bluuebunny/crossref_metadata_2025 huggingface dataset:
Optical characteristics of highly conductive n-type GaN prepared by pulsed sputtering deposition
Authors: Ueno Kohei , Taiga Fudetani , Kobayashi Atsushi , Fujioka Hiroshi
Published: December 2019

We have characterized highly conductive Si-doped GaN films with a high electron mobility of 112 cm2V−1s−1 at an electron concentration of 2.9 × 1020 cm−3, prepared using pulsed sputtering deposition (PSD). With an increase in the doping concentration, the absorption edge was found to shift toward a higher energy level, owing to the Burstein-Moss effect, thus making this material suitable for the transparent conductive tunneling electrodes of visible and ultraviolet-A light-emitting diodes. The full width at half maximum value of the near-band-edge (NBE) emissions in a photoluminescence spectrum measured at 77 K was as small as 185 meV, even for the sample with the highest electron concentration of 2.9 × 1020 cm−3. Such sharp NBE emissions from PSD-grown heavily Si-doped GaN films can be explained by an analytical model with a low compensation ratio θ of around 0.1, which is consistent with the exceptionally high observed electron mobility. These results indicate the strong potential of the low-temperature PSD growth technique for the formation of high-quality, heavily Si-doped GaN.
Electroretinographic recordings with skin electrodes to assess effects of vitrectomy with gas tamponade on eyes with rhegmatogenous retinal detachment
Authors: Shibuya Masayuki , Yoshikawa Yuji , Katsumoto Takeshi , Shoji Takuhei , Kondo Hiromi , Miyakoshi Hitomi , Shinoda Kei
Published: December 2019

The purpose of this study was to evaluate the retinal function by electroretinograms (ERGs) recorded with the RETeval system using skin electrodes after pars plana vitrectomy (PPV) with gas tamponade in eyes with a rhegmatogeneous retinal detachment (RRD). Flicker ERGs were recorded from 17 eyes with an RRD before (baseline), within 2 weeks after the PPV when the size of the tamponade gas was approximately one-half of the vitreous cavity (P1), and when the gas had been completely absorbed (P2). The amplitudes of the flicker ERGs at each phase were compared to that at the baseline. The median (25th, 75th percentile) of the amplitude was 10.0 µV (5.5, 13.0 µV) at the baseline, 11.7 µV at P1 (7.8, 14.8 µV; P = 0.003), and 17.1 µV at P2 (11.7 23.3 μV; P < 0.001). The ratio of the amplitudes in the affected eye to that in the fellow eye at the baseline and at each phase was calculated, and the ratio of the amplitudes at P1 and P2 were significantly and positively correlated (P = 0.723, P = 0.001; Spearman’s rank correlation coefficient). We conclude that recordings the flicker ERGs with skin electrodes can be used to assess the physiology of eyes even with the vitreous cavity half-filled with the gas used to tamponade the retina.
Serial dependence in a simulated clinical visual search task
Authors: Manassi Mauro , Kristjánsson Árni , Whitney David
Published: December 2019

In everyday life, we continuously search for and classify objects in the environment around us. This kind of visual search is extremely important when performed by radiologists in cancer image interpretation and officers in airport security screening. During these tasks, observers often examine large numbers of uncorrelated images (tumor x-rays, checkpoint x-rays, etc.) one after another. An underlying assumption of such tasks is that search and recognition are independent of our past experience. Here, we simulated a visual search task reminiscent of medical image search and found that shape classification performance was strongly impaired by recent visual experience, biasing classification errors 7% more towards the previous image content. This perceptual attraction exhibited the three main tuning characteristics of Continuity Fields: serial dependence extended over 12 seconds back in time (temporal tuning), it occurred only between similar tumor-like shapes (feature tuning), and only within a limited spatial region (spatial tuning). Taken together, these results demonstrate that serial dependence influences shape perception and occurs in visual search tasks. They also raise the possibility of a detrimental impact of serial dependence in clinical and practically relevant settings, such as medical image perception.
Effects of Acute Aerobic Exercise on Response Inhibition in Adult Patients with ADHD
Authors: Mehren A. , Özyurt J. , Thiel C. M. , Brandes M. , Lam A. P. , Philipsen A.
Published: December 2019

Previous studies suggest beneficial effects of aerobic exercise on executive functions, which are a core deficit in ADHD. The aim of the present fMRI study was to investigate acute effects of aerobic exercise on inhibitory control and related brain activation in adult patients with ADHD. 23 patients and 23 matched healthy controls performed on a Go/No-go task in an MRI scanner, following both, an exercise condition involving 30 min of cycling at moderate intensity, and a control condition. ADHD patients compared to healthy controls showed increased brain activation during successful inhibition in the exercise compared to the control condition in parietal, temporal, and occipital regions. Exercise did not improve behavioral performance in either group, but in ADHD patients, exercise-related increases in brain activation and behavioral task performance (i.e., correct inhibition rate) negatively correlated with correct inhibition rate in the control condition. Thus, patients with worse inhibition performance showed stronger exercise-related enhancements, indicating that the lack of improvements on the behavioral level for the whole patient group could be due to ceiling effects. Our findings might be an important step in understanding the neural basis of exercise effects and could, in the long term, help in developing alternative treatment approaches for ADHD.
The Impact of MRI Features and Observer Confidence on the Treatment Decision-Making for Patients with Untreated Glioma
Authors: Due-Tønnessen Paulina , Pinho Marco C. , Emblem Kyrre E. , Hald John K. , Kanoto Masafumi , Abildgaard Andreas , Sederevicius Donatas , Groote Inge R. , Rapalino Otto , Bjørnerud Atle
Published: December 2019

In a blind, dual-center, multi-observer setting, we here identify the pre-treatment radiologic features by Magnetic Resonance Imaging (MRI) associated with subsequent treatment options in patients with glioma. Study included 220 previously untreated adult patients from two institutions (94 + 126 patients) with a histopathologically confirmed diagnosis of glioma after surgery. Using a blind, cross-institutional and randomized setup, four expert neuroradiologists recorded radiologic features, suggested glioma grade and corresponding confidence. The radiologic features were scored using the Visually AcceSAble Rembrandt Images (VASARI) standard. Results were retrospectively compared to patient treatment outcomes. Our findings show that patients receiving a biopsy or a subtotal resection were more likely to have a tumor with pathological MRI-signal (by T2-weighted Fluid-Attenuated Inversion Recovery) crossing the midline (Hazard Ratio; HR = 1.30 [1.21–1.87], P < 0.001), and those receiving a biopsy sampling more often had multifocal lesions (HR = 1.30 [1.16–1.64], P < 0.001). For low-grade gliomas (N = 50), low observer confidence in the radiographic readings was associated with less chance of a total resection (P = 0.002) and correlated with the use of a more comprehensive adjuvant treatment protocol (Spearman = 0.48, P < 0.001). This study may serve as a guide to the treating physician by identifying the key radiologic determinants most likely to influence the treatment decision-making process.
Revealing interactions of layered polymeric materials at solid-liquid interface for building solvent compatibility charts for 3D printing applications
Authors: Erokhin Kirill S. , Gordeev Evgeniy G. , Ananikov Valentine P.
Published: December 2019

Poor stability of 3D printed plastic objects in a number of solvents limits several important applications in engineering, chemistry and biology. Due to layered type of assembling, 3D-printed surfaces possess rather different properties as compared to bulk surfaces made by other methods. Here we study fundamental interactions at the solid-liquid interface and evaluate polymeric materials towards advanced additive manufacturing. A simple and universal stability test was developed for 3D printed parts and applied to a variety of thermoplastics. Specific modes of resistance/destruction were described for different plastics and their compatibility to a representative scope of solvents (aqueous and organic) was evaluated. Classification and characterization of destruction modes for a wide range of conditions (including geometry and 3D printing parameters) were carried out. Key factors of tolerance to solvent media were investigated by electron microscopy. We show that the overall stability and the mode of destruction depend on chemical properties of the polymer and the nature of interactions at the solid-liquid interface. Importantly, stability also depends on the layered microstructure of the sample, which is defined by 3D printing parameters. Developed solvent compatibility charts for a wide range of polymeric materials (ABS, PLA, PLA-Cu, PETG, SBS, Ceramo, HIPS, Primalloy, Photoresin, Nylon, Nylon-C, POM, PE, PP) and solvents represent an important benchmark for practical applications.
Patient-Derived Cells to Guide Targeted Therapy for Advanced Lung Adenocarcinoma
Authors: Kim Seok-Young , Lee Ji Yeon , Kim Dong Hwi , Joo Hyeong -Seok , Yun Mi Ran , Jung Dongmin , Yun Jiyeon , Heo Seong Gu , Ahn Beung -Chul , Park Chae Won , Pyo Kyoung Ho , Chun You Jin , Hong Min Hee , Kim Hye Ryun , Cho Byoung Chul
Published: December 2019

Adequate preclinical model and model establishment procedure are required to accelerate translational research in lung cancer. We streamlined a protocol for establishing patient-derived cells (PDC) and identified effective targeted therapies and novel resistance mechanisms using PDCs. We generated 23 PDCs from 96 malignant effusions of 77 patients with advanced lung adenocarcinoma. Clinical and experimental factors were reviewed to identify determinants for PDC establishment. PDCs were characterized by driver mutations and in vitro sensitivity to targeted therapies. Seven PDCs were analyzed by whole-exome sequencing. PDCs were established at a success rate of 24.0%. Utilizing cytological diagnosis and tumor colony formation can improve the success rate upto 48.8%. In vitro response to a tyrosine kinase inhibitor (TKI) in PDC reflected patient treatment response and contributed to identifying effective therapies. Combination of dabrafenib and trametinib was potent against a rare BRAF K601E mutation. Afatinib was the most potent EGFR-TKI against uncommon EGFR mutations including L861Q, G719C/S768I, and D770_N771insG. Aurora kinase A (AURKA) was identified as a novel resistance mechanism to olmutinib, a mutant-selective, third-generation EGFR-TKI, and inhibition of AURKA overcame the resistance. We presented an efficient protocol for establishing PDCs. PDCs empowered precision medicine with promising translational values.
Quantum Mechanics can be understood through stochastic optimization on spacetimes
Authors: Lindgren Jussi , Liukkonen Jukka
Published: December 2019

The main contribution of this paper is to explain where the imaginary structure comes from in quantum mechanics. It is shown how the demand of relativistic invariance is key and how the geometric structure of the spacetime together with the demand of linearity are fundamental in understanding the foundations of quantum mechanics. We derive the Stueckelberg covariant wave equation from first principles via a stochastic control scheme. From the Stueckelberg wave equation a Telegrapher’s equation is deduced, from which the classical relativistic and nonrelativistic equations of quantum mechanics can be derived in a straightforward manner. We therefore provide meaningful insight into quantum mechanics by deriving the concepts from a coordinate invariant stochastic optimization problem, instead of just stating postulates.
Winter weather controls net influx of atmospheric CO2 on the north-west European shelf
Authors: Kitidis Vassilis , Shutler Jamie D. , Ashton Ian , Warren Mark , Brown Ian , Findlay Helen , Hartman Sue E. , Sanders Richard , Humphreys Matthew , Kivimäe Caroline , Greenwood Naomi , Hull Tom , Pearce David , McGrath Triona , Stewart Brian M. , Walsham Pamela , McGovern Evin , Bozec Yann , Gac Jean-Philippe , van Heuven Steven M. A. C. , Hoppema Mario , Schuster Ute , Johannessen Truls , Omar Abdirahman , Lauvset Siv K. , Skjelvan Ingunn , Olsen Are , Steinhoff Tobias , Körtzinger Arne , Becker Meike , Lefevre Nathalie , Diverrès Denis , Gkritzalis Thanos , Cattrijsse André , Petersen Wilhelm , Voynova Yoana G. , Chapron Bertrand , Grouazel Antoine , Land Peter E. , Sharples Jonathan , Nightingale Philip D.
Published: December 2019

Shelf seas play an important role in the global carbon cycle, absorbing atmospheric carbon dioxide (CO2) and exporting carbon (C) to the open ocean and sediments. The magnitude of these processes is poorly constrained, because observations are typically interpolated over multiple years. Here, we used 298500 observations of CO2 fugacity (fCO2) from a single year (2015), to estimate the net influx of atmospheric CO2 as 26.2 ± 4.7 Tg C yr−1 over the open NW European shelf. CO2 influx from the atmosphere was dominated by influx during winter as a consequence of high winds, despite a smaller, thermally-driven, air-sea fCO2 gradient compared to the larger, biologically-driven summer gradient. In order to understand this climate regulation service, we constructed a carbon-budget supplemented by data from the literature, where the NW European shelf is treated as a box with carbon entering and leaving the box. This budget showed that net C-burial was a small sink of 1.3 ± 3.1 Tg C yr−1, while CO2 efflux from estuaries to the atmosphere, removed the majority of river C-inputs. In contrast, the input from the Baltic Sea likely contributes to net export via the continental shelf pump and advection (34.4 ± 6.0 Tg C yr−1).
Maintenance of Deep Lung Architecture and Automated Airway Segmentation for 3D Mass Spectrometry Imaging
Authors: Scott Alison J. , Chandler Courtney E. , Ellis Shane R. , Heeren Ron M. A. , Ernst Robert K.
Published: December 2019

Mass spectrometry imaging (MSI) is a technique for mapping the spatial distributions of molecules in sectioned tissue. Histology-preserving tissue preparation methods are central to successful MSI studies. Common fixation methods, used to preserve tissue morphology, can result in artifacts in the resulting MSI experiment including delocalization of analytes, altered adduct profiles, and loss of key analytes due to irreversible cross-linking and diffusion. This is especially troublesome in lung and airway samples, in which histology and morphology is best interpreted from 3D reconstruction, requiring the large and small airways to remain inflated during analysis. Here, we developed an MSI-compatible inflation containing as few exogenous components as possible, forgoing perfusion, fixation, and addition of salt solutions upon inflation that resulted in an ungapped 3D molecular reconstruction through more than 300 microns. We characterized a series of polyunsaturated phospholipids (PUFA-PLs), specifically phosphatidylinositol (-PI) lipids linked to lethal inflammation in bacterial infection and mapped them in serial sections of inflated mouse lung. PUFA-PIs were identified using spatial lipidomics and determined to be determinant markers of major airway features using unsupervised hierarchical clustering. Deep lung architecture was preserved using this inflation approach and the resulting sections are compatible with multiple MSI modalities, automated interpretation software, and serial 3D reconstruction.
Restoration of liver sinusoidal cell phenotypes by statins improves portal hypertension and histology in rats with NASH
Authors: Bravo Miren , Raurell Imma , Hide Diana , Fernández-Iglesias Anabel , Gil Mar , Barberá Aurora , Salcedo Maria Teresa , Augustin Salvador , Genescà Joan , Martell María
Published: December 2019

Non-alcoholic steatohepatitis (NASH) is a common chronic liver disorder in developed countries, with the associated clinical complications driven by portal hypertension (PH). PH may precede fibrosis development, probably due to endothelial dysfunction at early stages of the disease. Our aim was to characterize liver sinusoidal endothelial cell (LSEC) dedifferentiation/capillarization and its contribution to PH in NASH, together with assessing statins capability to revert endothelial function improving early NASH stages. Sprague-Dawley rats were fed with high fat glucose-fructose diet (HFGFD), or control diet (CD) for 8 weeks and then treated with simvastatin (sim) (10 mg·kg−1·day−1), atorvastatin (ato) (10 mg·kg−1·day−1) or vehicle during 2 weeks. Biochemical, histological and hemodynamic determinations were carried out. Sinusoidal endothelial dysfunction was assessed in individualized sorted LSEC and hepatic stellate cells (HSC) from animal groups and in whole liver samples. HFGFD rats showed full NASH features without fibrosis but with significantly increased portal pressure compared with CD rats (10.47 ± 0.37 mmHg vs 8.30 ± 0.22 mmHg; p < 0.001). Moreover, HFGFD rats showed a higher percentage of capillarized (CD32b−/CD11b−) LSEC (8% vs 1%, p = 0.005) showing a contractile phenotype associated to HSC activation. Statin treatments caused a significant portal pressure reduction (sim: 9.29 ± 0.25 mmHg, p < 0.01; ato: 8.85 ± 0.30 mmHg, p < 0.001), NASH histology reversion, along with significant recovery of LSEC differentiation and a regression of HSC activation to a more quiescent phenotype. In an early NASH model without fibrosis with PH, LSEC transition to capillarization and HSC activation are reverted by statin treatment inducing portal pressure decrease and NASH features improvement.
Inducing Tumor Suppressive Microenvironments through Genome Edited CD47−/− Syngeneic Cell Vaccination
Authors: Jayaraman Rukmini Subhadra , Bi Huanjing , Sen Puloma , Everhart Benjamin , Jin Sha , Ye Kaiming
Published: December 2019

Tumors can escape from the immune system by overexpressing CD47 and other checkpoint blockades. CD47 is expressed ubiquitously by all cells in the body, posing an obstacle for CD47 blocking treatments due to their systemic toxicity. We performed a study to determine how the tumor microenvironment changes after vaccination with genome edited CD47−/− syngeneic tumor cells. We discovered that inactivated CD47-depleted mouse melanoma cells can protect mice from melanoma. Our animal study indicated that 33% of vaccinated mice remained tumor-free, and 100% of mice had 5-fold reduced growth rates. The characterization of immunomodulatory effects of the vaccine revealed a highly anti-tumorigenic and homogenous microenvironment after vaccination. We observed consistently that in the tumors that failed to respond to vaccines, there were reduced natural killer cells, elevated regulatory T cells, M2-type macrophages, and high PD-L1 expression in these cells. These observations suggested that the tumor microenvironments became more suppressive to tumor growth after vaccination, suggesting a potential new immunotherapy for solid tumors.
A Biochemiluminescent Sialidase Assay for Diagnosis of Bacterial Vaginosis
Authors: Wu Shengjun , Lin Xuexiang , Hui Kwok Min , Yang Su , Wu Xuanlan , Tan Yichen , Li Meimei , Qin Ai-Qing , Wang Qingxi , Zhao Qi , Ding Pengfei , Shi Kaisheng , Li X. James
Published: December 2019

Bacterial vaginosis (BV) is a common condition among women of reproductive age. A sensitive, quantitative and rapid assay is needed for the diagnosis of and, particularly, therapy monitoring for BV. Bacterial sialidase appears to play an important role in bacterial biofilms on vaginal epithelium, a condition closely associated with BV. Here, we report a biochemiluminescent sialidase assay that uses a substrate derivatized with firefly luciferin. In the presence of sialidase in the reaction, the substrate is cleaved to release luciferin, which is subsequently oxidized by firefly luciferase to generate a light signal. Thus, the light signal intensity can be used to detect and measure the relative concentration of sialidase in a vaginal sample as a means of BV diagnosis. All reagents are present in a reagent bead and sample buffer, enabling essentially a one-step assay. The assay is highly sensitive and quantitative, with a sensitivity and specificity of 95.40% and 94.94%, respectively, compared to the Amsel method. Interestingly, only 27.6% of those with BV had high levels of sialidase activity with a signal to cutoff ratio of 10 or more. The assay may be used for diagnosis of BV, risk assessment of BV patients in terms of sialidase activity levels, and monitoring antibiotic therapy.
Detection of circulating sarcoma tumor cells using a microfluidic chip-type cell sorter
Authors: Hasegawa Nobuhiko , Takeda Nakamura Ikuko , Ueno Toshihide , Kojima Shinya , Kawazu Masahito , Akaike Keisuke , Okubo Taketo , Takagi Tatsuya , Suehara Yoshiyuki , Hayashi Takuo , Saito Tsuyoshi , Kaneko Kazuo , Mano Hiroyuki , Kohsaka Shinji
Published: December 2019

Analyses of circulating tumor cells have been shown to be effective for the detection of cancer relapse and prognosis prediction. However, research regarding its utility in sarcoma remains scarce. In this study, the microfluidic chip-type cell sorter On-chip Sort was used to construct a system for detecting circulating sarcoma cells (CSCs). A pilot study using normal fibroblast or sarcoma cell lines was designed to establish a reliable protocol to separate CSCs by On-chip Sort. A single CSC was separated and recovered from 10 ml of whole blood from a patient with locally advanced myxofibrosarcoma. The nonsynonymous mutation for KMT2B p.Ile2602Val identified in the formalin-fixed paraffin-embedded tumor sample was also confirmed in the CSC. Use of the developed protocol may allow CSCs to become an early predictor for metastasis and recurrence of sarcoma. Further, it may aid in optimizing post-operative therapies for patients without metastasis.
Sensitivity of reaction time to the magnitude of rewards reveals the cost-structure of time
Authors: Steverson Kai , Chung Hui-Kuan , Zimmermann Jan , Louie Kenway , Glimcher Paul
Published: December 2019

The Drift-Diffusion Model (DDM) is the prevalent computational model of the speed-accuracy trade-off in decision making. The DDM provides an explanation of behavior by optimally balancing reaction times and error rates. However, when applied to value-based decision making, the DDM makes the stark prediction that reaction times depend only on therelativeutility difference between the options and not on absolute utility magnitudes. This prediction runs counter to evidence that reaction times decrease with higher utility magnitude. Here, we ask if and how it could be optimal for reaction times to show this observed pattern. We study an algorithmic framework that balances the cost of delaying rewards against the utility of obtained rewards. We find that the functional form of the cost of delay plays a key role, with the empirically observed pattern becoming optimal under multiplicative discounting. We add to the empirical literature by testing whether utility magnitude affects reaction times using a novel methodology that does not rely on functional form assumptions for the subjects’ utilities. Our results advance the understanding of how and why reaction times are sensitive to the magnitude of rewards.
Differentiation of thyroid nodules on US using features learned and extracted from various convolutional neural networks
Authors: Lee Eunjung , Ha Heonkyu , Kim Hye Jung , Moon Hee Jung , Byon Jung Hee , Huh Sun , Son Jinwoo , Yoon Jiyoung , Han Kyunghwa , Kwak Jin Young
Published: December 2019

Thyroid nodules are a common clinical problem. Ultrasonography (US) is the main tool used to sensitively diagnose thyroid cancer. Although US is non-invasive and can accurately differentiate benign and malignant thyroid nodules, it is subjective and its results inevitably lack reproducibility. Therefore, to provide objective and reliable information for US assessment, we developed a CADx system that utilizes convolutional neural networks and the machine learning technique. The diagnostic performances of 6 radiologists and 3 representative results obtained from the proposed CADx system were compared and analyzed.
The host generalist phytopathogenic fungus Sclerotinia sclerotiorum differentially expresses multiple metabolic enzymes on two different plant hosts
Authors: Allan Jefferson , Regmi Roshan , Denton-Giles Matthew , Kamphuis Lars G. , Derbyshire Mark C.
Published: December 2019

Sclerotinia sclerotiorum is a necrotrophic fungal pathogen that infects upwards of 400 plant species, including several economically important crops. The molecular processes that underpin broad host range necrotrophy are not fully understood. This study used RNA sequencing to assess whether S. sclerotiorum genes are differentially expressed in response to infection of the two different host crops canola (Brassica napus) and lupin (Lupinus angustifolius). A total of 10,864 of the 11,130 genes in the S. sclerotiorum genome were expressed. Of these, 628 were upregulated in planta relative to in vitro on at least one host, suggesting involvement in the broader infection process. Among these genes were predicted carbohydrate-active enzymes (CAZYmes) and secondary metabolites. A considerably smaller group of 53 genes were differentially expressed between the two plant hosts. Of these host-specific genes, only six were either CAZymes, secondary metabolites or putative effectors. The remaining genes represented a diverse range of functional categories, including several associated with the metabolism and efflux of xenobiotic compounds, such as cytochrome P450s, metal-beta-lactamases, tannases and major facilitator superfamily transporters. These results suggest that S. sclerotiorum may regulate the expression of detoxification-related genes in response to phytotoxins produced by the different host species. To date, this is the first comparative whole transcriptome analysis of S. sclerotiorum during infection of different hosts.
New statistical method identifies cytokines that distinguish stool microbiomes
Authors: Yang Dake , Johnson Jethro , Zhou Xin , Deych Elena , Shands Berkley , Hanson Blake , Sodergren Erica , Weinstock George , Shannon William D.
Published: December 2019

Regressing an outcome or dependent variable onto a set of input or independent variables allows the analyst to measure associations between the two so that changes in the outcome can be described by and predicted by changes in the inputs. While there are many ways of doing this in classical statistics, where the dependent variable has certain properties (e.g., a scalar, survival time, count), little progress on regression where the dependent variable are microbiome taxa counts has been made that do not impose extremely strict conditions on the data. In this paper, we propose and apply a new regression model combining the Dirichlet-multinomial distribution with recursive partitioning providing a fully non-parametric regression model. This model, called DM-RPart, is applied to cytokine data and microbiome taxa count data and is applicable to any microbiome taxa count/metadata, is automatically fit, and intuitively interpretable. This is a model which can be applied to any microbiome or other compositional data and software (R package HMP) available through the R CRAN website.
Multimodal alterations of directed connectivity profiles in patients with attention-deficit/hyperactivity disorders
Authors: Muthuraman Muthuraman , Moliadze Vera , Boecher Lena , Siemann Julia , Freitag Christine M. , Groppa Sergiu , Siniatchkin Michael
Published: December 2019

Functional and effective connectivity measures for tracking brain region interactions that have been investigated using both electroencephalography (EEG) and magnetoencephalography (MEG) bringing up new insights into clinical research. However, the differences between these connectivity methods, especially at the source level, have not yet been systematically studied. The dynamic characterization of coherent sources and temporal partial directed coherence, as measures of functional and effective connectivity, were applied to multimodal resting EEG and MEG data obtained from 11 young patients (mean age 13.2 ± 1.5 years) with attention-deficit/hyperactivity disorder (ADHD) and age-matched healthy subjects. Additionally, machine-learning algorithms were applied to the extracted connectivity features to identify biomarkers differentiating the two groups. An altered thalamo-cortical connectivity profile was attested in patients with ADHD who showed solely information outflow from cortical regions in comparison to healthy controls who exhibited bidirectional interregional connectivity in alpha, beta, and gamma frequency bands. We achieved an accuracy of 98% by combining features from all five studied frequency bands. Our findings suggest that both types of connectivity as extracted from EEG or MEG are sensitive methods to investigate neuronal network features in neuropsychiatric disorders. The connectivity features investigated here can be further tested as biomarkers of ADHD.
A novel Arabidopsis pathosystem reveals cooperation of multiple hormonal response-pathways in host resistance against the global crop destroyer Macrophomina phaseolina
Authors: Schroeder Mercedes M. , Lai Yan , Shirai Miwa , Alsalek Natalie , Tsuchiya Tokuji , Roberts Philip , Eulgem Thomas
Published: December 2019

Dubbed as a “global destroyer of crops”, the soil-borne fungus Macrophomina phaseolina (Mp) infects more than 500 plant species including many economically important cash crops. Host defenses against infection by this pathogen are poorly understood. We established interactions between Mp and Arabidopsis thaliana (Arabidopsis) as a model system to quantitatively assess host factors affecting the outcome of Mp infections. Using agar plate-based infection assays with different Arabidopsis genotypes, we found signaling mechanisms dependent on the plant hormones ethylene, jasmonic acid and salicylic acid to control host defense against this pathogen. By profiling host transcripts in Mp-infected roots of the wild-type Arabidopsis accession Col-0 and ein2/jar1, an ethylene/jasmonic acid-signaling deficient mutant that exhibits enhanced susceptibility to this pathogen, we identified hundreds of genes potentially contributing to a diverse array of defense responses, which seem coordinated by complex interplay between multiple hormonal response-pathways. Our results establish Mp/Arabidopsis interactions as a useful model pathosystem, allowing for application of the vast genomics-related resources of this versatile model plant to the systematic investigation of previously understudied host defenses against a major crop plant pathogen.
Distribution of the parasitic isopod Tachaea chinensis in China
Authors: Xu Weibin , Han Zhibin , Xing Yuenan , Li Xin , Zhao Yingying , Chen Qijun , Li Yingdong
Published: December 2019

Tachaea chinensis Thielemann, 1910 (Isopoda: Corallanidae) is a branchial ectoparasite that attaches onto shrimps and prawns. However, the distribution of T. chinensis in China, especially its epidemiology, remains unclear. We determined the prevalence of T. chinensis on the ridgetail white prawn (Exopalaemon carinicauda Holthuis, 1950) in Jiangsu Province. Fifty ponds in 10 shrimp farms were assessed. Isopod species were identified by morphological features and mitochondrial 16S rRNA gene analysis. A literature review was performed to determine the geographical distribution of T. chinensis in China. Published data revealed that T. chinensis was geographically distributed throughout five provinces in China, including Liaoning, Tianjin, Henan, Hubei, and Guangxi. A total of 998 T. chinensis were collected from 50 ridgetail white prawn ponds in Yancheng City and Rudong County. Tachaea chinensis prevalence ranged from 0.98% to 4.42% in Yancheng City and 0.62% to 0.92% in Rudong County. This is the first study to investigate the geographical distribution of T. chinensis in China and determine the prevalence of T. chinensis on the ridgetail white prawn in Jiangsu Province. Overall, we provide available data that fill gaps in the epidemiology of T. chinensis.
Experimental evaluation of a self-propelling bio-inspired needle in single- and multi-layered phantoms
Authors: Scali M. , Breedveld P. , Dodou D.
Published: December 2019

In percutaneous interventions, reaching targets located deep inside the body with minimal tissue damage and patient pain requires the use of long and thin needles. However, when pushed through a solid substrate, a structure with a high aspect ratio is prone to buckle. We developed a series of multi-element needles with a diameter smaller than 1 mm and a length larger than 200 mm, and we experimentally evaluated the performance of a bio-inspired insertion mechanism that prevents needle buckling of such slender structures. The needles consisted of Nitinol wires and advance into a substrate by pushing the wires forward one after the other, followed by pulling all the wires simultaneously backward. The resulting net push force is low, allowing the needles to self-propel through the substrate. We investigated the effect of the needle design parameters (number of wires and their diameter) and substrate characteristics (stiffness and number of layers) on the needle motion. Three needle prototypes (consisting of six 0.25-mm wires, six 0.125-mm wires, and three 0.25-mm wires, respectively) were inserted into single- and multi-layered tissue-mimicking phantoms. The prototypes were able to move forward in all phantoms without buckling. The amount of needle slip with respect to the phantom was used to assess the performance of the prototypes. The six-wire 0.25-mm prototype exhibited the least slip among the three prototypes. Summarizing, we showed that a bio-inspired motion mechanism prevents buckling in very thin (diameter <1 mm), long (length >200 mm) needles, allowing deep insertion into tissue-mimicking phantoms.
Forecasting of landslide displacements using a chaos theory based wavelet analysis-Volterra filter model
Authors: Li Yuanyao , Sun Ronglin , Yin Kunlong , Xu Yong , Chai Bo , Xiao Lili
Published: December 2019

Landslide displacement time series can directly reflects landslide deformation and stability characteristics. Hence, forecasting of the non-linear and non-stationary displacement time series is necessary and significant for early warning of landslide failure. Traditionally, conventional machine learning methods are adopted as forecasting models, these forecasting models mainly determine the input and output variables experientially and does not address the non-stationary characteristics of displacement time series. However, it is difficult for these conventional machine learning methods to obtain appropriate input-output variables, to determine appropriate model parameters and to acquire satisfied prediction performance. To deal with these drawbacks, this study proposes the wavelet analysis (WA) to decompose the displacement time series into low- and high-frequency components to address the non-stationary characteristics; then proposes thee chaos theory to obtain appropriate input-output variables of forecasting models, and finally proposes Volterra filter model to construct the forecasting model. The GPS monitoring cumulative displacement time series, recorded on the Shuping and Baijiabao landslides, distance measuring equipment monitoring displacements on the Xintan landslide in Three Gorges Reservoir area of China, are used as test data of the proposed chaotic WA-Volterra model. The chaotic WA-support vector machine (SVM) model and single chaotic Volterra model without WA method, are used as comparisons. The results show that there are chaos characteristics in the GPS monitoring displacement time series, the non-stationary characteristics of landslide displacements are captured well by the WA method, and the model input-output variables are selected suitably using chaos theory. Furthermore, the chaotic WA-Volterra model has higher prediction accuracy than the chaotic WA-SVM and single chaotic Volterra models.
Crebl2 regulates cell metabolism in muscle and liver cells
Authors: Tiebe Marcel , Lutz Marilena , Senyilmaz Tiebe Deniz , Teleman Aurelio A.
Published: December 2019

We previously identified Drosophila REPTOR and REPTOR-BP as transcription factors downstream of mTORC1 that play an important role in regulating organismal metabolism. We study here the mammalian ortholog of REPTOR-BP, Crebl2. We find that Crebl2 mediates part of the transcriptional induction caused by mTORC1 inhibition. In C2C12 myoblasts, Crebl2 knockdown leads to elevated glucose uptake, elevated glycolysis as observed by lactate secretion, and elevated triglyceride biosynthesis. In Hepa1-6 hepatoma cells, Crebl2 knockdown also leads to elevated triglyceride levels. In sum, this works identifies Crebl2 as a regulator of cellular metabolism that can link nutrient sensing via mTORC1 to the metabolic response of cells.
ezTrack: An open-source video analysis pipeline for the investigation of animal behavior
Authors: Pennington Zachary T. , Dong Zhe , Feng Yu , Vetere Lauren M. , Page-Harley Lucia , Shuman Tristan , Cai Denise J.
Published: December 2019

Tracking animal behavior by video is one of the most common tasks in the life sciences. Although commercial software exists for executing this task, they often present enormous cost to the researcher and can entail purchasing hardware that is expensive and lacks adaptability. Additionally, the underlying code is often proprietary. Alternatively, available open-source options frequently require model training and can be challenging for those inexperienced with programming. Here we present an open-source and platform independent set of behavior analysis pipelines using interactive Python that researchers with no prior programming experience can use. Two modules are described. One module can be used for the positional analysis of an individual animal, amenable to a wide range of behavioral tasks. A second module is described for the analysis of freezing behavior. For both modules, a range of interactive plots and visualizations are available to confirm that chosen parameters produce the anticipated results. Moreover, batch processing tools for the fast analysis of multiple videos is provided, and frame-by-frame output makes alignment with biological recording data simple. Lastly, options for cropping video frames to mitigate the influence of fiberoptic/electrophysiology cables, analyzing specified portions of time, and defining regions of interest, are readily implemented.
Differential IL-17A response to S. pneumoniae in adenoid tissue of children with sleep disordered breathing and otitis media with effusion
Authors: Huang Chien-Chia , Wu Pei-Wen , Lee Ta-Jen , Chen Chyi-Liang , Wang Chun-Hua , Tsai Chi-Neu , Chiu Cheng-Hsun
Published: December 2019

Streptococcus pneumonia, one of the major colonizers in nasopharyngeal adenoids, has been the predominant pathogen causing acute otitis media (AOM) in children. Recent evidence suggests an association between IL-17A-mediated immune response and the clearance of pneumococcal colonization in nasopharyngeal adenoids. Here, we evaluated the expressions of IL-17A and associated genes in hypertrophic adenoid tissues of children with sleep-disordered breathing (SDB) and otitis media with effusion (OME) and their association with pneumococcal carriage. Sixty-six pediatric patients with adenoid hypertrophy were enrolled. During adenoidectomy, nasopharyngeal swab and adenoid tissues were used to determine pneumococcal carriage and IL-17A expression. Our results revealed significantly higher levels of IL-17A and IL-17A:IL-10 mRNA in the SDB patients positive for nasopharyngeal pneumococcal carriage than those negative. However, these differences were not significant in the OME group. These results suggested, in OME patients, prolonged or chronic pneumococcal carriage may occur because of insufficient IL-17A-mediated mucosal clearance, and could further lead to AOM and OME development.
Heavy metal contents and enzymatic activity in soils exposed to the impact of road traffic
Authors: Jaworska Hanna , Lemanowicz Joanna
Published: December 2019

The aim of the research was to evaluate the influence of car traffic on the content of selected heavy metals in soil from a park area, and to define the dependency between their content and enzyme activity. Soil samples were collected from 13 points located along a communication route, each 100 m from the next and 50 m from the border of the road. Soil material was obtained from two depths (0–20 cm and 20–40 cm) and analysed for: pH in H2O and in KCl, OC, and texture by laser method. Total content of heavy metals (Pb, Cd, Zn, Cu, Ni), available phosphorus and the activity of selected enzymes: catalase, dehydrogenase, acidic and alkaline phosphatase were all determined. The examined soils have the texture of loamy sands or sands (USDA 2012), slightly acidic or neutral pH, Organic Carbon (OC) content in the range from 3.50 to 13.80 g kg−1. The total contents of elements in surface horizons were, in order of decreasing concentrations: Pb>Zn>Cu>Ni>Cd, although in subsurface horizons it was Zn>Pb>Cu>Ni>Cd. Contamination Factor (CF) determined for Ni, Pb, Cd, Zn, Cu reaches higher values in samples from subsurface horizons, which confirms the influence of car traffic on the content of heavy metals in the surrounding soils. The calculated CF shows contamination is moderate for Ni, Cd, Zn and Cu and high for Pb and Cu. The investigated soils may be classified as class IV (low) in terms of available phosphorus. The activity of the examined enzymes was higher in soil samples collected from the 0–20 cm layer than from 20–40 cm. The correlation analysis indicates a significant positive dependency between OC content in soils and enzymatic activity. Principal Component Analysis (PCA) was also performed. Two principal components PC1 and PC2 account for 66.57% of the variability.
ADAR1 function affects HPV replication and is associated to recurrent human papillomavirus-induced dysplasia in HIV coinfected individuals
Authors: Pujantell Maria , Badia Roger , Galván-Femenía Iván , Garcia-Vidal Edurne , de Cid Rafael , Alcalde Carmen , Tarrats Antonio , Piñol Marta , Garcia Francesc , Chamorro Ana M. , Revollo Boris , Videla Sebastian , Parés David , Corral Javier , Tural Cristina , Sirera Guillem , Esté José A. , Ballana Ester , Riveira-Muñoz Eva
Published: December 2019

Infection by human papillomavirus (HPV) alters the microenvironment of keratinocytes as a mechanism to evade the immune system. A-to-I editing by ADAR1 has been reported to regulate innate immunity in response to viral infections. Here, we evaluated the role of ADAR1 in HPV infectionin vitroandin vivo. Innate immune activation was characterized in human keratinocyte cell lines constitutively infected or not with HPV. ADAR1 knockdown induced an innate immune response through enhanced expression of RIG-I-like receptors (RLR) signaling cascade, over-production of type-I IFNs and pro-inflammatory cytokines. ADAR1 knockdown enhanced expression of HPV proteins, a process dependent on innate immune function as no A-to-I editing could be identified in HPV transcripts. A genetic association study was performed in a cohort of HPV/HIV infected individuals followed for a median of 6 years (range 0.1–24). We identified the low frequency haplotype AACCAT significantly associated with recurrent HPV dysplasia, suggesting a role of ADAR1 in the outcome of HPV infection in HIV+ individuals. In summary, our results suggest that ADAR1-mediated innate immune activation may influence HPV disease outcome, therefore indicating that modification of innate immune effectors regulated by ADAR1 could be a therapeutic strategy against HPV infection.
Target of initial sub-movement in multi-component arm-reaching strategy
Authors: Peternel Luka , Babič Jan
Published: December 2019

Goal-directed human reaching often involves multi-component strategy with sub-movements. In general, the initial sub-movement is fast and less precise to bring the limb’s endpoint in the vicinity of the target as soon as possible. The final sub-movement then corrects the error accumulated during the previous sub-movement in order to reach the target. We investigate properties of a temporary target of the initial sub-movement. We hypothesise that the peak spatial dispersion of movement trajectories in the axis perpendicular to the movement is in front of the final reaching target, and that it indicates the temporary target of the initial sub-movement. The reasoning is that the dispersion accumulates, due to signal-dependent noise during the initial sub-movement, until the final corrective sub-movement is initiated, which then reduces the dispersion to successfully reach the actual target. We also hypothesise that the reaching movement distance and size of the actual target affect the properties of the temporary target of the initial sub-movement. The increased reaching movement distance increases the magnitude of peak dispersion and moves its location away from the actual target. On the other hand, the increased target size increases the magnitude of peak dispersion and moves its location closer to the actual target.
Magnetic resonance microscopy and correlative histopathology of the infarcted heart
Authors: Perez-Terol Itziar , Rios-Navarro Cesar , de Dios Elena , Morales Jose M. , Gavara Jose , Perez-Sole Nerea , Diaz Ana , Minana Gema , Segura-Sabater Remedios , Bonanad Clara , Bayés-Genis Antoni , Husser Oliver , Monmeneu Jose V. , Lopez-Lereu Maria P. , Nunez Julio , Chorro Francisco J. , Ruiz-Sauri Amparo , Bodi Vicente , Monleon Daniel
Published: December 2019

Delayed enhancement cardiovascular magnetic resonance (MR) is the gold-standard for non-invasive assessment after myocardial infarction (MI). MR microscopy (MRM) provides a level of detail comparable to the macro objective of light microscopy. We used MRM and correlative histopathology to identify infarct and remote tissue in contrast agent-free multi-sequence MRM in swine MI hearts. One control group (n = 3 swine) and two experimental MI groups were formed: 90 min of ischemia followed by 1 week (acute MI = 6 swine) or 1 month (chronic MI = 5 swine) reperfusion. Representative samples of each heart were analysed by contrast agent-free multi-sequence (T1-weighting, T2-weighting, T2*-weighting, T2-mapping, and T2*-mapping). MRM was performed in a 14-Tesla vertical axis imager (Bruker-AVANCE 600 system). Images from MRM and the corresponding histopathological stained samples revealed differences in signal intensities between infarct and remote areas in both MI groups (p-value < 0.001). The multivariable models allowed us to precisely classify regions of interest (acute MI: specificity 92% and sensitivity 80%; chronic MI: specificity 100% and sensitivity 98%). Probabilistic maps based on MRM images clearly delineated the infarcted regions. As a proof of concept, these results illustrate the potential of MRM with correlative histopathology as a platform for exploring novel contrast agent-free MR biomarkers after MI.