bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling and force analysis of drum devices based on the geometry of the material segment
Authors: Teruchcov V , Cupschev A , Konovalov V , Rodionov Yu
Published: August 2019

The aim of the research is the numerical simulation of the drum mixer operation, including the identification of geometrical indicators of a material pile in a rotating drum for conducting the force analysis and determining the expended power. The influence of the required performance of the drum device on the parameters of its container with regard to the filling degree is determined analytically using the mixer as an example. The functional model of the central angle of the material segment on the filling degree of the container is established. The expressions for the parameters of a material segment in a rotating container are revealed. They allowed for determining the torque and power consumption of the drive based on the power analysis. The graphic material of changes in the calculated indicators in the modeling process is presented.
Stepper hydraulic motor with pneumatic (jet) control system in machines with hydromechanical forming links
Authors: Vanin V A , Kolodin A N , Rodina A A
Published: August 2019

The practical feasibility of using hydraulic links based on a stepper hydraulic drive with a jet control system in the internal circuits of machine tools has been considered. The application of hydraulic links based on stepper hydraulic motor in the internal circuits of the machines is constrained by the lack of fast-retrofitting control systems, functionally similar to switches, meeting the requirements of high accuracy (low step cost), high reliability requirements (no impulse skip).
Simulation of graphene-containing viscous fluid motion in the gap between static and rotating discs
Authors: Pershin V , Alhilo Z , Baranov A , Memetov N , Tugolukov E
Published: August 2019

The motion of a graph-containing viscous fluid between stationary and rotating disks is considered. The initial differential equations of motion for the elementary volume of a liquid are compiled and the initial conditions are determined. Assuming that the flow in the gap is a Couette flow, an analytical solution has been obtained to change the radial and angular coordinates of the elementary volume with time. With the use of the mathematical package Maple, characteristic trajectories of the movement of elementary volumes of fluid in the gap between a fixed and rotating disk with different consumption characteristics and geometry are obtained. Calculated speed, time of stay and the path traveled by an elementary volume, depending on the initial coordinate of the thickness of the gap.
The models of physical processes of bees winter aggregation
Authors: Oskin S V , Ovsyannikov D A , Tsokur D S
Published: August 2019

The analysis of physical processes happening in beehives was carried out for 15 000 bees in winter aggregation. In the current study changes of bees aggregation volume during winter season as well as bonds between heating, air exchange and humidity were considered. Simulation of physical in-hive processes was carried out with the help of software Comsol 5.3. Temperature fields analysis confirms the availability of the high thermal insulation ability of bees. On the surface of the bees aggregation the temperature is +12°C. In spite of temperature fluctuations outside the aggregation, inside of the latter temperature is maintained at the level of +25°C…+32°C. Within the aggregation temperature is distributed uneven, and there are zones of higher temperature values not exceeding +34°C, which is not harmful for bees. Analysis of air exchange processes demonstrates that the air velocity near the beehive entrance is 0.03…0.1 meters per second, and in the central inlet – 0.12…0.17 meters per second. The highest air velocity values – exceeding 0.19 meters per second – are achieved inside of the bees aggregation. Humidity level within beehives is uneven. Identity of thermal fields obtained with thermal camera and results of the simulation demonstrates the high level of its concordance.
Investigation of the regeneration of precipitating convective cloud in basin topography area
Authors: Fitriani R , Trilaksono N J , Hadi T W
Published: August 2019

The occurrence of precipitation in basin topography area at Bandung can be generated from repeatedly formed convective clouds in one diurnal cycle, which also is detected as multiple rain peaks during a day. In satellite observations, the formation of a new convective cell after dissipation stage of the predecessor cell around or in the same location indicates a regeneration process. The daily convective activities were analyzed during February–May 2017 to understand the regeneration of precipitating convective clouds in Bandung area. The rainfall events were obtained from cumulative distribution function (CDF) at the highest percentages of daily precipitation. This study proposed regeneration index (RegI) as initial identification for convective cloud regeneration from daily rainfall data with multiple peaks. The cases that obtained through the RegI were then verified by satellite data. Both cases at 27 February and 1 May 2017 show that the regeneration of convective cloud was detected in the study area. The precipitating convective clouds initiate in the north Bandung while regenerate and propagate southward. These cases suggest that the highest percentages of daily rainfall in basin topography area can be generated by multiple convective clouds.
The influence of aerosol on the sunlight divergence in the atmospheric Indonesia
Authors: Rosida
Published: August 2019

Solar radiation is the source of energy for the earth. The amount of solar radiation that reaching the earth’s surface, is strongly influenced by the interaction of solar radiation with the atmospheric that is passed through. This paper analyzes the effect of aerosols on solar radiation balance in the Indonesian atmosphere using radiation data from the Clouds and the Earth’s Radiant Energy System (CERES) and aerosol optical depth that is obtained from the Moderate Resolution Imaging Spectroradiometer (MODIS) - Terra, from March 2000 to February 2016. Aerosol optical depth data (AOD) and shortwave (SW) radiation that reach the top of atmosphere and the earth’s surface were analyzed spatially and temporally with the observation area of the 150S – 150N and 900W – 1500E. Moreover, the sample of several locations was analyzed such as Palangkaraya, Pontianak, Banjarmasin and Samarinda, to look at the cases of forest fires which generate aerosols that quite high. Results of data analysis showed a significant influence of aerosols on the divergence of short-wave solar radiation in the atmosphere of Indonesia. The divergence of short-wave radiation shows how much solar radiation is absorbed in the atmosphere. Some cities such as Palangkaraya and Pontianak showed a strong correlation (0.7 - 0.95) between AOD and the value of shortwave radiation divergence. Temporal pattern from time series analysis showed that the increase in the value of AOD due to the fires incident, give the biggest influence on the decrease in solar radiation that reaches the earth’s surface.
Simulation of Sea Breeze Events in Gulf of Jakarta under Different Synoptic Condition: An Application of WRF Model
Authors: Rosita Dewi D M Pera , Fatmasari D , Gustari I
Published: August 2019

The behaviour of the sea breeze developing along the Gulf of Jakarta during days with different synoptic condition is examined using observational data and simulations from the Weather Research and Forecasting (WRF). An objective and systematic selection method is used to detect sea breeze days from observational data. The simulation used three nested grids at 27, 9 and 3 km resolution covering Gulf of Jakarta and its joining region for sea breeze event at November 22th, 2016 which formed under offshore large-scale ambient wind, January 20th, 2017 which formed under westerly large-scale ambient wind, and August 10th, 2017 which formed under easterly large-scale ambient wind. Results show that the development of sea breeze circulation under offshore ambient wind produced lower 10-m wind speed simulation, while sea breeze conditions under westerly large-scale ambient wind are associated with highest surface wind speeds reaching 9.5 ms-1 in Gulf of Jakarta. Sea breeze simulation also indicates the formation of calm zone which is 22 - 56 km away from the Jakarta Gulf coastline. Model also shows the formation of thermal internal boundary layer that are about 300-700 m near the coast gradually merged with the mixing layer inland. Performance of WRF on the simulated circulation is studied by conducting value of correlation, RMSE, and MBE. Overall, model simulation agrees fairly well with the observations taken at a near-surface meteorological station.
PWM control method to eliminate Common Mode Voltage in three level T-Type inverters
Authors: Tran Vinh-Thanh , Hai-Quach Thanh , Do Duc-Tri , Choi Youn-Ok , Jung Pan-Gum , Cho Geum-Bae
Published: August 2019

In this paper, Common-mode voltage (CMV) is responsible for overvoltage stress to the winding insulation and bearing damage of an AC motor. High dv/dt of CMV causes leakage currents, which create noise problems to the equipment installed near the converter. This paper presented modulation strategy to eliminate CMV three level T-Type inverter (Zero CMV 3L T2I) that substantially eliminates CMV. The principles of selecting suitable triangle carrier signals for the T-Type is described. This PWM control method can mitigate the peak value to 95% as compared to the conventional sinusoidal pulse width modulation method. A prototype is constructed to verify the operating principle of the three-level T-Type inverter. Simulation and experimental results are presented.
Exact solutions for restricted incompressible Navier–Stokes equations with Dirichlet boundary conditions
Authors: García-Casado Manuel
Published: August 2019

This paper exposes how to obtain a relation that have to be hold for all free-divergence velocity fields that evolve according to Navier–Stokes equations. However, checking the violation of this relation requires a huge computational effort. To circumvent this problem it is proposed an additional ansatz to free-divergence Navier–Stokes fields. This makes available six degrees of freedom which can be tuned. When they are tuned adequately, it is possible to find finite L
2 norms of the velocity field for volumes of

R

3

and for

t
∈
[

t

0

,
∞
)

. In particular, the kinetic energy of the system is bounded when the field components u

i
are class C
3 functions on

R

3

×
[

t

0

,
∞
)

that hold Dirichlet boundary conditions. This additional relation lets us conclude that Navier–Stokes equations with no-slip boundary conditions have not unique solution. Moreover, under a given external force the kinetic energy can be computed exactly as a funtion of time.
RAG-Web: RNA structure prediction/design using RNA-As-Graphs
Authors: Meng Grace , Tariq Marva , Jain Swati , Elmetwaly Shereef , Schlick Tamar
Published: August 2019

We launch a webserver for RNA structure prediction and design corresponding to tools developed using our RNA-As-Graphs (RAG) approach. RAG uses coarse-grained tree graphs to represent RNA secondary structure, allowing the application of graph theory to analyze and advance RNA structure discovery. Our webserver consists of three modules: (a) RAG Sampler: samples tree graph topologies from an RNA secondary structure to predict corresponding tertiary topologies, (b) RAG Builder: builds three-dimensional atomic models from candidate graphs generated by RAG Sampler, and (c) RAG Designer: designs sequences that fold onto novel RNA motifs (described by tree graph topologies). Results analyses are performed for further assessment/selection. The Results page provides links to download results and indicates possible errors encountered. RAG-Web offers a user-friendly interface to utilize our RAG software suite to predict and design RNA structures and sequences.

Availability and implementation

The webserver is freely available online at: http://www.biomath.nyu.edu/ragtop/.

Supplementary information

Supplementary data are available at Bioinformatics online.
A Second Case of Human Conjunctival Infestation With Thelazia gulosa and a Review of T. gulosa in North America
Authors: Bradbury Richard S , Gustafson Dianne Travers , Sapp Sarah G H , Fox Mark , de Almeida Marcos , Boyce Michelle , Iwen Peter , Herrera Vicki , Ndubuisi Mackevin , Bishop Henry S
Published: August 2019

We describe a second case of human infection caused by Thelazia gulosa (the cattle eye worm), likely acquired in California. For epidemiologic purposes, it is important to identify all Thelazia recovered from humans in North America to the species level.
Assessing major bleeding risk in atrial fibrillation patients concurrently taking non-vitamin K antagonist oral anticoagulants and antiepileptic drugs
Authors: Wang Chun-Li , Wu Victor Chien-Chia , Chang Kuo-Hsuan , Tu Hui-Tzu , Kuo Chang-Fu , Huang Yu-Tung , Chu Pao-Hsien , Kuo Chi-Ching , Chang Shang-Hung
Published: August 2019

Aims

This study compared the risk of major bleeding between atrial fibrillation (AF) patients who took non-vitamin K antagonist oral anticoagulants (NOACs) and antiepileptic drugs (AEDs) concurrently and those who took only NOACs.

Methods and results

We performed a retrospective cohort study using Taiwan National Health Insurance database and included AF patients who received NOAC prescriptions from 1 June 2012 to 31 December 2017. The major bleeding risks of person-quarters exposed to NOAC and 11 concurrent AEDs (carbamazepine, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, pregabalin, topiramate, valproic acid, and zonisamide) were compared with person-quarters exposed to NOAC alone. Adjusted incidence rate differences between NOAC with or without concurrent AEDs were estimated using Poisson regression models weighted by the inverse probability of treatment. Among 104 319 patients (age 75.0 ± 10.3 years; men, 56.2%), 8546 major bleeding events occurred during 731 723 person-quarters with NOAC prescriptions. Concurrent AED use was found in 15.3% of NOAC-treated patients. Concurrent use of NOAC with valproic acid, phenytoin, or levetiracetam increased adjusted incidence rates per 1000 person-years of major bleeding more significantly than NOAC alone: 153.49 for NOAC plus valproic acid vs. 55.06 for NOAC alone [difference 98.43, 95% confidence interval (CI) 82.37–114.49]; 135.83 for NOAC plus phenytoin vs. 54.43 for NOAC alone (difference 81.4, 95% CI 60.14–102.66); and 132.96 for NOAC plus levetiracetam vs. 53.08 for NOAC alone (difference 79.88, 95% CI 64.47–95.30).

Conclusion

For AF patients, the concurrent use of NOACs and valproic acid, phenytoin, or levetiracetam was associated with a higher risk of major bleeding.
Age Differences in Intertemporal Choice: The Role of Task Type, Outcome Characteristics, and Covariates
Authors: Löckenhoff Corinna E , Samanez-Larkin Gregory R
Published: August 2019

Objectives

Prior research has revealed age differences in the preferred timing of monetary outcomes, but results are inconsistent across studies. The present study examined the role of task type, outcome characteristics, and a range of theoretically implicated covariates that may contribute to variations in age effects.

Method

Two types of intertemporal choice paradigms (temporal discounting and sequence construction) were administered to a diverse life-span sample (n = 287, aged 18–87). The design experimentally manipulated outcome delay (months vs years), amount (hundreds vs thousands), and valence (gain vs loss) while statistically controlling for a range of potential covariates including demographics, affect, personality, time perspective, subjective health, and numeracy.

Results

In the temporal discounting task, no significant age differences were observed and this pattern did not differ by outcome delay, amount, or valence. In the sequence-construction task, age was associated with a preference for sequences of decreasing impact in the gain condition but not in the loss condition, whereas outcome delay and amount did not moderate age effects. Age patterns in discounting and sequences preferences remained unchanged after controlling for covariates.

Discussion

These findings converge with prior studies reporting weak or null effects of age in temporal discounting tasks and suggest that inconsistent results are not due to variations in outcome valence, delay, or amount across studies. Findings also add to the scarce evidence for age differences sequence-preferences. After discussing methodological limitations, we consider implications for future research and practice.
The Effectiveness of Psychoeducational and Financial Intervention to Support Caregivers of Individuals With Alzheimer’s Disease in Poland
Authors: Leszko Magdalena
Published: August 2019

Background and Objectives

The goal of this study is to create data-driven guidelines and tools for caregivers and health care professionals that will enable caregivers to be prepared for future caregiving-related challenges and decrease their levels of stress.

Research Design and Methods

A total of 60 spousal caregivers of individuals with Alzheimer’s disease (AD) living in Poland were recruited for this study. The participants were assigned to two different groups. The intervention group was provided with a five-session training focused on teaching coping strategies for managing difficult behaviors and provided with a stipend for a period of 6 months (a financial aid program recently launched by the local agency). A control group was not provided with any of the interventions but asked to complete the questionnaires. The effectiveness of each intervention was assessed at a baseline and 6 months after baseline evaluation.

Results

Caregivers who received financial and educational training reported significantly decreased levels of depression and caregiver burden in comparison to the control group. The majority of caregivers emphasized that caregiving created financial problems and that their work has been underestimated by the government.

Discussion and Implications

This project addresses several issues of central importance to the success of building research foundation for the interventions. The results have the potential of generating more efficient and personalized interventions that address the needs of the caregiver as they occur, leading to increased knowledge of AD and decreased levels of depression and caregiver burden.
Should Surgical Inflammatory Bowel Disease Patients Be Given Extended Venous Thromboembolic Prophylaxis Postoperatively?
Authors: Lightner Amy L
Published: August 2019

Venous thromboembolism is increased in inflammatory bowel disease surgical patients. Optimal management and prevention of portomeseteric venous thromboembolism is largely unknown, as are risk factors for development in the postoperative period.
On symmetric primitive potentials
Authors: Nabelek Patrik , Zakharov Dmitry , Zakharov Vladimir
Published: August 2019

The concept of a primitive potential for the Schrödinger operator on the line was introduced in Dyachenko et al. (2016, Phys. D, 333, 148–156), Zakharov, Dyachenko et al. (2016, Lett. Math. Phys., 106, 731–740) and Zakharov, Zakharov et al. (2016, Phys. Lett. A, 380, 3881–3885). Such a potential is determined by a pair of positive functions on a finite interval, called the dressing functions, which are not uniquely determined by the potential. The potential is constructed by solving a contour problem on the complex plane. In this article, we consider a reduction where the dressing functions are equal. We show that in this case, the resulting potential is symmetric, and describe how to analytically compute the potential as a power series. In addition, we establish that if the dressing functions are both equal to one, then the resulting primitive potential is the elliptic one-gap potential.
A case of successful conservative management of gallstone ileus
Authors: Monib Sherif , Elkorety Mohamed , Thomson Simon
Published: August 2019

Gallstone ileus is an uncommon complication of cholelithiasis but an established cause of mechanical bowel obstruction in the elderly. Perforation of the small intestine proximal to the obstructing gallstone is rare, only a handful of cases having been reported. Management is mainly surgical, but conservative treatment is occasionally appropriate. We report the case of an 86-year-old female who presented with a clinical picture of bowel obstruction, proven to be related to gallstone ileus which resolved spontaneously. We discuss the role of conservative management for this condition.
Urban tree pests and natural enemies respond to habitat at different spatial scales
Authors: Parsons Sarah E , Frank Steven D
Published: August 2019

Trees provide many ecosystem services in our urban environments. However, city trees are often stressed by pests that are typically higher than those in nearby natural areas. Our research highlights a potential mismatch in scale between the habitat elements that affect the densities of pests and their natural enemies on city trees. We tested a well-known ecological concept, the enemies hypothesis, in the city, where relationships of pests and their enemies have not been thoroughly studied. To test our hypothesis that natural enemies and aphid predation services on urban trees increase with more local structural complexity around trees, we collected data on crape myrtle trees on NC State University’s campus from 2016 to 2017. We measured local structural complexity of vegetation around study trees, quantified impervious cover among other urban habitat elements, collected crape myrtle aphids (Tinocallis kahawaluokalani) and their natural enemies on trees, and performed predation experiments. We found that aphid abundance was positively correlated with more impervious cover within 100 m of crape myrtle trees. Alternatively, greater local structural complexity within the 10 × 10 m area around crape myrtles correlated with a higher abundance of natural enemies. Aphid predation was mostly predicted by local structural complexity and impervious cover within 20 m of crape myrtle trees. Together, these findings suggest that although the impervious nature of our cities may mean higher densities of some pests, local landscapes around trees can play an important role in maintaining natural enemies and predation services that help regulate pest populations.
Changes on the viral capsid surface during the evolution of porcine circovirus type 2 (PCV2) from 2009 till 2018 may lead to a better receptor binding
Authors: Wei Ruifang , Xie Jiexiong , Theuns Sebastiaan , Nauwynck Hans J
Published: August 2019

Porcine circovirus type 2 (PCV2) is the primary causative agent of porcine circovirus-associated diseases (PCVAD). Three major PCV2 genotypes (PCV2a, PCV2b, and PCV2d) have been identified globally. Despite their worldwide distribution, the prevalence and genetic evolution of PCV2 in Belgium has not previously been determined. In this study, 319 samples from animals suffering from diseases likely to be associated with PCV2 were collected from 2009 to 2018 and analysed by virus titration. The overall prevalence of PCV2 in PCVAD-suspected cases was 15.7 per cent (50/319). The phylogenetic analysis demonstrated that at least three genotypes (PCV2a, PCV2b, and PCV2d) circulated in Belgium from 2009 till 2018, and that PCV2 evolved from PCV2a to PCV2b and from PCV2d-1 to PCV2d-2. Sequence comparison among the forty-three PCV2 isolates showed that they had 89.7–100 per cent nucleotide-sequence and 88.5–100 per cent amino-acid-sequence identities. Three amino acid sites were under positive selection. Three-dimensional analysis of genotype-specific amino acids revealed that most of the mutations were on the outside of the cap protein with a few conserved mutations present on the inner side. Mutations toward more basic amino acids were found on the upper and tail parts of two connecting capsid proteins which form one big contact region, most probably involved in receptor binding. The lower part was relatively conserved. This polarity change together with the formation of an extruding part drive the virus to a more efficient GAG receptor binding. Taken together, these results showed a genotype shift from PCV2a to PCV2b and later on from PCV2d-1 to PCV2d-2, and a PCV2 evolution toward a better receptor binding capacity.
Heterochronic regulation of lung development via the Lin28‐Let‐7 pathway
Authors: Gulman Nelly Komarovsky , Armon Leah , Shalit Tali , Urbach Achia
Published: August 2019

The heterochronic gene Lin28 regulates diverse developmental processes. It was shown previously that global Lin28A overexpression during mouse embryogenesis results in perinatal lethality. However, the reason for this early lethality has not been elucidated. Here, we showed that Lin28A overexpression prevents normal lung development via the inhibition of the Let‐7 micro RNAs, thus causing the perinatal lethality. We further found that Lin28A overexpression in lung mesenchymal cells, but not epithelial cells, is sufficient to recapitulate the lung phenotype. Moreover, we defined the specific time window wherein Lin28A expression exerts its effect. Deep characterization of the transgenic lungs suggests that the Lin28A‐Let‐7 pathway delays the transition from one developmental stage to another but does not completely abrogate the differentiation capacity of the lung progenitor cells. Finally, we suggested that the effect of Lin28A‐Let‐7 on embryonic lung development is mediated at least in part through the TGF‐p1‐signaling pathway. Altogether, these findings define for the first time the Lin28‐Let‐7 pathway as a critical heterochronic regulator of lung development.—Komarovsky Gulman, N., Armon, L., Shalit, T., Urbach, A. Heterochronic regulation of lung development via the Lin28‐Let‐7 pathway. FASEB J. 33, 12008‐12018 (2019). www.fasebj.org
Attenuation of amyloid‐β generation by atypical protein kinase C‐mediated phosphorylation of engulfment adaptor PTB domain containing 1 threonine 35
Authors: Chau Dennis Dik‐Long , Yung Kristen Wing‐Yu , Chan William Wai‐Lun , An Ying , Hao Yan , Chan Ho‐Yin Edwin , Ngo Jacky Chi‐Ki , Lau Kwok‐Fai
Published: August 2019

Amyloid‐β (Aβ) is derived from the proteolytic processing of amyloid precursor protein (APP), and the deposition of extracellular Aβ to form amyloid plaques is a pathologic hallmark of Alzheimer's disease (AD). Although reducing Aβ generation and accumulation has been proposed as a means of treating the disease, adverse side effects and unsatisfactory efficacy have been reported in several clinical trials that sought to lower Aβ levels. Engulfment adaptor phosphotyrosine‐binding (PTB) domain containing 1 (GULP1) is a molecular adaptor that has been shown to interact with APP to alter Aβ production. Therefore, the modulation of the GULP1‐APP interaction may be an alternative approach to reducing Aβ. However, the mechanisms that regulate GULP1‐APP binding remain elusive. As GULP1 is a phosphoprotein, and because phosphorylation is a common mechanism that regulates protein interaction, we anticipated that GULP1 phosphorylation would influence GULP1‐APP interaction and thereby Aβ production. We show here that the phosphorylation of GULP1 threonine 35 (T35) reduces GULP1‐APP interaction and suppresses the stimulatory effect of GULP1 on APP processing. The residue is phosphorylated by an isoform of atypical PKC (PKCζ). Overexpression of PKCζ reduces both GULP1‐APP interaction and GULP1‐mediated Aβ generation. Moreover, the activation of PKCζ via insulin suppresses APP processing. In contrast, GULP1‐mediated APP processing is enhanced in PKCζ knockout cells. Similarly, PKC ɩ,*** another member of atypical PKC, also decreases GULP1‐mediated APP processing. Intriguingly, our X‐ray crystal structure of GULP1 PTB‐APP intracellular domain (AICD) peptide reveals that GULP1T35 is not located at the GULP1‐AICD binding interface; rather, it immediately precedes the β1‐α2loop that forms a portion of the binding groove for the APP helix αC. Phosphorylating the residue may induce an allosteric effect on the conformation of the binding groove. Our results indicate that GULP1 T35 phosphorylation is a mechanism for the regulation of GULP1‐APP interaction and thereby APP processing. Moreover, the activation of atypical PKC, such as by insulin, may confer a beneficial effect on AD by lowering GULP1‐mediated Ap production.—Chau, D. D.‐L., Yung K. W.‐Y., Chan, W. W.‐L., An, Y., Hao, Y., Chan, H.‐Y. E., Ngo, J. C.‐K., Lau, K.‐F. Attenuation of amyloid‐β generation by atypical protein kinase C‐mediated phosphorylation of engulfment adaptor PTB domain containing 1 threonine 35. FASEB J. 33, 12019‐12035 (2019). www.fasebj.org
Seeded propagation of α‐synuclein aggregation in mouse brain using protein misfolding cyclic amplification
Authors: Nicot Simon , Verchère Jérémy , Bélondrade Maxime , Mayran Charly , Bétemps Dominique , Bougard Daisy , Baron Thierry
Published: August 2019

α‐Synuclein (α‐syn) protein aggregation is associated with several neurodegenerative disorders collectively referred to as synucleinopathies, including Parkinson's disease. We used protein misfolding cyclic amplification (PMCA) to study α‐syn aggregation in brain homogenates of wild‐type or transgenic mice expressing normal (D line) or A53T mutant (M83 line) human α‐syn. We found that sonication‐incubation cycles of M83 mouse brain gradually produce large quantities of SDS‐resistant α‐syn aggregates, involving both human and mouse proteins. These PMCA products, containing partially proteinase K‐resistant α‐syn species, are competent to accelerate the onset of neurologic symptoms after intracerebral inoculation to young M83 mice and to seed aggregate formation of α‐syn following PMCA, including in D and wild‐type mouse brain substrates. PMCA seeding activity in the M83 diseased brain correlates positively with regions mostly targeted by the α‐syn pathology in this model. Our data indicate that similar to prions, PMCA can reproduce some characteristics of α‐syn aggregation and seeded propagation in vitro in a complex milieu. This opens new opportunities for the molecular study of synucleinopathies.—Nicot, S., Verchère, J., Bélondrade, M., Mayran, C., Bétemps, D., Bougard, D., Baron, T. Seeded propagation of α‐synuclein aggregation in mouse brain using protein misfolding cyclic amplification. FASEB J. 33, 12073‐12086 (2019). www.fasebj.org
Noninvasive longitudinal quantification of β‐cell mass with [111In]‐labeled exendin‐4
Authors: Fujita Naotaka , Fujimoto Hiroyuki , Hamamatsu Keita , Murakami Takaaki , Kimura Hiroyuki , Toyoda Kentaro , Saji Hideo , Inagaki Nobuya
Published: August 2019

Currently, quantifying β‐cell mass (BCM) requires harvesting the pancreas. In this study, we investigated a potential noninvasive method to quantify BCM changes longitudinally using [Lys12(111In‐BnDTPA‐Ahx)] exendin‐4 ([111In]‐Ex4) and single‐photon emission computed tomography (SPECT). We used autoradiography and transgenic mice expressing green fluorescent protein under the control of mouse insulin 1 gene promotor to evaluate the specificity of [111In]‐Ex4 toward β cells. Using nonobese diabetic (NOD) mice, we injected [111In]‐Ex4 (3.0 MBq) intravenously and performed SPECT 30 min later, repeating this at a 2‐wk interval. After the second scan, we harvested the pancreas and calculated BCM from immunohistochemically stained pancreatic sections. Specific accumulation of [111In]‐Ex4 in β cells was confirmed by autoradiography, with a significant correlation (r = 0.94) between the fluorescent and radioactive signal intensities. The radioactive signal from the pancreas in the second SPECT scan significantly correlated (r = 0.89) with BCM calculated from the immunostained pancreatic sections. We developed a regression formula to estimate BCM from the radioactive signals from the pancreas in SPECT scans. BCM can be quantified longitudinally and noninvasively by SPECT imaging with [111In]‐Ex4. This technique successfully demonstrated longitudinal changes in BCM in NOD mice before and after onset of hyperglycemia.—Fujita, N., Fujimoto, H., Hamamatsu, K., Murakami, T., Kimura, H., Toyoda, K., Saji, H., Inagaki, N. Noninvasive longitudinal quantification of β‐cell mass with [111In]‐labeled exendin‐4. FASEB J. 33, 11836‐11844 (2019). www.fasebj.org
IL‐1Ra protects hematopoietic cells from chemotoxicity through p53‐induced quiescence
Authors: Ye Hao , Qian Lan , Zhu Shunying , Deng Shaorong , Wang Xia , Zhu Jiang , Chan Gerald L. , Yu Yan , Han Wei
Published: August 2019

The protection of constantly proliferating gut epithelia and hematopoietic tissues from cytotoxicity could improve conventional chemotherapy efficacy and widen its therapeutic window. Previously, we reported that, in mouse models, pretreatment of recombinant human IL‐1 receptor antagonist (rhIL‐1Ra) protected both types of vulnerable tissues from chemotherapeutics. Here, we showed that rhIL‐1Ra treatment up‐regulated the protein levels of phosphorylated p38, p53, and p21 and induced transient hematopoietic stem/progenitor cell (HS/PC) quiescence. Knockout of IL‐1 receptor I (IL‐1RI), p53, or p21 alleles and pharmacological inactivation of p38 mapped the rhIL‐1Ra pathway in the induction of HS/PC quiescence. Therefore, rhIL‐1Ra administration before but not after chemotherapy alleviated 5‐fluorouracil‐induced neutropenia. In addition, in vivo and in vitro cell proliferation assays revealed that the rhIL‐1Ra treatment did not affect cancer cell proliferation or chemosensitivity. Lastly, we propose an IL‐1/IL‐1Ra pathway (IL‐1RI → p38 → p53 → p21), which regulates HS/PC quiescence. The rhIL‐1Ra may provide a new route for p53‐based cyclotherapy, which spares normal cells but kills cancer cells during chemotherapy.—Ye, H., Qian, L., Zhu, S., Deng, S., Wang, X., Zhu, J., Chan, G. L., Yu, Y., Han, W. IL‐1Ra protects hematopoietic cells from chemotoxicity through p53‐induced quiescence. FASEB J. 33, 12135‐12145 (2019). www.fasebj.org
TREM2 deficiency aggravates α‐synuclein–induced neurodegeneration and neuroinflammation in Parkinson's disease models
Authors: Guo Ying , Wei Xinbing , Yan Hua , Qin Yue , Yan Shaoqi , Liu Jia , Zhao Yong , Jiang Fan , Lou Haiyan
Published: August 2019

Variants in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2) are known to increase the risk of developing Alzheimer disease and Parkinson's disease (PD). However, the potential role of TREM2 effect on synucleinopathy has not been characterized. In this study, we investigated whether loss of TREM2 function affects α‐synucleinopathy both in vitro and in vivo. In vitro, BV2 microglial cells were exposed to α‐synuclein (α‐syn) in the presence or absence of TREM2 small interference RNA. For in vivo studies, wild‐type controls and TREM2 gene knockout mice were intracranially injected in the substantia nigra with adeno‐associated viral vectors expressing human α‐syn (AAV‐SYN) to induce PD. Our results revealed that knockdown of TREM2 aggravated α‐syn‐induced inflammatory responses in BV2 cells and caused greater apoptosis in SH‐SY5Y cells treated with BV2‐conditioned medium. In mice, TREM2 knockout exacerbated dopaminergic neuron loss in response to AAV‐SYN. Moreover, both in vitro and in vivo TREM2 deficiency induced a shift from an anti‐inflammatory toward a proinflammatory activation status of microglia. These data suggest that impairing microglial TREM2 signaling aggravates proinflammatory responses to α‐syn and exacerbates α‐syn‐induced neurodegeneration by modulating microglial activation state.—Guo, Y., Wei, X., Yan, H., Qin, Y., Yan, S., Liu, J., Zhao, Y., Jiang, F., Lou, H. TREM2 deficiency aggravates α‐synuclein‐induced neurodegeneration and neuroinflammation in Parkinson's disease models. FASEB J. 33, 12164–12174 (2019). www.fasebj.org
Enzymatic and nonenzymatic protein acetylations control glycolysis process in liver diseases
Authors: Li Juan , Wang Tongxin , Xia Jun , Yao Weilei , Huang Feiruo
Published: August 2019

Impaired glycolysis has pathologic effects on the occurrence and progression of liver diseases, and it appears that glycolysis is increased to different degrees in different liver diseases. As an important post‐translational modification, reversible lysine acetylation regulates almost all cellular processes, including glycolysis. Lysine acetylation can occur enzymatically with acetyltransferases or nonenzymatically with acetyl‐coenzyme A. Accompanied by the progression of liver diseases, there seems to be a temporal and spatial variation between enzymatic and nonenzymatic acetylations in the regulation of glycolysis. Here, we summarize the most recent findings on the functions and targets of acetylation in controlling glycolysis in the different stages of liver diseases. In addition, we discuss the differences and causes between enzymatic and nonenzymatic acetylations in regulating glycolysis throughout the progression of liver diseases. Then, we review these new discoveries to provide the potential implications of these findings for therapeutic interventions in liver diseases.—Li, J., Wang T., Xia, J., Yao, W., Huang, F. Enzymatic and nonenzymatic protein acetylations control glycolysis process in liver diseases. FASEB J. 33, 11640–11654 (2019). www.fasebj.org
Blockade of lncRNA‐ASLNCS5088–enriched exosome generation in M2 macrophages by GW4869 dampens the effect of M2 macrophages on orchestrating fibroblast activation
Authors: Chen Jialin , Zhou Renpeng , Liang Yimin , Fu Xiujun , Wang Danru , Wang Chen
Published: August 2019

In hypertrophic scar (HS) formation, the type 2 immune response induces the alternatively activated macrophages (M2), which manipulate fibroblasts to differentiate into myofibroblasts with active biologic functions and proliferation. Myofibroblasts express α‐smooth muscle actin (α‐SMA) and synthesize and produce additional collagen type I and collagen type III, inducing HS formation. However, studies on the mechanism of M2 macrophage modulation are only based on the recognition of profibrotic factors such as TGF‐β1 secreted by macrophages. The influence of exosomes from M2 macrophages on scar formation is still unknown. Both M2 macrophages and myofibroblasts highly express glutaminases (GLSs). GLS is a critical enzyme in glutaminolysis and is important for M2 macrophage and fibroblast polarization. In this study, we found that in a TGF‐β1‐stimulated coculture system, a long noncoding RNA (lncRNA) named lncRNA‐ASLNCS5088 was enriched in M2 macrophage‐derived exosomes. This lncRNA could be transferred with high efficiency to fibroblasts and acted as an endogenous sponge to adsorb microRNA‐200c‐3p, resulting in increased GLS and α‐SMA expression. Pretreatment with GW4869, which impairs M2 macrophage exosome synthesis, ameliorated these pathologic changes in fibroblasts in vitro. Local injection in the late scar formation period with GW4869 reduced α‐SMA+ fibroblasts and alleviated the fibrosis of tissue after wound healing in vivo.—Chen, J., Zhou, R., Liang, Y., Fu, X., Wang, D., Wang, C. Blockade of lncRNA‐ASLNCS5088–enriched exosome generation in M2 macrophages by GW4869 dampens the effect of M2 macrophages on orchestrating fibroblast activation. FASEB J. 33, 12200–12212 (2019). www.fasebj.org
Survival Bias in Mendelian Randomization Studies
Authors: Smit Roelof A. J. , Trompet Stella , Dekkers Olaf M. , Jukema J. Wouter , le Cessie Saskia
Published: August 2019

It has been argued that survival bias may distort results in Mendelian randomization studies in older populations. Through simulations of a simple causal structure we investigate the degree to which instrumental variable (IV)-estimators may become biased in the context of exposures that affect survival. We observed that selecting on survival decreased instrument strength and, for exposures with directionally concordant effects on survival (and outcome), introduced downward bias of the IV-estimator when the exposures reduced the probability of survival till study inclusion. Higher ages at study inclusion generally increased this bias, particularly when the true causal effect was not equal to null. Moreover, the bias in the estimated exposure-outcome relation depended on whether the estimation was conducted in the one- or two-sample setting. Finally, we briefly discuss which statistical approaches might help to alleviate this and other types of selection bias. See video abstract at, http://links.lww.com/EDE/B589.
The synonymous 903C>G mutation in the alpha 1,4-galactosyltransferase gene in a Chinese woman with habitual abortion
Authors: Lv Xiaoying , Chen Yongquan , Luo Yuanyuan , Li Lingbo , Wang Houzhao
Published: August 2019

Rationale:

Habitual abortion is caused by complex and diverse factors, such as genetic factors, immune factors, endocrine factors, viruses, bacterial infections, and so on. Allogeneic antibodies, generated due to blood-group incompatibilities between a female and her fetus, are sometimes important for habitual abortion.

Patient concerns:

A 26-year-old woman had undergone abortions 3 times in July 2015 (17 weeks pregnant), March 2017 (15 weeks of gestation) and February 2018 (16 weeks pregnant) before she came to the Reproductive Medicine Center of our hospital for prenatal examinations without pregnancy.

Diagnoses:

Unexplained habitual abortion.

Interventions:

A series of serological tests and nucleotide sequence of 1,4-galactosyltransferase (A4GALT) gene were performed.

Outcomes:

The patient was the rare p phenotype in P1Pk blood system and the patient's habitual abortion was caused by anti-PP1Pk antibody which was generated naturally in persons with p phenotype. There was a mutation (903C>G, CCC>CCG) in the 3rd exon of A4GALT gene, which is likely a significant contributor to p phenotype.

Lessons:

This is the first case of habitual abortion caused by p phenotype due to independent 903C>G homozygous mutation with no similar record reported before, which indicates that it is a new class of mutation that leads to p phenotype.
Laparoscopic spleen-preserving pancreatic resection for intrapancreatic accessory spleen
Authors: Li Le , Liu Xiaohua , Chen Jinming , Liu Zhonghua , Li Qiang , Shi Ying
Published: August 2019

Introduction:

Intrapancreatic accessory spleen (IPAS) has been rarely noted radiologically because the spatial resolution of conventional images was low. The infrequent presence of the accessory spleen in the pancreatic tissue could lead to inappropriate diagnosis, thereby necessitating a therapeutic approach. The present study reported such cases and summarized the available imaging findings to reduce unnecessary invasive surgeries.

Patient concerns:

The patient's complaint was “a pancreatic mass was found for half a month.”

Diagnosis:

IPAS was eventually diagnosed by pathology.

Interventions:

Laparoscopic spleen-preserving pancreatic resection.

Outcomes:

Postoperative course was uneventful and the patient was discharged from our hospital after 10 days.

Conclusions:

When an asymptomatic pancreatic mass is detected, the diagnosis of IPAS should not be excluded, especially if the lesion has the same imaging features as the spleen. As a definite diagnosis of IPAS is difficult by a single examination, multiple techniques might be essential.
Correlation between cervical lordosis and cervical disc herniation in young patients with neck pain
Authors: Gao Kun , Zhang Jiliang , Lai Jinquan , Liu Weidong , Lyu Hanqing , Wu Yihong , Lin Zhanpeng , Cao Yafei
Published: August 2019

Abnormal cervical curvature and cervical disc herniation are closely related to neck pain and should be taken into account before any treatment. However, studies have rarely reported on the correlation between cervical lordosis and cervical disc herniation in patients with neck pain. Therefore, in this study, we collect young neck pain patients with abnormal cervical curvature to evaluate the relationship between cervical lordosis and cervical disc herniation.

Three hundred patients below 40 years old with neck pain were enrolled. Patient sex, age, apical vertebra, segment of intervertebral disc protrusionl, sagittal diameter of spinal duramater, saggital diameter of spinal canal, height of disc space were recorded, and the cervical curvature, and degree of cervical spinal cord compression (G/F ratio) were calculated. The change of degree of disc herniation and degree of cervical spinal cord compression were analyzed in different cervical curvature groups. Further more, collected these patients who had improved cervical curvature over a period of time, to compare the changes of degree of disc herniation, G/F ratio, and height of disc space.

The median age of patients with kyphosis was lower than those with lordosis and straight cervical spine. The degree of disc herniation was higher in the straight and kyphosis groups compared to the lordosis group. Cervical lordosis was inversely correlated with the degree of disc herniation and positively with G/F ratio. Cervical curvature was significantly affected by sex, age, and the degree of disc herniation. With the improvement of cervical lordotic curvature, the degree of disc herniation decreased and height of disc space increased.

The degree of disc herniation and cervical spinal cord compression are inversely correlated to cervical lordosis in young neck pain patients, and the degree of disc herniation and height of disc space can recover with the recovery of cervical lordotic curvature. These findings may indicating a link between cervical curvature and degenerative changes which have important clinical implications.
Multi-organ embolism caused by oscillating aortic valve vegetation
Authors: Huang Guang , Tang Yu , Xiong Rong , Xu Ainan
Published: August 2019

Introduction:

Valvular vegetation is often due to rheumatic heart disease and infective endocarditis. However, multi-arterial embolism can happen in older patients with no history of infection, fever, and cardiac symptoms. We describe a case of multi-organ embolism caused by oscillating aortal valve vegetation.

Patient concerns:

An 80-year-old woman without a history of infection, fever, and heart symptoms showed sudden loss of consciousness and symptoms of a multi-vessel embolism. Magnetic resonance imaging revealed multiple patchy ischemic foci in both cerebral hemispheres in the same time-phase, and echocardiography showed regurgitation in the aortic valve due to an abnormally hypo-hyperechoic mass measuring about 7.7 × 17.2 mm and oscillating aortic valve vegetation, which was induced by cardiac contraction.

Diagnosis:

Multiple organ cardiac embolisms caused by oscillating aortic valve vegetation.

Interventions:

Anti-platelet, fluid-supplement, and vascular-dilating therapies as well as intravenous diazepam were given to the patient.

Outcome:

The patient died of epileptic attack secondary to the cerebral embolism.

Conclusions:

The patient's whole-body multi-vessel ischemic events in nearly the same time-phase should have encouraged us to consider the possibility of cardiogenic embolism and thus early examination and treatment, although she was old with a relatively poor response due to early infection and physical discomfort. Clinicians should be aware that aortic valve vegetation induces generalized multi-organ embolism in the setting of infective endocarditis in order to ensure prompt recognition and treatment of this fatal complication.