bluuebunny/crossref_metadata_2025_split huggingface dataset:
Towards comprehensive and quantitative proteomics for diagnosis and therapy of human disease
Authors: Cifani Paolo , Kentsis Alex 
Published: September 2016

AbbreviationsDDAData Dependent AcquisitionDIAData Independent AcquisitionPRMParallel Reaction MonitoringPTMpost-translational modificationSAXstrong anion exchange (chromatography)SCXStrong cation exchange (chromatography)AbstractDespite superior analytical features, mass spectrometry proteomics remains seldom used for the basic investigation and clinical treatment of human disease. This need is particularly pressing for childhood diseases that can be rare in incidence and variable in presentation. Modern mass spectrometry enables detailed functional characterization of the pathogenic biochemical processes, as achieved by accurate and comprehensive quantification of proteins and their regulatory chemical modifications. Here, we describe how high-accuracy mass spectrometry in combination with high-resolution chromatographic separations can be leveraged to meet these analytical requirements in a mechanism-focused manner. We review the quantification methods capable of producing accurate measurements of protein abundance and post-translational modification stoichiometries. We then discuss how experimental design and chromatographic resolution can be leveraged to achieve comprehensive functional characterization of biochemical processes in complex biological proteomes. Finally, we describe current approaches for quantitative analysis of a common functional protein modification: reversible phosphorylation. In all, current instrumentation and methods of high-resolution chromatography and mass spectrometry proteomics are poised for immediate translation into improved diagnostic and therapeutic strategies for pediatric and adult diseases.
Cooperativity and modularity in protein folding
Authors: Sasai Masaki , Chikenji George , Terada Tomoki P. 
Published: September 2016

AbstractA simple statistical mechanical model proposed by Wako and Saitô has explained the aspects of protein folding surprisingly well. This model was systematically applied to multiple proteins by Muñoz and Eaton and has since been referred to as the Wako-Saitô-Muñoz-Eaton (WSME) model. The success of the WSME model in explaining the folding of many proteins has verified the hypothesis that the folding is dominated by native interactions, which makes the energy landscape globally biased toward native conformation. Using the WSME and other related models, Saitô emphasized the importance of the hierarchical pathway in protein folding; folding starts with the creation of contiguous segments having a native-like configuration and proceeds as growth and coalescence of these segments. Theϕ-values calculated for barnase with the WSME model suggested that segments contributing to the folding nucleus are similar to the structural modules defined by the pattern of native atomic contacts. The WSME model was extended to explain folding of multi-domain proteins having a complex topology, which opened the way to comprehensively understanding the folding process of multi-domain proteins. The WSME model was also extended to describe allosteric transitions, indicating that the allosteric structural movement does not occur as a deterministic sequential change between two conformations but as a stochastic diffusive motion over the dynamically changing energy landscape. Statistical mechanical viewpoint on folding, as highlighted by the WSME model, has been renovated in the context of modern methods and ideas, and will continue to provide insights on equilibrium and dynamical features of proteins.
A new foreperiod effect on single-trial phase coherence. Part I: existence and relevance
Authors: Rapela Joaquin , Westerfield Marissa , Townsend Jeanne , Makeig Scott 
Published: September 2016

AbstractExpecting events in time leads to more efficient behavior. A remarkable early finding in the study of temporal expectancy is the foreperiod effect on reaction times; i.e., the fact that the time period between a warning signal and an impendent stimuli, to which subjects are instructed to respond as quickly as possible, influences reaction times. Recently it has been shown that the phase of oscillatory activity preceding stimulus presentation is related to behavior. Here we connect both of these findings by reporting a novel foreperiod effect on the inter-trial phase coherence triggered by a stimulus to which subjects do not respond. Until now, inter-trial phase coherence has been used to describe a regularity in the phases of groups of trials. We propose a single-trial measure of inter-trial phase coherence and prove its soundness. Equipped with this measure, and using a multivariate decoding method, we demonstrate that the foreperiod duration modulates single-trial phase coherence. In principle, this modulation could be an artifact due to the decoding method used to detect it. We show that this is not the case, since the modulation can also be observed with a very simple averaging method. Although real, the single-trial modulation of inter-trial phase coherence by the foreperiod duration could just reflect a nuisance in our data. We argue against this possibility by showing that the strength of the modulation correlates with subjects’ behavioral measures, both error rates and mean-reaction times. We anticipate that the new foreperiod effect on inter-trial phase coherence, and the decoding method used here to detect it, will be important tools to understand cognition at the single-trial level. In Part II of this manuscript, we support this claim, by showing that attention modulates the strength of the new foreperiod effect in a trial-by-trial basis.
Primary Evidence of a Donut-Like, Fourth Spatial Dimension in the Brain
Authors: Peters James F. , İnan Ebubekir , Tozzi Arturo , Ramanna Sheela 
Published: September 2016

ABSTRACTWe introduce a novel method for the measurement of information in fMRI neuroimages, i.e., nucleus clustering’s Rényi entropy derived from strong proximities in feature-based Voronoï tessellations, e.g., maximal nucleus clustering (MNC). We show how MNC is a novel, fast and inexpensive image-analysis technique, independent from the standard blood-oxygen-level dependent signals, which facilitates the objective detection of hidden temporal patterns of entropy/information in zones of fMRI images generally not taken into account by the subjective standpoint of the observer. In order to evaluate the potential applications of MNC, we looked for the presence of a fourth dimension’s distinctive hallmarks in a temporal sequence of 2D images taken during spontaneous brain activity. Indeed, recent findings suggest that several brain activities, such as mind-wandering and memory retrieval, might take place in the functional space of a four dimensional hypersphere, which is a double donut-like structure undetectable in the usual three dimensions. We found that the Rényi entropy is higher in MNC areas than in the surrounding ones, and that these temporal patterns closely resemble the trajectories predicted by the possible presence of a hypersphere in the brain.
Detecting consistent patterns of directional adaptation using differential selection codon models
Authors: Parto Sahar , Lartillot Nicolas 
Published: September 2016

AbstractBackgroundPhylogenetic codon models are often used to characterize the selective regimes acting on protein coding sequences. Recent methodological developments have led to models explicitly accounting for the interplay between mutation and selection, by explicitly modelling the amino acid fitness landscape along the sequence. However, thus far, most of these models have assumed that the fitness landscape is constant over time. Fluctuations of the fitness landscape may often be random or depend on complex and unknown factors. However, some organisms may be subject to systematic changes in selective pressure, resulting in reproducible molecular adaptations across independent lineages subject to similar conditions.ResultsHere, we developed a codon-based differential selection model, which aims to detect and quantify the fine-grained consistent patterns of adaptation at the protein-coding level, as a function of external conditions experienced by the organism under investigation. The model parameterizes the global mutational pressure, as well as the site- and condition-specific amino acid selective preferences. This phylogenetic model is implemented in a Bayesian MCMC framework. After validation with simulations, we applied our method to a dataset of HIV sequences from patients with known HLA genetic background. Our differential selection model detects and characterizes differentially selected coding positions specifically associated with two different HLA alleles.Conclusionour differential selection model is able to identify consistent molecular adaptations as a function of repeated changes in the environment of the organism. These models can be applied to many other problems, ranging from viral adaptation to evolution of life-history strategies in plants or animals.
Swedish military officers through other nations’ eyes
Authors: Larsson Gerry , Brandow Carina , Fors Brandebo Maria , Ohlsson Alicia , Åselius Gunnar 
Published: August 2016

Purpose
Globalisation of working life means that many organisations are manned by people from different countries. A potentially critical factor is how members from various nations are looked upon by their partner countries. Such perception may be more or less accurate and affect organisational outcomes. The military is no exception as modern warfare is characterised by multinational composition of task forces. The aim of this paper was to gain a deeper understanding of how military officers from other nations perceive Swedish military officers and their leadership qualities in particular.

Design/methodology/approach
Interviews were conducted with 20 military officers representing ten nations. Interview questions were deduced from the Developmental leadership model. Responses were first coded inductively according to the constant comparative method. Generated categories were then deductively related to this leadership model.

Findings
The analysis resulted in positive and negative patterns. The positive picture included Swedish officers being perceived as calm, competent and generally good at exhibiting exemplary leadership behaviour, showing individualised consideration and creating an inspiring atmosphere. The negative side included opinions such as Swedish officers being too emotionally restrained, exhibiting poor self-confidence, discussing too much before making decisions and having difficulties giving negative feedback. The results are discussed in relation to the Developmental leadership model and the stereotype concept.

Research limitations/implications
Small sample size and a focus on military organisations imply a low degree of generalisability.

Practical implications
Three suggestions regarding Swedish officer education are presented: officer students should be given an increased awareness of how they are perceived by others, decision-making without group support and giving negative feedback in a constructive, straight forward, but still considerate way, should be practiced and more attention should be paid to emotion management.

Originality/value
The paper addresses an increasing tendency in work organisations – a multinational composition of the work force. The foundation of study in leadership theory and the stereotype concept is new.
Transition from conventional to light‐emitting diode street lighting changes activity of urban bats
Authors: Lewanzik Daniel , Voigt Christian C. 
Published: September 2016

Summary

Light pollution is rapidly increasing and can have deleterious effects on biodiversity, yet light types differ in their effect on wildlife. Among the light types used for street lamps, light‐emitting diodes (LEDs) are expected to become globally predominant within the next few years.

In a large‐scale field experiment, we recorded bat activity at 46 street lights for 12 nights each and investigated how the widespread replacement of conventional illuminants by LEDs affects urban bats: we compared bat activity at municipal mercury vapour (MV) street lamps that were replaced by LEDs with control sites that were not changed.

Pipistrellus pipistrellus was the most frequently recorded species; it was 45% less active at LEDs than at MV street lamps, but the activity did not depend on illuminance level. Light type did not affect the activity of Pipistrellus nathusii, Pipistrellus pygmaeus or bats in the Nyctalus/Eptesicus/Vespertilio (NEV) group, yet the activity of P. nathusii increased with illuminance level. Bats of the genus Myotis increased activity 4·5‐fold at LEDs compared with MV lights, but illuminance level had no effect.

Decreased activity of P. pipistrellus, which are considered light tolerant, probably paralleled insect densities around lights. Further, our results suggest that LEDs may be less repelling for light‐averse Myotis spp. than MV lights. Accordingly, the transition from conventional lighting techniques to LEDs may greatly alter the anthropogenic impact of artificial light on urban bats and might eventually affect the resilience of urban bat populations.

Synthesis and applications. At light‐emitting diodes (LEDs), the competitive advantage – the exclusive ability to forage on insect aggregations at lights – is reduced for light‐tolerant bats. Thus, the global spread of LED street lamps might lead to a more natural level of competition between light‐tolerant and light‐averse bats. This effect could be reinforced if the potential advantages of LEDs over conventional illuminants are applied in practice: choice of spectra with relatively little energy in the short wavelength range; reduced spillover by precisely directing light; dimming during low human activity times; and control by motion sensors. Yet, the potential benefits of LEDs could be negated if low costs foster an overall increase in artificial lighting.
Educational Achievement and the Allocation of School Resources
Authors: Cobb‐Clark Deborah A. , Jha Nikhil 
Published: September 2016

AbstractThe debate on school resources and educational outcomes has focused almost exclusively on spending levels. We extend this by analysing the relationship between student achievement and schools' budget allocations using panel data. Per‐pupil expenditure has no apparent link to improvement in students' standardised test scores. However, the allocation of the budget matters for student achievement in some grades. Ancillary teaching staff are linked to faster growth in numeracy and literacy in primary‐ and middle‐schools. Spending on experienced teachers is also important for writing achievement in the primary‐school years. On the whole, we find very little evidence of inefficient spending patterns.
Bayesian Vector Autoregressions
Authors: Woźniak Tomasz 
Published: September 2016

AbstractThis article provides an introduction to the burgeoning academic literature on Bayesian vector autoregressions, benchmark models for applied macroeconomic research. I first explain Bayes’ theorem and the derivation of the closed‐form solution for the posterior distribution of the parameters of the model's given data. I further consider parameter shrinkage, a distinguishing feature of the prior distributions commonly employed in the analysis of large data. Finally, I describe the mechanisms that enable feasible computations for these linear models that efficiently extract the information content of many variables for economic forecasting and other applications.
Possible Mechanisms of Ethanol‐Mediated Colorectal Carcinogenesis: The Role of Cytochrome P4502E1, Etheno‐DNA Adducts, and the Anti‐Apoptotic Protein Mcl‐1
Authors: Koehler Bruno Christian , Arslic‐Schmitt Tatjana , Peccerella Theresa , Scherr Anna‐Lena , Schulze‐Bergkamen Henning , Bruckner Thomas , Gdynia Georg , Jäger Dirk , Mueller Sebastian , Bartsch Helmut , Seitz Helmut K. 
Published: September 2016

BackgroundChronic alcohol consumption is a risk factor for colorectal cancer. The mechanisms by which ethanol (EtOH) exerts its carcinogenic effect on the colorectal mucosa are not clear and may include oxidative stress with the action of reactive oxygen species (ROS) generated through EtOH metabolism via cytochrome P4502E1 (CYP2E1) leading to carcinogenic etheno‐DNA adducts. ROS may also induce apoptosis. However, the effect of chronic EtOH consumption on CYP2E1, etheno‐DNA adducts as well as anti‐apoptotic proteins in the colorectal mucosa of heavy drinkers without colorectal inflammation is still not known.MethodsRectal biopsies from 32 alcoholics (>60 g EtOH/d) and from 12 controls (<20 g EtOH/d) were histologically examined, and immunohistochemistry for CYP2E1 and etheno‐DNA adducts was performed. Apoptosis (cleaved PARP) as well as anti‐apoptotic proteins including Bcl‐xL, Bcl‐2, and Mcl‐1 were immunohistochemically determined.ResultsNo significant difference in mucosal CYP2E1 or etheno‐DNA adducts was observed between alcoholics and control patients. However, CYP2E1 and etheno‐DNA adducts correlated significantly when both groups were combined (p < 0.001). In addition, although apoptosis was found not to be significantly affected by EtOH, the anti‐apoptotic protein Mcl‐1, but neither Bcl‐xL nor Bcl‐2, was found to be significantly increased in heavy drinkers as compared to controls (p = 0.014).ConclusionsAlthough colorectal CYP2E1 was not found to be significantly increased in alcoholics, CYP2E1 correlated overall with the level of etheno‐DNA adducts in the colorectal mucosa, which identifies CYP2E1 as an important factor in colorectal carcinogenesis. Most importantly, however, is the up‐regulation of the anti‐apoptotic protein Mcl‐1 in heavy drinkers counteracting apoptosis and possibly stimulating cancer development.
Detection of incidental colorectal pathology on positron emission tomography/computed tomography
Authors: Mui Milton , Akhurst Timothy , Warrier Satish K. , Lynch A. Craig , Heriot Alexander G. 
Published: September 2016

BackgroundPositron emission tomography/computed tomography (PET/CT) is an important modality in cancer imaging. With its increasing availability and use, it is not uncommon to detect incidental focal colorectal
18F‐FDG uptake which poses a diagnostic challenge, as they may be associated with malignant or pre‐malignant colorectal lesions. The aim of our study is to determine the proportion of these findings which represents true pathology.MethodsPatients with incidental focal colorectal
18F‐FDG uptake on PET/CT who subsequently underwent colonoscopy between January 2002 to September 2013 were identified from a prospective database in a tertiary referral centre. PET/CT results were correlated with colonoscopy and pathology results in these patients. Positive predictive values (PPVs) and 95% confidence intervals (CIs) of PET/CT in the detection of incidental colorectal pathology were calculated.ResultsA total of 148 patients (92 men and 56 women), with a mean age 73 years (range of 36 to 93 years) were included in the study. A total of 170 foci of colorectal
18F‐FDG uptake were detected on PET/CT. Of these, 101 foci corresponded to a malignant or pre‐malignant lesion (PPV 59%; 95% CI: 52–67%). On a per‐patient analysis, 93 patients had at least one focus of colorectal
18F‐FDG uptake which corresponded to a pre‐malignant or malignant lesion (PPV 63%; 95% CI: 54–71%).ConclusionFocal colorectal
18F‐FDG uptake on PET/CT is associated with a significant proportion of malignant or pre‐malignant lesions. Further evaluation with colonoscopy is recommended.
Transition zone pull‐through in Hirschsprung's disease: a tertiary hospital experience
Authors: Ghosh Dhruva N. , Liu Yingrui , Cass Daniel T. , Soundappan Soundappan S. V. 
Published: September 2016

BackgroundPull‐through of ganglionic bowel is essential for successful treatment of Hirschsprung's disease. We studied the incidence of transition zone pull‐through in our institution and compared its outcome with ganglionic bowel pull‐through.MethodsChildren who underwent Soave's pull‐through for Hirschsprung's disease from January 2005 to November 2012 were studied. Patients were divided into two groups: ganglionic bowel pull‐throughs (Group 1) and transition zone pull‐throughs (Group 2). Demographics, presentations, surgical procedure, post‐operative results and complications including redo procedures were recorded and reviewed along with histopathology reports.ResultsFifty patients underwent Soave's pull‐through for Hirschsprung's disease in our group. The median age at surgery was 13.5 days in Group 1 and 22.5 days in Group 2. Transition zone pull‐through occurred in eight children (16%). Transition zone pull‐through was attributed to errors in histologic interpretation (n = 5), sampling (n = 2) and surgical technique (n = 1). The transition zone was significantly longer in Group 2 (P = 0.002). Constipation and enterocolitis were the main complications needing therapy. One child in Group 2 required surgery for adhesive intestinal obstruction.ConclusionsThe length of the transition zone in children with transition zone pull‐through was significantly longer. Though our children with transition zone pull‐through did not require redo surgery the possibility of redo surgery remains. Transition zone pull‐through should still be considered an error and should be prevented.
Pilot manikin study showed that a supraglottic airway device improved simulated neonatal ventilation in a low‐resource setting
Authors: Pejovic Nicolas J. , Trevisanuto Daniele , Nankunda Jolly , Tylleskär Thorkild 
Published: September 2016

AbstractAimWe compared the performance of personnel in a low‐resource setting when they used the I‐gel cuffless neonatal laryngeal mask or a face mask on a neonatal airway management manikin.MethodsAt Mulago Hospital, Uganda, 25 doctors, nurses and midwives involved in neonatal resuscitation were given brief training with the I‐gel and face mask. Then, every participant was observed positioning both devices on three consecutive occasions. The success rate and insertion times leading to effective positive pressure ventilation (PPV) were recorded. Participants rated the perceived efficiency of the devices using a five‐point Likert scale.ResultsThe I‐gel achieved a 100% success rate on all three occasions, but the face mask was significantly less effective in achieving effective PPV and the failure rates at the first, second and third attempts were 28%, 8% and 20%, respectively. The perceived efficiency of the devices was significantly superior for the I‐gel (4.7 ± 0.4) than the face mask (3.3 ± 0.8).ConclusionThe I‐gel was more effective than the face mask in establishing PPV in the manikin, and user satisfaction was higher. These encouraging manikin data could be a stepping stone for clinical research on the use of the I‐gel for neonatal resuscitation in low‐resource settings.