bluuebunny/crossref_metadata_2025 huggingface dataset:
Heavily phosphorus doped germanium: Strong interaction of phosphorus with vacancies and impact of tin alloying on doping activation
Authors: Vohra Anurag , Khanam Afrina , Slotte Jonatan , Makkonen Ilja , Pourtois Geoffrey , Porret Clement , Loo Roger , Vandervorst Wilfried
Published: June 2019

We examined the vacancy trapping proficiency of Sn and P atoms in germanium using positron annihilation spectroscopy measurements, sensitive to the open-volume defects. Epitaxial Ge1−xSnx films were grown by chemical vapor deposition with different P concentrations in the ∼3.0×1019–1.5×1020 cm−3 range. We corroborate our findings with first principles simulations. Codoping of Ge with a Sn concentration of up to 9% is not an efficient method to suppress the free vacancy concentration and the formation of larger phosphorus–vacancy complexes. Experimental results confirm an increase in the number of P atoms around the monovacancy with P-doping, leading to dopant deactivation in epitaxial germanium–tin layers with similar Sn content. Vice versa, no impact on the improvement of maximum achieved P activation in Ge with increasing Sn-doping has been observed. Theoretical calculations also confirm that Pn-V (vacancy) complexes are energetically more stable than the corresponding SnmPn-V and Snm-V defect structures with the same number of alien atoms (Sn or P) around the monovacancy. The strong attraction of vacancies to the phosphorus atoms remains the dominant dopant deactivation mechanism in Ge as well as in Ge1−xSnx.
Thermodynamics of 3D diamond-like epitaxial (film) morphologies on 1D modulated substrate: Weak crystallization theory
Authors: Erukhimovich Igor , Kriksin Yury
Published: June 2019

Being inspired by recent theoretical findings in block copolymer ordering, we present, within the simplest version of the Landau weak crystallization theory, a consistent treatment of the thin film thermodynamics. It is first shown that a proper design of the period of a 1D modulated substrate results in the formation of a 3D morphology whose symmetry is close to a cubic diamond one and differs from the latter due to a symmetry violation caused by the block copolymer-substrate interaction. The corresponding phase portraits are built. With a decrease in the temperature, the diamondlike morphology becomes less stable until it turns (via the 1st order phase transition) into the lamellar phase. On the contrary, with an increase in the substrate selectivity, the lamellae become less stable and, finally, turn into the diamondlike morphology.
Phase-sensitive imaging of microwave currents in superconductive circuits
Authors: Karpov A. , Zhuravel A. P. , Averkin A. S. , Chichkov V. I. , Ustinov A. V.
Published: June 2019

We propose an improved measuring technique for microwave currents in superconductive circuits, demonstrate it experimentally, and validate the experimental data with numerical simulations. Contemporary superconductive electronics widely uses planar circuits with micrometer-scale elements for a variety of applications. With the rise of complexity of a circuit and increase in the number of its components, a simple impedance measurement is often not efficient for the diagnosis of problems, nor for clarifying the physics underlying the circuit response. The established Laser Scanning Microscopy (LSM) technique generates micrometer-scale images of the amplitude of the microwave currents in a planar superconductive circuit, but not the phase of the oscillating currents. Here, we present a more powerful type of LSM imaging containing signal phase information. We employ a fast-optical modulator in order to synchronize the phase of the laser intensity oscillation with the phase of the probing microwave signal. The loss induced in a laser illuminated area strongly depends on the phase difference between the RF probing signal and the laser beam modulation. As a proof of concept, we present the phase-sensitive LSM measurements of the inner mode currents in a planar superconductive resonator and confirm the data with numerical simulation of the resonator's electrodynamics.
Reading In, Looking Out: Hermeneutics by Implication in an Early Fifteenth-Century Anthology
Authors: White James
Published: June 2019

This article investigates aspects of mise-en-page in British Library Add. MS. 27261, an anthology of twenty-three texts on mixed subjects produced for Eskandar Soltān (d. 818/1415), grandson of Timur and self-styled ruler of territories in southern Iran during the early fifteenth century. It examines the juxtaposition of literary and scientific texts together with images in Add. MS. 27261, and explores the correlations that these juxtapositions create. It concludes that the London anthology should be seen as a coherent intellectual enterprise, and as an interpretative project designed to feed Eskandar’s experiments with different forms of knowledge.
Phosphoinositides modulate the voltage dependence of two-pore channel 3
Authors: Shimomura Takushi , Kubo Yoshihiro
Published: June 2019

Two-pore channels, or two-pore Na+ channels (TPCs), contain two homologous domains, each containing a functional unit typical of voltage-dependent cation channels. Each domain is considered to be responsible for either phosphoinositide (PI) binding or voltage sensing. Among the three members of the TPC family, TPC1 and TPC2 are activated by PI(3,5)P2, while TPC3 has been thought not to be affected by any PIs. Here, we report that TPC3 is sensitive to PI(3,4)P2 and PI(3,5)P2, but not to PI(4,5)P2, and that the extremely slow increase in TPC3 currents induced by depolarization in Xenopus oocytes is due to the production of PI(3,4)P2. Similarly to TPC1, the cluster of basic amino acid residues in domain I is critical for PI sensitivity, but with a slight variation that may allow TPC3 to be sensitive to both PI(3,4)P2 and PI(3,5)P2. We also found that TPC3 has a unique PI-dependent modulation mechanism of voltage dependence, which is achieved by a specific bridging interaction between domain I and domain II. Taken together, these findings show that TPC3 is a unique member of the TPC family that senses PIs and displays a strong coupling between PI binding and voltage-dependent gating.
A comparative study of high-quality C-face and Si-face 3C-SiC(1 1 1) grown on off-oriented 4H-SiC substrates
Authors: Shi Yuchen , Jokubavicius Valdas , Höjer Pontus , Ivanov Ivan G , Yazdi G Reza , Yakimova Rositsa , Syväjärvi Mikael , Sun Jianwu
Published: June 2019

We present a comparative study of the C-face and Si-face of 3C-SiC(111) grown on off-oriented 4H-SiC substrates by the sublimation epitaxy. By the lateral enlargement method, we demonstrate that the high-quality bulk-like C-face 3C-SiC with thickness of ~1 mm can be grown over a large single domain without double positioning boundaries (DPBs), which are known to have a strongly negative impact on the electronic properties of the material. Moreover, the C-face sample exhibits a smoother surface with one unit cell height steps while the surface of the Si-face sample exhibits steps twice as high as on the C-face due to step-bunching. High-resolution XRD and low temperature photoluminescence measurements show that C-face 3C-SiC can reach the same high crystalline quality as the Si-face 3C-SiC. Furthermore, cross-section studies of the C- and Si-face 3C-SiC demonstrate that in both cases an initial homoepitaxial 4H-SiC layer followed by a polytype transition layer are formed prior to the formation and lateral expansion of 3C-SiC layer. However, the transition layer in the C-face sample is extending along the step-flow direction less than that on the Si-face sample, giving rise to a more fairly consistent crystalline quality 3C-SiC epilayer over the whole sample compared to the Si-face 3C-SiC where more defects appeared on the surface at the edge. This facilitates the lateral enlargement of 3C-SiC growth on hexagonal SiC substrates.
An adaptive loop gain selection for CLEAN deconvolution algorithm
Authors: Zhang Li , Xu Long , Zhang Ming , Wu Zhong-Zu
Published: June 2019

Radio interferometry significantly improves the resolution of observed images, and the final result also relies heavily on data recovery. The Cotton-Schwab CLEAN (CS-Clean) deconvolution approach is a widely used reconstruction algorithm in the field of radio synthesis imaging. However, parameter tuning for this algorithm has always been a difficult task. Here, its performance is improved by considering some internal characteristics of the data. From a mathematical point of view, a peak signal-to-noise-based (PSNR-based) method was introduced to optimize the step length of the steepest descent method in the recovery process. We also found that the loop gain curve in the new algorithmis a good indicator of parameter tuning. Tests show that the new algorithm can effectively solve the problem of oscillation for a large fixed loop gain and provides a more robust recovery.
Search for H i emission from superdisk candidates associated with radio galaxies
Authors: Anand Abhijeet , Roy Nirupam , Gopal-Krishna
Published: June 2019

Giant gaseous layers (termed “superdisks”) have been hypothesized in the past to account for the strip-like radio emission gap (or straight-edged central brightness depression) observed between twin radio lobes, in over a dozen relatively nearby powerful Fanaroff-Riley Class II radio galaxies. They could also provide a plausible alternative explanation for a range of observations. Although a number of explanations have been proposed for the origin of the superdisks, little is known about their material content. Some X-ray observations of superdisk candidates indicate the presence of hot gas, but a cool dusty medium also seems to be common. If they are entirely or partly composed of neutral gas, then it may be directly detectable and we report here a first attempt to detect/image any neutral hydrogen gas present in the superdisks that are inferred to be present in four nearby radio galaxies. We have not found a positive H i signal in any of the four sources, resulting in tight upper limits on the H i number density in the postulated superdisks, estimated directly from the central rms noise values of the final radio continuum subtracted image. The estimated ranges of the upper limit on neutral hydrogen number density and column density are 10−4-10−3 atoms per cm3 and 1019−1020 atoms per cm2, respectively. No positive H i signal is detected even after combining all the four available H i images (with inverse variance weighting). This clearly rules out an H i dominated superdisk as a viable model to explain these structures, however, the possibility of a superdisk being composed of warm/hot gas still remains open.
Development of Calculus Material Model For Special Purpose of Accounting Expertise
Authors: Mizan  , Fakriah  , Amri Mustika
Published: June 2019

This study aims to determine the functional relationship of calculus subject teaching material models that can encourage students’ interests, talents and learning motivation towards the achievement of accounting expertise in the Commerce Department of Politeknik Negeri Lhokseumawe (PNL). The sample of this study were 100 Accounting Study Program students from the Department of Commerce who were registered as second grade which had completed financial mathematics course. The data collection techniques in this study were using questionnaires and data analysis methods. The easiest process to understand accounting expertise is by using teaching materials of algebraic and integral differential calculus, specifically algebraic differentiation can be used anywhere especially in calculating interest. The results showed that firstly, the development of calculus teaching material models between student interest has been assumed to have a positive and significant effect on the GPA of Accounting Students, especially for the Diploma three of Accounting Study Program at the PNL. Secondly, the development of calculus teaching material model has a positive and significant effect on the student motivation of Accounting at PNL. Third, the development of calculus teaching material model for the specific purpose of accounting expertise, students’ interest and motivation are dominantly influent the GPA of the students.
Solid State Fermentation of Rice Straw Pulp with a Local Trichoderma reesei for Single Cell Protein Production: Effects of Temperature, Initial Medium pH and Fermentation Time
Authors: Novita E , Zaki M , Said S D
Published: June 2019

Indonesia is one among countries that produce abundant of rice straw every year generated as post-harvesting residue from paddy field all over country. This abundant amount residue is highly potential to be utilized as carbon source in producing single cell protein (SCP) in solid state fermentation system. SCP is a microbial protein that can be used as alternative protein for substitution of available conventional protein sources such as; fish meal, soy bean, and corn Stover for animal feed production. This research was conducted to evaluating the effects of initial medium pH of substrate (mixed rice straw pulp-urea), fermentation time and fermentation temperature on SCP production by Trichoderma reesei in solid state fermentation (SSF). The results showed that the highest SCP yield (19.71%) was produced at the initial medium pH of 5 and temperature of 30 °C at SSF conditions of C/N ratio 20:1 for 12 days of fermentation time.
Occupational Health and Safety in Chemical Engineering Laboratory of Politeknik Negeri Lhokseumawe
Authors: Fitriah N , Mardani
Published: June 2019

As well as we known each laboratory has some role and regulation conducted for occupational health and safety (OHS). OHS is a multidisciplinary concept that concentrates on the safety, health, and welfare of people engaged in work or employment and worker awareness of health and safety-related rights and responsibilities. The workers often forgot on their own security, firstly it was much found in a laboratory. Chemical engineering laboratory needs to apply occupational health and safety (OHS) to reduce some accidents like fire, toxicity and another factor it could be a hazard for the environment. Therefore, to improve about OHS, the employee will give knowledge and understanding how to applied OHS. This study seeks to examine the relationship and impact of occupational health and safety on employees’ chemical engineering laboratory in Politeknik Negeri Lhokseumawe.
Laboratory study of additional use nano silica composite and bagasse ash to improve the strength of cement drilling
Authors: Rita N , Mursyidah  , Erfando T , Herfansyah H , Ramadhan R
Published: June 2019

The effect of increasing cement prices and expensive additive will have an impact on the cost of cementing of oil and gas wells. So, the need for a strategy undertaken in order to minimize the cost of cementing other than that a good cement strength with additive alternative materials is necessary. Strategies are carried out by using materials that are economical and environmentally friendly in which the material is organic waste materials that have elements of silica and are pozzolanic. As for organic ingredients that are pozzolanic is bagasse ash. In addition, to reduce the level of cement pores, it is necessary to add additional additives by using nanosilica. Testing of the physical properties of cement conducted in laboratory research is by testing strength on cement with additives of bagasse ash added nanosilica into drilling cement suspension with temperature conditioning research 120°F pressure 14.7 psi and 24 hours in the water bath. The results of the research on several scenarios of the concentration of the addition of bagasse ash showed that the optimal compressive strength value obtained was 991.83 psi and the optimal shear bond strength obtained was 97,49 psi at the concentration of ash bagasse in 5% and nanosilica 0,019% in drilling cement.
Removing Escherichia Coli Bacteria in River Water using Ceramic Membrane from Mixed Clay and Fly Ash Material
Authors: Diana S , Fauzan R , Elfiana E
Published: June 2019

The existence of water lately is quite alarming, especially in urban areas. The increasing of river water pollution through industrial and domestic waste, herbicide / pesticide and also the contaminant left-over cause the quality of river water getting worse beyond the allowance limit of standard for clean and drinking water. The most important criteria in examining clean and drinking is the ingredient test of microbiology with Escherichia Coli (E. Coli) bacteria, which is a patogenic bacteria to human, as the indicator. This study aims to remove E.Coli bacteria in water river in Geudong, Lhokseumawe using membrane filter made of ceramic mixturing with clay and fly ash n various compositions; clay:fly ash (40%:60%), clay:fly ash (50%:50%) and clay:fly ash (60%:40%). The ceramic membrane was made with sintering method in 700°C temperature for 4 hours and the filtration test was done in varios of operating pressure; 0,25; 0,50; 0,75, 1,00 and 1,25 bar. The result of the study showed that ceramic membrane with the composition of clay:fly ash (40%:60%) was able to reject E-Coli up to 99,048% with operating pressure 0,25 bar. Using Scanning Electron Microscopy (SEM) test, it is known that the ceramic membrane with the composition of clay-fly ash (40%:60%) is included as microfiltration membrane with pore size 1,6 μm – 2 μm.
Dynamic Braking Application on Three Phase Induction Motor using PLC
Authors: Ir. Muhaimin M. T
Published: June 2019

The use of an induction motor requires the process of stopping the motor speed quickly, using mechanically and electrically generated braking torque. Dynamic braking, which is done by making a magnetic field stationary motor. This condition is carried out by injecting a DC current into the three phase induction motor stator coil after the connection of the stator coil is released from the AC supply voltage source. The advantages of dynamic braking include ease of speed regulation of three-phase induction motors and mechanical losses can be reduced. A system for reversing the direction of star-delta three phase induction motor rotation with Programmable Logic Control (PLC) as a controller. requires an exchange of rotating directions from the direction of turning right to turn left. The process of changing the direction of rotation of the motor requires dynamic braking, the braking process is carried out by injecting a DC current into the stator coil of an induction motor, which is related to PLC. By applying dynamic braking on a three phase induction motor it is obtained faster than without dynamic braking. The injection current is given to a 3-phase induction motor of 1 KW for dynamic braking of 2.2 A. The timing of the motor stops for a minimum load of 100 Watt without braking at 6.2 seconds and with braking of 4.4 seconds, for a maximum load of 600 W, without braking.
Physical routes for the synthesis of kesterite
Authors: Ratz T , Brammertz G , Caballero R , León M , Canulescu S , Schou J , Gütay L , Pareek D , Taskesen T , Kim D-H , Kang J-K , Malerba C , Redinger A , Saucedo E , Shin B , Tampo H , Timmo K , Nguyen N D , Vermang B
Published: June 2019

This paper provides an overview of the physical vapor technologies used to synthesize Cu2ZnSn(S,Se)4 thin films as absorber layers for photovoltaic applications. Through the years, CZT(S,Se) thin films have been fabricated using sequential stacking or co-sputtering of precursors as well as using sequential or co-evaporation of elemental sources, leading to high-efficient solar cells. In addition, pulsed laser deposition of composite targets and monograin growth by the molten salt method were developed as alternative methods for kesterite layers deposition. This review presents the growing increase of the kesterite-based solar cell efficiencies achieved over the recent years. A historical description of the main issues limiting this efficiency and of the experimental pathways designed to prevent or limit these issues is provided and discussed as well. A final section is dedicated to the description of promising process steps aiming at further improvements of solar cell efficiency, such as alkali doping and bandgap grading.
Impact and Effectiveness of State-Level Tuberculosis Interventions in California, Florida, New York, and Texas: A Model-Based Analysis
Authors: Shrestha Sourya , Cherng Sarah , Hill Andrew N , Reynolds Sue , Flood Jennifer , Barry Pennan M , Readhead Adam , Oxtoby Margaret , Lauzardo Michael , Privett Tom , Marks Suzanne M , Dowdy David W
Published: June 2019

The incidence of tuberculosis (TB) in the United States has stabilized, and additional interventions are needed to make progress toward TB elimination. However, the impact of such interventions depends on local demography and the heterogeneity of populations at risk. Using state-level individual-based TB transmission models calibrated to California, Florida, New York, and Texas, we modeled 2 TB interventions: 1) increased targeted testing and treatment (TTT) of high-risk populations, including people who are non–US-born, diabetic, human immunodeficiency virus (HIV)-positive, homeless, or incarcerated; and 2) enhanced contact investigation (ECI) for contacts of TB patients, including higher completion of preventive therapy. For each intervention, we projected reductions in active TB incidence over 10 years (2016–2026) and numbers needed to screen and treat in order to avert 1 case. We estimated that TTT delivered to half of the non–US-born adult population could lower TB incidence by 19.8%–26.7% over a 10-year period. TTT delivered to smaller populations with higher TB risk (e.g., HIV-positive persons, homeless persons) and ECI were generally more efficient but had less overall impact on incidence. TTT targeted to smaller, highest-risk populations and ECI can be highly efficient; however, major reductions in incidence will only be achieved by also targeting larger, moderate-risk populations. Ultimately, to eliminate TB in the United States, a combination of these approaches will be necessary.
Increased planting density of Chinese milk vetch (Astragalus sinicus) weakens phosphorus uptake advantage by rapeseed (Brassica napus) in a mixed cropping system
Authors: Zhang Deshan , Li Hongbo , Fu Zishi , Cai Shumei , Xu Sixin , Zhu Haitao , Shen Jianbo
Published: June 2019

Neighbouring plants can affect plant growth through altering root morphological and physiological traits, but how exactly root systems respond to neighbouring plants with varied density, determining nutrient uptake and shoot growth is poorly understood. In a pot-based experiment, rapeseed was grown alone (single rapeseed), or mixed with 3, 6, or 15 Chinese milk vetch plants. As controls, monocropped Chinese milk vetch was grown at the same planting density, 3, 6, or 15 plants per pot. Root interaction between rapeseed and Chinese milk vetch facilitated phosphorus (P) uptake in rapeseed grown with 3 plants of Chinese milk vetch. As the planting density of Chinese milk vetch in mixture increased, there was a decrease in citrate concentration and acid phosphatase activity but an increase in the total root length of Chinese milk vetch per pot, resulting in decreases in rapeseed root biomass, total root length and P uptake when rapeseed was grown with 6 or 15 Chinese milk vetch plants relative to rapeseed grown with 3 plants. These results demonstrate that the enhanced nutrient utilization induced by root interaction at low planting densities was eliminated by the increased planting density of the legume species in rapeseed/Chinese milk vetch mixed cropping system, suggesting that root/rhizosphere management through optimizing legume planting density is important for improving crop productivity and nutrient-use efficiency.
Graphlet Laplacians for topology-function and topology-disease relationships
Authors: Windels Sam F L , Malod-Dognin Noël , Pržulj Nataša
Published: June 2019

Motivation

Laplacian matrices capture the global structure of networks and are widely used to study biological networks. However, the local structure of the network around a node can also capture biological information. Local wiring patterns are typically quantified by counting how often a node touches different graphlets (small, connected, induced sub-graphs). Currently available graphlet-based methods do not consider whether nodes are in the same network neighbourhood. To combine graphlet-based topological information and membership of nodes to the same network neighbourhood, we generalize the Laplacian to the Graphlet Laplacian, by considering a pair of nodes to be ‘adjacent’ if they simultaneously touch a given graphlet.

Results

We utilize Graphlet Laplacians to generalize spectral embedding, spectral clustering and network diffusion. Applying Graphlet Laplacian-based spectral embedding, we visually demonstrate that Graphlet Laplacians capture biological functions. This result is quantified by applying Graphlet Laplacian-based spectral clustering, which uncovers clusters enriched in biological functions dependent on the underlying graphlet. We explain the complementarity of biological functions captured by different Graphlet Laplacians by showing that they capture different local topologies. Finally, diffusing pan-cancer gene mutation scores based on different Graphlet Laplacians, we find complementary sets of cancer-related genes. Hence, we demonstrate that Graphlet Laplacians capture topology-function and topology-disease relationships in biological networks.

Availability and implementation

http://www0.cs.ucl.ac.uk/staff/natasa/graphlet-laplacian/index.html

Supplementary information

Supplementary data are available at Bioinformatics online.
GMSimpute: a generalized two-step Lasso approach to impute missing values in label-free mass spectrum analysis
Authors: Li Qian , Fisher Kate , Meng Wenjun , Fang Bin , Welsh Eric , Haura Eric B , Koomen John M , Eschrich Steven A , Fridley Brooke L , Chen Y Ann
Published: June 2019

Motivation

Missingness in label-free mass spectrometry is inherent to the technology. A computational approach to recover missing values in metabolomics and proteomics datasets is important. Most existing methods are designed under a particular assumption, either missing at random or under the detection limit. If the missing pattern deviates from the assumption, it may lead to biased results. Hence, we investigate the missing patterns in free mass spectrometry data and develop an omnibus approach GMSimpute, to allow effective imputation accommodating different missing patterns.

Results

Three proteomics datasets and one metabolomics dataset indicate missing values could be a mixture of abundance-dependent and abundance-independent missingness. We assess the performance of GMSimpute using simulated data (with a wide range of 80 missing patterns) and metabolomics data from the Cancer Genome Atlas breast cancer and clear cell renal cell carcinoma studies. Using Pearson correlation and normalized root mean square errors between the true and imputed abundance, we compare its performance to K-nearest neighbors’ type approaches, Random Forest, GSimp, a model-based method implemented in DanteR and minimum values. The results indicate GMSimpute provides higher accuracy in imputation and exhibits stable performance across different missing patterns. In addition, GMSimpute is able to identify the features in downstream differential expression analysis with high accuracy when applied to the Cancer Genome Atlas datasets.

Availability and implementation

GMSimpute is on CRAN: https://cran.r-project.org/web/packages/GMSimpute/index.html.

Supplementary information

Supplementary data are available at Bioinformatics online.
‘You Decide’: Relationship-Based Knowledge and Parents’ Participation in High-Risk Child Protection Crisis Interventions
Authors: Saar-Heiman Yuval , Krumer-Nevo Michal
Published: June 2019

In the scholarly writing on child protection, there is a broad consensus regarding the importance of parents’ participation in knowledge-production processes. However, there is limited research on the conditions required to make parental participation possible in high-risk crisis situations. In particular, there is a dearth of writing that takes into consideration the context of poverty that influences families’ lives and the power imbalances between social workers and parents that are evident in these processes. Through a case illustration of a high-risk crisis situation in the Israeli child protection system, this article examines the potential contribution of a developing critical paradigm—the Poverty-Aware Paradigm—to the promotion of parents’ participation in high-risk crisis situations. Specifically, it points to ‘relationship-based knowledge’ as an organizing axis for knowledge production, and to its derivative, ‘dialogue on power/knowledge’, as a useful practice in child protection interventions. The case analysis reveals three distinguishing features of this dialogue: (i) the social worker holds a dialectic stance regarding knowledge; (ii) the social worker and the parents negotiate their interpretations; and (iii) the social worker shares common hopes and worries with the parents.
Dynamic functional connectivity changes associated with dementia in Parkinson’s disease
Authors: Fiorenzato Eleonora , Strafella Antonio P , Kim Jinhee , Schifano Roberta , Weis Luca , Antonini Angelo , Biundo Roberta
Published: June 2019

Dynamic functional connectivity captures temporal variations of functional connectivity during MRI acquisition and it may be a suitable method to detect cognitive changes in Parkinson’s disease. In this study, we evaluated 118 patients with Parkinson’s disease matched for age, sex and education with 35 healthy control subjects. Patients with Parkinson’s disease were classified with normal cognition (n = 52), mild cognitive impairment (n = 46), and dementia (n = 20) based on an extensive neuropsychological evaluation. Resting state functional MRI and a sliding-window approach were used to study the dynamic functional connectivity. Dynamic analysis suggested two distinct connectivity ‘States’ across the entire group: a more frequent, segregated brain state characterized by the predominance of within-network connections, State I, and a less frequent, integrated state with strongly connected functional internetwork components, State II. In Parkinson’s disease, State I occurred 13.89% more often than in healthy control subjects, paralleled by a proportional reduction of State II. Parkinson’s disease subgroups analyses showed the segregated state occurred more frequently in Parkinson’s disease dementia than in mild cognitive impairment and normal cognition groups. Further, patients with Parkinson’s disease dementia dwelled significantly longer in the segregated State I, and showed a significant lower number of transitions to the strongly interconnected State II compared to the other subgroups. Our study indicates that dementia in Parkinson’s disease is characterized by altered temporal properties in dynamic connectivity. In addition, our results show that increased dwell time in the segregated state and reduced number of transitions between states are associated with presence of dementia in Parkinson’s disease. Further studies on dynamic functional connectivity changes could help to better understand the progressive dysfunction of networks between Parkinson’s disease cognitive states.
CDEK: Clinical Drug Experience Knowledgebase
Authors: Griesenauer Rebekah H , Schillebeeckx Constantino , Kinch Michael S
Published: June 2019

The Clinical Drug Experience Knowledgebase (CDEK) is a database and web platform of active pharmaceutical ingredients with evidence of clinical testing as well as the organizations involved in their research and development. CDEK was curated by disambiguating intervention and organization names from ClinicalTrials.gov and cross-referencing these entries with other prominent drug databases. Approximately 43% of active pharmaceutical ingredients in the CDEK database were sourced from ClinicalTrials.gov and cannot be found in any other prominent compound-oriented database. The contents of CDEK are structured around three pillars: active pharmaceutical ingredients (n = 22 292), clinical trials (n = 127 223) and organizations (n = 24 728). The envisioned use of the CDEK is to support the investigation of many aspects of drug development, including discovery, repurposing opportunities, chemo- and bio-informatics, clinical and translational research and regulatory sciences.
Gravitational field calculation in spherical coordinates using variable densities in depth
Authors: Soler Santiago R , Pesce Agustina , Gimenez Mario E , Uieda Leonardo
Published: June 2019

We present a new methodology to compute the gravitational fields generated by tesseroids (spherical prisms) whose density varies with depth according to an arbitrary continuous function. It approximates the gravitational fields through the Gauss–Legendre Quadrature along with two discretization algorithms that automatically control its accuracy by adaptively dividing the tesseroid into smaller ones. The first one is a preexisting 2-D adaptive discretization algorithm that reduces the errors due to the distance between the tesseroid and the computation point. The second is a new density-based discretization algorithm that decreases the errors introduced by the variation of the density function with depth. The amount of divisions made by each algorithm is indirectly controlled by two parameters: the distance-size ratio and the delta ratio. We have obtained analytical solutions for a spherical shell with radially variable density and compared them to the results of the numerical model for linear, exponential, and sinusoidal density functions. The heavily oscillating density functions are intended only to test the algorithm to its limits and not to emulate a real world case. These comparisons allowed us to obtain optimal values for the distance-size and delta ratios that yield an accuracy of 0.1 per cent of the analytical solutions. The resulting optimal values of distance-size ratio for the gravitational potential and its gradient are 1 and 2.5, respectively. The density-based discretization algorithm produces no discretizations in the linear density case, but a delta ratio of 0.1 is needed for the exponential and most sinusoidal density functions. These values can be extrapolated to cover most common use cases, which are simpler than oscillating density profiles. However, the distance-size and delta ratios can be configured by the user to increase the accuracy of the results at the expense of computational speed. Finally, we apply this new methodology to model the Neuquén Basin, a foreland basin in Argentina with a maximum depth of over 5000 m, using an exponential density function.
Recent advances in novel therapies for lipid disorders
Authors: Tirronen Annakaisa , Hokkanen Krista , Vuorio Taina , Ylä-Herttuala Seppo
Published: June 2019

The prevalence of lipid disorders is alarmingly increasing in the Western world. They are the result of either primary causes, such as unhealthy lifestyle choices or inherited risk factors, or secondary causes like other diseases or medication. Atypical changes in the synthesis, processing and catabolism of lipoprotein particles may lead to severe hypercholesterolemia, hypertriglyceridemia or elevated Lp(a). Although cholesterol-lowering drugs are the most prescribed medications, not all patients achieve guideline recommended cholesterol levels with the current treatment options, emphasising the need for new therapies. Also, some lipid disorders do not have any treatment options but rely only on stringent dietary restriction. Patients with untreated lipid disorders carry a severe risk of cardiovascular disease, diabetes, non-alcoholic fatty liver disease and pancreatitis among others. To achieve better treatment outcome, novel selective gene expression and epigenetic targeting therapies are constantly being developed. Therapeutic innovations employing targeted RNA technology utilise small interfering RNAs, antisense oligonucleotides, long non-coding RNAs and microRNAs to regulate target protein production whereas viral gene therapy provides functional therapeutic genes and CRISPR/Cas technology relies on gene editing and transcriptional regulation. In this review, we will discuss the latest advances in clinical trials for novel lipid-lowering therapies and potential new targets in pre-clinical phase.
Outcomes of left atrial appendage occlusion using the AtriClip device: a systematic review
Authors: Toale Conor , Fitzmaurice Gerard J , Eaton Donna , Lyne Jonathan , Redmond Karen C
Published: June 2019

Atrial fibrillation increases lifetime stroke risk. The left atrial appendage (LAA) is thought to be the source of embolic strokes in up to 90% of cases, and occlusion of the LAA may be safer than the alternative of oral anticoagulation. Occlusion devices, such as the AtriClipTM (AtriCure, Mason, OH, USA) enable safe and reproducible epicardial clipping of the LAA. A systematic review was performed in May 2018, based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, using the keyword ‘AtriClip’. A total of 68 papers were identified and reviewed; 11 studies were included. Data including demographics, medical history intervention(s) performed, periprocedural outcomes and follow-up were assessed and analysed. A total of 922 patients were identified. LAA occlusion was achieved in 902 out of 922 patients (97.8%). No device-related adverse events were reported across the studies. The reported incidence of stroke or transient ischaemic attack post-clip placement ranged from 0.2 to 1.5/100 patient-years. Four hundred and seventy-seven of 798 patients (59.7%) had ceased anticoagulation on follow-up. The AtriClip device is safe and effective in the management of patients with atrial fibrillation, either as an adjunct in patients undergoing cardiac surgery or as a stand-alone thoracoscopic procedure.
Are younger cohorts in the USA and England ageing better?
Authors: de la Fuente Javier , Caballero Francisco Félix , Verdes Emese , Rodríguez-Artalejo Fernando , Cabello María , de la Torre-Luque Alejandro , Sánchez-Niubó Albert , María Haro Josep , Ayuso-Mateos José Luis , Chatterji Somnath
Published: June 2019

Background

Whether worldwide increases in life expectancy are accompanied by a better health status is still a debate. People age differently, and there is a need to disentangle whether healthy-ageing pathways can be shaped by cohort effects. This study aims to analyse trends in health status in two large nationally representative samples of older adults from England and the USA.

Methods

The sample comprised 55 684 participants from the first seven waves of the English Longitudinal Study of Ageing (ELSA), and the first 11 waves of the Health and Retirement Study (HRS). A common latent health score based on Bayesian multilevel item response theory was used. Two Bayesian mixed-effects multilevel models were used to assess cohort effects on health in ELSA and HRS separately, controlling for the effect of household wealth and educational attainment.

Results

Similar ageing trends were found in ELSA (β = –0.311; p < 0.001) and HRS (β = –0.393; p < 0.001). The level of education moderated the life-course effect on health in both ELSA (β = –0.082; p < 0.05) and HRS (β = –0.084; p < 0.05). A birth-year effect was found for those belonging to the highest quintiles of household wealth in both ELSA (β = 0.125; p < 0.001) and HRS (β = 0.170; p < 0.001).

Conclusions

Health inequalities have increased in recent cohorts, with the wealthiest participants presenting a better health status in both the USA and English populations. Actions to promote health in the ageing population should consider the increasing inequality scenario, not only by applying highly effective interventions, but also by making them accessible to all members of society.
Local and Nonlocal Singular Liouville Equations in Euclidean Spaces
Authors: Hyder Ali , Mancini Gabriele , Martinazzi Luca
Published: June 2019

We study the metrics of constant $Q$-curvature in the Euclidean space with a prescribed singularity at the origin, namely solutions to the equation $$\begin{equation*} (-\Delta)^{\frac{n}{2}}w=e^{nw}-c\delta_{0} \ \textrm{on}\ {\mathbb{R}}^n, \end{equation*}$$under a finite volume condition. We analyze the asymptotic behavior at infinity and the existence of solutions for every $n\ge 3$ also in a supercritical regime. Finally, we state some open problems.
Compartmentalization of a Multidrug-Resistant Cytomegalovirus UL54 Mutant in a Stem Cell Transplant Recipient with Encephalitis
Authors: Piret Jocelyne , Schibler Manuel , Pham Van Dung , Hantz Sébastien , Giannotti Federica , Masouridi-Levrat Stavroula , Kaiser Laurent , Goyette Nathalie , Alain Sophie , Shi Rong , Boivin Guy
Published: June 2019

We report a case of cytomegalovirus encephalitis in a hematopoietic stem cell transplant recipient. A previously uncharacterized V787E mutation in UL54 was identified in cerebrospinal fluid but not plasma specimens. For the V787E recombinant virus, the half maximal effective concentrations for ganciclovir, foscarnet, and cidofovir were 8.6-, 3.4- and 2.9-fold higher than for wild-type virus, and the replicative capacity was lower. The introduction of a bulkier and negatively charged glutamate residue at position 787 could destabilize the finger domain of UL54 DNA polymerase. Viral genotyping of cerebrospinal fluid is warranted in subjects with cytomegalovirus encephalitis, owing to the low penetration of antivirals in this compartment.
Combination of MexAB-OprM overexpression and mutations in efflux regulators, PBPs and chaperone proteins is responsible for ceftazidime/avibactam resistance in Pseudomonas aeruginosa clinical isolates from US hospitals
Authors: Castanheira Mariana , Doyle Timothy B , Smith Caitlin J , Mendes Rodrigo E , Sader Helio S
Published: June 2019

Objectives

To evaluate ceftazidime/avibactam resistance mechanisms among Pseudomonas aeruginosa clinical isolates and compare with isolates susceptible to this combination.

Methods

During 2015, 2548 P. aeruginosa isolates were collected in 106 US hospitals and 46 (1.8%) were resistant to ceftazidime/avibactam. These isolates were matched with 109 ceftazidime/avibactam-susceptible isolates resistant to other antipseudomonal agents and were evaluated for the presence of β-lactam resistance mechanisms using WGS analysis and quantitative real-time PCR. Results were analysed using logistic regression comparing the isolate groups to understand the mechanisms of ceftazidime/avibactam resistance.

Results

Two isolates carried the MBLs blaVIM-1 and blaVIM-2 and another three had unique alterations or deletions in the chromosomal AmpC Ω-loop associated with ceftazidime/avibactam resistance. Overexpression of mexA (+27.4%), disruptions in ampP (+21.7%), mexR (+17.1%) and mexZ (+14.6%) and alterations in ctpA (+13.0%), dnaK (+17.8%) and ftsI (+20.8%) were significantly more prevalent among ceftazidime/avibactam-resistant isolates when compared with their susceptible counterparts independently or in combination. The combination of dnaK alterations and mexA overexpression was more common among ceftazidime/avibactam-resistant by 82×; mexR disruptions and mexA overexpression by 45×; and other two- or three-genotype interactions that included alterations/disruptions in dnaK, ftsI, nalD, mexR, mexZ and mexA overexpression by 6.5× to 34×.

Conclusions

Resistance to ceftazidime/avibactam among P. aeruginosa clinical isolates has been shown to be a complex interplay of resistance mechanisms that can affect ceftazidime and/or avibactam and some similar findings were reported in laboratory isolates exposed to ceftazidime ± avibactam.
Pedigree-Based Estimation of Reproductive Value
Authors: Hunter Darren C , Pemberton Josephine M , Pilkington Jill G , Morrissey Michael B
Published: June 2019

How successful an individual or cohort is, in terms of their genetic contribution to the future population, is encapsulated in the concept of reproductive value, and is crucial for understanding selection and evolution. Long-term studies of pedigreed populations offer the opportunity to estimate reproductive values directly. However, the degree to which genetic contributions, as defined by a pedigree, may converge on their long-run values within the time frames of available data sets, such that they may be interpreted as estimates of reproductive value, is unclear. We develop a system for pedigree-based calculation of the expected genetic representation that both individuals and cohorts make to the population in the years following their birth. We apply this system to inference of individual and cohort reproductive values in Soay sheep (Ovis aries) from St Kilda, Outer Hebrides. We observe that these genetic contributions appear to become relatively stable within modest time frames. As such, it may be reasonable to consider pedigree-based calculations of genetic contributions to future generations as estimates of reproductive value. This approach and the knowledge that the estimates can stabilize within decades should offer new opportunities to analyze data from pedigreed wild populations, which will be of value to many fields within evolutionary biology and demography.
Local semi-analytic models of magnetic flux transport in protoplanetary discs
Authors: Leung Philip K C , Ogilvie Gordon I
Published: June 2019

The evolution of a large-scale poloidal magnetic field in an accretion disc is an important problem because it determines the launching of winds and the feasibility of the magnetorotational instability to generate turbulence or channel flows. Recent studies, both semi-analytical calculations and numerical simulations, have highlighted the crucial role non-ideal magnetohydrodynamic effects (Ohmic resistivity, Hall drift, and ambipolar diffusion), relevant in the protoplanetary disc context, might play in magnetic flux evolution in the disc. We investigate the flux transport in discs through the use of two 1D semi-analytic models in the vertical direction, exploring regimes where different physical source terms and effects dominate. The governing equations for both models are derived by performing an asymptotic expansion in the limit of a thin disc, with the different regimes isolated through setting the relative order of the leading terms between variables. Flux transport rates and vertical structure profiles are calculated for a range of diffusivities and disc magnetizations. We found that Ohmic and ambipolar diffusivities drive radially outward flux transport with an outwardly inclined field. A wind outflow drives inward flux transport, which is significantly enhanced in the presence of Hall drift in the positive polarity case, $\eta _\mathrm{ H} (\boldsymbol{B}_\mathrm{ z} \cdot \boldsymbol{\Omega }) \gt 0$, an effect which has only been briefly noted before. Coupled only with outward inclination, the Hall effect reduces the flux transport given by a background Ohmic and/or ambipolar diffusivity, but drives no flux transport when it is the only non-ideal effect present.