bluuebunny/crossref_metadata_2025 huggingface dataset:
Why haploinsufficiency persists
Authors: Morrill Summer A. , Amon Angelika
Published: May 2019

Significance

For most genes, a single copy is enough to support normal growth and development of diploid organisms, but a small subset of genes known as haploinsufficient (HI) genes exhibit extreme sensitivity to decreased gene dosage. Given the relatively high frequency of gene-inactivating mutations over the lifespan of an organism, and cell-to-cell variability in gene expression, haploinsufficiency represents a significant barrier to organismal fitness. Why the expression of these genes has not been modulated over evolutionary time to eliminate their haploinsufficiency remains unexplained. We find that the limit of haploinsufficient genes on organismal fitness cannot be overcome by an increase in expression because haploinsufficient genes also confer a fitness disadvantage when encoded in extra copy, leaving these genes evolutionarily “stuck.”
Multiphase reactivity of polycyclic aromatic hydrocarbons is driven by phase separation and diffusion limitations
Authors: Zhou Shouming , Hwang Brian C. H. , Lakey Pascale S. J. , Zuend Andreas , Abbatt Jonathan P. D. , Shiraiwa Manabu
Published: May 2019

Significance

Polycyclic aromatic hydrocarbons (PAHs) are among the most prominent toxic compounds in the air. Heterogeneous reactions involving O
3
can change the toxicity of PAHs, but the reaction mechanism and kinetics remain to be elucidated. Based on new experiments combined with state-of-the-art kinetic and thermodynamic models, we show that phase separation plays a critical role in the ozonolysis of PAHs mixed with secondary organic aerosols and organic oils. Ozonolysis products of PAHs phase separate to form viscous surface crusts, which protect underlying PAHs from ozonolysis to prolong their chemical lifetime. These results have significant implications for outdoor and indoor air quality by affecting PAH long-range transport and fate in indoor environments.
NAD
+
-capped RNAs are widespread in the
Arabidopsis
transcriptome and can probably be translated
Authors: Wang Yuan , Li Shaofang , Zhao Yonghui , You Chenjiang , Le Brandon , Gong Zhizhong , Mo Beixin , Xia Yiji , Chen Xuemei
Published: May 2019

As the most common RNA cap in eukaryotes, the 7-methylguanosine (m
7
G) cap impacts nearly all processes that a messenger RNA undergoes, such as splicing, polyadenylation, nuclear export, translation, and degradation. The metabolite and redox agent, nicotinamide adenine diphosphate (NAD
+
), can be used as an initiating nucleotide in RNA synthesis to result in NAD
+
-capped RNAs. Such RNAs have been identified in bacteria, yeast, and human cells, but it is not known whether they exist in plant transcriptomes. The functions of the NAD
+
cap in RNA metabolism or translation are still poorly understood. Here, through NAD captureSeq, we show that NAD
+
-capped RNAs are widespread in
Arabidopsis thaliana
. NAD
+
-capped RNAs are predominantly messenger RNAs encoded by the nuclear and mitochondrial genomes, but not the chloroplast genome. NAD
+
-capped transcripts from the nuclear genome appear to be spliced and polyadenylated. Furthermore, although NAD
+
-capped transcripts constitute a small proportion of the total transcript pool from any gene, they are enriched in the polysomal fraction and associate with translating ribosomes. Our findings implicate the existence of as yet unknown mechanisms whereby the RNA NAD
+
cap interfaces with RNA metabolic processes as well as translation initiation. More importantly, our findings suggest that cellular metabolic and/or redox states may influence, or be regulated by, mRNA NAD
+
capping.
Torque-dependent remodeling of the bacterial flagellar motor
Authors: Wadhwa Navish , Phillips Rob , Berg Howard C.
Published: May 2019

Significance

The molecular machines that carry out important biological functions in living cells are often made from smaller units that self-assemble inside the cell. Despite decades of research into the function of assembled molecular complexes, little is known about how their assembly itself is regulated to accommodate varying environmental conditions. We measure how the assembly of the bacterial flagellar motor depends on its operational parameters, such as speed and torque. Based on these measurements, we use tools from statistical physics to construct a model for the regulated self-assembly, which largely captures the observed kinetics. This work advances our understanding of how interactions between protein subunits can be tuned by external stimuli to functionally control the formation of macromolecular assemblies.
Estimating power plant CO2 emission using OCO-2 XCO2 and high resolution WRF-Chem simulations
Authors: Zheng Tao , Nassar Ray , Baxter Martin
Published: May 2019

Anthropogenic CO2 emission from fossil fuel combustion has major impacts on the global climate. The Orbiting Carbon Observatory 2 (OCO-2) observations have previously been used to estimate individual power plant emissions with a Gaussian plume model assuming constant wind fields. The present work assesses the feasibility of estimating power plant CO2 emission using high resolution chemistry transport model simulations with OCO-2 observation data. In the new framework, 1.33 km Weather Research and Forecasting-Chem (WRF)-Chem simulation results are used to calculate the Jacobian matrix, which is then used with the OCO-2 XCO2 data to obtain power plant daily mean emission rates, through a maximum likelihood estimation. We applied the framework to the seven OCO-2 observations of near mid-to-large coal burning power plants identified in Nassar et al (2017 Geophys. Res. Lett. 44, 10045–53). Our estimation results closely match the reported emission rates at the Westar power plant (Kansas, USA), with a reported value of 26.67 ktCO2/day, and our estimated value at 25.82–26.47 ktCO2/day using OCO-2 v8 data, and 22.09–22.80 ktCO2/day using v9 data. At Ghent, KY, USA, our estimations using three versions (v7, v8, and v9) range from 9.84–20.40 ktCO2/day, which are substantially lower than the reported value (29.17 ktCO2/day). We attribute this difference to diminished WRF-Chem wind field simulation accuracy. The results from the seven cases indicate that accurate estimation requires accurate meteorological simulations and high quality XCO2 data. In addition, the strength and orientation (relative to the OCO-2 ground track) of the XCO2 enhancement are important for accurate and reliable estimation. Compared with the Gaussian plume model based approach, the high resolution WRF-Chem simulation based approach provides a framework for addressing varying wind fields, and possible expansion to city level emission estimation.
Disaster Risk Assessment of Transmission Lines Based on TOPSIS
Authors: Chen Taowei , Zhu Ling , Xia Qiao , Deng Honglei , Zhou Chen
Published: May 2019

It is of great significance to ensure the safe and reliable operation of the power grid by effectively evaluating the disaster risk of the power grid lines and arranging the sequence of line guard reasonably. A disaster risk assessment method of transmission lines based on TOPSIS is proposed in this paper where six typical natural disasters of the line are considered, the comprehensive risk values of different lines under different disasters combined with the hazards of line accidents is determined, the risk assessment of multiple transmission lines are realized, and its feasibility is verified by applying it to multiple transmission lines in a certain area of China Southern power grid.
Research on Distributed Protection in Switch Stations Based on GOOSE
Authors: Jiang Xin , Yun Baoji
Published: May 2019

The application of IEC61850 standard and the development of smart terminal unit (STU) technology provide a powerful platform for secondary protection research of distribution network. Aiming at the problems of override trip in the protection of the incoming line and feeders on traditional 10kV switching stations, a scheme combining distributed voltage loss protection and overcurrent protection is proposed. The smart terminal unit collects and processes the operation data, realizes data exchange through GOOSE network communication, and cooperates to realize the protection function of the switch stations. In this paper, a protection logic diagram based on the GOOSE mechanism is constructed, which realizes the protection function of feeder lines fault lockout incoming line breakers and the bus line fault lockout busbar automatic transfer switch.
Study on the Reactive Power Control in Hybrid DC Asynchronous Interconnection System
Authors: Han Yan , Jia Yang , Keshan Che , Hui Chen , Wenli Yang , Ke Liu , Jixiu Bao
Published: May 2019

Reactive power control of hybrid DC asynchronous interconnection system has a vital impact on the safety, reliability and high quality of AC/DC power transmission system. The LCC-HVDC unit and MMC-HVDC unit share the same station control system in the hybrid DC asynchronous interconnected system. Firstly, this paper studies the reactive power switching control of LCC-HVDC system, including five subfunctions and control strategies of the reactive power switching control. Secondly, the reactive power auxiliary control of LCC-HVDC system including low load reactive power regulation function and Gamma-Kick function is studied. And the shortcomings of using reactive power auxiliary control are pointed out. Finally, the reactive power control of MMC-HVDC system is deeply studied. The mathematical model of MMC-HVDC control system is established. Reactive power control of MMC-HVDC can be used to replace reactive power auxiliary control of LCC-HVDC to improve the converter utilization and service life
A Line Loss Calculation Method for Arbitrary Partition of Power Grid Based on Measurement Resource and Matpower
Authors: Yi Kai , Wang WeiZhou , Bai RunQing , He Xin , Jing TianJun
Published: May 2019

The existing four-division management method for line loss in smart grids has problems such as the inability to verify line loss contemporaneity and low application flexibility. Considering that the rich data resources provided by data acquisition devices such as measurement meters in the smart grid are not fully utilized, an arbitrary partitioning line loss calculation method that fully utilizes measurement data resources is proposed. The method classifies the grid nodes according to the type of measurement data, obtains complete line power data, and then formulates the boundary equivalence principle of grid partition to realize arbitrary region partition of the power network. On the basis of network partition, the power loss of each subnetwork is calculated by using the power flow of matpower, which greatly increases the flexibility of smart grids line loss management. Taking a power grid in a certain area of Gansu as a case study, the effectiveness of the calculation method is verified.
Support Vector Machine based on clustering algorithm for interruptible load forecasting
Authors: Yu Xiang , Bu Guangfeng , Peng Bingyue , Zhang Chen , Yang Xiaolan , Wu Jun , Ruan Wenqing , Yu Yu , Tang Liangcai , Zou Ziqing
Published: May 2019

Accurately forecast interruptible load can help to alleviate the power supply tension during peak load and make scheduling more flexible. Support vector machine (SVM) method which has been widely used in load forecasting usually selects a period of date close to the forecast day without considering the information characteristics of itself. An interruptible load forecasting method based on clustering algorithm is proposed in this paper. This method puts forward a new idea to select the sample of prediction model which takes full account of the weather and date information of the forecast day and solve the problem that the traditional SVM method cannot properly reflect it. In this paper, the principles of clustering algorithm and support vector machine are introduced firstly. Then K-means clustering algorithm is used to classify the historical data, and the support vector machine forecasting model is constructed by using the categories of the forecast day membership. Finally, the prediction is carried out by combining with the actual data. The results show that the prediction accuracy of this method is more than 95%, and it has higher precision.
Research on Position Sensorless Control of PMSM Based on Improved SMO
Authors: Guoqing Zhang , Xinhong Xiong , Yousheng Zheng , Yanhui Zhang , Lianbo Chen , Xinyu Wu , Wei Feng
Published: May 2019

The sliding mode observer (SMO) can effectively achieve the permanent magnet synchronous motor (PMSM) to perform position sensorless control, but there are still drawbacks of system chattering and high complexity. In this paper, an improved SMO is established based on hyperbolic tangent function and Kalman filter. The system chattering is effectively suppressed, and the accuracy of position and speed observation error is significantly improved without phase compensation. It is found that the convergence rate of the hyperbolic tangent function has a strong correlation with the system chattering degree and the speed observation error. When a is between 3 and 4, the speed error accuracy of the improved SMO is the optimum situation.
Prediction of Bearing Remaining Useful Life based on Mutual Information and Support Vector Regression Model
Authors: Sui Wentao , Zhang Dan , Qiu Xiaomei , Zhang Wei , Yuan Lin
Published: May 2019

In order to evaluate the degradation state of the mechanical equipment and master the information of the remaining useful life (RUL) of the bearing accurately, this paper presents a method for predicting the remaining useful life of bearings based on mutual information (MI) and support vector regression (SVR) model. The proposed method includes two steps of online and offline, the offline step is used to build a degradation model of the bearing by learning, the online step uses the degradation model to predict the remaining useful life. By analyzing the experimental data of bearing full lifetime degradation, the results show that the method can effectively simulate the bearing degradation process and predict the remaining useful life of the bearing.
Research on Optimal placement for GIC mitigation with Blocking Device
Authors: Ning Xiaoliang , Liu Qing , Cui Xikai , Wang Chendong , Wang Yinglan
Published: May 2019

Geomagnetically induced current (GIC) caused by geomagnetic storms flows between the power grid and the earth would threaten the stable operation of the power system. Capacitor blocking device connected in series at transformer neutral point can directly block the DC path. However, due to the complexity of the DC path in the power system, before the installation of the blocking device, if global considerations are not taken into account, the adverse effects of GIC will not be reduced. Therefore, to study the position optimization of the capacitor blocking device is of great value. This optimization of placement of capacitor blocking device is proposed in this paper. Applying the idea of genetic algorithm, the installation quantity and installation position of the blocking device were calculated and compared with the traditional GIC non-optimal method, which verified the superiority of the genetic algorithm optimization solution.
Influence Maximization: A Time-Space Efficient Algorithm
Authors: Xia Ganming
Published: May 2019

Influence maximization is the problem of finding a small subset of nodes (seed nodes) in a social network that could maximize the spread the influence. The algorithm problem of computing influence estimation and influence maximization have been extensively studied for decades. In this paper, we studied the reverse influence sampling method proposed by Byogs et al. in 2014, and some other improved algorithms. We proposed a new algorithm TESA (Time-Space Efficient Algorithm). On large social networks, TESA saves more space than existing algorithms and runs faster. We used data sets tested in the literature to evaluate TESA experimentally and showed that it was superior to the most advanced solutions in terms of running time and memory footprint.
DA-U-Net: Densely Connected Convolutional Networks and Decoder with Attention Gate for Retinal Vessel Segmentation
Authors: Wu Cong , Zou Yixuan , Zhan Jinhao
Published: May 2019

The segmentation of retinal vessels is greatly significant for doctors to diagnose the fundus diseases. However, existing methods have various problems in the segmentation of the retinal vessels, such as insufficient segmentation of retinal vessels, weak anti-noise interference ability. Aiming to the shortcomings of existed methods, this paper proposes an improved model based on the U-Net networks, which contains densely-connected convolutional network and a novel attention gate (AG) model, referred as Densely-Attention-U-Net (DA-U-Net), to automatically segment the retinal blood vessels. The method can alleviate the vanishing-gradient problem, strengthen feature propagation, substantially reduce the number of parameters, and automatically learn to focus on target structures without additional supervision. By verifying the method on the DRIVE datasets, the segmentation accuracy rate is 96.09%, higher than that of U-Net and R2U-Net.
A Gait Patterns Recognition Approach Based on Surface Electromyography and Three-axis Acceleration Signals
Authors: Hao Jinghan , Yang Peng , Chen Lingling , Geng Yanli
Published: May 2019

In this paper, an approach based on combining surface electromyography(sEMG) and three-axis acceleration(ACC) signal was proposed to recognize 5 different kinds basis daily gait patterns, including walking on the ground, going up stairs, going down stairs, going up slope and going down slope. Firstly, the gait related sEMG signal and three-axis ACC signal were collected from the lower limbs of subjects. Secondly, the de-noising of sEMG signal was finished and the segmentation of the fusion signal was done. Thirdly, the features of fusion signal were extracted. Finally, a classifier based on 2-stream hidden Markov model (HMM) was built to recognize 5 kinds of basis daily gait patterns. The experiment obtained an average recognition accuracy of 94.32%, which is 4.15% higher than the accuracy by adopting sEMG signal only (Average 90.17%), and 9.60% higher than the accuracy by adopting ACC signal only (Average 84.72%). The result demonstrated that it can improve the recognition accuracy of gait patterns effectively to combine sEMG signal and three-axis ACC signal.
Implementing smooth functions of a Hermitian matrix on a quantum computer
Authors: Subramanian Sathyawageeswar , Brierley Stephen , Jozsa Richard
Published: May 2019

We consider methods for implementing smooth functions f(A) of a sparse Hermitian matrix A on a quantum computer, and analyse a further combination of these techniques which has advantages of simplicity and resource consumption in some cases. Our construction uses the linear combination of unitaries method with Chebyshev polynomial approximations. The query complexity we obtain is



log

C

ϵ

where ϵ is the approximation precision, and C > 0 is an upper bound on the magnitudes of the derivatives of the function f over the domain of interest. The success probability depends on the 1-norm of the Taylor series coefficients of f, the sparsity d of the matrix, and inversely on the smallest singular value of the target matrix f(A).
Selective vs Complete Sampling in Hysterectomy Specimens Performed for Atypical Hyperplasia
Authors: Bryant Bronwyn H , Doughty Elizabeth , Kalof Alexandra N
Published: May 2019

Objectives

Atypical hyperplasia of the endometrium is a significant risk factor for uterine endometrioid carcinoma (EC) and an indication for hysterectomy. Standard sampling of these specimens includes evaluation of the entire endometrium to identify possible EC. We evaluated a method of selective sampling in an effort to balance resource utilization with diagnostic accuracy in the detection of EC.

Methods

Histologic diagnoses based on selective sampling (exclusion of every other block of endometrium) were compared with the original diagnosis based on complete sampling.

Results

Double-blinded review of these cases using selective sampling detected EC in 92% of hysterectomies, including all high-grade/high-stage carcinomas. Selective sampling had an 82% agreement with the original diagnoses, with most discordant diagnoses attributable to interobserver variability. Adjusting for interobserver variability increased diagnostic agreement between selective and complete sampling to 96%.

Conclusions

Selective sampling is a feasible method to save time and resources while maintaining diagnostic accuracy.
MTTFsite: cross-cell type TF binding site prediction by using multi-task learning
Authors: Zhou Jiyun , Lu Qin , Gui Lin , Xu Ruifeng , Long Yunfei , Wang Hongpeng
Published: May 2019

Motivation

The prediction of transcription factor binding sites (TFBSs) is crucial for gene expression analysis. Supervised learning approaches for TFBS predictions require large amounts of labeled data. However, many TFs of certain cell types either do not have sufficient labeled data or do not have any labeled data.

Results

In this paper, a multi-task learning framework (called MTTFsite) is proposed to address the lack of labeled data problem by leveraging on labeled data available in cross-cell types. The proposed MTTFsite contains a shared CNN to learn common features for all cell types and a private CNN for each cell type to learn private features. The common features are aimed to help predicting TFBSs for all cell types especially those cell types that lack labeled data. MTTFsite is evaluated on 241 cell type TF pairs and compared with a baseline method without using any multi-task learning model and a fully shared multi-task model that uses only a shared CNN and do not use private CNNs. For cell types with insufficient labeled data, results show that MTTFsite performs better than the baseline method and the fully shared model on more than 89% pairs. For cell types without any labeled data, MTTFsite outperforms the baseline method and the fully shared model by more than 80 and 93% pairs, respectively. A novel gene expression prediction method (called TFChrome) using both MTTFsite and histone modification features is also presented. Results show that TFBSs predicted by MTTFsite alone can achieve good performance. When MTTFsite is combined with histone modification features, a significant 5.7% performance improvement is obtained.

Availability and implementation

The resource and executable code are freely available at http://hlt.hitsz.edu.cn/MTTFsite/ and http://www.hitsz-hlt.com:8080/MTTFsite/.

Supplementary information

Supplementary data are available at Bioinformatics online.
DeepSymmetry: using 3D convolutional networks for identification of tandem repeats and internal symmetries in protein structures
Authors: Pagès Guillaume , Grudinin Sergei
Published: May 2019

Motivation

Thanks to the recent advances in structural biology, nowadays 3D structures of various proteins are solved on a routine basis. A large portion of these structures contain structural repetitions or internal symmetries. To understand the evolution mechanisms of these proteins and how structural repetitions affect the protein function, we need to be able to detect such proteins very robustly. As deep learning is particularly suited to deal with spatially organized data, we applied it to the detection of proteins with structural repetitions.

Results

We present DeepSymmetry, a versatile method based on 3D convolutional networks that detects structural repetitions in proteins and their density maps. Our method is designed to identify tandem repeat proteins, proteins with internal symmetries, symmetries in the raw density maps, their symmetry order and also the corresponding symmetry axes. Detection of symmetry axes is based on learning 6D Veronese mappings of 3D vectors, and the median angular error of axis determination is less than one degree. We demonstrate the capabilities of our method on benchmarks with tandem-repeated proteins and also with symmetrical assemblies. For example, we have discovered about 7800 putative tandem repeat proteins in the PDB.

Availability and implementation

The method is available at https://team.inria.fr/nano-d/software/deepsymmetry. It consists of a C++ executable that transforms molecular structures into volumetric density maps, and a Python code based on the TensorFlow framework for applying the DeepSymmetry model to these maps.

Supplementary information

Supplementary data are available at Bioinformatics online.
NX4: a web-based visualization of large multiple sequence alignments
Authors: Solano-Roman A , Cruz-Castillo C , Offenhuber D , Colubri A
Published: May 2019

Multiple Sequence Alignments (MSAs) are a fundamental operation in genome analysis. However, MSA visualizations such as sequence logos and matrix representations have changed little since the nineties and are not well suited for displaying large-scale alignments. We propose a novel, web-based MSA visualization tool called NX4, which can handle genome alignments comprising thousands of sequences. NX4 calculates the frequency of each nucleotide along the alignment and visually summarizes the results using a color-blind friendly palette that helps identifying regions of high genetic diversity. NX4 also provides the user with additional assistance in finding these regions with a ‘focus + context’ mechanism that uses a line chart of the Shannon entropy across the alignment. The tool offers geneticists an easy-to-use and scalable analysis for large MSA studies.

Availability and implementation

NX4 is freely available at https://www.nx4.io, and its source code at https://github.com/NX4/nx4.

Supplementary information

Supplementary data are available at Bioinformatics online
Morphological variation in genetically divergent populations of the common whelk, Buccinum undatum (Gastropoda: Buccinidae), across the North Atlantic
Authors: Magnúsdóttir Hildur , Pálsson Snæbjörn , Westfall Kristen Marie , Jónsson Zophonías O , Örnólfsdóttir Erla Björk
Published: May 2019

The variation in shelled marine gastropod morphology across small spatial scales can reflect restricted population connectivity, resulting in evolution or plastic responses to environmental heterogeneity. The common whelk, Buccinum undatum, is a subtidal gastropod, ubiquitous in the North Atlantic, that exhibits considerable spatial variation in shell morphology and colour. Given that species delimitation in shelled marine gastropods is often based on shell characteristics, such morphological variation can lead to taxonomic confusion. Phylogeographical analysis based on mitochondrial DNA and microsatellites suggested cryptic species composed of Western and Eastern North Atlantic common whelk populations, the separation of which dates to the onset of the Pleistocene glaciation ~2.1 Mya. Divergence within the Eastern North Atlantic is more recent and characterized by isolation by distance. In the present study, phenotypic variation in shell morphology across the North Atlantic range is analysed and compared with molecular divergence. The morphological variation of B. undatum populations reflected the pattern observed for the molecular markers only for certain comparisons of populations and might, in other cases, reflect larger constraints on the morphological variation and, possibly, the impact of environmental influences.
Twenty Years of the Rome Statute of the International Criminal Court: Appraising the State of National Implementing Legislation in Asia
Authors: Birkett Daley J
Published: May 2019

The International Criminal Court relies on its State Parties to incorporate, or implement, its constituent instrument, the Rome Statute, into their domestic legal systems to enable its effective functioning. First, State Parties are obliged to give effect to their explicit obligation to cooperate with the Court under the Rome Statute. Second, although not required to do so, to avoid their national legal systems being found by the Court to be unable to investigate and/or prosecute the crimes under its jurisdiction in accordance with the principle of complementarity, they should also implement the definition and prohibition of these offences in their national legal frameworks. This article appraises the status of the domestic implementation of the Rome Statute, both crimes and cooperation, in Asia. The article concludes that few Asian State Parties to the Rome Statute have incorporated the treaty’s provisions into their domestic laws in a holistic manner, with the absence of cooperation legislation, enabling State Parties to assist the Court, particularly striking.
Cryptococcal Meningitis Screening and Community-based Early Adherence Support in People With Advanced Human Immunodeficiency Virus Infection Starting Antiretroviral Therapy in Tanzania and Zambia: A Cost-effectiveness Analysis
Authors: Kimaro Godfather Dickson , Guinness Lorna , Shiri Tinevimbo , Kivuyo Sokoine , Chanda Duncan , Bottomley Christian , Chen Tao , Kahwa Amos , Hawkins Neil , Mwaba Peter , Mfinanga Sayoki Godfrey , Harrison Thomas S , Jaffar Shabbar , Niessen Louis W
Published: May 2019

Background

A randomized trial demonstrated that among people living with late-stage human immunodeficiency virus (HIV) infection initiating antiretroviral therapy, screening serum for cryptococcal antigen (CrAg) combined with adherence support reduced all-cause mortality by 28%, compared with standard clinic-based care. Here, we present the cost-effectiveness.

Methods

HIV-infected adults with CD4 count <200 cells/μL were randomized to either CrAg screening plus 4 weekly home visits to provide adherence support or to standard clinic-based care in Dar es Salaam and Lusaka. The primary economic outcome was health service care cost per life-year saved as the incremental cost-effectiveness ratio (ICER), based on 2017 US dollars. We used nonparametric bootstrapping to assess uncertainties and univariate deterministic sensitivity analysis to examine the impact of individual parameters on the ICER.

Results

Among the intervention and standard arms, 1001 and 998 participants, respectively, were enrolled. The annual mean cost per participant in the intervention arm was US$339 (95% confidence interval [CI], $331–$347), resulting in an incremental cost of the intervention of US$77 (95% CI, $66–$88). The incremental cost was similar when analysis was restricted to persons with CD4 count <100 cells/μL. The ICER for the intervention vs standard care, per life-year saved, was US$70 (95% CI, $43–$211) for all participants with CD4 count up to 200 cells/μL and US$91 (95% CI, $49–$443) among those with CD4 counts <100 cells /μL. Cost-effectveness was most sensitive to mortality estimates.

Conclusions

Screening for cryptococcal antigen combined with a short period of adherence support, is cost-effective in resource-limited settings.
Fibroblast growth factor 23 and tubular sodium handling in young patients with incipient chronic kidney disease
Authors: Freundlich Michael , Cuervo Carlos , Abitbol Carolyn L
Published: May 2019

Background

Experimental studies have shown fibroblast growth factor 23 (FGF23)-mediated upregulation of the distal tubule sodium/chloride (Na+Cl−) co-transporter leading to increased Na reabsorption, volume expansion and hypertension. However, data on the associations of FGF23 with renal Na regulation and blood pressure (BP) are lacking in young CKD patients.

Methods

FGF23 and other determinants of mineral metabolism, plasma renin activity (PRA), fractional excretion of Na (FENa) and BP, were analyzed at a single center in 60 patients aged 5–22 years with CKD Stages 1 (n = 33) and Stages 2–3 (n = 27) defined by cystatin C- and creatinine-based estimating equations (estimated glomerular filtration rate, eGFR). Associations between FGF23 and renal Na handling were explored by regression analysis.

Results

Median FGF23 levels were higher in CKD Stages 2–3 versus CKD 1 (119 versus 79 RU/mL; P < 0.05), with hyperparathyroidism [parathyroid hormone (PTH) >69 pg/mL] in only few subjects with CKD Stages 2–3. Median FENa was comparable in both subgroups, but with proportionally more values above the reference mean (0.55%) in CKD Stages 2–3 and 3-fold higher (1.6%) in CKD Stage 3. PRA was higher in CKD Stages 2–3 (P < 0.05). Meanwhile in CKD Stage 1, FGF23 did not associate with FENa, and in CKD Stages 2–3 FGF23 associated positively with FENa (r = 0.4; P < 0.05) and PTH (r = 0.45; P < 0.05), and FENa associated with FE of phosphate (r = 0.6; P < 0.005). Neither FGF23 nor FENa was associated with systolic or diastolic BP in either subgroup. The negative association of eGFR by cystatin with FENa remained the strongest predictor of FENa by multivariable linear regression in CKD Stages 2–3.

Conclusions

The elevated FGF23, FENa and PRA and the positive association of FGF23 with FENa do not suggest FGF23-mediated increased tubular Na reabsorption and volume expansion as causing hypertension in young patients with incipient CKD.
Incidence and outcome of peri-procedural transcatheter heart valve embolization and migration: the TRAVEL registry (TranscatheteR HeArt Valve EmboLization and Migration)
Authors: Kim Won-Keun , Schäfer Ulrich , Tchetche Didier , Nef Holger , Arnold Martin , Avanzas Pablo , Rudolph Tanja , Scholtz Smita , Barbanti Marco , Kempfert Jörg , Mangieri Antonio , Lauten Alexander , Frerker Christian , Yoon Sung-Han , Holzamer Andreas , Praz Fabien , De Backer Ole , Toggweiler Stefan , Blumenstein Johannes , Purita Paola , Tarantini Giuseppe , Thilo Christian , Wolf Alexander , Husser Oliver , Pellegrini Costanza , Burgdorf Christof , Antolin Rosa Ana Hernandez , Díaz Victor A Jiménez , Liebetrau Christoph , Schofer Niklas , Möllmann Helge , Eggebrecht Holger , Sondergaard Lars , Walther Thomas , Pilgrim Thomas , Hilker Michael , Makkar Raj , Unbehaun Axel , Börgermann Jochen , Moris Cesar , Achenbach Stephan , Dörr Oliver , Brochado Bruno , Conradi Lenard , Hamm Christian W
Published: May 2019

Aims

Peri-procedural transcatheter valve embolization and migration (TVEM) is a rare but potentially devastating complication of transcatheter aortic valve implantation (TAVI). We sought to assess the incidence, causes, and outcome of TVEM in a large multicentre cohort.

Methods and results

We recorded cases of peri-procedural TVEM in patients undergoing TAVI between January 2010 and December 2017 from 26 international sites. Peri-procedural TVEM occurred in 273/29 636 (0.92%) TAVI cases (age 80.8 ± 7.3 years; 53.8% female), of which 217 were to the ascending aorta and 56 to the left ventricle. The use of self-expanding or first-generation prostheses and presence of a bicuspid aortic valve were independent predictors of TVEM. Bail-out measures included repositioning attempts using snares or miscellaneous tools (41.0%), multiple valve implantations (83.2%), and conversion to surgery (19.0%). Using 1:4-propensity matching, we identified a cohort of 235 patients with TVEM (TVEMPS) and 932 patients without TVEM (non-TVEMPS). In the matched cohort, all-cause mortality was higher in TVEMPS than in non-TVEMPS at 30 days (18.6% vs. 4.9%; P < 0.001) and after 1 year (30.5% vs. 16.6%; P < 0.001). Major stroke was more frequent in TVEMPS at 30 days (10.6% vs. 2.8%; P < 0.001), but not at 1 year (4.6% vs. 1.9%; P = 0.17). The need for emergent cardiopulmonary support, major stroke at 30 days, and acute kidney injury Stages 2 and 3 increased the risk of 1-year mortality, whereas a better renal function at baseline was protective.

Conclusion

Transcatheter valve embolization and migration occurred in approximately 1% and was associated with increased morbidity and mortality.
How Multiple Retrievals Affect Neural Reactivation in Young and Older Adults
Authors: St-Laurent Marie , Buchsbaum Bradley R
Published: May 2019

Objectives

Aging can reduce the specificity with which memory episodes are represented as distributed patterns of brain activity. It remains unclear, however, whether repeated encoding and retrieval of stimuli modulate this decline. Memory repetition is thought to promote semanticization, a transformative process during which episodic memory becomes gradually decontextualized and abstracted. Because semantic memory is considered more resilient to aging than context-rich episodic memory, we hypothesized that repeated retrieval would affect cortical reinstatement differently in young versus older adults.

Methods

We reanalyzed data from young and older adults undergoing functional magnetic resonance imaging while repeatedly viewing and recalling short videos. We derived trial-unique multivariate measures of similarity between video-specific brain activity patterns elicited at perception and at recall, which we compared between age groups at each repetition.

Results

With repetition, memory representation became gradually more distinct from perception in young adults, as reinstatement specificity converged downward toward levels observed in the older group. In older adults, alternative representations that were item-specific but orthogonal to patterns elicited at perception became more salient with repetition.

Discussion

Repetition transformed dominant patterns of memory representation away and orthogonally from perception in young and older adults, respectively. Although distinct, both changes are consistent with repetition-induced semanticization.
Premature Aging Among Trauma Survivors—The Longitudinal Implications of Sleep Disruptions on Telomere Length and Cognitive Performance
Authors: Aloni Roy , Levin Yafit , Uziel Orit , Solomon Zahava
Published: May 2019

Objectives

Sleep is necessary for brain function as well as physical and cognitive processes. Sleep disruptions, common with aging, intensify among trauma survivors. Moreover, former prisoners-of-war (ex-POWs) often experience premature aging. This study investigates the longitudinal effects of sleep disruptions for ex-POWs in relation to cognitive performance and telomere length as well as between cognition and telomeres.

Method

This study included Israeli veterans from the 1973 Yom Kippur War who participated in four assessments (1991, 2003, 2008, 2015): (a) ex-POWs (n = 99), and (b) veterans who not were captured (controls) (n = 101). Among both groups, sleep disruptions were assessed using a self-report item in all four assessments. Cognitive performance was assessed using the Montreal Cognitive Assessment (MOCA) and telomere length was assessed via total white blood cells (leukocytes) from whole blood samples using Southern blot, both were measured only among ex-POWs in 2015. We conducted descriptive statistics, repeated measures, correlations, and path analyses.

Results

Sleep disruptions were related to lower cognitive performance but not to shorter telomeres. Moreover, cognitive performance and telomere length were found to be related when sleep disruptions were taken into consideration.

Conclusion

Interpersonal trauma was shown to be a unique experience resulting in sleep disruptions over time, leading to cognitive impairment. These findings highlight the importance of viewing trauma survivors at high-risk for sleep disruptions. Therefore, it is imperative to inquire about sleep and diagnose cognitive disorders to help identify and treat premature aging.
Universities and innovation ecosystems: a dynamic capabilities perspective
Authors: Heaton Sohvi , Siegel Donald S , Teece David J
Published: May 2019

Universities play an important role in innovation ecosystems. In addition to developing human capital and advancing technology, they are increasingly expected to participate as economic development partners with industry and local, state, and national governments. Models such as the “Triple Helix” have been advanced to frame the assessment of interactions among academia, industry, and governments that may foster economic development. Such models highlight the boundary-spanning roles of universities and provide a predetermined list of actions universities could take to strengthen their ecosystem. Unfortunately, the flexible and entrepreneurial management of universities required to make this model work has virtually been ignored in the academic literature. We propose the dynamic capabilities framework to guide how universities might manage their innovation ecosystems. We use this framework to analyze the role of the university throughout the ecosystem lifecycle. These concepts are then illustrated with three case studies of universities that have engaged with partners in local economies to launch new industries, fostering entrepreneurship, and revitalize neighborhoods.
Genus Integration, Abelianization, and Extended Monodromy
Authors: Contreras Ivan , Fernandes Rui Loja
Published: May 2019

Given a Lie algebroid we discuss the existence of a smooth abelian integration of its abelianization. We show that the obstructions are related to the extended monodromy groups introduced recently in [9]. We also show that this groupoid can be obtained by a path-space construction, similar to the Weinstein groupoid of [6], but where the underlying homotopies are now supported in surfaces with arbitrary genus. As an application, we show that the prequantization condition for a (possibly non-simply connected) manifold is equivalent to the smoothness of an abelian integration. Our results can be interpreted as a generalization of the classical Hurewicz theorem.
Is it ethical to isolate study participants to prevent HIV transmission during trials with an analytical treatment interruption?
Authors: Eyal Nir , Magalhaes Monica
Published: May 2019

This commentary considers an extreme idea for protecting against human immunodeficiency virus (HIV) transmission to sex partners of individuals participating in HIV remission studies with an analytical treatment interruption (ATI). Other human challenge studies, such as studies of influenza, commonly isolate participants during the trial, to protect their contacts and the community against infection. Why should HIV studies with a treatment interruption be any different, one might wonder? This article concludes that isolation should not be used in HIV remission studies with an ATI but also shows that the matter is complex.
Efficacy of colistin alone and in various combinations for the treatment of experimental osteomyelitis due to carbapenemase-producing Klebsiella pneumoniae
Authors: Crémieux Anne-Claude , Dinh Aurélien , Nordmann Patrice , Mouton William , Tattevin Pierre , Ghout Idir , Jayol Aurelie , Aimer Omar , Gatin Laure , Verdier Marie-Clémence , Saleh-Mghir Azzam , Laurent Frédéric
Published: May 2019

Objectives

In a new experimental model of carbapenemase-producing Klebsiella pneumoniae osteomyelitis we evaluated the efficacy of colistin alone and in various combinations and examined the emergence of colistin-resistant strains and cross-resistance to host defence peptides (HDPs).

Methods

KPC-99YC is a clinical strain with intermediate susceptibility to meropenem (MIC = 4 mg/L) and full susceptibility to gentamicin, colistin and tigecycline (MICs = 1 mg/L) and fosfomycin (MIC = 32 mg/L). Time–kill curves were performed at 4× MIC. Osteomyelitis was induced in rabbits by tibial injection of 2 × 108 cfu. Treatment started 14 days later for 7 days in seven groups: (i) control; (ii) colistin; (iii) colistin + gentamicin; (iv) colistin + tigecycline; (v) colistin + meropenem; (vi) colistin + meropenem + gentamicin; and (vii) colistin + fosfomycin.

Results

In vitro, colistin was rapidly bactericidal, but regrowth occurred after 9 h. Combinations of colistin with meropenem or fosfomycin were synergistic, whereas combination with tigecycline was antagonistic. In vivo, colistin alone was not effective. Combinations of colistin with meropenem or fosfomycin were bactericidal (P < 0.001) and the addition of gentamicin enhanced the efficacy of colistin + meropenem (P = 0.025). Tigecycline reduced the efficacy of colistin (P = 0.007). Colistin-resistant strains emerged in all groups except colistin + fosfomycin and two strains showed cross-resistance to HDP LL-37.

Conclusions

In this model, combinations of colistin plus meropenem, with or without gentamicin, or colistin plus fosfomycin were the only effective therapies. The combination of colistin and tigecycline should be administered with caution, as it may be antagonistic in vitro and in vivo.
Was Television Responsible for a New Generation of Smokers?
Authors: Thomas Michael
Published: May 2019

Consumers’ response to mass media can be difficult to assess because individuals choose for themselves the amount of media they consume, and that choice may be correlated with their other consumption decisions. To avoid this selection problem, this article examines the introduction of television to the US, during which some cities gained access to television years before others. This natural experiment makes it possible to estimate the causal impact of television on the decision to start smoking, a consumer behavior with important public health implications. Difference-in-differences analyses of television’s introduction indicate that (1) television did cause people to start smoking, (2) 16- to 21-year-olds were particularly affected by television, and (3) much of the response to television occurred within a couple of years of its introduction. Our preferred estimates suggest that television increased the share of smokers in the population by 5–15 percentage points, generating roughly 11 million additional smokers between 1946 and 1970. More broadly, these results offer causal evidence that (1) mass media can have a large influence on consumers, potentially affecting their health, (2) media exerts an especially strong influence on teens, and (3) mass media can influence consumers more than typical changes in prices.
The Canal + Judgment: Your Favourite Domestic Channels, in Luxembourg (Take 2) – Absolute Territorial Protection
Authors: Mavroghenis Stephen , Fajardo Pedro
Published: May 2019

Judgment of 12 December 2018 Case T‑873/16, Groupe Canal + SA v European Commission (EU:T:2018:904).

The General Court reaffirms its position on the illegality of absolute territorial protection clauses in distribution contracts and confirms an Article 9 of Regulation 1/2003 decision that made binding commitments wider than the concerns expressed in the preliminary assessment.
The RNF20/40 complex regulates p53-dependent gene transcription and mRNA splicing
Authors: Wu Chen , Cui Yaqi , Liu Xiuhua , Zhang Feng , Lu Lin-Yu , Yu Xiaochun
Published: May 2019

p53 is a key transcription factor to regulate gene transcription. However, the molecular mechanism of chromatin-associated p53 on gene transcription remains elusive. Here, using unbiased protein affinity purification, we found that the RNF20/40 complex associated with p53 on the chromatin. Further analyses indicated that p53 mediated the recruitment of the RNF20/40 complex to p53 target gene loci including p21 and PUMA loci and regulated the transcription of p21 and PUMA via the RNF20/40 complex-dependent histone H2B ubiquitination (ubH2B). Lacking the RNF20/40 complex suppressed not only ubH2B but also the generation of the mature mRNA of p21 and PUMA. Moreover, ubH2B was recognized by the ubiquitin-binding motif of pre-mRNA processing splicing factor 8 (PRPF8), a subunit in the spliceosome, and PRPF8 was required for the maturation of the mRNA of p21 and PUMA. Our study unveils a novel p53-dependent pathway that regulates mRNA splicing for tumor suppression.