bluuebunny/crossref_metadata_2025 huggingface dataset:
Perinatal fluoxetine treatment and dams’ early life stress history have opposite effects on aggressive behavior while having little impact on sexual behavior of male rat offspring
Authors: Houwing Danielle J. , Esquivel-Franco Diana C. , Ramsteijn Anouschka S. , Schuttel Kirsten , Struik Eline L. , Arling Chantal , de Boer Sietse F. , Olivier Jocelien D. A.
Published: July 2020

Rationale

Many depressed women continue antidepressant treatment during pregnancy. Selective serotonin reuptake inhibitor (SSRI) treatment during pregnancy increases the risk for abnormal social development of the child, including increased aggressive or defiant behavior, with unknown effects on sexual behavior.

Objectives

Our aim was to investigate the effects of perinatal SSRI treatment and maternal depression, both separately and combined, on aggressive and sexual behavior in male rat offspring.

Methods

Heterozygous serotonin transporter (SERT± ) knockout dams exposed to early life stress (ELSD) were used as an animal model of maternal depression. Early life stress consisted of separating litters from their mother for 6 h a day on postnatal day (PND)2–15, resulting in a depressive-like phenotype in adulthood. Depressive-like dams were treated with fluoxetine (FLX, 10 mg/kg) or vehicle throughout pregnancy and lactation (gestational day 1 until PND 21). Male offspring were tested for aggressive and sexual behavior in adulthood. As lifelong reductions in SERT expression are known to alter behavioral outcome, offspring with normal (SERT+/+) and reduced (SERT± ) SERT expression were assessed.

Results

Perinatal FLX treatment reduced offensive behavior and the number of animals attacking and increased the latency to attack, especially in SERT+/+ offspring. Perinatal FLX treatment reduced the mounting frequency in SERT+/+ offspring. ELSD increased offensive behavior, without affecting sexual behavior in SERT± offspring.

Conclusions

Overall, our research demonstrates that perinatal FLX treatment and ELSD have opposite effects on aggressive behavior, with little impact on sexual behavior of male offspring.
Safety of azithromycin in pediatrics: a systematic review and meta-analysis
Authors: Zeng Linan , Xu Peipei , Choonara Imti , Bo Zhenyan , Pan Xiangchen , Li Wenyan , Ni Xiaofeng , Xiong Tao , Chen Can , Huang Leshan , Qazi Shamim Ahmad , Mu Dezhi , Zhang Lingli
Published: July 2020

Purpose

To evaluate the toxicity of azithromycin in neonates, infants, and children.

Methods

A systematic review was performed for relevant studies using Medline (Ovid), PubMed, Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, and International Pharmaceutical Abstracts. We calculated the pooled incidence of adverse drug reactions (ADRs) associated with azithromycin based on prospective studies (RCTs and prospective cohort studies) and analyzed the risk difference (RD) of ADRs between azithromycin and placebo or other antibiotics using meta-analysis of RCTs.

Results

We included 133 studies with 4243 ADRs reported in 197,675 neonates, infants, and children who received azithromycin. The safety of azithromycin as MDA in pediatrics was poorly monitored. The main ADRs were diarrhea and vomiting. In prospective non-MDA studies, the most common toxicity was gastrointestinal ADRs (938/1967; 47.7%). The most serious toxicities were cardiac (prolonged QT or irregular heart beat) and idiopathic hypertrophic pyloric stenosis (IHPS). Compared with placebo, azithromycin did not show increased risk ADRs based on RCTs (risk difference − 0.17 to 0.07). The incidence of QT prolonged was higher in the medium-dosage group (10–30 mg/kg/day) than that of low-dosage group (≤ 10 mg/kg/day) (82.0% vs 1.2%).

Conclusion

The safety of azithromycin as MDA needs further evaluation. The most common ADRs are diarrhea and vomiting. The risk of the most serious uncommon ADRs (cardiac-prolonged QT and IHPS) is unknown.
Multimodal validation of focal enhancement in intracranial aneurysms as a surrogate marker for aneurysm instability
Authors: Larsen Naomi , Flüh Charlotte , Saalfeld Sylvia , Voß Samuel , Hille Georg , Trick David , Wodarg Fritz , Synowitz Michael , Jansen Olav , Berg Philipp
Published: July 2020

Purpose

Circumferential enhancement on MR vessel wall imaging has been proposed as a biomarker of a higher risk of rupture in intracranial aneurysms. Focal enhancement is frequently encountered in unruptured aneurysms, but its implication for risk stratification and patient management remains unclear. This study investigates the association of focal wall enhancement with hemodynamic and morphological risk factors and histologic markers of wall inflammation and degeneration.

Methods

Patients with an unruptured middle cerebral artery aneurysm who underwent 3D rotational angiography and 3T MR vessel wall imaging showing focal wall enhancement were included. Hemodynamic parameters were calculated based on flow simulations and compared between enhanced regions and the entire aneurysm surface. Morphological parameters were semiautomatically extracted and quantitatively associated with wall enhancement. Histological analysis included detection of vasa vasorum, CD34, and myeloperoxidase staining in a subset of patients.

Results

Twenty-two aneurysms were analyzed. Enhanced regions were significantly associated with lower AWSS, lower maxOSI, and increased LSA. In multivariate analysis, higher ellipticity index was an independent predictor of wall enhancement. Histologic signs of inflammation and degeneration and higher PHASES score were significantly associated with focal enhancement.

Conclusion

Focal wall enhancement is colocalized with hemodynamic factors that have been related to a higher rupture risk. It is correlated with morphological factors linked to rupture risk, higher PHASES score, and histologic markers of wall destabilization. The results support the hypothesis that focal enhancement could serve as a surrogate marker for aneurysm instability.
18F‐fluorocholine PET/CT in MEN1 Patients with Primary Hyperparathyroidism
Authors: Gauthé Mathieu , Dierick‐Gallet Anne , Delbot Thierry , Bricaire Léopoldine , Bertherat Jérôme , North Marie‐Odile , Cochand‐Priollet Beatrix , Bouchard Phillipe , Talbot Jean‐Noël , Groussin Lionel , Gaujoux Sébastien
Published: July 2020

Background

Primary hyperparathyroidism (HPT1) is the most frequent endocrinopathy in multiple endocrine neoplasia type 1 (MEN1). Its surgical management is challenging. We aimed to describe and compare the imaging findings of parathyroid ultrasound (US), sestaMIBI scintigraphy (sestaMIBI), and 18F‐fluorocholine (FCH) PET/CT in a series of MEN1 patients with HPT1.

Methods

Retrospective analysis of a cohort of MEN1 patients with HPT1 assessed by parathyroid US, sestaMIBI scintigraphy and SPECT/CT, and FCH‐PET/CT for potential surgery between 2015 and 2019.

Results

Twenty‐two patients with a confirmed diagnosis of MEN1 who presented with HPT1 and were assessed by the 3 imaging modalities were included. After imaging workups, 11 patients were operated on for the first time, 4 underwent a redo surgery, and 7 did not undergo an operation. The overall patient‐based positivity rate of imaging was 91% (20 of 22) for parathyroid US and 96% (21 of 22) for both sestaMIBI and FCH‐PET/CT. The 3 imaging modalities demonstrated negative findings in 1/22 patient who did not undergo surgery. Overall, 3 pathologic glands were not detected by any imaging technique. SestaMIBI and FCH‐PET/CT both resulted in the same 3 false‐positive results in ectopic areas with a significant uptake on two thymic carcinoid tumors and one inflammatory lymph node. FCH‐PET/CT provided more surgically relevant data than sestaMIBI in 4/11 patients with initial surgery and in 1/4 patient who underwent redo surgery.

Conclusions

Compared to sestaMIBI scintigraphy, FCH‐PET/CT provides additional information regarding the number of pathologic parathyroid glands and their localization in MEN1 patients with HPT1.
Trübung der Intraokularlinse nach kombinierter Katarakt- und minimal-invasiver Glaukomchirurgie (MIGS)
Authors: Kern Christoph , Priglinger Siegfried , Mackert Marc J.
Published: July 2020

Drei Wochen nach komplikationsloser kombinierter minimal-invasiver Glaukom- und Kataraktoperation kam es zu einer Sehverschlechterung durch die Eintrübung der Intraokularlinse. Durch die Nichtanwendung der postoperativen antiinflammatorischen Lokaltherapie kam es zu einer homogenen Fibrinbildung auf der Linsenvorderfläche sowie einer beginnenden Vernarbung des Sickerkissens. Wir führten ein Needling mit 5‑Fluorouracil sowie eine Linsenpolitur mit dem Nd:YAG-Laser durch und erreichten so eine suffiziente Druckkontrolle und Sehverbesserung.
Modulation of spinal excitability following neuromuscular electrical stimulation superimposed to voluntary contraction
Authors: Borzuola Riccardo , Labanca Luciana , Macaluso Andrea , Laudani Luca
Published: July 2020

Purpose

Neuromuscular electrical stimulation (NMES) superimposed on voluntary muscle contraction has been recently shown as an innovative training modality within sport and rehabilitation, but its effects on the neuromuscular system are still unclear. The aim of this study was to investigate acute responses in spinal excitability, as measured by the Hoffmann (H) reflex, and in maximal voluntary contraction (MVIC) following NMES superimposed to voluntary isometric contractions (NMES + ISO) compared to passive NMES only and to voluntary isometric contractions only (ISO).

Method

Fifteen young adults were required to maintain an ankle plantar-flexor torque of 20% MVC for 20 repetitions during each experimental condition (NMES + ISO, NMES and ISO). Surface electromyography was used to record peak-to-peak H-reflex and motor waves following percutaneous stimulation of the posterior tibial nerve in the dominant limb. An isokinetic dynamometer was used to assess maximal voluntary contraction output of the ankle plantar flexor muscles.

Results

H-reflex amplitude was increased by 4.5% after the NMES + ISO condition (p < 0.05), while passive NMES and ISO conditions showed a decrease by 7.8% (p < 0.05) and no change in reflex responses, respectively. There was no change in amplitude of maximal motor wave and in MVIC torque during each experimental condition.

Conclusion

The reported facilitation of spinal excitability following NMES + ISO could be due to a combination of greater motor neuronal and corticospinal excitability, thus suggesting that NMES superimposed onto isometric voluntary contractions may provide a more effective neuromuscular stimulus and, hence, training modality compared to NMES alone.
Variplex™ test system fails to reliably detect SARS-CoV-2 directly from respiratory samples without RNA extraction
Authors: Eckel Florian , Küsters Franziska , Drossel Bernhard , Konert Markus , Mattes Hans , Schopf Stefan
Published: July 2020

Diagnosis of COVID is performed by PCR methods, but their capacity is limited by the requirement of high-level facilities and instruments. The loop-mediated isothermal amplification (LAMP) method has been utilized for the detection of isolated virus-specific RNA. Preliminary data suggest the possibility of isothermal amplification directly from respiratory samples without RNA extraction. All patients admitted to our hospital were screened for SARS-CoV-2 by routine. Respiratory samples were tested by variplex system based on LAMP method directly without RNA extraction and by PCR. Primary endpoint was the false-negative rate of variplex test compared with PCR as gold standard. In 109 patients variplex test and PCR assay were performed simultaneously. Median age was 80 years and male/female ratio was 40/60%. The prevalence of PCR-confirmed COVID diagnosis was 43.1%. Variplex test was positive in 13.8%. False-negative rate of variplex test compared with PCR was 83.0%. The potential of LAMP technology using isolated RNA has been demonstrated impressively by others, and excellent sensitivity and specificity of detecting SARS-CoV-2 has been reported. However, without RNA extraction, the variplex test system failed to reliably detect SARS-CoV-2 directly in respiratory samples.
Base level changes based on Basin Filling Modelling: a case study from the Paleocene Lishui Sag, East China Sea Basin
Authors: Li Jing-Zhe , Liu Pi-Yang , Zhang Jin-Liang , Sun Shu-Yu , Sun Zhi-Feng , Du Dong-Xing , Zhang Ming
Published: July 2020

Estimation of base level changes in geological records is an important topic for petroleum geologists. Taking the Paleocene Upper Lingfeng Member of Lishui Sag as an example, this paper conducted a base level reconstruction based on Basin Filling Modelling (BFM). The reconstruction was processed on the ground of a previously interpreted seismic stratigraphic framework with several assumptions and simplification. The BFM is implemented with a nonlinear diffusion equation solver written in R coding that excels in shallow marine stratigraphic simulation. The modeled results fit the original stratigraphy very well. The BFM is a powerful tool for reconstructing the base level, and is an effective way to check the reasonableness of previous interpretations. Although simulation solutions may not be unique, the BFM still provides us a chance to gain some insights into the mechanism and dynamic details of the stratigraphy of sedimentary basins.
Enduring Methods – Editors’ Introduction
Authors: Jansen Jan , Doortmont Michel R. , Hanson John H. , van den Bersselaar Dmitri
Published: July 2020

The 2020 volume of History in Africa is the eleventh produced by the current editorial team. It will also be the last, as we are handing over to a brand-new team, consisting of esteemed colleagues Lorelle Semley, Sandra Barnes, Bayo Holsey, and Egodi Uchendu.
The POlarised GLEAM Survey (POGS) II: Results from an all-sky rotation measure synthesis survey at long wavelengths
Authors: Riseley C. J. , Galvin T. J. , Sobey C. , Vernstrom T. , White S. V. , Zhang X. , Gaensler B. M. , Heald G. , Anderson C. S. , Franzen T. M. O. , Hancock P. J. , Hurley-Walker N. , Lenc E. , Van Eck C. L.
Published: July 2020

The low-frequency linearly polarised radio source population is largely unexplored. However, a renaissance in low-frequency polarimetry has been enabled by pathfinder and precursor instruments for the Square Kilometre Array. In this second paper from the POlarised GaLactic and Extragalactic All-Sky MWA Survey-the POlarised GLEAM Survey, or POGS-we present the results from our all-sky MWA Phase I Faraday Rotation Measure survey. Our survey covers nearly the entire Southern sky in the Declination range$-82^\circ$to$+30^\circ$at a resolution between around three and seven arcminutes (depending on Declination) using data in the frequency range 169−231 MHz. We have performed two targeted searches: the first covering 25 489 square degrees of sky, searching for extragalactic polarised sources; the second covering the entire sky South of Declination$+30^\circ$, searching for known pulsars. We detect a total of 517 sources with 200 MHz linearly polarised flux densities between 9.9 mJy and 1.7 Jy, of which 33 are known radio pulsars. All sources in our catalogues have Faraday rotation measures in the range$-328.07$to$+279.62$rad m−2. The Faraday rotation measures are broadly consistent with results from higher-frequency surveys, but with typically more than an order of magnitude improvement in the precision, highlighting the power of low-frequency polarisation surveys to accurately study Galactic and extragalactic magnetic fields. We discuss the properties of our extragalactic and known-pulsar source population, how the sky distribution relates to Galactic features, and identify a handful of new pulsar candidates among our nominally extragalactic source population.
Conservative discontinuous Galerkin schemes for nonlinear Dougherty–Fokker–Planck collision operators
Authors: Hakim Ammar , Francisquez Manaure , Juno James , Hammett Gregory W.
Published: July 2020

We present a novel discontinuous Galerkin algorithm for the solution of a class of Fokker–Planck collision operators. These operators arise in many fields of physics, and our particular application is for kinetic plasma simulations. In particular, we focus on an operator often known as the ‘Lenard–Bernstein’ or ‘Dougherty’ operator. Several novel algorithmic innovations, based on the concept of weak equality, are reported. These weak equalities are used to define weak operators that compute primitive moments, and are also used to determine a reconstruction procedure that allows an efficient and accurate discretization of the diffusion term. We show that when two integrations by parts are used to construct the discrete weak form, and finite velocity-space extents are accounted for, a scheme that conserves density, momentum and energy exactly is obtained. One novel feature is that the requirements of momentum and energy conservation lead to unique formulas to compute primitive moments. Careful definition of discretized moments also ensure that energy is conserved in the piecewise linear case, even though the kinetic-energy term,

$v^{2}$

is not included in the basis set used in the discretization. A series of benchmark problems is presented and shows that the scheme conserves momentum and energy to machine precision. Empirical evidence also indicates that entropy is a non-decreasing function. The collision terms are combined with the Vlasov equation to study collisional Landau damping and plasma heating via magnetic pumping.
Temperature Control on Silicate Weathering Intensity and Evolution of the Neogene East Asian Summer Monsoon
Authors: Ren Xueping , Nie Junsheng , Saylor Joel E. , Wang Xiaoxue , Liu Fangbin , Horton Brian K.
Published: July 2020

Accurately reconstructing the evolution of the Asian monsoon is predicated on understanding the impact of temperature, precipitation, and tectonic paleogeography on silicate weathering proxies over million year timescales. We find that decreasing trends in chemical weathering proxies in both the northern and southern Tibetan Plateau match those from benthic oxygen isotope and sea surface temperature stacks since the late Miocene. In contrast, a synthesis of magnetic parameter‐based records and marine clastic flux records reveals stronger monsoon precipitation during both the warm middle Miocene and cool late Miocene, supporting model simulations showing that both paleogeography and atmospheric CO2 content are important in controlling the summer monsoon. This trend of increasing monsoon precipitation contrasts with the record of decreasing chemical weathering, suggesting that chemical weathering proxies are mainly regulated by temperature at million year timescales, rather than precipitation. These findings clarify reconstructions of the Cenozoic evolution of the East Asian summer monsoon.
MEIS1 down-regulation by MYC mediates prostate cancer development through elevated HOXB13 expression and AR activity
Authors: Whitlock Nichelle C. , Trostel Shana Y. , Wilkinson Scott , Terrigino Nicholas T. , Hennigan S. Thomas , Lake Ross , Carrabba Nicole V. , Atway Rayann , Walton Elizabeth D. , Gryder Berkley E. , Capaldo Brian J. , Ye Huihui , Sowalsky Adam G.
Published: July 2020

Localized prostate cancer develops very slowly in most men, with the androgen receptor (AR) and MYC transcription factors amongst the most well-characterized drivers of prostate tumorigenesis. Canonically, MYC up-regulation in luminal prostate cancer cells functions to oppose the terminally differentiating effects of AR. However, the effects of MYC up-regulation are pleiotropic and inconsistent with a poorly proliferative phenotype. Here we show that increased MYC expression and activity are associated with the down-regulation of MEIS1, a HOX-family transcription factor. Using RNA-seq to profile a series of human prostate cancer specimens laser capture microdissected on the basis of MYC immunohistochemistry, MYC activity, and MEIS1 expression were inversely correlated. Knockdown of MYC expression in prostate cancer cells increased the expression of MEIS1 and increased the occupancy of MYC at the MEIS1 locus. Finally, we show in laser capture microdissected human prostate cancer samples and the prostate TCGA cohort that MEIS1 expression is inversely proportional to AR activity as well as HOXB13, a known interacting protein of both AR and MEIS1. Collectively, our data demonstrate that elevated MYC in a subset of primary prostate cancers functions in a negative role in regulating MEIS1 expression, and that this down-regulation may contribute to MYC-driven development and progression.
The cardiolipin-binding peptide elamipretide mitigates fragmentation of cristae networks following cardiac ischemia reperfusion in rats
Authors: Allen Mitchell E. , Pennington Edward Ross , Perry Justin B. , Dadoo Sahil , Makrecka-Kuka Marina , Dambrova Maija , Moukdar Fatiha , Patel Hetal D. , Han Xianlin , Kidd Grahame K. , Benson Emily K. , Raisch Tristan B. , Poelzing Steven , Brown David A. , Shaikh Saame Raza
Published: July 2020

Mitochondrial dysfunction contributes to cardiac pathologies. Barriers to new therapies include an incomplete understanding of underlying molecular culprits and a lack of effective mitochondria-targeted medicines. Here, we test the hypothesis that the cardiolipin-binding peptide elamipretide, a clinical-stage compound under investigation for diseases of mitochondrial dysfunction, mitigates impairments in mitochondrial structure-function observed after rat cardiac ischemia-reperfusion. Respirometry with permeabilized ventricular fibers indicates that ischemia-reperfusion induced decrements in the activity of complexes I, II, and IV are alleviated with elamipretide. Serial block face scanning electron microscopy used to create 3D reconstructions of cristae ultrastructure reveals that disease-induced fragmentation of cristae networks are improved with elamipretide. Mass spectrometry shows elamipretide did not protect against the reduction of cardiolipin concentration after ischemia-reperfusion. Finally, elamipretide improves biophysical properties of biomimetic membranes by aggregating cardiolipin. The data suggest mitochondrial structure-function are interdependent and demonstrate elamipretide targets mitochondrial membranes to sustain cristae networks and improve bioenergetic function.
Conformational flexibility of fatty acid-free bovine serum albumin proteins enables superior antifouling coatings
Authors: Ma Gamaliel Junren , Ferhan Abdul Rahim , Jackman Joshua A. , Cho Nam-Joon
Published: July 2020

Bovine serum albumin (BSA) protein is widely used to fabricate antifouling coatings for nanobiotechnology applications. Numerous BSA protein options are commercially available and obtained through different purification methods, however, there is no guidance on which ones are preferable for antifouling coatings. Herein, we investigate the real-time fabrication of antifouling coatings composed of BSA proteins obtained through different purification methods, and report significant differences in ultrathin film coating properties and ability to mitigate serum biofouling and to prevent nanoparticle-induced immune reactions. Mechanistic studies unravel the source of these performance variations, which are related to some BSA proteins containing fatty acid stabilizers while other BSA proteins are fatty acid-free depending on the purification method. Fatty acid-free BSA proteins exhibit greater conformational flexibility and less charge repulsion, which allow them to form more rigidly attached and tightly packed coatings on flat surfaces and nanoparticles that result in superior application performance.
Structural tuning of Zn(ii)-MOFs based on pyrazole functionalized carboxylic acid ligands for organic dye adsorption
Authors: Liu Xiao-Ting , Chen Si-Si , Li Si-Miao , Nie Hong-Xiang , Feng Yao-Qing , Fan Yi-Ning , Yu Mei-Hui , Chang Ze , Bu Xian-He
Published: July 2020

Two Zn(ii)-MOFs based on pyrazole functionalized carboxylic ligands have been constructed, which exhibit favorable selective adsorption of organic cationic dyes.
Low temperature consolidation of hydroxyapatite-reduced graphene oxide nano-structured powders
Authors: Nosrati Hassan , Sarraf-Mamoory Rasoul , Zolfaghari Emameh Reza , Le Dang Quang Svend , Canillas Perez Maria , Bünger Cody Eric
Published: July 2020

In this study, hydroxyapatite-reduced graphene oxide (HA-rGO) powders were first synthesized in situ using a hydrothermal method.
The expanding world of protein kinase-like families in bacteria: forty families and counting
Authors: Gradowski Marcin , Baranowski Bartosz , Pawłowski Krzysztof
Published: July 2020

The protein kinase-like clan/superfamily is a large group of regulatory, signaling and biosynthetic enzymes that were historically regarded as typically eukaryotic proteins, although bacterial members have also been known for a long time. In this review, we explore the diversity of bacterial protein kinase like families, and discuss functional versatility of these enzymes, both the ones acting within the bacterial cell, and those acting within eukaryotic cells as effectors during infection. We focus on novel bacterial kinase-like families discovered in the last five years. A bioinformatics perspective is held here, hence sequence and structure comparison overview is presented, and also a comparison of genomic neighbourhoods of the families. We perform a phylum-level census of the families. Also, we discuss apparent pseudokinases that turned out to perform alternative catalytic functions by repurposing their atypical kinase-like active sites. We also highlight some ‘unpopular' kinase-like families that await characterisation.
The evolution of multicellularity and cancer: views and paradigms
Authors: Nedelcu Aurora M.
Published: July 2020

Conceptually and mechanistically, the evolution of multicellularity required the integration of single cells into new functionally, reproductively and evolutionary stable multicellular individuals. As part of this process, a change in levels of selection occurred, with selection at the multicellular level overriding selection at the cell level. The stability of multicellular individuals is dependent on a combination of mechanisms that supress within-group evolution, by both reducing the occurrence of somatic mutations as well as supressing somatic selection. Nevertheless, mutations that, in a particular microenvironment, confer mutant lineages a fitness advantage relative to normal somatic cells do occur, and can result in cancer. This minireview highlights several views and paradigms that relate the evolution of multicellularity to cancer. As a phenomenon, cancer is generally understood as a failure of multicellular systems to suppress somatic evolution. However, as a disease, cancer is interpreted in different frameworks: (i) a breakdown of cooperative behaviors underlying the evolution of multicellularity, (ii) a disruption of molecular networks established during the emergence of multicellularity to impose constraints on single-celled units, or (iii) an atavistic state resulting from reactivating primitive programs that originated in the earliest unicellular species. A number of assumptions are common in all the views relating cancer as a disease to the evolution of multicellularity. For instance, cancer is considered a reversal to unicellularity, and cancer cells are thought to both resemble unicellular organisms and benefit from ancestral-like traits. Nevertheless, potential limitations of current paradigms should be acknowledged as different perspectives can provide novel insights with potential therapeutic implications.
Current pivotal strategies leading a difficult target protein to a sample suitable for crystallographic analysis
Authors: Yamashita Atsuko
Published: July 2020

Crystallographic structural analysis is an essential method for the determination of protein structure. However, crystallization of a protein of interest is the most difficult process in the analysis. The process is often hampered during the sample preparation, including expression and purification. Even after a sample has been purified, not all candidate proteins crystallize. In this mini-review, the current methodologies used to overcome obstacles encountered during protein crystallization are sorted. Specifically, the strategy for an effective crystallization is compared with a pipeline where various expression hosts and constructs, purification and crystallization conditions, and crystallization chaperones as target-specific binder proteins are assessed by a precrystallization screening. These methodologies are also developed continuously to improve the process. The described methods are useful for sample preparation in crystallographic analysis and other structure determination techniques, such as cryo-electron microscopy.
Flow-Heat Conjugate Numerical Simulation Based on the Time-Domain Method
Authors: Li Hongyang , Zheng Yun
Published: July 2020

For the popups of the applicability of the time-domain based unsteady flow-heat coupling numerical simulation method in physical problems with time-period characteristic, the cases of the plate convection heat transfer and the hollow blunt-nosed blade with periodic hot spots were conducted through the internal CFD code namely HGFS. The unsteady results are analysed both in the time——domain and the frequency-domain and the main conclusions are as follows:the numerical simulation results of the plate convection heat transfer indicate that the time-scale of heat convention in the fluid domain is 10-3 s order of magnitude, while that of heat conduction in solid domain is seconds. Thus, the disparity of time scale may lead to a sharp increase in the amount of calculation, and even lead to failure of the calculation method based on time-domain. The unsteady numerical simulation of the simplified turbine blade with hot spots shows that, when the sweep frequency increases to 5 times of the original, the first-order amplitude of the temperature wave in the blade decreases to 50.4%, from 0.343 K to 0.173 K, and the corresponding penetration depth decreases to 42.8%, from 5.21 mm to 2.23 mm. The temperature fluctuation amplitude and penetration depth reduce significantly with the increasing of frequency.
Relativity Research of Total Pressure and Regulating Valve in Continuous Wind Tunnel and Its Application
Authors: Chen Dan , Yang Xiaosong , Li Gang , Guo Shouchun , Chen Tianyi
Published: July 2020

As the main adjusting means of the total pressure for the continuous transonic wind tunnel, the characteristics of regulating valve directly affect the flow field performance of the wind tunnel, therefore, it is important to analyze and establish the correlation between the regulating valve and the total pressure, and it is necessary to select the appropriate regulating valve and its combination accordingly. Firstly, in terms of the pressure regulation principle of the wind tunnel pressure regulating system, combining with the flow characteristics of the regulating valve, the correlation between the position control of the regulating valve and the total pressure control of the wind tunnel is established, then the static test is conducted to verify the relationship. In order to shorten the flow field stability time under the negative pressure of 0.6m continuous transonic wind tunnel, based on the established theory, the valve system is optimized and reformed, and the blowing test is carried out. The results show that the time of optimized Mach number polar curve decreases by 40%~50%, which greatly improves the test efficiency, which further proves that the present analysis is correct and effective, and can provide reference for the design of pressure regulating system in continuous transonic wind tunnel.
A Zero-Velocity Update Method for Adaptive Particle Filtering
Authors: Guo Yuyang , Xu Xiangbo , Ji Miaoxin
Published: July 2020

Aiming at the low precision of Kalman filter in dealing with non-linear and non-Gaussian models and the serious particle degradation in standard particle filter, a zero-velocity correction algorithm of adaptive particle filter is proposed in this paper. In order to improve the efficiency of resampling, the adaptive threshold is combined with particle filter. In the process of resampling, the degradation co-efficient is introduced to judge the degree of particle degradation, and the particles are re-sampled to ensure the diversity of particles. In order to verify the effectiveness and feasibility of the proposed algorithm, a hardware platform based on the inertial measurement unit (IMU) is built, and the state space model of the system is established by using the data collected by IMU, and experiments are carried out. The experimental results show that, compared with Kalman filter and classical particle filter, the positioning accuracy of adaptive particle filter in zero-velocity range is improved by 40.6% and 19.4% respectively. The adaptive particle filter (APF) can correct navigation errors better and improve pedestrian trajectory accuracy.
A novel self-assembling peptide for hemostasis during endoscopic submucosal dissection: a randomized controlled trial
Authors: Subramaniam Sharmila , Kandiah Kesavan , Chedgy Fergus , Fogg Carole , Thayalasekaran Sreedhari , Alkandari Asma , Baker-Moffatt Michelle , Dash Joanne , Lyons-Amos Mark , Longcroft-Wheaton Gaius , Brown James , Bhandari Pradeep
Published: July 2020

Background Endoscopic submucosal dissection (ESD) is associated with a risk of bleeding. Bleeding is usually treated with diathermy, although this does carry a risk of mucosal thermal injury. Purastat is a topical hemostat that may be effective in controlling bleeding during ESD, thereby reducing the use of heat therapy. The aim of this study was to assess the reduction in heat therapy used in the interventional group (Purastat) compared with the control group. The secondary aims were to compare the procedure length, time for hemostasis, delayed bleeding rate, adverse events, and wound healing between the groups.

Methods This was a single-center randomized controlled trial of 101 patients undergoing ESD. Participants were randomized to a control group where diathermy was used to control bleeding or an interventional group where Purastat could be used. Follow-up endoscopy was performed at 4 weeks to assess wound healing.

Results There was a significant reduction in the use of heat therapy for intraprocedural hemostasis in the interventional group compared with controls (49.3 % vs. 99.6 %, P < 0.001). There were no significant differences in the procedure length, time for hemostasis, and delayed bleeding rate between the groups. Complete wound healing at 4 weeks was noted in 48.8 % of patients in the interventional group compared with 25.0 % of controls (P = 0.02).

Conclusions This study has demonstrated that Purastat is an effective hemostat that can reduce the need for heat therapy for bleeding during ESD. It may also have a role in improving post-resection wound healing.
Prevalence and Impact of Coagulation Dysfunction in COVID-19 in China: A Meta-Analysis
Authors: Jin Shanen , Jin Yiyang , Xu Bai , Hong Jun , Yang Xianghong
Published: July 2020

Background The aim of this meta-analysis is to assess the prevalence of coagulation dysfunction in Chinese COVID-19 patients and to determine the association of coagulopathy with the severity and prognosis of COVID-19.

Methods A meta-analysis of the prevalence of different abnormal coagulation indicators in COVID-19 patients in China was performed. The difference of coagulation indicators and the incidence of DIC were compared between severe cases and nonsevere cases as well as nonsurvivors and survivors, respectively.

Results A total of 22 Chinese studies involving 4,889 confirmed COVID-19 inpatients were included. The average D-dimer value of COVID-19 patients is 0.67 µg/mL (95% confidence interval [CI]: 0.56–0.78), and 29.3% (95% CI: 20.1–38.5%) of patients showed elevated D-dimer values. Severe patients had significantly higher D-dimer levels and prolonged prothrombin time (PT) compared with nonsevere patients. Nonsurvivors had significantly higher D-dimer levels, prolonged PT, and decreased platelet count compared with survivors. In total, 6.2% (95% CI: 2.6–9.9%) COVID-19 patients were complicated by disseminated intravascular coagulation (DIC), in which the log risk ratio in nonsurvivors was 3.267 (95% CI: 2.191–4.342, Z = 5.95, p < 0.05) compared with that in survivors.

Conclusion The prevalence of coagulopathy in Chinese COVID-19 inpatients is high, and both the abnormal coagulation indicators and DIC are closely associated with the severity and poor prognosis of these COVID-19 patients. Therefore, attention should be paid to coagulation dysfunction in COVID-19 patients. Closely monitoring of coagulation indicators and application of appropriate anticoagulation may improve the prognosis of COVID-19 inpatients in China.
Developing social and civic competence in secondary education through the implementation and evaluation of teaching units and educational environments
Authors: Fuentes-Moreno Concepcion , Sabariego-Puig Marta , Ambros-Pallarés Alba
Published: July 2020

Recent international research in social science teaching highlights difficulties adolescents face when constructing social and citizenship awareness, and their own identity. To shed more light on this process, the present study is framed in the context of social science classrooms, and more specifically around how social and civic competence is developed via particular teaching methodologies and specific learning environments in Spain. The focus is on the analysis of democratic citizenship, as it is commonly accepted in the theoretical and epistemological bases of social sciences that citizenship education is one of the aims of the educational system. The objective of this study is to evaluate the effects of implementing two teaching units on the development of social and civic competence among 110 students in five secondary and high schools in Catalonia. A qualitative observational method is used to identify, describe and analyze the implementation and effects of both teaching units on a hermeneutic-interpretative basis. An ethnographic perspective is used to obtain accounts of education professionals and students. In addition, 19 field notes are analyzed using QSRNVIVO 12 software on two dimensions: citizenship and classroom climate. There are two main findings: first, regarding the formative value of both sequences regarding democratic, active and critical citizenship; the second, regarding the importance of the classroom environment created for this purpose by designing ad hoc learning spaces using active methodologies to contribute to the development of active and responsible citizenship. The conclusions highlight two important issues. The subject of History in secondary education should be vindicated as a key instrument to build democratic awareness, based on the skills of active and critical citizenship. Furthermore, there is a relationship between the development of critical and active citizenship and the creation of learning environments that foster reflection, analysis, interpretation and dialog. The implications of this study pose an important challenge for the study of social sciences. Initial teacher training methodology and syllabi should be reviewed, the importance of the Humanities in our society should be defended, and classrooms and schools should be democratized to promote active participation in citizenship education.
Magnetic bottle electron spectrometer driven by electron pulses
Authors: Barba Žiga , Bučar Klemen , Krušič Špela , Žitnik Matjaž
Published: July 2020

We report an electron scattering experiment on argon gas where a keV electron beam is used as a probe and electrons are collected with a magnetic bottle spectrometer. For this purpose, we have built a thermionic gun that produces electron pulses with nanosecond duration by sweeping the beam across a small aperture. To reach the target, electrons must pass through the hole in an axially symmetric arrangement of strong permanent magnets required to operate the magnetic bottle. From the recorded multi-hit sequence of electron arrival times on the microchannel plate detector, a kinetic energy spectrum is built that allows an analysis of the elastic and inelastic electron scattering channels by means of the coincidence technique. After a description of the instrumental configuration and discussion of suitable working parameters, the results of an angle-integrated (e, 2e) experiment are presented for 800 eV electron scattering on argon atoms.
Molecular dynamics study of lipid bilayers modeling outer and inner leaflets of plasma membranes of mouse hepatocytes. I. Differences in physicochemical properties between the two leaflets
Authors: Andoh Yoshimichi , Hayakawa Shiho , Okazaki Susumu
Published: July 2020

Outer and inner leaflets of plasma cell membranes have different lipid compositions, and the membrane properties of each leaflet can differ from each other significantly due to these composition differences. However, because of the experimental difficulty in measuring the membrane properties for each leaflet separately, the differences are not well understood at a molecular level. In this study, we constructed two lipid bilayer systems, modeling outer and inner leaflets of plasma membranes of mouse hepatocytes based on experimental composition data. The ion concentration in the interlamellar water phase was also set to match the concentration in extra- and intracellular fluids. The differences in physical properties between the outer and inner leaflets of mouse hepatocyte cell membrane models were investigated by performing 1.2 μs-long all-atomistic molecular dynamics calculations under physiological temperature and pressure conditions (310.15 K and 1 atm). The calculated electron density profiles along the bilayer normal for each model bilayer system captured well the asymmetric feature of the experimental electron density profile across actual cell plasma membranes, indicating that our procedure of modeling the outer and inner leaflets of the cell plasma membranes was satisfactory. We found that compared to the outer leaflet model, the inner leaflet model had a very bulky and soft structure in the lateral direction. To confirm the differences, membrane fluidity was measured from the lateral diffusivity and relaxation times. The fluidity was significantly higher in the inner leaflet model than in the outer leaflet model. We also discuss two topics that are of wide interest in biology, i.e., the interdigitation of acyl tails of lipid molecules between two monolayers and the lateral concentration fluctuation of lipid molecules in the bilayers.
The gain-of-function allele
bamA

E470K

bypasses the essential requirement for BamD in β-barrel outer membrane protein assembly
Authors: Hart Elizabeth M. , Gupta Meera , Wühr Martin , Silhavy Thomas J.
Published: July 2020

Significance

The assembly of β-barrel outer membrane proteins (OMPs) is broadly conserved in diderm bacteria as well as in mitochondria and chloroplasts. The β-barrel assembly machine (BAM), which assembles OMPs into the outer membrane of gram-negative microbes, contains two essential proteins, BamA and BamD. Here we identify a genetic background in which BamD is nonessential, indicating that BamD does not function in OMP catalysis, but rather plays a regulatory role in OMP assembly. BamD is not conserved in the complexes that assemble OMPs in chloroplasts and mitochondria, likely because these organelles, unlike bacteria, inhabit a carefully controlled cytoplasmic environment.
Vibrational properties of 1D- and 3D polynuclear spin crossover Fe(II) urea-triazoles polymer chains and quantification of intrachain cooperativity
Authors: Wolny Juliusz A , Hochdörffer Tim , Sadashivaiah Sakshath , Auerbach Hendrik , Jenni Kevin , Scherthan Lena , Li Ai-Min , von Malotki Christian , Wille Hans-Christian , Rentschler Eva , Schünemann Volker
Published: July 2020

The vibrational dynamics of the iron centres in 1D and 3D spin crossover Fe(II) 4-alkyl-urea triazole chains have been investigated by synchrotron based nuclear inelastic scattering. For the 1D system, the partial density of phonon states has been modelled with density functional theory methods. Furthermore, spin dependent iron ligand distances and vibrational modes were obtained. The previously introduced intramolecular cooperativity parameter H
coop (Rackwitz et al, Phys. Chem. Chem. Phys. 2013, 15, 15450) has been determined to −31 kJ mol−1 for [Fe(n-Prtrzu)3(tosylate)2] and to +27 kJ mol−1 for [Fe(n-Prtrzu)3(BF4)2]. The change of sign in H
coop is in line with the incomplete and gradual character of the spin transition for the former as well as with the sharp transition for the latter reported previously (Rentschler and von Malotki, Inorg. Chem., Act. 2008, 361, 3646). This effect can be ascribed to the networks of intramolecular interactions in the second coordination sphere of the polymer chains, depending on the spin state of the iron centres. In addition, we observe a decreased coupling and coherence when comparing the system which displays a sharp spin transition to the system with an incomplete soft transition by analyzing molecular modes involving a movement of the iron centres.
A GPU-accelerated fully 3D OSEM image reconstruction for a high-resolution small animal PET scanner using dual-ended readout detectors
Authors: Zeng Tianyi , Gao Juan , Gao Dongfang , Kuang Zhonghua , Sang Ziru , Wang Xiaohui , Hu Lingzhi , Chen Qun , Chu Xu , Liang Dong , Liu Xin , Yang Yongfeng , Zheng Hairong , Hu Zhanli
Published: July 2020

In this work, a GPU-accelerated fully 3D ordered-subset expectation maximization (OSEM) image reconstruction with point spread function (PSF) modeling was developed for a small animal PET scanner with a long axial field of view (FOV). Dual-ended readout detectors that provided high depth of interaction (DOI) resolution were used for the small animal PET scanner to simultaneously achieve uniform high spatial resolution and high sensitivity. First, we developed a novel sinogram generation method, in which the dimension of the sinogram was determined first and then an event was assigned to a few neighboring sinogram elements by using weights that are inversely proportional to the distance from the measured line of response (LOR) to the LOR of the sinogram elements. System geometric symmetry, precomputation of LOR-driven ray-tracing and texture memory were applied to accelerate the GPU-based reconstruction. We developed a spatially variant PSF model where the PSF parameters were obtained by using point source images measured at 18 positions in the FOV and a spatial invariant PSF model where the PSF parameters were obtained by using only one image measured at the center FOV. The performance of the image reconstruction method was evaluated by using simulated phantom data as well as phantom and in-vivo mouse data acquired on the scanner. The results showed that the proposed reconstruction method provided better spatial resolution, a higher contrast recovery coefficient and lower noise than the OSEM reconstruction and was more than 1000 times faster than the CPU-based reconstruction. The spatially variant PSF model did not result in any spatial resolution improvement compared to the spatial invariant PSF model, and thus, the latter that is much easier to implement in image reconstruction and can be used in a small animal PET scanner using detectors with very high DOI resolution. A whole body 18F-FDG mouse image with high resolution and a high contrast to noise ratio was obtained by using the proposed reconstruction method.