bluuebunny/crossref_metadata_2025 huggingface dataset:
Episodic evolution of a eukaryotic NADK repertoire of ancient provenance
Authors: Vickman Oliver , Erives Albert J
Published: January 2019

NAD kinase (NADK) is the sole enzyme that phosphorylates nicotinamide adenine dinucleotide (NAD+/NADH) into NADP+/NADPH, which provides the chemical reducing power in anabolic (biosynthetic) pathways. While prokaryotes typically encode a single NADK, eukaryotes encode multiple NADKs. How these different NADK genes are all related to each other and those of prokaryotes is not known. Here we conduct phylogenetic analysis of NADK genes and identify major clade-defining patterns of NADK evolution. First, almost all eukaryotic NADK genes belong to one of two ancient eukaryotic sister clades corresponding to cytosolic ("cyto") and mitochondrial ("mito") clades. Secondly, we find that the cyto-clade NADK gene is duplicated in connection with loss of the mito-clade NADK gene in several eukaryotic clades or with acquisition of plastids in Archaeplastida. Thirdly, we find that horizontal gene transfers from proteobacteria have replaced mitochondrial NADK genes in only a few rare cases. Last, we find that the eukaryotic cyto and mito paralogs are unrelated to independent duplications that occurred in sporulating bacteria, once in mycelial Actinobacteria and once in aerobic endospore-forming Firmicutes. Altogether these findings show that the eukaryotic NADK gene repertoire is ancient and evolves episodically with major evolutionary transitions.
Comprehensive analysis of tumour initiation, spatial and temporal progression under multiple lines of treatment
Authors: Leshchiner Ignaty , Livitz Dimitri , Gainor Justin F. , Rosebrock Daniel , Spiro Oliver , Martinez Aina , Mroz Edmund , Lin Jessica J. , Stewart Chip , Kim Jaegil , Elagina Liudmila , Bozic Ivana , Mino-Kenudson Mari , Rooney Marguerite , Ou Sai-Hong Ignatius , Wu Catherine J. , Rocco James W. , Engelman Jeffrey A. , Shaw Alice T. , Getz Gad
Published: January 2019

Driver mutations alter cells from normal to cancer through several evolutionary epochs: premalignancy, early malignancy, subclonal diversification, metastasis and resistance to therapy. Later stages of disease can be explored through analyzing multiple samples collected longitudinally, on or between successive treatments, and finally at time of autopsy. It is also possible to study earlier stages of cancer development through probabilistic reconstruction of developmental trajectories based on mutational information preserved in the genome. Here we present a suite of tools, called Phylogic N-Dimensional with Timing (PhylogicNDT), that statistically model phylogenetic and evolutionary trajectories based on mutation and copy-number data representing samples taken at single or multiple time points. PhylogicNDT can be used to infer: (i) the order of clonal driver events (including in pre-cancerous stages); (ii) subclonal populations of cells and their phylogenetic relationships; and (iii) cell population dynamics. We demonstrate the use of PhylogicNDT by applying it to whole-exome and whole-genome data of 498 lung adenocarcinoma samples (434 previously available and 64 of newly generated data). We identify significantly different progression trajectories across subtypes of lung adenocarcinoma (EGFR mutant, KRAS mutant, fusion-driven and EGFR/KRAS wild type cancers). In addition, we study the progression of fusion-driven lung cancer in 21 patients by analyzing samples from multiple timepoints during treatment with 1st and next generation tyrosine kinase inhibitors. We characterize their subclonal diversification, dynamics, selection, and changes in mutational signatures and neoantigen load. This methodology will enable a systematic study of tumour initiation, progression and resistance across cancer types and therapies.
Identifying complex motifs in massive omics data with a variable-convolutional layer in deep neural network
Authors: Li Jing-Yi , Jin Shen , Tu Xin-Ming , Ding Yang , Gao Ge
Published: January 2019

Motif identification is among the most common and essential computational tasks for bioinformatics and genomics. Here we proposed a novel convolutional layer for deep neural network, named Variable Convolutional (vConv) layer, for effective motif identification in high-throughput omics data by learning kernel length from data adaptively. Empirical evaluations on DNA-protein binding and DNase footprinting cases well demonstrated that vConv-based networks have superior performance to their convolutional counterparts regardless of model complexity. Meanwhile, vConv could be readily integrated into multi-layer neural networks as an “in-place replacement” of canonical convolutional layer. All source codes are freely available on GitHub for academic usage.
Characterization of Dyspnea in Lung Cancer Survivors Following Curative-Intent Therapy
Authors: Ha Duc , Ries Andrew L.
Published: January 2019

Purpose

Dyspnea is highly-prevalent in lung cancer survivors following curative-intent therapy. We aimed to identify clinical determinants of dyspnea and characterize its relationship with functional exercise capacity (EC).

Methods

In an analysis of data from a cross-sectional study of lung cancer survivors who completed curative-intent therapy for stage I-IIIA disease ≥1 month previously, we tested a thorough list of comorbidities, lung function, and lung cancer characteristics. We assessed dyspnea using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer Module 13 (LC13) and functional EC the six-minute walk. We verified results with the University of California San Diego Shortness of Breath Questionnaire (SOBQ).

Results

In 75 participants at a median of 12 months since completing treatment, the mean (SD) LC13-Dyspnea score was 35.3 (26.2); 60% had abnormally-high dyspnea. In multivariable linear regression analyses, significant clinical determinants of dyspnea were [β (95% confidence interval)]: psychiatric illness [−20.8 (−32.4, −9.09) forNo/Yes], heart failure with reduced ejection fraction [−15.5 (−28.0, −2.97) forNo/Yes], and forced expiratory volume in 1 second [−0.28 (−0.49, −0.06) for each% predicted]. Dyspnea was an independent predictor of functional EC [−1.54 (−2.43, −0.64) for eachpoint]. These results were similar with the SOBQ.

Conclusion

We identified clinical determinants of dyspnea which have pathophysiological bases. Dyspnea was independently associated with functional EC. Behavioral interventions to promote exercise in lung cancer survivors following curative-intent therapy may need to also optimize medical therapy for cardiopulmonary and/or psychiatric disease and reduce dyspnea to be effective.
Awareness of danger inside the egg? Evidence of innate and learned predator recognition in cuttlefish embryo.
Authors: Mezrai Nawel , Arduini Lorenzo , Dickel Ludovic , Chiao Chuan-Chin , Darmaillacq Anne-Sophie
Published: January 2019

Predation exerts one of the greatest selective pressures on prey organisms. Many studies showed the existence of innate anti-predator responses mostly in early stages of juveniles vertebrate. Learning is also possible but risky since it can cause death. There is now growing evidence that embryonic learning exists in animals but few studies have tested explicitly for learning in embryos. Here, Sepia pharaonis cuttlefish embryos respond to the presence or odour of a predator fish but not to a non-predator fish. Interestingly, embryos can learn to associate a non-threatening stimulus with an alarm signal: cuttlefish ink. After several paired exposures, they respond to the harmless fish as if it were dangerous. Our results demonstrate both innate and acquired predator recognition in a cephalopod. Embryos response is a decrease of ventilation rate. Such response is adaptive, especially in a translucent egg, since it reduces movement and hence the risk of being detected; this freezing-like behaviour may also reduce bioelectric field, which lessens shark predation risk. Last, our result is the first report of associative learning in an invertebrate embryo. This shows that a cuttlefish embryo can have both genetic predator avoidance skills and possesses enough cognitive abilities plasticity to learn and retain new threats before hatching. The combination of these mechanisms is an impressive example of the early adaptability of cephalopod molluscs. This amount of behavioural plasticity gives the newly-hatched sepia a huge selective advantage when dealing with known or new threats.
Determinants of Heart Rate Recovery and Heart Rate Variability in Lung Cancer Survivors Eligible for Long-Term Cure
Authors: Ha Duc , Malhotra Atul , Ries Andrew L. , O’Neal Wesley T. , Fuster Mark M.
Published: January 2019

Background

Lung cancer survivors are at increased risk for autonomic dysfunction. We aimed to identify determinants of parasympathetic nervous system (PNS) function as reflected by heart rate recovery (HRR) and heart rate variability (HRV) in lung cancer survivors eligible for long-term cure.

Methods

We performed a cross-sectional study of consecutive lung cancer survivors who completed curative-intent therapy for stage I-IIIA ≥1 month previously. We tested a comprehensive list of variables related to baseline demographics, comorbidities, lung cancer characteristics, and physiological/functional measures using univariable and multivariable (MVA) linear regression analyses. We defined HRR as the difference in heart rate (HR) at 1-minute following and the end of the six-minute walk test (6MWT), and HRV the standard deviation of normal-to-normal R-R intervals (SDNN) and root-mean-square-of-successive-differences (rMSSD) from routine single 10-s electrocardiographs (ECGs).

Results

In 69 participants, the mean (standard deviation, SD) HRR was -10.6 (6.7) beats. In MVAs, significant independent determinants of HRR [β (95% confidence interval)] were: age [0.17 (0.04, 0,30) for each year] and HR change associated with the 6MWT [0.01 (0.007, 0.02) for each beats/min. In 41 participants who had ECGs available for HRV measurements, the mean (SD) SDNN and rMSSD were 19.1 (15.6) and rMSSD 18.2 (14.6) ms, respectively. In MVAs, significant determinants of HRV were: total lung capacity [0.01 (0.00, 0.02), p=0.047 for each % predicted] and HRR [-0.04 (-0.07, -0.003) for each beat] for natural logarithm (Ln-)SDNN; and [0.01 (0.00, 0.02)] and [-0.04 (-0.07, -0.01)] for Ln-rMSSD, respectively.

Conclusions

We measured determinants of HRR and HRV in lung cancer survivors eligible for long-term cure. HRR and/or HRV may be useful as indicators to stratify patients in interventional studies aimed at improving PNS function in lung cancer survivors, including through exercise training.
Semantic richness and density effects on language production: Electrophysiological and behavioral evidence
Authors: Rabovsky Milena , Schad Daniel , Rahman Rasha Abdel
Published: January 2019

Language production ultimately aims to convey meaning. Yet, words differ widely in the richness and density of their semantic representations and these differences impact conceptual and lexical processes during speech planning. Here, we replicate the recent finding that semantic richness, measured as the number of associated semantic features according to semantic feature production norms, facilitates object naming. In contrast, intercorrelational semantic feature density, measured as the degree of intercorrelation of a concept’s features, presumably resulting in the coactivation of closely related concepts, has an inhibitory influence. We replicate the behavioral effects and investigate their relative time course and electrophysiological correlates. Both the facilitatory effect of high semantic richness and the inhibitory influence of high feature density were reflected in an increased posterior positivity starting at about 250 ms, in line with previous reports of posterior positivities in paradigms employing contextual manipulations to induce semantic interference during language production. Furthermore, amplitudes at the same posterior electrode sites were positively correlated with object naming times between about 230 and 380 ms. The observed effects follow naturally from the assumption of conceptual facilitation and simultaneous lexical competition, and are difficult to explain by language production theories dismissing lexical competition.
Loud music and the specific sound stress open the blood-brain barrier: new fundamental, biomedical, and social aspects
Authors: Semyachkina-Glushkovskaya O. , Chekhonin V. , Bragin D. , Bragina O. , Vodovozova E. , Alekseeva A. , Salmin V. , Morgun A. , Malinovskaya N. , Osipova E. , Boytsova E. , Tohidpour A. , Shirokov A. , Navolokin N. , Yang Y. , Zhang C. , Feng W. , Abdurashitov A. , Ulanova M. , Shushunova N. , Khorovodov A. , Terskov A. , Shareef A. Esmat , Pavlov A. , Luo Q. , Zhu D. , Tuchin V. , Kurths. J.
Published: January 2019

The blood-brain barrier (BBB) poses a significant challenge for drug brain delivery. The limitation of our knowledge about the nature of BBB explains the slow progress in the therapy of brain diseases and absence of methods for drug brain delivery in the clinical practice.

Here we show that BBB opens for low/high weight molecules and nanocarriers after exposure of loud music/sound of 90 dB and 100 dB (regardless its frequency) as being easily produced by MP3/MP4 players, kitchen appliances, loudspeakers at concerts. The role of sound, sound-induced stress and molecular mechanisms behind is discussed in the framework of BBB opening as an informative platform for a novel fundamental knowledge about the nature of BBB and for the development of a non-invasive brain drug delivery technology.

Social aspects of music/sound-induced opening of BBB provide completely new information about noise and healthy life conditions that will stimulate new research in this field.
Comparing Task-Relevant Information Across Different Methods of Extracting Functional Connectivity
Authors: Stulz Sophie Benitez , Insabato Andrea , Deco Gustavo , Gilson Matthieu , Senden Mario
Published: January 2019

The concept of brain states, functionally relevant large-scale activity patterns, has become popular in neuroimaging. Not all components of such patterns are equally characteristic for each brain state, but machine learning provides a possibility for extracting and comparing the structure of brain states from functional data. However, their characterization in terms of functional connectivity measures varies widely, from cross-correlation to phase coherence, and the idea that different measures provide similar or coherent information is a common assumption made in neuroimaging. Here, we compare the brain state signatures extracted from of phase coherence, pairwise covariance, correlation, regularized covariance and regularized precision for a dataset of subjects performing five different cognitive tasks. In addition, we compare the classification performance in identifying the tasks for each connectivity measure. The measures are evaluated in their ability to discriminate the five tasks with two types of cross-validation: within-subject cross-validation, which reflects the stability of the signature over time; and between-subject cross-validation, which aims at extracting signatures that generalize across subjects. Secondly, we compare the informative features (connections or links between brain regions/areas) across measures to test the assumption that similar information is obtained about brain state signatures from different connectivity measures. In our results, the different types of cross-validation give different classification performance and emphasize that functional connectivity measures on fMRI require observation windows of sufficient duration. Furthermore, we find that informative links for the classification, meaning changes between tasks that are consistent across subjects, are entirely uncorrelated between BOLD correlations and covariances. These results indicate that the corresponding FC signature can strongly differ across FC methods used and that interpretation is subject to caution in terms of subnetworks related to a task.
A Bistable Mechanism Mediated by Integrins Controls Mechanotaxis of Leukocytes
Authors: Hornung Alexander , Sbarrato Thomas , Garcia-Seyda Nicolas , Aoun Laurene , Luo Xuan , Biarnes-Pelicot Martine , Theodoly Olivier , Valignat Marie-Pierre
Published: January 2019

The recruitment of leukocytes from blood vessels to inflamed zones is guided by biochemical and mechanical stimuli, with mechanisms only partially deciphered. We studied here the guidance by flow of primary human effector T lymphocytes crawling on substrates coated with ligands of integrins LFA-1 (αLβ2) and VLA-4 (α4β1), and showed that cells segregated in two populations of opposite orientation for combined adhesion. Sharp decisions of orientation were shown to rely on a bistable mechanism between LFA-1-mediated upstream and VLA-4-dominant downstream phenotypes. At the molecular level, bistability results from a differential front-rear polarization of both integrins affinity, combined with an inhibiting crosstalk of LFA-1 toward VLA-4. At the cellular level, directivity with or against the flow is mechanically mediated by the passive orientation of detached uropod or lamellipod by flow. This complete chain of logical events provides a unique mechanistic picture of a guiding mechanism, from stimuli to cell orientation.

Significance

Cellular guidance is crucial to many biological functions, but the precise mechanisms remain unclear. We have analyzed here an original phenotype of flow-guided cells mimicking leukocytes crawling into the blood vessels and showed that thecontrolling parameterof cells decision to migrate upstream or downstream was therelative numberof two specific adhesion molecules, the integrins LFA-1 and VLA-4. The spatial polarisation of integrins affinity and an intermutually feedback of their activation create a bistable system where cells adhere either by their tip or their tail and orient respectively downstream or upstream. This mechanism therefore proposes a complete chain of event from stimuli to cell orientation and differs strongly from the chemotaxis paradigm because stimuli trigger no signaling.
A complex containing lysine-acetylated actin inhibits the formin INF2
Authors: A Mu , Fung Tak Shun , Kettenbach Arminja N. , Chakrabarti Rajarshi , Higgs Henry
Published: January 2019

INF2 is a member of the formin family of actin assembly factors. Dominant mis-sense mutations in INF2 link to two diseases: focal segmental glomerulosclerosis (FSGS), a kidney disease; and Charcot-Marie-Tooth disease (CMTD), a neuropathy. All disease mutations map to the autoinhibitory Diaphanous Inhibitory Domain (DID). Curiously, purified INF2 is not autoinhibited, suggesting the existence of additional cellular inhibitors. We purified an INF2 inhibitor from mouse brain, and identified it as a complex between lysine-acetylated actin (KAc-actin) and cyclase-associated protein (CAP). Inhibition of INF2 by CAP/KAc-actin requires INF2 DID. Treatment of CAP/KAc-actin with histone deacetylase 6 (HDAC6) releases INF2 inhibition, while HDAC6 inhibitors block cellular INF2 activation. INF2 disease mutants are poorly inhibited by CAP/KAc-actin, suggesting that FSGS and CMTD result from reduced CAP/KAc-actin binding. This is the first demonstrated role for lysine-acetylated actin: regulation of an actin assembly factor by a novel mechanism, which we call facilitated auto-inhibition.
PTBP1 mRNA isoforms and regulation of their translation
Authors: Arake de Tacca Luisa M , Pulos Mia C , Floor Stephen N , Cate Jamie
Published: January 2019

Polypyrimidine tract-binding proteins (PTBPs) are RNA binding proteins that regulate a number of post-transcriptional events. Human PTBP1 transits between the nucleus and cytoplasm and is thought to regulate RNA processes in both. However, information about PTBP1 mRNA isoforms and regulation of PTPB1 expression remain incomplete. Here we mapped the major PTBP1 mRNA isoforms in HEK293T cells, and identified alternative 5' and 3' untranslated regions (5' UTRs, 3' UTRs) as well as alternative splicing patterns in the protein coding region. We also assessed how the observed PTBP1 mRNA isoforms contribute to PTBP1 expression in different phases of the cell cycle. Previously, PTBP1 mRNAs were shown to crosslink to eukaryotic translation initiation factor 3 (eIF3). We find that eIF3 binds differently to each PTBP1 mRNA isoform in a cell cycle-dependent manner. We also observe a strong correlation between eIF3 binding to PTBP1 mRNAs and repression of PTBP1 levels during the S phase of the cell cycle. Our results provide evidence of translational regulation of PTBP1 protein levels during the cell cycle, which may affect downstream regulation of alternative splicing and translation mediated by PTBP1 protein isoforms.
Synaptic vesicles transiently dock to refill release sites
Authors: Kusick Grant F , Chin Morven , Raychaudhuri Sumana , Lippmann Kristina , Adula Kadidia P , Hujber Edward J , Vu Thien , Davis M Wayne , Jorgensen Erik M , Watanabe Shigeki
Published: January 2019

Synaptic vesicles fuse with the plasma membrane to release neurotransmitter following an action potential, after which new vesicles must ‘dock’ to refill vacated release sites. To capture synaptic vesicle exocytosis at cultured mouse hippocampal synapses, we induced single action potentials by electrical field stimulation then subjected neurons to high-pressure freezing to examine their morphology by electron microscopy. During synchronous release, multiple vesicles can fuse at a single active zone; this multivesicular release is augmented by increasing extracellular calcium. Fusions during synchronous release are distributed throughout the active zone, whereas fusions during asynchronous release are biased toward the center of the active zone. Immediately after stimulation, the total number of docked vesicles across all synapses decreases by ∼40%. Between 8 and 14 ms, new vesicles are recruited to the plasma membrane and fully replenish the docked pool in a calcium-dependent manner, but docking of these vesicles is transient and they either undock or fuse within 100 ms. These results demonstrate that recruitment of synaptic vesicles to release sites is rapid and reversible.
Structure-guided design of a pure orthosteric antagonist of integrin αlIbβ3 that inhibits thrombosis but not clot retraction
Authors: Adair Brian D. , Alonso José L. , van Agthoven Johannes , Hayes Vincent , Ahn Hyun Sook , Xiong Jian-Ping , Poncz Mortimer , Arnaout M. Amin
Published: January 2019

Platelet integrin αlIbβ3 plays a critical role in both hemostasis and thrombosis. Current αIIbβ3 antagonists are potent anti-thrombotic drugs, but also cause adverse outcomes, which limited their clinical use. Drug-induced serious bleeding, thrombocytopenia and paradoxical thrombosis have been linked to impaired clot retraction and to conformational changes in αIIbβ3 that promote binding of preformed antibodies, natural ligands or both to αIIbβ3. We have used structure-guided design to generate the orthosteric inhibitor Hr10 that acts as a pure αIIbβ3 antagonist, i.e. it does not induce the conformational changes in αIIbβ3. Hr10 is as effective as the partial agonist drug eptifibatide in blocking platelet aggregation and arteriolar thrombosis in mice. In contrast to eptifibatide, however, Hr10 preserved thrombin-induced clot retraction, suggesting that it may not perturb hemostasis. Our structure-based approach can find general utility in designing pure orthosteric inhibitors for other integrins, in providing vital tools for dissecting structure-activity relationships in αIIbβ3, and potentially in offering safer alternatives for human therapy.
Accurate Modeling of Brain Responses to Speech
Authors: Wong Daniel D.E. , Di Liberto Giovanni M. , de Cheveigné Alain
Published: January 2019

Perceptual processes can be probed by fitting stimulus-response models that relate measured brain signals such as electroencephalography (EEG) to the stimuli that evoke them. These models have also found application for the control of devices such as hearing aids. The quality of the fit, as measured by correlation, classification, or information rate metrics, indicates the value of the model and the usefulness of the device. Models based on Canonical Correlation Analysis (CCA) achieve a quality of fit that surpasses that of commonly-used linear forward and backward models. Here, we show that their performance can be further improved using several techniques that capture the time-varying and context-dependent relationships within the data, including adaptive beamforming, CCA weight optimization, and recurrent neural networks that capture the time-varying and context-dependent relationships within the data. We demonstrate these results using a match-vs-mismatch classification paradigm, in which the classifier must decide which of two stimulus samples produced a given EEG response and which is a randomly chosen stimulus sample. This task captures the essential features of the more complex auditory attention decoding (AAD) task explored in many other studies.
Bioluminescent Multi-Characteristic Opsin for monitoring visual cortical activity upon optical stimulation
Authors: Batabyal Subrata , Gajjeraman Sivakumar , Nagai Takeharu , Wright Weldon , Mohanty Samarendra
Published: January 2019

Non-invasive detection of neural activity is important for the diagnosis of neurological diseases, evaluation of therapeutic outcomes, and collection of real-time feedback for stimulation based therapeutic approaches. In the case of vision loss, due to retinal degeneration, optic neuropathy, or enucleation of the eye, there is a need to map changes in visual cortical activity during disease progression and subsequent vision restoration by retinal, optic nerve or cortical stimulation. Existing technologies allow interrogation of neuronal circuits by both read and write activity, albeit with inherent limitations. Here, we present the development of bioluminescent multi-characteristic opsin (bMCO-11), which is comprised of a highly photosensitive ambient light-activatable domain and a Ca2+-sensitive bioluminescence reporter. The high quantum efficiency of bMCO-11 enables light activation and recording of cellular activity upon local as well as wide area optical stimulation. Furthermore, persistent Ca2+influx was achieved by bioluminescence based cyclic activation of the opsin-domain of bMCO-11 by transporting the ions only into bMCO expressing cells. This allowed us to continuously monitor visual cortical activity in wild type and retinal degenerated mice, without requiring any additional external excitation source.
PGN_0297 is an essential component of the type IX secretion system (T9SS) in Porphyromonas gingivalis: Tn‐seq analysis for exhaustive identification of T9SS‐related genes
Authors: Naito Mariko , Tominaga Takashi , Shoji Mikio , Nakayama Koji
Published: January 2019

The type IX secretion system (T9SS) was originally discovered in Porphyromonas gingivalis, one of the pathogenic bacteria associated with periodontal disease and is now known to be present in many members of the phylum Bacteroidetes. The T9SS secretes a number of potent virulence factors, including the highly hydrolytic proteases called gingipains, across the outer membrane in P. gingivalis. To understand the entire machinery of T9SS, an exhaustive search for T9SS‐related genes in P. gingivalis using the mariner family transposon (Tn) and Tn‐seq analysis was performed. Seven hundred and two Tn insertion sites in Tn mutants with no colony pigmentation that is associated with Lys‐gingipain (Kgp) defectiveness were determined, and it was found that the Tn was inserted in the kgp gene and 54 T9SS‐related candidate genes. Thirty‐three out of the 54 genes were already known as T9SS‐related genes. Furthermore, deletion mutant analysis of the remaining 21 genes revealed that they were not related to the T9SS. The 33 T9SS‐related genes include a gene for PGN_0297, which was found to be associated with the T9SS components PorK and PorN. A PGN_0297 gene deletion mutant was constructed, and it was found that the mutant showed no colony pigmentation, hemagglutination or gingipain activities, indicating that PGN_0297 was an essential component of the T9SS. The 33 genes did not include the six genes (gppX, omp17, porY, rfa, sigP and wzx) that were also reported as T9SS‐related genes. gppX deletion and insertion mutants were constructed, and it was found that they did not show deficiency in the T9SS.
Manager skill and portfolio size with respect to a benchmark
Authors: Bolshakov Andrei , Chincarini Ludwig B.
Published: January 2019

Investment managers often manage a portfolio with respect to a benchmark. Typically, they use a mean‐variance optimization framework to maximize the information ratio of their portfolio. We develop an unconventional approach to this question. Given a set of assumptions, we ask what optimal percentage of the benchmark stocks the portfolio manager should select. This optimal portfolio depends on Fisher's and Wallenius's noncentral hypergeometric distributions. We find that the optimal selectivity of a benchmark universe varies from 50% to 80%. These results are provocative, given that many enhanced index portfolio managers select a low percentage of the benchmark universe.
Plastomes of Betulaceae and phylogenetic implications
Authors: Yang Xiao‐Yue , Wang Ze‐Fu , Luo Wen‐Chun , Guo Xin‐Yi , Zhang Cai‐Hua , Liu Jian‐Quan , Ren Guang‐Peng
Published: January 2019

Betulaceae is a well‐defined family of Fagales, including six living genera and more than 160 modern species. Species of the family have high ecological and economic value for the abundant production of wood. However, phylogenetic relationships within Betulaceae have remained partly unresolved, likely due to the lack of a sufficient number of informative sites used in previous studies. Here, we re‐investigate the Betulaceae phylogeny with whole chloroplast genomes from 24 species (17 newly assembled), representing all genera of the family. All the 24 plastomes are relatively conserved with four regions, and each genome is ∼158–161 kb long, with 111 genes. The six genera are all monophyletic in the plastome tree, whereas Ostrya Scop. is nested in the Carpinus clade in the internal transcribed spacer tree. Further incongruencies are also detected within some genera between species. Incomplete lineage sorting and/or hybrid introgression during the diversification of the family could account for such incongruencies. Our dating analysis, based on four fossils, suggests that the most recent common ancestors of the extant genera date back to the mid‐ to late Miocene, and confirms that Betulaceae started to diversify in the upper Cretaceous/early Paleocene. Our results highlight the significance of using more informative sites in resolving phylogenetic relationships. Plastome data and increased taxon sampling will help to better understand the evolutionary history of Betulaceae in the future.
The consequences of an introgression event
Authors: Barton Nicholas H.
Published: January 2019

Hanemaaijer et al. (Molecular Ecology, 27, 2018) describe the genetic consequences of the introgression of an insecticide resistance allele into a mosquito population. Linked alleles initially increased, but many of these later declined. It is hard to determine whether this decline was due to counter‐selection, rather than simply to chance.
Upswing of Innovation
Authors: Costabile Thomas
Published: January 2019

New products and ideas seem to be adopted at an ever-increasing rate. These technologies are reshaping the world. Mechanical Engineering magazine’s Emerging Technology Awards honor five ascending technologies this year. The editors have examined the trends in each of ASME’s five core technologies—energy, manufacturing, robotics, bioengineering, and pressure technology—and looked for recent innovations that have hit the marketplace. And from dozens of contenders, the editors have found five that seem poised to make an extraordinary impact on the coming decade.
Aviation, Gas Turbines and the ‘Three Worlds’
Authors: Herzner Fred
Published: January 2019

In the aviation industry, the safety of the people who fly is directly linked to the decisions that are made by the employees of the organizations that produce the airplanes and engines that power them. As a member of such an organization, Mr. Herzner experienced the gravity of making such decisions when he was involved with an airplane accident where 111 people lost their lives. That experience caused him to reflect on how and why such decisions get made. He drew some important conclusions and used them to formulate recommendations on how to make decisions which avoid such devastating consequences.

However when several recent very big events involving large organizations came into the news, he used them to benchmark his recommendations. What he found was several of those event involved unethical behavior. That was an eye-opener because he had never been involved with such behavior. That led him to modify his perspective on how decisions get made.

Using all of that, Mr. Herzner describes the principles that influence how decisions get made and makes recommendations on how organizations and the people in them can avoid what he calls the ‘doomsday event”.
The Largest Wind Turbine Ever
Authors: Winters Jeffrey , Saunders Zina
Published: January 2019

Vincent Schellings, a mechanical engineer who is the engineering and product development general manager for GE’s offshore wind business was tasked with managing the design and fabrication of the world’s largest wind turbine. This article looks closely the Haliade-X that is intended to produce 12 MW at full capacity.
Wearable Holographic Computer
Authors: Shah Agam , Saunders Zina
Published: January 2019

Alex Kipman, technical fellow at Microsoft, who led a team through years of research and development to produce the HoloLens, recaps the development journey of the mixed reality headset in this article.
Printed Parts for a Lighter Flight
Authors: Thilmany Jean , Saunders Zina
Published: January 2019

Bastian Schäfer, an Airbus engineer, believes the ability to 3-D print airplane parts—including the plane’s very skeleton structure—will revolutionize air travel. Schäfer is project manager on what his group calls the Bionic Partition Project. The project itself is under the purview of the Airbus Emerging Technologies and Concepts Group, led by Peter Sander. Working under Schäfer, the group has created a 3-D printed partition to separate the seating area on the A320 from the galley.
Quenching an Enormous Thirst
Authors: Kosowatz John , Saunders Zina
Published: January 2019

Water scarcity is happening in many more places around the globe. To comabt it, seawater desalination is often a technology of last resort, due to the high energy costs needed to power the industrial-sized plants. Israel’s IDE Technologies offered an alternative to thermal technology: reverse osmosis. This article delves deeper into the technology.
An Information-Theoretic Framework for Complex Systems
Authors: Agharazi Hanieh , Theeranaew Wanchat , Richard M. Kolacinski , Lopaor Kenneth A.
Published: January 2019

We propose an information-theoretic framework for modeling complex systems as a communication network where physical devices can be organized into subsystems and subsystems are communicating through an information channel governed by the dynamics of the system.
Controllability and Observability Gramians as Information Metrics for Optimal Design of Networked Control Systems
Authors: Çela Arben , Niculescu Silviu-Iulian , Natowicz René , Reama Abdellatif
Published: January 2019

This paper addresses the problem of optimal control and scheduling of Networked Control Systems over limited bandwidth deterministic networks using some insight on the interplay between the control and information theory. The motivation is related to the necessity of choice a communication sequence which maximize control signal impact on the plant behavior. The solution is obtained by decomposing the overall problem in a twofold one. The first level problem aims obtaining the periodic off-line or static scheduling function of control signals based on system properties, communication constrains, periodicity of scheduling sequence, performance criteria and maximization of the degree of reachability/observability of the periodic system. A Mixed Integer Quadratic Programming (MIQP) problem is formulated and solved obtaining a periodic and stable NCS. The solution of the second level problem is based on the structure of the static scheduling function obtained from the first level solution and the dependance of the degree of reachability/observability on the current state of the system.
Open Rotor Engines—Still an Open Question?
Authors: Langston Lee S.
Published: January 2019

A major factor in the continued domination of turbofan engines for economic airline propulsion, is the ability to increase bypass ratios. However, increasing fan diameters to go to ever higher bypass ratios increases nacelle weight, aerodynamic drag and duct losses. By eliminating the need for a fan duct, open rotor engines can effectively in-crease bypass ratios, resulting in a significant savings in fuel consumption.

Open rotor engines have been under intermittent development since the 1980s, sub-ject to rising and falling of fuel prices. Technical challenges that continue in their de-ployment include noise reduction, airframe integration and protection from propel-ler/fan blade failure.
Fault Tree Interval Analysis of Complex Systems Based on Universal Grey Operation
Authors: Zhang Feng , Tan Shiwang , Zhang Leilei , Wang Yameng , Gao Yang
Published: January 2019

The objective of this study is to propose a new operation method based on the universal grey number to overcome the shortcomings of typical interval operation in solving system fault trees. First, the failure probability ranges of the bottom events are described according to the conversion rules between the interval number and universal grey number. A more accurate system reliability calculation is then obtained based on the logical relationship between the AND gates and OR gates of a fault tree and universal grey number arithmetic. Then, considering an aircraft landing gear retraction system as an example, the failure probability range of the top event is obtained through universal grey operation. Next, the reliability of the aircraft landing gear retraction system is evaluated despite insufficient statistical information describing failures. The example demonstrates that the proposed method provides many advantages in resolving the system reliability problem despite poor information, yielding benefits for the function of the interval operation, and overcoming the drawback of solution interval enlargement under different orders of interval operation.
Impact of HIV-1 Infection and Antiretroviral Therapy on Bone Homeostasis and Mineral Density in Vertically Infected Patients
Authors: Donà D. , Mozzo E. , Luise D. , Lundin R. , Padoan A. , Rampon O. , Giaquinto C.
Published: January 2019

Daily assumption of antiretroviral drugs and HIV-related immune activation lead to important side effects, which are particularly evident in vertically infected patients. Bone homeostasis impairment and reduction of bone mineral density (BMD) is one of the most important side effects. Primary aim of this study is to assess the prevalence of bone homeostasis alterations in a group of vertically infected patients; secondary aim is to analyze the relationship between bone homeostasis alterations and anthropometric data, severity of HIV infection, and antiretroviral therapy. We studied 67 patients with vertically transmitted HIV-1 (aged 6-31 years), followed by the Pediatric Infectious Disease Unit of the University Hospital of Padua, Italy. We analyzed bone turnover markers (P1NP and CTx) and we performed lumbar spine and femoral dual energy X-ray absorption densitometry (DXA). Personal and anthropometric data and information on HIV-infection severity and antiretroviral therapy were collected for all patients. We found that BMD values recorded by DXA showed a significant correlation with age, race, BMI, physical activity, and antiretroviral therapy duration. P1NP was increased in 43% of patients, while CTX in 61% of them. P1NP alteration was related to age, race, BMI, physical activity, therapy duration, and ever use of protease inhibitors and nucleotide reverse transcriptase inhibitors. CTX alteration was found to be correlated only with age. In conclusion, our study confirms that a wide percentage of HIV vertically infected patients show reduced BMD and impaired bone homeostasis. Strict monitoring is needed in order to early identify and treat these conditions.
Emergency Department and Radiological Cost of Delayed Diagnosis of Cannabinoid Hyperemesis
Authors: Zimmer David I. , McCauley Ross , Konanki Varun , Dynako Joseph , Zackariya Nuha , Shariff Faadil , Miller Joseph , Binz Sophia , Walsh Mark
Published: January 2019

Background. Chronic cannabis use has become prevalent with decriminalization, medical prescription, and recreational legalization in numerous US states. With this increasing incidence of chronic cannabis use a new clinical syndrome has become apparent in emergency departments and hospitals across the country, termed Cannabinoid Hyperemesis (CH). CH has been described as cyclical vomiting and abdominal pain in the setting of chronic cannabis use, which is often temporarily relieved by hot showers. CH presents a diagnostic challenge to clinicians who do not have a high clinical suspicion for the syndrome and can result in high costs and resource utilization for hospitals and patients. This study investigates the expenditures associated with delayed CH evaluation and delayed diagnosis. Methods. This is a retrospective observational study of 17 patients diagnosed with CH at three medical centers in the United States from 2010 to 2015, consisting of two academic centers and a community hospital. Emergency department (ED) costs were calculated and analyzed for patients eventually diagnosed with CH. Results. For the 17 patients treated, the total cost for combined ED visits and radiologic evaluations was an average of $76,920.92 per patient. On average these patients had 17.9 ED visits before the diagnosis of CH was made. Conclusion. CH provides a diagnostic challenge to clinicians without a high suspicion of the syndrome and may become increasingly prevalent with current trends toward cannabis legalization. The diagnosis of CH can be made primarily through a thorough history and physical examination. Awareness of this syndrome can save institutions money, prevent inappropriate utilization of healthcare resources, and save patients from unnecessary diagnostic tests.
QoS Prediction for Neighbor Selection via Deep Transfer Collaborative Filtering in Video Streaming P2P Networks
Authors: Ma Wenming , Zhang Qian , Mu Chunxiao , Zhang Meng
Published: January 2019

To expand the server capacity and reduce the bandwidth, P2P technologies are widely used in video streaming systems in recent years. Each client in the P2P streaming network should select a group of neighbors by evaluating the QoS of the other nodes. Unfortunately, the size of video streaming P2P network is usually very large, and evaluating the QoS of all the other nodes is resource-consuming. An attractive way is that we can predict the QoS of a node by taking advantage of the past usage experiences of a small number of the other clients who have evaluated this node. Therefore, collaborative filtering (CF) methods could be used for QoS evaluation to select neighbors. However, we might use different QoS properties for different video streaming policies. If a new video steaming policy needs to evaluate a new QoS property, but the historical experiences include very few evaluation data for this QoS property, CF methods would incur severe overfitting issues, and the clients then might get unsatisfied recommendation results. In this paper, we proposed a novel neural collaborative filtering method based on transfer learning, which can evaluate the QoS with few historical data by evaluating the other different QoS properties with rich historical data. We conduct our experiments on a large real-world dataset, the QoS values of which are obtained from 339 clients evaluating on the other 5825 clients. The comprehensive experimental studies show that our approach offers higher prediction accuracy than the traditional collaborative filtering approaches.
Exclusive Breastfeeding Practice and Associated Factors among Mothers in Boditi Town, Wolaita Zone, Southern Ethiopia, 2018: A Community-Based Cross-Sectional Study
Authors: Azeze Gedion Asnake , Gelaw Kelemu Abebe , Gebeyehu Natnael Atnafu , Gesese Molalegn Mesele , Mokonnon Taklu Marama
Published: January 2019

Background. Exclusive breastfeeding tops the table of life-saving interventions for newborns. A child who is exclusively breastfed is 14 times less likely to die in the first six months compared to its counterpart. Approximately 18,000 children globally still die every day and if current trend continues, some 60 million children under age 5 will die between 2017 and 2030, and half of them will be newborns. Five countries, including Ethiopia, accounted for half of all newborn deaths in the world.Objective. To assess the prevalence and associated factors of exclusive breastfeeding practice among mothers who have infants 6-12 months of age in Boditi Town, Wolaita Zone, Southern Ethiopia, 2018.Methods. Community-based cross-sectional study was conducted among 412 randomly selected mothers having 6 to 12 month infants from April 1 to 14, 2018. A pretested interviewer administered questionnaire was used for data collection. The data were entered using Epi Data version 3.1 and analyzed using SPSS version 20. Descriptive statistics was made. Bivariate and multivariate logistic regression was also carried out to see the effect of each independent variable on the dependent variable.Results. Of 412 mother-infant pairs sampled, 403 were participated, which made a response rate of 97.8%. Prevalence of EBF computed using since birth dietary recall method was 64.8% (95% C.I= 60.0, 69.0). From multivariable analysis, child birth attended by health care provider (AOR = 5.303, 95% C.I = 1.613, 17.436), postnatal care utilization (AOR = 1.91, C.I = 1.083, 3.370), and mothers who did not report any breast related problem for the first six months after child birth (AOR = 1.864, C.I = 1.090, 3.189) were factors positively associated with exclusive breastfeeding practice.Conclusion. Although the prevalence of exclusive breastfeeding practice in this study was relatively high, more effort to meet World Health Organization (WHO) recommendations is still necessary to benefit from its intervention. There is a need to promote child births to be attended by health care providers and postnatal care utilization. Further, women should be educated on what to do and where to seek care if breast problem occurs after child birth.