection by Gemin5
Authors: Wahl Markus C. , Fischer Utz
Published: November 2016

Macromolecular complexes, rather than individual biopolymers, perform many cellular activities. Faithful assembly of these complexes in vivo is therefore a vital challenge of all cells, and its failure can have fatal consequences. To form functional complexes, cells use elaborate measures to select the “right” components and combine them into working entities. How assembly is achieved at the molecular level is unclear in many cases. Three groups (Jin and colleagues, pp. 2391–2403; Xu and colleagues, pp. 2376–2390; and Tang and colleagues in Cell Research) have now provided insights into how an assembly factor specifically recognizes substrate RNA molecules and enables their usage for assembly of Sm-class uridine-rich small nuclear RNA–protein complexes.
Raw diffraction data preservation and reuse: overview, update on practicalities and metadata requirements
Authors: Kroon-Batenburg Loes M. J. , Helliwell John R. , McMahon Brian , Terwilliger Thomas C.
Published: November 2016

A topical review is presented of the rapidly developing interest in and storage options for the preservation and reuse of raw data within the scientific domain of the IUCr and its Commissions, each of which operates within a great diversity of instrumentation. A résumé is included of the case for raw diffraction data deposition. An overall context is set by highlighting the initiatives of science policy makers towards an `Open Science' model within which crystallographers will increasingly work in the future; this will bring new funding opportunities but also new codes of procedure within open science frameworks. Skills education and training for crystallographers will need to be expanded. Overall, there are now the means and the organization for the preservation of raw crystallographic diffraction dataviadifferent types of archive, such as at universities, discipline-specific repositories (Integrated Resource for Reproducibility in Macromolecular Crystallography, Structural Biology Data Grid), general public data repositories (Zenodo, ResearchGate) and centralized neutron and X-ray facilities. Formulation of improved metadata descriptors for the raw data types of each of the IUCr Commissions is in progress; some detailed examples are provided. A number of specific case studies are presented, including an example research thread that provides complete open access to raw data.
The efficacy of sexual orientation anti-discrimination legislation
Authors: Hebl Michelle , Barron Laura , Cox Cody Brent , Corrington Abigail R.
Published: November 2016

Purpose

The purpose of this paper is to summarize the limited body of research that focuses on the efficacy of sexual orientation anti-discrimination legislation in reducing discrimination.

Design/methodology/approach

Reviews past research that documents overt and subtle forms of workplace discrimination against gay, lesbian, and bisexual individuals and describes how legislation plays an important role in changing social norms and underlying attitudes.

Findings

Empirically demonstrates that legislation effectively can reduce discrimination.

Originality/value

Informs legislative debate and promotes the expansion and adoption of national, state, and local legislation on sexual orientation anti-discrimination legislation.
Reflections from EDI Conference
Authors: Georgiadou Andri
Published: November 2016

Purpose

The purpose of this paper is to provide an overview of the research presented at the 2016 Equality, Diversity and Inclusion (EDI) Conference in Nicosia, Cyprus.

Design/methodology/approach

The report is based on six papers, of interest toEquality, Diversity and Inclusionreaders, which were selected from the proceedings and presentations made at the conference. The papers vary in terms of research design, methodology and approach. There was a mix of conceptual/review papers and empirical studies, using both quantitative and qualitative methods.

Findings

The papers presented new directions on equality, diversity and inclusion research. Findings from exploratory papers indicated the need to develop an understanding of the notion of solidarity and the divisive and inclusive elements of the enactment of solidarity. Empirical studies reveal that women and people from black and minority ethnic communities continue to be excluded and marginalized, whereas there is a call for greater consideration of age in the social, economic, political and market arenas.

Originality/value

This report integrates unique insights on “Equality, Diversity and Inclusion and Human Rights in Times of Austerity”, as these were presented and discussed at the EDI 2016 Conference.
Serious games as a virtual training ground for relocation to a new healthcare facility
Authors: Merschbrock Christoph , Lassen Ann Karina , Tollnes Tor , Munkvold Bjørn Erik
Published: November 2016

Purpose

This paper aims to enquire into how building information modelling (BIM) and gaming can be integrated to support professionals in their learning about the spatial layout of a new building. This knowledge is important to prepare building operation and facilities management (FM).

Design/methodology/approach

Ingrained in task–technology fit theory, this paper reports from a case study of a serious game staged in the graphical environment of a building information model. A series of interviews with the client, subject-matter experts and software developers involved in developing the game were conducted. The industrial setting for the study is a major hospital construction project in Norway. The project has been awarded BuildingSMART’s 2015 award for “outstanding open BIM practice”, making it Norway’s role model for BIM practice.

Findings

Importing and exporting geometry from BIM into a game engine remain challenging. The transfer of data between the two requires workarounds using intermediary software. Apart from issues related to technical interoperability, several sociotechnical challenges influential for the integration of BIM and gaming have been identified, related to: the collaboration among construction, operational and gaming experts; clear communication of information needs; and better contractual agreements.

Research limitations/implications

BIM’s geometric and semantic data enabled the creation of a sophisticated game for preparing building operation. Test-users perceived the game to be superior to classroom teaching for learning about the spatial layout of the building. However, quantifying the business value of the game for operation after occupancy of the new facilities was beyond the scope of this study.

Originality/value

The work presented exemplifies a novel application area of BIM and gaming technology in FM. The findings presented in this article are relevant for professionals and scholars seeking to expand the utility of BIM for starting up the operation of new facilities.
Organising in-house cleaning services in public FM
Authors: Klungseth Nora Johanne , Blakstad Siri Hunnes
Published: November 2016

Purpose

This paper aims to describe and discuss in-house cleaning services in local authorities to gain a better understanding of current practices. These descriptions are intended to increase researchers’, practitioners’ and educators’ understanding of the studied issue, as there at present does not exist a solid understanding of in-house cleaning services in local authorities. Previous studies provide little detailed information regarding the internal environment of facility management (FM) organisations, in particular with regard to FM organisations’ individual services.

Design/methodology/approach

This research is based on two descriptive case studies, one from Norway and one from the UK. The case studies are based on semi-structured, face-to-face in-depth interviews and document reviews.

Findings

The cases demonstrate that in-house cleaning services can be structured and managed in different ways, particularly with respect to the split in services, the management of staff and customer contracts, the span of control, the chain of command, self-managed leadership, cleaners’ hours of duty and the use of outsourcing.

Research limitations/implications

Although the previous research on particular FM services is limited, this paper’s detailed descriptions may stimulate further development and research within the field. The knowledge brought forward is part of bridging a knowledge gap on cleaning in FM research. This knowledge can contribute to advancements in the way this service is discussed and measured across contexts by encouraging more rigour and specific studies on cleaning.

Originality/value

This paper constitutes one of the first detailed descriptions of in-house cleaning organisation in local authorities. This is a type of service supply that is common in certain contexts and identified as beneficial to cost-saving in other contexts.
Facilities management unit: improving self-image before its customers
Authors: Ogbeifun Edoghogho , Mbohwa Charles , Pretorius Jan-Harm C.
Published: November 2016

Purpose

The purpose of this study is to explore the role of effective communication and the use of customer-friendly periodic report as tools for managing cordial relationship between facilities management (FM) operatives and their customers. FM functions require effective management of the relationships between the customers, workplace interface and support facilities, to facilitate the achievement of the objectives of the organisation. This suggests that FM operatives should continuously marry their performance priorities with the customers’ priorities and perception; otherwise, the FM operatives may be toiling without objective recognition of service or achieve improved customer satisfaction.

Design/methodology/approach

The case study method of qualitative research was adopted. The data were collected using the combination of in-depth interviews and evaluation of FM’s periodic reports from two universities in South Africa.

Findings

The FM units in both universities have a suitable operational system and use a modern computer-aided FM tool. However, the units have not been able to manage relationships with customers, largely because they have not been able to “deliver on promise” and have not learnt to use the soft skills of effective communication. The quality of the periodic reports from the units does not provide sufficient educative information for the end-users; the structure is not stakeholders-friendly.

Originality/value

The paper identifies that though FM units spend considerable time in the development, maintenance and effective running of support facilities, they pay little attention to documentation, reporting and use of the soft skills of effective communication, which are necessary ingredients for improved customer relationships.
Analysis of a new stabilized finite volume element method based on multiscale enrichment for the Navier-Stokes problem
Authors: Wen Juan , He Yinnian , Zhao Xin
Published: November 2016

Purpose

The purpose of this paper is to propose a new stabilized finite volume element method for the Navier-Stokes problem.

Design/methodology/approach

This new method is based on the multiscale enrichment and uses the lowest equal order finite element pairs P1/P1.

Findings

The stability and convergence of the optimal order in H1-norm for velocity and L2-norm for pressure are obtained.

Originality/value

Using a dual problem for the Navier-Stokes problem, the convergence of the optimal order in L2-norm for the velocity is obtained. Finally, numerical example confirms the theory analysis and validates the effectiveness of this new method.