bluuebunny/crossref_metadata_2025 huggingface dataset:
Smart parking sensors, technologies and applications for open parking lots: a review
Authors: Paidi Vijay , Fleyeh Hasan , Håkansson Johan , Nyberg Roger G.
Published: April 2018

Parking a vehicle in traffic dense environments often leads to excess time of driving in search for free space which leads to congestions and environmental pollution. Lack of guidance information to vacant parking spaces is one reason for inefficient parking behaviour. Smart parking sensors and technologies facilitate guidance of drivers to free parking spaces thereby improving parking efficiency. Currently, no such sensors or technologies is in use for open parking lot. This study reviews the literature on the usage of smart parking sensors, technologies, applications and evaluates their applicability to open parking lots. Magnetometers, ultrasonic sensors and machine vision were few of the widely used sensors and technologies on closed parking lots. However, this study suggests a combination of machine vision, convolutional neural network or multi‐agent systems suitable for open parking lots due to less expenditure and resistance to varied environmental conditions. Few smart parking applications show drivers the location of common open parking lots. No application provided real‐time parking occupancy information, which is a necessity to guide them along the shortest route to free space. To develop smart parking applications for open parking lots, further research is needed in the fields of deep learning and multi‐agent systems.
Dielectric properties of epoxy silica and boron nitride nanocomposites and moisture/temperature influences
Authors: Qiang Dayuan , Wang Yan , Chen George , Andritsch Thomas
Published: April 2018

The epoxy resin was filled with nano‐BN, surface treated, and untreated nano‐SiO2. Measurements of dielectric spectroscopy cover the range of frequency from 10−2 to 105 Hz and will relate to the hydration of samples. It was observed from the results that permittivity of pure epoxy was strongly affected by the water absorptions and a bit of temperature. Then it will allow us to extract the influence of water absorption on dielectric properties and proposed a relatively reliable method by using Monte‐Carlo simulation to estimate the average thickness of water shell or related relaxation peak of epoxy nanocomposites with spherical particles. At the end, the authors experimentally demonstrated the existence of two layer structure of water shell and concluded that surface treatment is able to reduce the water uptake, however, no obvious impact on modifying its effects on dielectric properties due to the limitation of thickness of tightly bonded layer. The ‘hydrophobic’ performance of BN nanocomposites is much better than silica ones, especially the no formation of water shell around the particles, and may be more suitable for application under environment with humidity.
Grid tied single‐stage inverter for low‐voltage PV systems with reactive power control
Authors: Sreekanth Thamballa , Lakshminarasamma Narasimhamurthy , Mishra Mahesh K.
Published: April 2018

Single‐stage DC–AC converter systems (SSCSs) are developed by merging both DC–DC and DC–AC conversion processes. These SSCS transfer power from photovoltaics (PV) to loads/grid in one stage. In this study, a PV‐based grid tied single‐stage DC–AC converter system (GTSS) for low‐voltage PV systems is presented. Generally, when SSCSs are connected to the grid, grid voltage template is used to generate reference current which is to be tracked. In doing so, the GTSS delivers power to the grid at a power factor other than unity. A suitable control scheme is implemented in this study to control active and reactive powers’ flow from the GTSS to the grid while continuously operating PV at maximum power point. The proposed control scheme of GTSS has attributes such as less complexity and requires simple proportional integral controller. Modelling of control loops in the proposed control scheme is mentioned. A detailed MATLAB/SIMULINK‐based simulation and experimental studies are conducted to validate the proposed control scheme.
Numerical method for probabilistic load flow computation with multiple correlated random variables
Authors: Huang Yu , Xu Qingshan , Yang Yang , Jiang Xianqiang
Published: April 2018

Grid complexity is increasing progressively as the deepening penetration of renewable power generation and unpredictable demand, which necessitates an exhaustive assessment of system parameters in a probabilistic manner. In this study, the authors employ a dimensional reduction integral method to tackle the above problems challenged by dimensionality. Their approach transforms the multivariate raw moments into a linear sum of several one‐dimensional integrals, which could be solved by Gauss quadrature. To handle the correlation between non‐Gaussian input variables, Nataf transformation is used to map the inputs into the independent normal domain. Instead of commonly used series expansion such as A‐type Gram–Charlier, Edgeworth or Cornish–Fisher, the probability distributions of output variables can be better approximated by C‐type Gram–Charlier series with the calculated moments. The salient feature of the proposed method is demonstrated in a modified IEEE 118‐bus test system with respect to both accuracy and run times.
Linear multitarget integrated probabilistic data association for multiple detection target tracking
Authors: Huang Yuan , Song Taek Lyul , Kim Da Sol
Published: April 2018

The point target assumption, which suggests that a target can generate at most one measurement at a time, is used in typical target tracking algorithms. However, in many practical applications, multiple scattering points of a target can be resolved using a high‐resolution sensor, which gives rise to the multiple detection problem. The typical algorithms with the point target assumption are not eligible for multiple detection tracking environments. The multiple detection joint integrated probabilistic data association algorithm is designed to solve the multiple detection multitarget tracking problem. However, the computational complexity of this algorithm grows exponentially with the number of tracks and measurement cells. Here, multiple detection linear multitarget integrated probabilistic data association is proposed to enhance computational efficiency by introducing the modulated clutter measurement density, which takes into account the contributions of clutter as well as other targets of each measurement cell. The computational complexity of the proposed algorithm is linear in the number of tracks and the number of measurement cells. Simulation results verify the applicability and efficiency of the proposed algorithm in multiple detection multitarget tracking scenarios.
Influence of electric brush‐plating voltage on hydrophobic behaviour of a cauliflower‐like Ni coating surface
Authors: Li Jing , Fan Fengyu , Li Qiang , Du Feng , Yu Huadong
Published: April 2018

The effect of the plating voltage on the surface roughness, morphology, chemical composition and wettability of the Ni coatings was investigated by means of Laser scanning confocal microscopy, scanning electronic microscope, X‐ray diffraction, energy‐dispersive spectroscopy, and water contact angle measurements. The results indicate that the evolution of surface morphology on Ni coatings prepared by brush‐plating depends strongly on the variation of plating voltage. The microstructure characterization shows that the typical hierarchical cauliflower‐like structures was formed uniformly on the as‐prepared Ni coatings. The combination of the porous morphology and hierarchical cauliflower‐like structures plays a crucial role in improving the hydrophobic property. In absence of surface chemical modification, the Ni coatings exhibit an excellent hydrophobicity and have a high contact angle of 141 degree. Based on the Cassie‐Baxier models, the relationship of two dimensionless geometrical parameters and the wetting property of the Ni coatings were investigated. It was demonstrated that to obtain the stable Cassie hydrophobic state, the aspect ratio and the water contact angle on the basal surface should be as large as possible and the spacing factor should be limited within a specific range for given aspect ratio and water contact angle on the basal surface.
Synthesis of magnetite (Fe3O4)–Avastin nanocomposite as a potential drug for AMD treatment
Authors: Zargarzadeh Mehrzad , MadaahHosseini Hamid Reza , Delavari Hamid , Irajirad Rasoul , Aghaie Ermia
Published: April 2018

Age‐related macular degeneration (AMD) is one of the prevailing causes of blindness in the aged over 50 years. There are several conventional treatments for AMD including laser therapy, surgery, and intravitreal injection of anti‐vascular endothelial growth factor directly into the eye. Intravitreal injection may result in various side effects such as increasing the eye pressure, eye infections, blurring vision; furthermore, it can negatively affect other body organs. In addition, large number of injections would be required to regenerate the lost vision. To overcome some of these obstacles, the work proposes a new drug delivery technique by using Avastin–Fe3O4 nanocomposites synthesised through co‐precipitation method with approximate size of 20 nm. The saturation magnetisation (Ms) of the synthesised iron oxide nanoparticles (NPs) was about 55.6648 emu/g which is completely suitable for movement of the (Avastin–Fe3O4) NPs. Besides, the results of the flow cytometry tests showed that 90.5% of NPs were Avastin loaded. The proposed new method can be replaced with conventional treatments as the long‐term sustained release of Avastin instead of several injections as well as declining the systemic side effects due to the high concentration of Avastin in the posterior segment of the eye.
Gram + ve bacterium Staphylococcus aureus: a potential source for the green biosynthesis of monodispersed, smaller selenium nanoparticles
Authors: Kora Aruna Jyothi
Published: April 2018

In the current communication, an effort has been made to utilise Gram + ve bacterium Staphylococcus aureus, as a potential, renewable source for the green biosynthesis of selenium nanoparticles. The time‐dependent bacterial biosynthesis of selenium nanoparticles was studied at different selenite concentrations. The green synthesised nanoparticles were probed with ultraviolet–visible spectra, inductively coupled plasma optical emission spectrometry, transmission electron microscope, X‐ray diffraction, zeta potential and Fourier transform infrared spectroscopy characterisation tools. The strain produced red coloured, protein capped, amorphous, nearly monodispersed spherical nanoparticles of 3.6 nm size. This is the first report, in which the smallest selenium nanoparticles with the narrow size distribution of 2.8–4.7 nm were biosynthesised by the bacteria. Thus, paving a way for the commercial production of size‐controlled smaller, selenium nanoparticles.
Effect of incorporation of highly‐ordered a‐Ge:H nanoparticles on the performance of perovskite solar cells
Authors: Li Zhenglong , Ni Jian , Zhang Shuaiyuan , Li Chang , Du Yangyang , Zhang Yaofang , Cai Hongkun , Li Juan , Zhang Jianjun
Published: April 2018

To improve light absorption, in this study, the narrow band gap highly‐ordered free‐standing hydrogenated amorphous germanium nanoparticles (a‐Ge:H NPs) were introduced into the CH3NH3PbI3−x Clx films. Here, the NPs were fabricated by means of the radio frequency plasma enhanced chemical vapour deposition system. The effects of hydrogen dilution ratio (RH) on the microstructure and bonding configuration of a‐Ge:H NPs were investigated by Raman, transmission electron microscopy and Fourier transform infrared spectroscopy measurements. As RH increases, an improvement in the structure order of a‐Ge:H NPs was observed. Compared with the pure CH3NH3PbI3−x Clx films, the light absorption of the hybrid a‐Ge:H NPs/CH3NH3PbI3−x Clx active layers was improved, and the surface coverage of the hybrid active layers nearly reached 100%. This new finding provided a novel way to solve the universal unfavourable surface coverage problem that existed in the ultrasonic spray‐coating process. Meanwhile, compared with the device that is based on pure CH3NH3PbI3−x Clx films, due to the enhanced light absorption in the visible range, a ∼14.6% enhancement in the power conversion efficiency was achieved based on the hybrid a‐Ge:H NPs/CH3NH3PbI3−x Clx active layers.
3D multilayered Bi4O5Br2 nanoshells displaying excellent visible light photocatalytic degradation behaviour for resorcinol
Authors: Hu Hanmei , Xu Juanjuan , Deng Chonghai , Wang Man , Zhou Xiaoyu , Le Huirong
Published: April 2018

High‐ordered three‐dimensional multilayered Bi4O5Br2 nanoshells have been fabricated successfully via a green ultrasound‐assisted anion exchange reaction followed by a calcination treatment approach. The products are characterised by X‐ray diffraction, field‐emission scanning electron microscopy, transmission electron microscopy, high‐resolution transmission electron microscopy, UV–vis diffuse reflectance spectrum and N2 adsorption/desorption isotherms. The results reveal that ternary Bi4O5Br2 nanoshells possess a pure monoclinic phase with the average thickness of ca. 12 nm, and the walls are of 10–12 layers constructed by nanograins with 10 nm in size. The specific surface is measured to be 36.18 m2 g‐1 and the band gap energy Eg value is calculated to be 2.52 eV. The possible formation process for Bi4O5Br2 nanoshells is simply proposed. According to the photocatalytic degradation for resorcinol under visible light irradiation, the as‐prepared Bi4O5Br2 nanoshells exhibit excellent photocatalytic performance, which is not only far beyond the degradation rate of BiOBr precursor nanosheets but also superior to that of other reported Bi4O5Br2 architectures, suggesting a practical application for the treatment of organic pollutants.
Electrochemical etching of lightweight nanotips for high quality‐factor quartz tuning fork force sensor: atomic force microscopy applications
Authors: Hussain Danish , Song Jianmin , Zhang Hao , Meng Xianghe , Xie Hui
Published: April 2018

Commercially available quartz tuning forks (QTFs) can be transformed into self‐sensing and actuating force sensors by micro‐assembling a sharp tip on the apex of a tine. Mass of the tip is critical in determining the quality (Q)‐factor of the sensor, therefore, fabrication of the lightweight nanotips is a precondition for high Q‐factor QTF sensors. The work reports fabrication of very lightweight tungsten nanotips with a two‐step electrochemical etching technique which can be used to develop high Q‐factor QTF force sensor. First, a tungsten wire with protective coating at one end (1–2 mm) is etched with a trapezoidal waveform to form a lengthy (∼2–5 mm) and slender (diameter ∼10–40 μm) micro‐needle. In the second step, sharp tip apex is fabricated with a direct current etching. High Q‐factor (6600–8000) QTF force sensors have been developed with the fabricated nanotips. Atomic force microscope scanning of nano‐grating and a triblock copolymer surface validates the scanning performance of the developed sensors.
Cost‐effective chemical solution synthesis of bismuth telluride nanostructure for thermoelectric applications
Authors: Mamur Hayati , Dilmac Omer Faruk , Korucu Haluk , Bhuiyan Mohammad Ruhul Amin
Published: April 2018

In this work, the bismuth telluride (Bi2Te3) nanostructure for thermoelectric applications was successfully synthesised by a new cost‐effective chemical solution process. Firstly, the metal solutions of bismuth (III) nitrate pentahydrate and tellurium dioxide were mixed together at room temperature with adjusting the hydrodynamic atmosphere and introduced the sodium hydroxide. After that, different characterisation parameters, such as X‐ray diffraction, atomic force microscopy (AFM), scanning electron microscopy (SEM), energy dispersive X‐ray, and transverse electron microscopy (TEM) were obtained. Then, the average crystalline size of the Bi2Te3 nanostructure was found 23 nm. According to these obtained results, the materials consist of every specimen in nano range dimension in AFM studies. The elemental of Bi and Te were arranged with their quite stoichiometric atomic ratio observed by SEM. Ultimately, the TEM micrographs showed that the powders exhibited an aggregate phenomenon, and the primary crystalline size was about low dimension.
Fabrication and characterisation of new type of magnetic nanoanion exchanger particles for enteric losartan potassium delivery
Authors: Amareh Nazanin , Ahmad Panahi Homayon , Moeinpour Farid
Published: April 2018

Magnetite nanoparticles (MNPs) were synthesised and grafted with polymer containing brilliant cresyl blue for the exchange of losartan potassium. The resulted polymeric nanoparticles were characterised with Fourier transform infrared spectroscopy, elemental analysis, thermogravimetric analysis and transmission electron microscopy. The effects of the exchange parameters such as sample pH, temperature and contact time on sorption of losartan potassium were investigated. The sorption capacity of the functionalised sorbent was 19.4 mg g−1. The equilibrium adsorption data of losartan potassium on modified nanoparticles were analysed by Langmuir, Freundlich, Temkin, Dubinin–Radushkevich and Redlich–Peterson equations. Nearly, 74% of losartan potassium was released in simulated gastric fluid of pH 1.2 in 15 h and 50% in simulated intestinal fluid pH 7.4 in 30 h. These results have shown the utility of losartan potassium loaded–modified MNPs for enteric drug delivery.
From Autotransplantation to Allotransplantation: A Perspective on the Future of Reconstructive Microsurgery
Authors: Levin L.
Published: April 2018

It has been half a century since Susumu Tamai reported on the first thumb replantation. The evolution of reconstructive microsurgery has continually added new applications of the operating microscope for reconstructive surgery and has had profound impact on countless patients. From the time of Harold Gillies until today, the reconstructive ladder has evolved to a reconstructive elevator with the “penthouse” floor being represented by vascularized composite allotransplantation.
Effects of Transfusion on Free Flap Survival: Searching for an Optimal Hemoglobin Threshold for Transfusion
Authors: Kim Min Ji , Woo Kyong-Je , Kang So Ra , Park Bo Young
Published: April 2018

Background Microsurgical free tissue transfer is a popular technique nowadays. Because of its considerably exquisite procedure, various risk factors can affect surgical outcome. However, current key practices, especially those in blood transfusion, are in contention due to the lack of enough evidence. Therefore, the objective of this study was to investigate the impact of perioperative blood transfusion on microsurgical complication.

Methods Data of a total of 168 patients who underwent microvascular free tissue transfer from 2013 through 2016 were retrospectively reviewed. Age, comorbidity, anatomical surgical site, preoperative and postoperative lowest hemoglobin (Hb) level, estimated blood volume loss, and final clinical flap outcome were compared between patients with and without transfusion treatment. Factors with a significance of p < 0.05 in univariate analysis were included in the multivariate logistic regression model to identify independent risk factors.

Results Of 168 patients, 72 (43%) were in the transfusion group. Cross analysis statistics showed that flap failure in the transfusion group was 3.6 times higher (p = 0.018) than that in the control group. Multivariable analysis revealed that age (p = 0.083) and perioperative lowest Hb level (p = 0.021) remained as significant predictors of flap failure. Receiver-operating characteristic curve analysis showed that the appropriate lower limit of transfusion commencement of Hb was 8.75 g/dL (area under the curve: 0.721).

Conclusion A transfusion during perioperative period of free flap did not increase its failure rate. Rather than appropriate transfusion strategy, perioperative lowest Hb level, and age were significant predictors of flap failure. Therefore, transfusion can be confidently used in patients who undergo free flap without any hesitation. Results of this study provide practical evidence of performing perioperative transfusion for free tissue transfer patients.
Evolution Under Dietary Restriction Decouples Survival From Fecundity in Drosophila melanogaster Females
Authors: Zajitschek Felix , Georgolopoulos Grigorios , Vourlou Anna , Ericsson Maja , Zajitschek Susanne R K , Friberg Urban , Maklakov Alexei A
Published: April 2018

One of the key tenets of life-history theory is that reproduction and survival are linked and that they trade-off with each other. When dietary resources are limited, reduced reproduction with a concomitant increase in survival is commonly observed. It is often hypothesized that this dietary restriction effect results from strategically reduced investment in reproduction in favor of somatic maintenance to survive starvation periods until resources become plentiful again. We used experimental evolution to test this “waiting-for-the-good-times” hypothesis, which predicts that selection under sustained dietary restriction will favor increased investment in reproduction at the cost of survival because “good-times” never come. We assayed fecundity and survival of female Drosophila melanogaster fruit flies that had evolved for 50 generations on three different diets varying in protein content—low (classic dietary restriction diet), standard, and high—in a full-factorial design. High-diet females evolved overall increased fecundity but showed reduced survival on low and standard diets. Low-diet females evolved reduced survival on low diet without corresponding increase in reproduction. In general, there was little correspondence between the evolution of survival and fecundity across all dietary regimes. Our results contradict the hypothesis that resource reallocation between fecundity and somatic maintenance underpins life span extension under dietary restriction.
The Rapid Prediction of Carbapenem Resistance in Patients With Klebsiella pneumoniae Bacteremia Using Electronic Medical Record Data
Authors: Sullivan Timothy , Ichikawa Osamu , Dudley Joel , Li Li , Aberg Judith
Published: April 2018

Background

The administration of active antibiotics is often delayed in cases of carbapenem-resistant gram-negative bacteremia. Using electronic medical record (EMR) data to rapidly predict carbapenem resistance in patients with Klebsiella pneumoniae bacteremia could help reduce the time to active therapy.

Methods

All cases of Klebsiella pneumoniae bacteremia at Mount Sinai Hospital from September 2012 through September 2016 were included. Cases were randomly divided into a “training set” and a “testing set.” EMR data from the training set cases were reviewed, and significant risk factors for carbapenem resistance were entered into a multiple logistic regression model. Performance was assessed by repeated K-fold cross-validation and by applying the training set model to the testing set. All cases were also reviewed to determine the time to effective antibiotic therapy.

Results

A total of 613 cases of Klebsiella pneumoniae bacteremia were included, 61 (10%) of which were carbapenem-resistant. The training and testing sets consisted of 460 and 153 cases, respectively. The regression model derived from the training set correctly predicted 73% of carbapenem-resistant cases and 59% of carbapenem-susceptible cases in the testing set (sensitivity, 73%; specificity, 59%; positive predictive value, 16%; negative predictive value, 95%). The mean area under the receiver operator characteristic curve of the K-fold cross-validation repeats was 0.731. Patients with carbapenem-resistant infections received active antibiotics significantly later than those with susceptible infections (40.4 hours vs 9.6 hours, P < .0001).

Conclusions

A multiple logistic regression model using EMR data can generate rapid, sensitive predictions of carbapenem resistance in patients with Klebsiella pneumoniae bacteremia, which could help shorten the time to effective therapy in these cases.
Multihospital Outbreak of a Middle East Respiratory Syndrome Coronavirus Deletion Variant, Jordan: A Molecular, Serologic, and Epidemiologic Investigation
Authors: Payne Daniel C , Biggs Holly M , Al-Abdallat Mohammad Mousa , Alqasrawi Sultan , Lu Xiaoyan , Abedi Glen R , Haddadin Aktham , Iblan Ibrahim , Alsanouri Tarek , Al Nsour Mohannad , Sheikh Ali Sami , Rha Brian , Trivedi Suvang U , Rasheed Mohammed Ata Ur , Tamin Azaibi , Lamers Mart M , Haagmans Bart L , Erdman Dean D , Thornburg Natalie J , Gerber Susan I
Published: April 2018

Background

An outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) in Jordan in 2015 involved a variant virus that acquired distinctive deletions in the accessory open reading frames. We conducted a molecular and seroepidemiologic investigation to describe the deletion variant’s transmission patterns and epidemiology.

Methods

We reviewed epidemiologic and medical chart data and analyzed viral genome sequences from respiratory specimens of MERS-CoV cases. In early 2016, sera and standardized interviews were obtained from MERS-CoV cases and their contacts. Sera were evaluated by nucleocapsid and spike protein enzyme immunoassays and microneutralization.

Results

Among 16 cases, 11 (69%) had health care exposure and 5 (31%) were relatives of a known case; 13 (81%) were symptomatic, and 7 (44%) died. Genome sequencing of MERS-CoV from 13 cases revealed 3 transmissible deletions associated with clinical illness during the outbreak. Deletion variant sequences were epidemiologically clustered and linked to a common transmission chain. Interviews and sera were collected from 2 surviving cases, 23 household contacts, and 278 health care contacts; 1 (50%) case, 2 (9%) household contacts, and 3 (1%) health care contacts tested seropositive.

Conclusions

The MERS-CoV deletion variants retained human-to-human transmissibility and caused clinical illness in infected persons despite accumulated mutations. Serology suggested limited transmission beyond that detected during the initial outbreak investigation.
The Hospital Antimicrobial Use Process: From Beginning to End
Authors: Truong William R , Yamaki Jason
Published: April 2018

Hospital antimicrobial stewardship (AMS) programs are responsible for ensuring that all antimicrobials are utilized in the most appropriate and safe manner to improve patient outcomes, prevent adverse drug reactions, and prevent the development of antimicrobial resistance. This Perspectives article outlines the hospital antimicrobial use process (AUP), the foundational system that ensures that all antimicrobials are utilized in the most appropriate and safe manner. The AUP consists of the following steps: antimicrobial ordering, order verification, preparation and delivery, administration, monitoring, and discharge prescribing. AMS programs should determine how each step contributes to how an antimicrobial is used appropriately or inappropriately at their institution. Through this understanding, AMS programs can integrate stewardship activities at each step to ensure that every opportunity is taken to optimize antimicrobial use during a patient’s treatment course. Hence, approaching AMS through the framework of a hospital’s AUP is essential to improving appropriate antimicrobial use.
Recovery after stroke: not so proportional after all?
Authors: Hope Thomas M.H. , Friston Karl , Price Cathy J. , Leff Alex P. , Rotshtein Pia , Bowman Howard
Published: April 2018

Background

The proportional recovery rule asserts that most stroke survivors recover a fixed proportion of lost function. Reports that the rule can be used to predict recovery, extraordinarily accurately, are rapidly accumulating. Here, we show that the rule may not be as powerful as it seems.

Methods

We provide a formal analysis of the relationship between baseline scores (X), outcomes (Y) and recovery (Y-X), to highlight the shortcomings of the proportional recovery rule, and illustrate those problems with simulations in which synthetic recovery data are derived from different types of recovery processes.

Findings

When the correlation between baseline scores and recovery is stronger than that between baselines scores and outcomes, the former can create an inflated impression of how predictable outcomes really are given baseline scores. This often happens when outcomes are less variable than baseline scores, as is common in empirical studies of recovery after stroke. Moreover, we cannot use the results of these correlations to distinguish proportional recovery from recovery which is either not consistently proportional, or not proportional at all.

Interpretation

Analyses relating baseline scores to subsequent change are a minefield: our formal analysis applies as consistently outside the area of stroke as it does within it. One implication of our analysis is that the proportional recovery rule is not as predictive of real recovery after stroke as recent empirical studies suggest. Another is that different analytical methods will be required to ascertain whether recovery is even proportional at all.
AAV-mediated progranulin delivery to a mouse model of progranulin deficiency causes T cell-mediated hippocampal degeneration
Authors: Amado Defne A. , Rieders Julianne M. , Diatta Fortunay , Hernandez-Con Pilar , Singer Adina , Zhang Junxian , Lancaster Eric , Davidson Beverly L. , Chen-Plotkin Alice S.
Published: April 2018

Adeno-associated virus (AAV)-mediated gene replacement is emerging as a safe and effective means of correcting single-gene mutations, and use of AAV vectors for treatment of diseases of the CNS is increasing. AAV-mediated progranulin gene (GRN) delivery has been proposed as a treatment for GRN-deficient frontotemporal dementia (FTD) and neuronal ceroid lipofuscinosis (NCL), and two recent studies using focal intraparenchymal AAV-Grn delivery to brain have shown moderate success in histopathologic and behavioral rescue in mouse FTD models. Here, we used AAV9 to deliver GRN to the lateral ventricle to achieve widespread expression in the Grn null mouse brain. We found that despite a global increase in progranulin throughout many brain regions, overexpression of GRN resulted in dramatic and selective hippocampal toxicity and degeneration affecting both neurons and glia. Histologically, hippocampal degeneration was preceded by T cell infiltration and perivascular cuffing, suggesting an inflammatory component to the ensuing neuronal loss. GRN delivery with an ependymal-targeting AAV for selective secretion of progranulin into the cerebrospinal fluid (CSF) similarly resulted in T cell infiltration as well as ependymal hypertrophy. Interestingly, overexpression of GRN in wild-type animals also provoked T cell infiltration. These results call into question the safety of GRN overexpression in the CNS, with evidence for both a region-selective immune response and cellular proliferative response following GRN gene delivery. Our results highlight the importance of careful consideration of target gene biology and cellular response to overexpression in relevant animal models prior to progressing to the clinic.

Significance Statement

Gene therapies using adeno-associated viral (AAV) vectors show great promise for many human diseases, including diseases that affect the central nervous system (CNS). Frontotemporal dementia (FTD) and neuronal ceroid lipofuscinosis (NCL) are neurodegenerative diseases resulting from loss of one or both copies of the gene encoding progranulin (GRN), and gene replacement has been proposed for these currently untreatable disorders. Here, we used two different AAV vectors to induce widespread brain GRN expression in mice lacking the gene, as well as in wild-type mice. Unexpectedly, GRN overexpression resulted in T cell infiltration, followed by marked hippocampal neurodegeneration. Our results call into question the safety of GRN overexpression in the CNS, with wider implications for development of CNS gene therapies.
Discovery of a Streptococcus pneumoniae serotype 33F capsular polysaccharide locus that lacks wcjE and contains a wcyO pseudogene
Authors: Manna Sam , Dunne Eileen M. , Ortika Belinda D. , Pell Casey L. , Kama Mike , Russell Fiona M. , Mungun Tuya , Mulholland E. Kim , Hinds Jason , Satzke Catherine
Published: April 2018

Objectives

As part of large on-going vaccine impact studies in Fiji and Mongolia, we identified 25/2750 (0.9%) of nasopharyngeal swabs by microarray that were positive for Streptococcus pneumoniae contained pneumococci with a divergent 33F capsular polysaccharide locus (designated ‘33F-1’). We investigated the 33F-1 capsular polysaccharide locus to better understand the genetic variation and its potential impact on serotyping results.

Methods

Whole genome sequencing was conducted on ten 33F-1 pneumococcal isolates. Initially, sequence reads were used for molecular serotyping by PneumoCaT. Phenotypic typing of 33F-1 isolates was then performed using the Quellung reaction and latex agglutination. Genome assemblies were used in phylogenetic analyses of each gene in the capsular locus to investigate genetic divergence.

Results

All ten pneumococcal isolates with the 33F-1 cps locus typed as 33F by Quellung and latex agglutination. Unlike the reference 33F capsule locus sequence, DNA microarray and PneumoCaT analyses found that 33F-1 pneumococci lack the wcjE gene, and instead contain wcyO with a frameshift mutation. Phylogenetic analyses found the wzg, wzh, wzd, wze, wchA, wciG and glf genes in the 33F-1 cps locus had higher DNA sequence similarity to homologues from other serotypes than to the 33F reference sequence.

Conclusions

We have discovered a novel genetic variant of serotype 33F, which lacks wcjE and contains a wcyO pseudogene. This finding adds to the understanding of molecular epidemiology of pneumococcal serotype diversity, which is poorly understood in low and middle-income countries.
Fast and global detection of periodic sequence repeats in large genomic resources
Authors: Mori Hideto , Evans-Yamamoto Daniel , Ishiguro Soh , Tomita Masaru , Yachie Nozomu
Published: April 2018

Periodically repeating DNA and protein elements are involved in various important biological events including genomic evolution, gene regulation, protein complex formation, and immunity. Notably, the currently used genome editing tools such as ZFNs, TALENs, and CRISPRs are also all associated with periodically repeating biomolecules of natural organisms. Despite the biological importance of periodically repeating sequences and the expectation that new genome editing modules could be discovered from such periodical repeats, no software that globally detects such structured elements in large genomic resources in a high-throughput and unsupervised manner has been developed. Here, we developed new software, SPADE (Search for Patterned DNA Elements), that exhaustively explores periodic DNA and protein repeats from large-scale genomic datasets based on k-mer periodicity evaluation. SPADE precisely captured reported genome-editing-associated sequences and other protein families involving repeating domains with significantly better performance than the other software designed for limited sets of repetitive biomolecular sequences.
Disturbance macroecology: integrating disturbance ecology and macroecology with different-age post-fire stands of a closed-cone pine forest
Authors: Newman Erica A. , Wilber Mark Q. , Kopper Karen E. , Moritz Max A. , Falk Donald A. , McKenzie Don , Harte John
Published: April 2018

Macroecological studies have generally restricted their scope to relatively steady-state systems, and as a result, how biodiversity and abundance metrics are expected to scale in disturbance-dependent ecosystems is unknown. We examine macroecological patterns in a fire-dependent forest of Bishop pine (Pinus muricata). We target two different-aged stands in a stand-replacing fire regime, one a characteristically mature stand with a diverse understory, and one more recently disturbed by a stand-replacing fire (17 years prior to measurement). We compare the stands using macroecological metrics of species richness, abundance and spatial distributions that are predicted by the Maximum Entropy Theory of Ecology (METE), an information-entropy based theory that has proven highly successful in predicting macroecological metrics across a wide variety of systems and taxa. Ecological patterns in the mature stand more closely match METE predictions than do data from the recently disturbed stand. This suggests METE’s predictions are more robust in late-successional, slowly changing, or steady-state systems than those in rapid flux with respect to species composition, abundances, and organisms’ sizes. Our findings highlight the need for a macroecological theory that incorporates natural disturbance and other ecological perturbations into its predictive capabilities, because most natural systems are not in a steady state.
Morphological variation and strain identification of insects using wings and I3S
Authors: Vyas-Patel Nayna , Mumford John D
Published: April 2018

Novel insect identification techniques often lead to speculation on whether the method could cope with any intraspecific variation that might occur in a species. Using I3S Classic (Interactive Individual Identification System, Classic) and images of mosquito wings, different mosquito strains were tested with a copy of the strain present or absent from the database which contained images of other strains of the test species. When a wing image of the exact species, strain and sex was present in the database, there was 100% (or near 100%) retrieval of the correct species and strain at rank one. When the exact strain was absent from the database, but other strains of the same species were present, the retrieval rates at rank one were again high (100%) in the majority of cases and when they were not, the correct species was generally retrieved at rank two. Out of 40 different species and strains tested, only three were significantly different at rank one when the exact strain was absent from the database. In general, images of field strains selected for each other and therefore were similar to each other in greater numbers and instances than for the laboratory strains tested. When a copy of a strain was absent from the database, but other strains/sibling species were present, I3S retrieved the correct strains/sibling species at rank one in the majority of cases. In the one case of transgenic mosquitoes tested, I3S could reliably be used to identify transgenic mosquitoes from the parent stock as they were retrieved 100% at rank one when both the transgenic and unmodified parent strains were present in the database. This indicates the potential of using I3S to distinguish transgenic or other selectively bred strains from a parent strain, also selectively bred and wild mosquitoes, at least in the first phase after field release. Similarly, hybrid strains, sibling species and members of species complexes as in theAnopheles gambiaespecies complex could also be correctly identified when copies of all the relevant species/strains/siblings were in the database. This contradicts the belief that only molecular characterisation could separateA. gambiaes.s. fromA. coluzzii, orA. arabiensis; I3S could accurately separate them all. I3S worked as it was set up to do, retrieving closely resembling images of the test insects from the database and ranking them in order of similarity. Dealing with any intraspecific variation was therefore not an issue if the software (I3S) was used systematically. I3S complements molecular and traditional taxonomic methods for species identification and the separation of sibling complexes and strains. In future, it should become the norm to maintain databases of insect wings and other body part images for use in image recognition.
Studies on squalene biosynthesis and the standardization of its extraction methodology fromSaccharomyces cerevisiae
Authors: Paramasivan Kalaivani , Rajagopal Kavya , Mutturi Sarma
Published: April 2018

Aims

The present work focuses on studies on squalene improvement in theS. cerevisiaeand development of squalene extraction procedure based on mechanical disruption of cells.

Methods and Results

In this study, a homogenization-based extraction method was developed and was compared to five conventional methods of squalene extraction. Squalene recovered from this novel procedure gave 3.5– fold, 10-fold, 16-fold and 8.1-fold higher yield than standard procedures viz., saponification with 60% KOH, acidic saponification, saponification with 18% KOH and glass beads method, respectively. Furthermore, this procedure has been evaluated on laboratoryS. cerevisiaestrains such as BY4742 and CEN.PK2-1C (native), deletion strains (ERG6andERG11) andtHMGloverexpressedS. cerevisiaestrains. When sonication method of cell lysis was replaced with homogenization it was found that the yields were significantly higher and reached a value of 9 mg/g DCW in case of BY4742. In addition, Squalene yield in ergosterol mutant strains has been analyzed and was found to be 1.8-fold and 3.4-fold higher inERG6andERG11deletion strains, respectively, than BY4742. Squalene was also found to be higher at the optimized temperature of 30°C and pH 6.0. Furthermore, tolerance ofS. cerevisiaeto external squalene at various concentration has been carried and found that the organism was tolerant up to 25 g/L of squalene.

Conclusions

Homogenization based mechanical disruption was observed to yield higher squalene and the SEM analysis corroborates these findings. The synergistic effect ofERG11downregulation andtHMG1over-expression has led to significant increase in squalene yield.

Significance and Impact of the Study

Sonication and homogenization has been used as a cell-disruption method for the first time in squalene extraction and squalene yield from homogenization method of cell lysis in BY4742 has been found to be 9 mg/g DCW which is the highest reported so far in a wild-type strain.
Multi-omics approach identifies novel pathogen-derived prognostic biomarkers in patients withPseudomonas aeruginosabloodstream infection
Authors: Willmann Matthias , Götting Stephan , Bezdan Daniela , Maček Boris , Velic Ana , Marschal Matthias , Vogel Wichard , Flesch Ingo , Markert Uwe , Schmidt Annika , Kübler Pierre , Haug Maria , Javed Mumina , Jentzsch Benedikt , Oberhettinger Philipp , Schütz Monika , Bohn Erwin , Sonnabend Michael , Klein Kristina , Autenrieth Ingo B , Ossowski Stephan , Schwarz Sandra , Peter Silke
Published: April 2018

Pseudomonas aeruginosais a human pathogen that causes health-care associated blood stream infections (BSI). AlthoughP. aeruginosaBSI are associated with high mortality rates, the clinical relevance of pathogen-derived prognostic biomarker to identify patients at risk for unfavorable outcome remains largely unexplored. We found novel pathogen-derived prognostic biomarker candidates by applying a multi-omics approach on a multicenter sepsis patient cohort. Multi-level Cox regression was used to investigate the relation between patient characteristics and pathogen features (2298 accessory genes, 1078 core protein levels, 107 parsimony-informative variations in reported virulence factors) with 30-day mortality. Our analysis revealed that presence of thehelPgene encoding a putative DEAD-box helicase was independently associated with a fatal outcome (hazard ratio 2.01, p = 0.05).helPis located within a region related to the pathogenicity island PAPI-1 in close proximity to apilgene cluster, which has been associated with horizontal gene transfer. BesideshelP, elevated protein levels of the bacterial flagellum protein FliL (hazard ratio 3.44, p < 0.001) and of a bacterioferritin-like protein (hazard ratio 1.74, p = 0.003) increased the risk of death, while high protein levels of a putative aminotransferase were associated with an improved outcome (hazard ratio 0.12, p < 0.001). The prognostic potential of biomarker candidates and clinical factors was confirmed with different machine learning approaches using training and hold-out datasets. ThehelPgenotype appeared the most attractive biomarker for clinical risk stratification due to its relevant predictive power and ease of detection.
Behavioral repeatability and foraging performance in wild free-flying nectarivorous bats (Glossophaga commissarisi)
Authors: Nachev Vladislav , Winter York
Published: April 2018

Animal individuals show patterns of behavior that are stable within individuals but different among individuals. Such individual differences are potentially associated with differences in foraging efficiency and in fitness. Furthermore, behavioral responses may be correlated in specific suites of so called behavioral syndromes that are consistent across different contexts and with time. Here we present a field investigation on individual differences between wild, free-flying nectarivorous bats (Glossophaga commissarisi) in the foraging context. We further investigated how individual differences effect foraging performance, and we examined their interdependence within hypothesized behavioral syndrome structures. Free-ranging bats were individually identified as they visited an array of 24 artificial flowers with nectar of high or low sugar concentration. We found that three behavioral measures of foraging behavior were individually stable over the two-month observation period. We investigated the link between individual behavioral measures and measures of foraging performance using generalized linear mixed models. Individual measures of foraging performance showed significant repeatability, and we found evidence that bats making more visits per bout tend to be slower in learning to avoid unprofitable flowers. We used a multi-response generalized linear mixed model to estimate between-individual correlations and compare hypothesized syndrome structures. There were no clear patterns of between-individual correlations among the behavioral measures in our study, despite the measures exhibiting significant repeatability. This may indicate that foraging performance depends on multiple individual behavior dimensions that are not adequately described by simple models of behavior syndromes.
Cycles of gene expression and genome response during mammalian tissue regeneration
Authors: Rib Leonor , Villeneuve Dominic , Praz Viviane , Hernandez Nouria , Guex Nicolas , Herr Winship ,   CycliX Consortium
Published: April 2018

Background

Compensatory liver hyperplasia — or regeneration — induced by two-thirds partial hepatectomy (PH) permits the study of synchronized activation of mammalian gene expression, particularly in relation to cell proliferation. Here, we measured genomic transcriptional responses and mRNA accumulation changes after PH and sham surgeries.

Results

During the first 10–20 hours, the PH- and sham-surgery responses were very similar, including parallel early activation of cell-division-cycle genes. After 20 hours, however, whereas post-PH livers continued with a robust and coordinate cell-division-cycle gene-expression response before returning to the resting state by one week, sham-surgery livers returned directly to a resting gene-expression state. Localization of RNA polymerase II (Pol II), and trimethylated histone H3 lysine 4 (H3K4me3) and 36 (H3K36me3) on genes dormant in the resting liver and activated during the PH response revealed a general de novo promoter Pol II recruitment and H3K4me3 increase during the early 10–20 hour phase followed by Pol II elongation and H3K36me3 accumulation in gene bodies during the later proliferation phase. H3K36me3, generally appearing at the first-internal exon, was preceded 5′ by H3K36me2; 3′ of the first-internal exon, in about half of genes H3K36me3 predominated and in the other half H3K36me2 and H3K36me3 co-existed. Further, we observed some unusual gene profiles with abundant Pol II but little evident H3K4me3 or H3K36me3 modification, indicating that these modifications are neither universal nor essential partners to Pol II transcription.

Conclusions

PH and sham surgical procedures on mice reveal striking early post-operatory gene expression similarities followed by synchronized mRNA accumulation and epigenetic histone mark changes specific to PH.