bluuebunny/crossref_metadata_2025 huggingface dataset:
Critical functions of microRNA‐30a‐5p‐E2F3 in cardiomyocyte apoptosis induced by hypoxia/reoxygenation
Authors: Lv Xiao‐Bing , Niu Qing‐Hui , Zhang Min , Feng Li , Feng Jia
Published: October 2020

The high‐mortality rate of cardiovascular diseases (CVDs) is associated with the myocardial ischemia and reperfusion (I/R). Recent investigations have revealed that microRNAs (miRNAs) exert vital functions in the apoptosis of cardiomyocyte cell. Nevertheless, the potential role of miR‐30a‐5p in the regulation of cardiomyocyte cell apoptosis needs to be illuminated. In the current study, we observed that hypoxia/reoxygenation (H/R) remarkably raised the level of miR‐30a‐5p but reduced the expression of E2F transcription factor 3 (E2F3) in H9c2 cardiomyocytes. In vivo, miR‐30a‐5p was found to be significantly upregulated in the hearts of rats following I/R. Downregulation of miR‐30a‐5p using anti‐miR‐30a‐5p decreased H9c2 cardiomyocytes apoptosis caused by H/R and promoted the proliferation of H9c2 inhibited by H/R. Moreover, E2F3 was a possible target gene of miR‐30a‐5p and upregulation of miR‐30a‐5p reduced the expression level of E2F3 in H9c2 cardiomyocytes. We further identified that E2F3 silencing reversed the effect of anti‐miR‐30a‐5p on the proliferation and apoptosis in H/R treated H9c2 cells. These studies suggested that downregulation of miR‐30a‐5p attenuated the impact of H/R on H9c2 cardiomyocytes through targeting E2F3.
Japanese Familial Cases of Frontotemporal Dementia and Parkinsonism with N279K Tau Gene Mutation
Authors: Oka Yuwa , Saiki Hidemoto , Hashimoto Yasumasa , Terada Yuta , Nakamura Takashi , Ayaki Takashi , Orimo Satoshi , Matsumoto Sadayuki
Published: October 2020

Background

Mutations in the tau gene linked to chromosome 17 cause frontotemporal dementia and parkinsonism (FTDP‐17).

Objective

This study presents 3 Japanese familial cases diagnosed with N279K tau gene mutation, including 1 autopsy‐confirmed case.

Methods

We compared the clinical presentations, cognitive functions, and images between the 3 familial cases diagnosed with N279K mutation.

Results

All 3 patients presented symptoms in their early 40s. One patient showed severe cognitive dysfunction and died in his sixth year after onset. The remaining 2 cases presented with parkinsonism‐dominant clinical features. Among the 2 cases, 1 presented the characteristic symptoms of progressive supranuclear palsy. The pathological features of the dementia‐dominant case showed frontal and temporal lobe‐dominant neuronal loss and gliosis. Tau‐positive neuronal and glial inclusions were found throughout. Further, tufted astrocytes and globose tangles were present whereas there were no Pick bodies and astrocytic plaques, compatible with pathology‐confirmed frontotemporal lobar degeneration (FTLD) ‐tau subtypes.

Conclusions

Patients with FTDP‐17 can be classified into the following 2 major groups: dementia and parkinsonism‐plus predominant phenotypes. Among our 3 cases, 1 showed dementia predominance whereas the other 2 showed parkinsonism predominance. Mutations in the microtubule‐associated protein tau (MAPT) present with several pathological features. Clinically, our case presented a behavioral variant frontotemporal dementia (bvFTD). However, morphologically, the observed glial and neuronal pathology met the criteria for progressive supranuclear palsy (PSP). This study highlights the clinical heterogeneity within and between families with same MAPT mutation. Few pathologically confirmed PSP cases have been reported with mutations in MAPT.
A Novel Duplication in ATXN2 as Modifier for Spinocerebellar Ataxia 3 (SCA3) and C9ORF72‐ALS
Authors: Laffita‐Mesa Jose Miguel , Nennesmo Inger , Paucar Martin , Svenningsson Per
Published: October 2020

Background

The ataxin‐2 (ATXN2) gene contains a cytosine‐adenine‐guanine repeat sequence ranging from 13 to 31 repeats, but when surpassing certain thresholds causes neurodegeneration. Genetic alterations in ATXN2 other than pathological cytosine adenine guanine (CAG) repeats are unknown.

Methods/Results

We have identified a 9–base pair duplication in the 2‐gene ATXN2 sense/antisense region. The duplication was found in a Swedish family with spinocerebellar ataxia 3 with parkinsonism, conferring a deviated age at onset unexplained by the concomitant presence of ATXN2 intermediate alleles. Similarly, C9ORF72 amyotrophic lateral sclerosis cases bearing the same duplication had earlier age at onset than those with C9ORF72 and ATXN2 intermediate alleles. No effect was evident in Parkinson's disease (PD) cases without known PD gene mutations.

Conclusions

We describe the first genetic alteration other than the known intermediate‐range CAG repeats in ATXN2. This 9–base pair duplication may act as an additional hit among carriers of pathological nucleotide expansions in ATXN3 and C9ORF72 with ATXN2 intermediate. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
First experimental investigation of simultaneously tracking two independently moving targets on an MRI‐linac using real‐time MRI and MLC tracking
Authors: Liu Paul Z. Y. , Dong Bing , Nguyen Doan Trang , Ge Yuanyuan , Hewson Emily A. , Waddington David E. J. , O'Brien Ricky , Liney Gary P. , Keall Paul J.
Published: October 2020

Purpose

High quality radiotherapy is challenging in cases where multiple targets with independent motion are simultaneously treated. A real‐time tumor tracking system that can simultaneously account for the motion of two targets was developed and characterized.

Methods

The multitarget tracking system was implemented on a magnetic resonance imaging (MRI)‐linac and utilized multi‐leaf collimator (MLC) tracking to adapt the radiation beam to phantom targets reproducing motion with prostate and lung motion traces. Multitarget tracking consisted of three stages: (a) pretreatment aperture segmentation where the treatment aperture was divided into segments corresponding to each target, (b) MR imaging where the positions of the two targets were localized, and (c) MLC tracking where an updated treatment aperture was calculated. Electronic portal images (EPID) acquired during irradiation were analyzed to characterize geometric uncertainty and tracking latency.

Results

Multitarget MLC tracking effectively accounted for the motion of both targets during treatment. The root‐mean‐square error between the centers of the targets and the centers of the corresponding MLC leaves were reduced from 5.5 mm without tracking to 2.7 mm with tracking for lung motion traces and reduced from 4.2 to 1.4 mm for prostate motion traces. The end‐to‐end latency of tracking was measured to be 328 ± 44 ms.

Conclusions

We have demonstrated the first experimental implementation of MLC tracking for multiple targets having independent motion. This technology takes advantage of the imaging capabilities of MRI‐linacs and would allow treatment margins to be reduced in cases where multiple targets are simultaneously treated.
How thin can you go? Performance of thin copper and aluminum RF coil conductors
Authors: Barta Radim , Volotovskyy Vyacheslav , Wachowicz Keith , Fallone B. Gino , De Zanche Nicola
Published: October 2020

Purpose

To evaluate the impact of emerging conductor technology on RF coils. Performance and resulting image quality of thin or alternate conductors (eg, aluminum instead of copper) and thicknesses (9‐600 μm) are compared in terms of SNR.

Methods

Eight prototype RF coils (15 cm × 15 cm square loops) were constructed and bench‐tested to measure quality factor. The coils used 6‐mm‐wide conducting strips of either copper or aluminum of a few different thicknesses (copper: 17, 32, 35, 127, 600 μm; aluminum: 9, 13, 20, 127 μm) on acetate projector sheets for backing. Corresponding image SNR was measured at 0.48 tesla (20.56 MHz).

Results

The coils spanned a range of unloaded quality factors from 89 to 390 and a fivefold range of losses. The image SNRs were consistent with the coils’ bench‐measured efficiencies (0.33‐0.73). Thin aluminum conductors (9 μm) led to the highest reduction in SNR (65% that of 127 μm copper). Thin copper (<32 μm) conductors lead to a much smaller decrease in SNR (approximately 10%) compared to 127 μm copper. No performance difference was observed between 127 μm thick copper and aluminum. The much thicker 600 μm copper bars only yield a 5% improvement in SNR.

Conclusion

Even at 0.48 tesla, copper RF coil conductors much thinner than those in conventional construction can be used while maintaining SNR greater than 50% that of thick copper. These emerging coil conductor technologies enable RF coil functionality that cannot be achieved otherwise.
Deep learning‐based method for reducing residual motion effects in diffusion parameter estimation
Authors: Gong Ting , Tong Qiqi , Li Zhiwei , He Hongjian , Zhang Hui , Zhong Jianhui
Published: October 2020

Purpose

Conventional motion‐correction techniques for diffusion MRI can introduce motion‐level–dependent bias in derived metrics. To address this challenge, a deep learning‐based technique was developed to minimize such residual motion effects.

Methods

The data‐rejection approach was adopted in which motion‐corrupted data are discarded before model‐fitting. A deep learning‐based parameter estimation algorithm, using a hierarchical convolutional neural network (H‐CNN), was combined with motion assessment and corrupted volume rejection. The method was designed to overcome the limitations of existing methods of this kind that produce parameter estimations whose quality depends strongly on a proportion of the data discarded. Evaluation experiments were conducted for the estimation of diffusion kurtosis and diffusion‐tensor–derived measures at both the individual and group levels. The performance was compared with the robust approach of iteratively reweighted linear least squares (IRLLS) after motion correction with and without outlier replacement.

Results

Compared with IRLLS, the H‐CNN‐based technique is minimally sensitive to motion effects. It was tested at severe motion levels when 70% to 90% of the data are rejected and when random motion is present. The technique had a stable performance independent of the numbers and schemes of data rejection. A further test on a data set from children with attention‐deficit hyperactivity disorder shows the technique can potentially ameliorate spurious group‐level difference caused by head motion.

Conclusion

This method shows great potential for reducing residual motion effects in motion‐corrupted diffusion‐weighted–imaging data, bringing benefits that include reduced bias in derived metrics in individual scans and reduced motion‐level–dependent bias in population studies employing diffusion MRI.
Horizontal vibration of a rigid strip footing on viscoelastic half‐space
Authors: Zheng Changjie , Cai Yuanjie , Luan Lubao , Kouretzis George , Ding Xuanming
Published: October 2020

This paper presented an analytical method for determining the response of a rigid strip foundation resting on the surface of a viscoelastic half‐space to horizontal dynamic loads, and the associated transient soil displacements resulting from the vibration of the footing. This mixed boundary value problem was solved by means of Jacobi orthogonal polynomials, a more efficient method compared to transforming the dual integral equations resulting from the boundary conditions to Fredholm integral equations. Displacements and stresses of the soil‐footing system were accordingly obtained by applying the inverse Fourier transform. Finally, we used the proposed solution to investigate the effects of material damping and Poisson's ratio of soil on the dynamic response of the strip footing, and the resulting soil displacements.
Carbon disulfide solvent, helping to clarify the Stokes shift in diphenylpolyenes
Authors: Catalán Javier
Published: October 2020

The Stokes shift found by Hausser et al. in diphenylpolyenes, which increases by lengthening its polyene chain, has received in the last 80 years a series of explanations, which we believe are not satisfactory. In this current work, using of CS2 as solvent for the fluorescence measurements of 1,6‐diphenylhexatriene (DPH) and 1,8‐diphenyloctatetraene (DPO) against temperature, it is concluded that the Stokes shift, shown by the diphenylpolyenes, is of structural origin and that it disappears from its photophysical behavior if it is possible that these compounds in their ground electronic state adopt a planar molecular structure, from which to initiate their photophysics.
Computational design of mixed chirality peptide macrocycles with internal symmetry
Authors: Mulligan Vikram Khipple , Kang Christine S. , Sawaya Michael R. , Rettie Stephen , Li Xinting , Antselovich Inna , Craven Timothy W. , Watkins Andrew M. , Labonte Jason W. , DiMaio Frank , Yeates Todd O. , Baker David
Published: October 2020

Cyclic symmetry is frequent in protein and peptide homo‐oligomers, but extremely rare within a single chain, as it is not compatible with free N‐ and C‐termini. Here we describe the computational design of mixed‐chirality peptide macrocycles with rigid structures that feature internal cyclic symmetries or improper rotational symmetries inaccessible to natural proteins. Crystal structures of three C2‐ and C3‐symmetric macrocycles, and of six diverse S2‐symmetric macrocycles, match the computationally‐designed models with backbone heavy‐atom RMSD values of 1 Å or better. Crystal structures of an S4‐symmetric macrocycle (consisting of a sequence and structure segment mirrored at each of three successive repeats) designed to bind zinc reveal a large‐scale zinc‐driven conformational change from an S4‐symmetric apo‐state to a nearly inverted S4‐symmetric holo‐state almost identical to the design model. These symmetric structures provide promising starting points for applications ranging from design of cyclic peptide based metal organic frameworks to creation of high affinity binders of symmetric protein homo‐oligomers. More generally, this work demonstrates the power of computational design for exploring symmetries and structures not found in nature, and for creating synthetic switchable systems.
Chlamydia trachomatis glyceraldehyde 3‐phosphate dehydrogenase: Enzyme kinetics, high‐resolution crystal structure, and plasminogen binding
Authors: Schormann Norbert , Campos Juan , Motamed Rachael , Hayden Katherine L. , Gould Joseph R. , Green Todd J. , Senkovich Olga , Banerjee Surajit , Ulett Glen C. , Chattopadhyay Debasish
Published: October 2020

Glyceraldehyde 3‐phosphate dehydrogenase (GAPDH) is an evolutionarily conserved essential enzyme in the glycolytic pathway. GAPDH is also involved in a wide spectrum of non‐catalytic cellular ‘moonlighting’ functions. Bacterial surface‐associated GAPDHs engage in many host interactions that aid in colonization, pathogenesis, and virulence. We have structurally and functionally characterized the recombinant GAPDH of the obligate intracellular bacteria Chlamydia trachomatis, the leading cause of sexually transmitted bacterial and ocular infections. Contrary to earlier speculations, recent data confirm the presence of glucose‐catabolizing enzymes including GAPDH in both stages of the biphasic life cycle of the bacterium. The high‐resolution crystal structure described here provides a close‐up view of the enzyme's active site and surface topology and reveals two chemically modified cysteine residues. Moreover, we show for the first time that purified C. trachomatis GAPDH binds to human plasminogen and plasmin. Based on the versatility of GAPDH's functions, data presented here emphasize the need for investigating the Chlamydiae GAPDH's involvement in biological functions beyond energy metabolism.
Therapeutic benefits of rutin and its nanoformulations
Authors: Negahdari Ramin , Bohlouli Sepideh , Sharifi Simin , Maleki Dizaj Solmaz , Rahbar Saadat Yalda , Khezri Khadijeh , Jafari Samira , Ahmadian Elham , Gorbani Jahandizi Negar , Raeesi Safa
Published: October 2020

Background

Rutin as a natural flavonoid compound has revealed an extensive range of therapeutic potentials.

Purpose

The current paper is focused on the numerous studies on rutin nanoformulations regarding its broad spectrum of therapeutic potentials.

Study and methods

A review was conducted in electronic databases (PubMed) to identify relevant published literature in English. No restrictions on publication date were imposed.

Results

The literature search provided 7,078 results for rutin. Among them, 25 papers were related to the potential biological activities of rutin nanoformulations. Polymeric nanoparticles were the most studied nanoformulations for rutin (14 titles) and lipid nanoparticles (5 titles) were in second place. The reviewed literature showed that rutin has been used as an antimicrobial, antifungal, and anti‐allergic agent. Improving the bioavailability of rutin using novel drug‐delivery methods will help the investigators to use its useful effects in the treatment of various chronic human diseases.

Conclusion

It can be concluded that the preparation of rutin nanomaterials for the various therapeutic objects confirmed the enhanced aqueous solubility as well as enhanced efficacy compared to conventional delivery of rutin. However, more investigations should be conducted to confirm the improved bioavailability of the rutin nanoformulations.
Inhibitory effects of cynaropicrin on human melanoma progression by targeting MAPK, NF‐κB, and Nrf‐2 signaling pathways in vitro
Authors: De Cicco Paola , Busà Rosalia , Ercolano Giuseppe , Formisano Carmen , Allegra Mario , Taglialatela‐Scafati Orazio , Ianaro Angela
Published: October 2020

Malignant melanoma is the deadliest skin cancer, due to its propensity to metastasize. MAPKs and NF‐κB pathways are constitutively activated in melanoma and promote cell proliferation, cell invasion, metastasis formation, and resistance to therapeutic regimens. Thus, they represent potential targets for melanoma prevention and treatment. Phytochemicals are gaining considerable attention for the management of melanoma because of their several cellular and molecular targets. A screening of a small library of sesquiterpenes lactones selected cynaropicrin, isolated from the aerial parts of Centaurea drabifolia subsp. detonsa, for its potential anticancer effect against melanoma cells. Treatment of human melanoma cells A375 with cynaropicrin resulted in inhibition of cell proliferation and induction of caspase‐3‐dependent apoptosis. Furthermore, cynaropicrin reduced several cellular malignant features such migration, invasion, and colonies formation through the inhibition of ERK1/2 and NF‐κB activity. Cynaropicrin was able to reduce intracellular reactive oxygen species generation, which are involved in all the stages of carcinogenesis. Indeed, cynaropicrin increased the expression of several antioxidant genes, such as glutamate–cysteine ligase and heme oxygenase‐1, by promoting the activation of the transcription factor Nrf‐2. In conclusion, our results individuate cynaropicrin as a potential adjuvant chemotherapeutic agent for melanoma by targeting several protumorigenic signaling pathways.
Robust optimal tracking control for multiplayer systems by off‐policy Q‐learning approach
Authors: Li Jinna , Xiao Zhenfei , Li Ping , Cao Jiangtao
Published: October 2020

In this article, a novel off‐policy cooperative game Q‐learning algorithm is proposed for achieving optimal tracking control of linear discrete‐time multiplayer systems suffering from exogenous dynamic disturbance. The key strategy, for the first time, is to integrate reinforcement learning, cooperative games with output regulation under the discrete‐time sampling framework for achieving data‐driven optimal tracking control and disturbance rejection. Without the information of state and input matrices of multiplayer systems, as well as the dynamics of exogenous disturbance and command generator, the coordination equilibrium solution and the steady‐state control laws are learned using data by a novel off‐policy Q‐learning approach, such that multiplayer systems have the capability of tolerating disturbance and follow the reference signal via the optimal approach. Moreover, the rigorous theoretical proofs of unbiasedness of coordination equilibrium solution and convergence of the proposed algorithm are presented. Simulation results are given to show the efficacy of the developed approach.
Limiting water range: Crop responses related to in‐season soil water dynamics, weather conditions, and subsoil compaction
Authors: Pulido‐Moncada Mansonia , Petersen Carsten T. , Munkholm Lars J.
Published: October 2020

The least limiting water range (LLWR) has been used as a soil structural quality indicator for identifying in‐season water dynamics, yet studies focusing on its use for detecting in‐season water stresses and their effect on crop response on severely compacted subsoils are scarce. The objectives of this study were, therefore, to examine the in‐season water dynamics on a tile‐drained soil with compacted subsoil in the light of two different approaches for calculating LLWR (standard LLWR by da Silva et al. [1994] and refined LLWR by Pulido‐Moncada & Munkholm [2019]) and to evaluate the crop response to aboveground and belowground conditions. Information on LLWRs was obtained from soil sampling in the most contrasting treatments of a compaction experiment: with and without compaction. In‐season water dynamics were measured from 2017 to 2019. The refined LLWR approach defined a wider range of water content nonlimiting for plant growth compared with the da Silva et al. approach. Compaction affected the LLWRs (p < .05), yet no significant effect of subsoil compaction on crop yield was found. Cumulative aeration and water stress day indicators identified from the refined LLWR were significantly related to grain yield (p < .05). The lower winter wheat yield in 2018 compared with 2019 seemed to be related to the direct impact of weather factors on aboveground growth and to aeration and water stresses. The apparent lack of compaction effect suggests further studies are needed to determine if in‐season stresses derived from the LLWRs can be related to crop development and yield under different soil and weather conditions.
Thermally induced changes in solubility and speciation of lead and iron minerals in a contaminated soil
Authors: Sonoda Kent , Hashimoto Yohey , Wang Shan‐Li
Published: October 2020

This study investigated the effects of thermal treatment on the solubility and speciation of lead (Pb) adsorbed on synthesized hematite (Pb‐Hm) and in an anthropogenically contaminated soil. The temperature of thermal treatment ranged from 100 to 900 °C, and the speciations of Pb and iron were determined using X‐ray absorption fine structure spectroscopy. In Pb‐Hm samples, the concentration of water‐extractable Pb significantly decreased after being treated at 300 and 600 °C (∼0.50 mg Pb L–1) compared with the untreated sample (9.83 mg Pb L–1). Under this temperature range, about 50% of the Pb‐Hm was transformed into massicot (β‐PbO). At 700 °C and above, a slight increase of water‐extractable Pb was probably caused by the formation of minium (Pb3O4). In the contaminated soil, water‐extractable Pb increased gradually from 0.30 to 0.40 mg Pb L–1 with increasing temperature from 25 to 200 °C; then it decreased rapidly to 0.09 mg Pb L–1 at 300 °C and further decreased to 0.004 mg Pb L–1 at 900 °C. Cerussite (PbCO3) and Pb associated with hematite were the major Pb species in the contaminated soil. In the process of thermal treatment, the significant decrease of water‐extractable Pb in the contaminated soil was caused by the transformation of cerussite into hematite‐associated Pb, accompanied by the transformation from ferrihydrite to hematite.
High‐resolution peak analysis in TOF SIMS data
Authors: Gelb Lev D. , Shahrokh Esfahani Negar , Walker Amy V.
Published: October 2020

High mass resolution time‐of‐flight secondary ion mass spectrometry (TOF SIMS) can provide a wealth of chemical information about a sample, but the analysis of such data is complicated by detector dead‐time effects that lead to systematic shifts in peak shapes, positions, and intensities. We introduce a new maximum‐likelihood analysis that incorporates the detector behavior in the likelihood function, such that a parametric spectrum model can be fit directly to as‐measured data. In numerical testing, this approach is shown to be the most precise and lowest‐bias option when compared with both weighted and unweighted least‐squares fitting of data corrected for dead‐time effects. Unweighted least‐squares analysis is the next best, while weighted least‐squares suffers from significant bias when the number of pulses used is small. We also provide best‐case estimates of the achievable precision in fitting TOF SIMS peak positions and intensities and investigate the biases introduced by ignoring background intensity and by fitting to just the intense part of a peak. We apply the maximum‐likelihood method to fit two experimental data sets: a positive‐ion spectrum from a multilayer MoS2 sample and a positive‐ion spectrum from a TiZrNi bulk metallic glass sample. The precision of extracted isotope masses and relative abundances obtained is close to the best‐case predictions from the numerical simulations despite the use of inexact peak shape functions and other approximations. Implications for instrument calibration, incorporation of prior information about the sample, and extension of this approach to the analysis of imaging data are also discussed.
First‐principle calculations of CrN(200)/Ni(111) interface: Atomic structure, stability, and electronic properties
Authors: Zhang Zhaolu , Chen Jiao , He Guangyu , Yang Guanjun
Published: October 2020

Atomic structure, adhesion energy, and electronic properties of the bonding nature at CrN(200)/Ni(111) interfacial region are studied by first‐principle calculations based on density functional theory (DFT). A new method for building the heterostructure of CrN(200)/Ni(111) is proposed to solve the large lattice mismatching between CrN(200) and Ni(111) slab. Three models (OT, ST, and TL) with different interface distance are built up, and the total energy for each of them is calculated. Comparing with other stacking sequence, TL sites with 1.9‐Å spacing at the interfacial region shows the biggest value of adhesion energy after geometry relaxation. Furthermore, the contour of charge density, partial charge density of states, and Bader charge values of the TL sites with 1.9‐Å spacing are plotted out and calculated. Results indicate that covalency bonding between Ni and N ions and metallic bonding between Ni and Cr atoms are formed at the interfacial region.
Numerical investigation on the shear behavior of prestressed concrete beams with small rectangular openings
Authors: Ye Jia‐Bin , Cai Jian , Zuo Zhi‐Liang , Chen Qing‐Jun , Tang Xu‐Lin , Zhao Xiaoqin
Published: October 2020

The numerical investigation focused on the shear behavior of prestressed concrete (PC) beams with small rectangular openings, using the software ABAQUS. Three variables, including the prestressing force, the height of the opening and its length, were considered. The numerical results exhibited a good agreement with the previous experimental outcomes, and the parametric analysis was conducted to study the local internal force distribution of two chords during the loading process. The results indicate that for RC beams with openings, the shear proportion variation of the top chord is stable as the opening size changes, while it decreases almost linearly with the increase of prestressing force for PC beams with openings. The position of contraflexure point is found to be proportional to the root of the reinforcement ratio of the chord, and it moves towards the support with the increase of the prestressing force. Furthermore, the empirical equations to determine the shear proportions and the position of contraflexure point between chords are established.
Protective effects of ethyl acetate extract from Shorea roxburghii against diabetes induced testicular damage in rats
Authors: Zhao Ling‐Ling , Makinde Emmanuel Ayobami , Olatunji Opeyemi Joshua
Published: October 2020

Diabetic mellitus is a chronic metabolic disorder that is associated with several complications including testicular dysfunction. This research investigated the protective action of the ethyl acetate extract from Shorea roxburghii (SRE) on diabetes induced testicular damage in rats. Diabetic rats were orally administered with SRE at doses of 100 and 400 mg/kg for 4 weeks. SRE improved the body weight gain, testes weight, testes index and increased serum concentration of testosterone. Furthermore, SRE increased the testicular antioxidant enzymes including superoxide dismutase, catalase and glutathione peroxidase. In addition, SRE ameliorated testicular inflammatory mediators such as myeloperoxidase, tumor necrosis factor alpha, interleukin 6, p38 MAPK and nuclear factor kappa B activation and decreased testicular cell apoptosis in the treated diabetic rats. SRE also raised sperm parameters after treatment of diabetic rats. Conclusively, our results suggested that SRE ameliorated diabetes induced testicular damage by inhibiting oxidative stress and inflammation.
Metatalk Moves: Examining Tools for Collective Academic Discourse Learning
Authors: Phillips Galloway Emily , McClain Janna B.
Published: October 2020

Educators are increasingly aware of the role of classroom talk in cultivating students’ language knowledge, which in turn supports their skilled reading comprehension. The result has been greater attention to teacher talk moves that transform class discussions into opportunities for language learning. However, less focus has been placed on the strategies used by students as they work together to both learn language and learn about language. The authors focus on a fourth‐grade classroom in which students scaffold one another’s language development through powerful language‐focused talk, or metatalk, during a small‐group vocabulary activity. By examining the characteristics of these metatalk episodes and delineating talk moves used by students within them, the authors make visible moves that educators might note and build from. This study informs instruction that capitalizes on the language knowledge held by individual learners in the service of collective language learning for all.
Wearable sweat sensing for prolonged, semicontinuous, and nonobtrusive health monitoring
Authors: Moonen Emma J.M. , Haakma Jelte R. , Peri Elisabetta , Pelssers Eduard , Mischi Massimo , den Toonder Jaap M.J.
Published: October 2020

Together with the upcoming market for wearable consumer technologies, noninvasive and continuous health monitoring has become a new trend in the healthcare landscape. In recent years, significant research has been targeted toward the development of wearable sensing devices for monitoring biomarker levels in nonobtrusively accessible biofluids such as tears, urine, saliva, and sweat. Sweat could be an ideal candidate for prolonged, semicontinuous, and nonobtrusive health monitoring because sweat is a continuously accessible biofluid containing physiologically and metabolically rich information. However, challenges still remain toward commercialized wearable sweat‐sensing devices, and the correlation between biomarker concentrations in sweat with health conditions still seems to be not fully understood. This review article aims to display the full scope of sweat sensing for health monitoring, starting from the fundamentals of human sweat, via modeling of the sweat gland physiology toward wearable sweat‐sensing devices in research and commercialization efforts. Finally, the challenges of sweat sensing that still have to be overcome toward the utilization of sweat sensing in the conventional healthcare settings are discussed.
Vitamin A deficiency and its treatment in captive Sunda pangolins
Authors: Zhang Fuhua , Min Yue , Yu Yishuang , Xu Na , Wang Wenhua , Wu Shibao
Published: October 2020

The high incidence of disease in captive pangolins is a major obstacle in pangolin‐conservation breeding programs. Therefore, elucidating pangolins’ susceptibility to disease is the key to conservation progress. At the Pangolin Research Base for Artificial Rescue and Conservation Breeding of South China Normal University (PRB‐SCNU), vitamin A deficiency was diagnosed in 14 captive Sunda pangolins. Typical eye signs included lacrimal eyes, keratopathy and a blank, milky orb. The afflicted pangolins were treated with vitamins A and D for 15–30 days; all individuals recovered. We report the detection and treatment of vitamin A deficiency in captive Sunda pangolins at the PRB‐SCNU. Our results could provide guidance for the future prevention and treatment of vitamin A deficiency and associated diseases in pangolin species, both to reduce the incidence of these diseases in captive pangolins and to aid conservation efforts.
TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling
Authors: Ciesielska Anna , Matyjek Marta , Kwiatkowska Katarzyna
Published: October 2020

Toll-like receptor (TLR) 4 belongs to the TLR family of receptors inducing pro-inflammatory responses to invading pathogens. TLR4 is activated by lipopolysaccharide (LPS, endotoxin) of Gram-negative bacteria and sequentially triggers two signaling cascades: the first one involving TIRAP and MyD88 adaptor proteins is induced in the plasma membrane, whereas the second engaging adaptor proteins TRAM and TRIF begins in early endosomes after endocytosis of the receptor. The LPS-induced internalization of TLR4 and hence also the activation of the TRIF-dependent pathway is governed by a GPI-anchored protein, CD14. The endocytosis of TLR4 terminates the MyD88-dependent signaling, while the following endosome maturation and lysosomal degradation of TLR4 determine the duration and magnitude of the TRIF-dependent one. Alternatively, TLR4 may return to the plasma membrane, which process is still poorly understood. Therefore, the course of the LPS-induced pro-inflammatory responses depends strictly on the rates of TLR4 endocytosis and trafficking through the endo-lysosomal compartment. Notably, prolonged activation of TLR4 is linked with several hereditary human diseases, neurodegeneration and also with autoimmune diseases and cancer. Recent studies have provided ample data on the role of diverse proteins regulating the functions of early, late, and recycling endosomes in the TLR4-induced inflammation caused by LPS or phagocytosis ofE. coli.In this review, we focus on the mechanisms of the internalization and intracellular trafficking of TLR4 and CD14, and also of LPS, in immune cells and discuss how dysregulation of the endo-lysosomal compartment contributes to the development of diverse human diseases.
Pilferer, murderer of innocents or prey? The potential impact of killer shrimp (Dikerogammarus villosus) on crayfish
Authors: Roje Sara , Švagrová Kateřina , Veselý Lukáš , Sentis Arnaud , Kouba Antonín , Buřič Miloš
Published: October 2020

Freshwater ecosystems worldwide are facing the establishment of non-native species, which, in certain cases, exhibit invasive characteristics. The impacts of invaders on native communities are often detrimental, yet, the number and spread of non-native invasive species is increasing. This is resulting in novel and often unexpected combinations of non-native and native species in natural communities. While the impact of invaders on native species is increasingly well-documented, the interactions of non-native invaders with other non-native invaders are less studied. We assessed the potential of an invasive amphipod, the killer shrimpDikerogammarus villosus(Sowinsky, 1894), to cope with other established invaders in European waters: North American crayfish of the Astacidae family—represented by signal crayfishPacifastacus leniusculus(Dana, 1852), and the Cambaridae family—represented by marbled crayfishProcambarus virginalisLyko, 2017. The main goal of this study was to investigate if killer shrimp, besides their role as prey of crayfish, can significantly influence their stocks by predating upon their eggs, hatchlings and free-moving early juveniles. Our results confirmed that killer shrimp can predate on crayfish eggs and hatchlings even directly from females abdomens where they are incubated and protected. As marbled crayfish have smaller and thinner egg shells as well as smaller juveniles than signal crayfish, they were more predated upon by killer shrimp than were signal crayfish. These results confirmed that the invasive killer shrimp can feed on different developmental stages of larger freshwater crustaceans and possibly other aquatic organisms.
Between two stools? Pharmacologists nominated for Nobel prizes in “physiology or medicine” and “chemistry” 1901–1950 with a focus on John Jacob Abel (1857–1938)
Authors: Pohar Michael , Hansson Nils
Published: October 2020

Since the early stages of its academic professionalization, pharmacology has been an interdisciplinary field strongly influenced by the natural sciences. Using the Nobel Prize as a lens to study the history of pharmacology, this article analyzes nominations of pharmacologists for two Nobel Prize categories, namely “chemistry” and “physiology or medicine” from 1901 to 1950. Who were they? Why were they proposed, and what do the Nobel dossiers say about excellence in pharmacology and research trends? This paper highlights the evaluation of “shortlisted” candidates, i.e., those candidates who were of particular interest for the members of the Nobel Committee in physiology or medicine. We focus on the US scholar John Jacob Abel (1857–1938), repeatedly referred to as the “Founder of American Pharmacology.” Nominated 17 times in both categories, Abel was praised by his nominators for both basic research as well as for his influential positions as editor and his work as chair at Johns Hopkins University. The Abel nominations were evaluated for the Nobel Committee in chemistry by the Swedish professor of chemistry and pharmaceutics Einar Hammarsten (1889–1968), particularly interested in Abel’s work on hormones in the adrenal glands and in the pituitary gland. Eventually, Hammarsten did not view Abel’s work prizeworthy, partly because other scholars had done—according to Hammarsten—more important discoveries in the same fields. In conclusion, analyses of Nobel Prize nominations help us to better understand various meanings of excellence in pharmacology during the twentieth century and beyond.
Maximal Fluctuations Around the Wulff Shape for Edge-Isoperimetric Sets in $$\varvec{{\mathbb {Z}}^d}$$: A Sharp Scaling Law
Authors: Mainini Edoardo , Schmidt Bernd
Published: October 2020

We derive a sharp scaling law for deviations of edge-isoperimetric sets in the lattice $${\mathbb {Z}}^d$$

Z

d

from the limiting Wulff shape in arbitrary dimensions. As the number n of elements diverges, we prove that the symmetric difference to the corresponding Wulff set consists of at most $$O(n^{(d-1+2^{1-d})/d})$$

O
(

n

(
d
-
1
+

2

1
-
d

)
/
d

)

lattice points and that the exponent $$(d-1+2^{1-d})/d$$

(
d
-
1
+

2

1
-
d

)
/
d

is optimal. This extends the previously found ‘$$n^{3/4}$$

n

3
/
4

laws’ for $$d=2,3$$

d
=
2
,
3

to general dimensions. As a consequence we obtain optimal estimates on the rate of convergence to the limiting Wulff shape as n diverges.
Preclinical evaluation of 5-methyltetrahydrofolate-based radioconjugates—new perspectives for folate receptor–targeted radionuclide therapy
Authors: Guzik Patrycja , Benešová Martina , Ratz Magdalena , Monné Rodríguez Josep M. , Deberle Luisa M. , Schibli Roger , Müller Cristina
Published: October 2020

Purpose

The folate receptor (FR) is frequently overexpressed in a variety of tumor types and, hence, an interesting target for radionuclide therapy. The aim of this study was to evaluate a new class of albumin-binding radioconjugates comprising 5-methyltetrahydrofolate (5-MTHF) as a targeting agent and to compare their properties with those of the previously established folic acid-based [177Lu]Lu-OxFol-1.

Methods

[177Lu]Lu-6R-RedFol-1 and [177Lu]Lu-6S-RedFol-1 were investigated in vitro using FR-positive KB tumor cells. Biodistribution studies were performed in KB tumor-bearing mice, and the areas under the curve (AUC0 → 120h) were determined for the uptake in tumors and kidneys. [177Lu]Lu-6R-RedFol-1 was compared with [177Lu]Lu-OxFol-1 in a therapy study over 8 weeks using KB tumor-bearing mice.

Results

Both radioconjugates demonstrated similar in vitro properties as [177Lu]Lu-OxFol-1; however, the tumor uptake of [177Lu]Lu-6R-RedFol-1 and [177Lu]Lu-6S-RedFol-1 was significantly increased in comparison with [177Lu]Lu-OxFol-1. In the case of [177Lu]Lu-6S-RedFol-1, also the kidney uptake was increased; however, renal retention of [177Lu]Lu-6R-RedFol-1 was similar to that of [177Lu]Lu-OxFol-1. This led to an almost 4-fold increased tumor-to-kidney AUC0 → 120h ratio of [177Lu]Lu-6R-RedFol-1 as compared with [177Lu]Lu-6S-RedFol-1 and [177Lu]Lu-OxFol-1. At equal activity, the therapeutic effect of [177Lu]Lu-6R-RedFol-1 was better than that of [177Lu]Lu-OxFol-1, reflected by a slower tumor growth and, consequently, an increased median survival time (49 days vs. 34 days).

Conclusion

This study demonstrated the promising potential of 5-MTHF-based radioconjugates for FR-targeting. Application of [177Lu]Lu-6R-RedFol-1 resulted in unprecedentedly high tumor-to-kidney ratios and, as a consequence, a superior therapeutic effect as compared with [177Lu]Lu-OxFol-1. These findings, together with the absence of early side effects, make [177Lu]Lu-6R-RedFol-1 attractive in view of a future clinical translation.
18F-FDG PET/CT versus anatomic imaging for evaluating disease extent and clinical trial eligibility in Erdheim-Chester disease: results from 50 patients in a registry study
Authors: Kirchner Julian , Hatzoglou Vaios , Buthorn Justin B. , Bossert Dana , Sigler Allison M. , Reiner Anne S. , Ulaner Gary A. , Diamond Eli L.
Published: October 2020

Objectives

The aim of this study was to [1] characterize distribution of Erdheim-Chester Disease (ECD) by 18F-FDG PET/CT and [2] determine the utility of metabolic (18F-FDG PET/CT) imaging versus anatomic imaging (CT or MRI) in evaluating ECD patients for clinical trial eligibility.

Methods

18F-FDG PET/CT and corresponding CT or MRI studies for ECD patients enrolled in a prospective registry study were reviewed. Sites of disease were classified as [1] detectable by 18F-FDG PET only, CT/MRI only, or both and as [2] measurable by modified PERCIST (mPERCIST) only, RECIST only, or both. Descriptive analysis was performed and paired t test for between-group comparisons.

Results

Fifty patients were included (mean age 51.5 years; range 18–70 years). Three hundred thirty-three disease sites were detected among all imaging modalities, 188 (56%) by both 18F-FDG PET and CT/MRI, 67 (20%) by 18F-FDG PET only, 75 (23%) by MRI brain only, and 3 (1%) by CT only. Of 178 disease sites measurable by mPERCIST or RECIST, 40 (22%) were measurable by both criteria, 136 (76%) by mPERCIST only, and 2 (1%) by RECIST only. On the patient level, 17 (34%) had mPERCIST and RECIST measurable disease, 30 (60%) had mPERCIST measurable disease only, and 0 had RECIST measurable disease only (p < 0.0001).

Conclusion

Compared with anatomic imaging, 18F-FDG PET/CT augments evaluation of disease extent in ECD and increases identification of disease sites measurable by formal response criteria and therefore eligibility for clinical trials. Complementary organ-specific anatomic imaging offers the capacity to characterize sites of disease in greater anatomic detail.

Trial registration

ClinicalTrials.gov Identifier: NCT03329274
Evaluation of Perioperative Intestinal Motility Using a Newly Developed Real‐Time Monitoring System During Surgery
Authors: Ogawa Maho , Namikawa Tsutomu , Oki Toyokazu , Munekage Masaya , Maeda Hiromichi , Kitagawa Hiroyuki , Dabanaka Ken , Sugimoto Takeki , Kobayashi Michiya , Sakata Osamu , Matsuda Kenichi , Hanazaki Kazuhiro
Published: October 2020

Background

This study aimed to investigate perioperative intestinal motility using a novel bowel sound monitoring system in patients undergoing breast and neck surgery.

Materials and methods

This study enrolled 52 patients who underwent surgery for breast cancer, thyroid tumor, and parathyroid tumor at Kochi Medical School from May 2019 to June 2020. Perioperative bowel sound counts (BSCs) were recorded using a newly developed real‐time analysis system in the operating theater. Clinical information and BSC per minute (cpm) data during the preanesthetic, preoperative, operative, postoperative periods, and period in recovery room were obtained to compare between each period. The Mann–Whitney U and Pearson Chi‐square tests were used in data analysis.

Results

The BSCs during the intraoperative period and postoperative period were significantly decreased compared to those during the preanesthetic period (0.07 cpm versus [vs.]. 1.4 cpm, P = 0.002 and 0.1 cpm vs. 1.4 cpm, P = 0.025, respectively). The preoperative BSC with a preanesthetic BSC < 1.4 was significantly lower than that with a preanesthetic BSC ≥ 1.4 (0.40 cpm vs. 1.78 cpm, P = 0.006). The preanesthetic, preoperative, and postoperative BSCs with an intraoperative BSC < 0.07 were significantly lower than those with an intraoperative BSC ≥ 0.07 (0.48 cpm vs. 2.83 cpm, P = 0.007; 0.40 cpm vs. 1.81 cpm, P = 0.008; and 0.07 cpm vs. 0.42 cpm, P = 0.006, respectively).

Conclusion

The real‐time bowel sound analysis system demonstrated an inhibitory effect associated with anesthetic and surgical stress on intestinal motility as the BSC sequentially.
Cardiac magnetic resonance T2 mapping and feature tracking in athlete’s heart and HCM
Authors: Gastl Mareike , Lachmann Vera , Christidi Aikaterini , Janzarik Nico , Veulemans Verena , Haberkorn Sebastian , Holzbach Leonie , Jacoby Christoph , Schnackenburg Bernhard , Berrisch-Rahmel Susanne , Zeus Tobias , Kelm Malte , Bönner Florian
Published: October 2020

Objectives

Distinguishing hypertrophic cardiomyopathy (HCM) from left ventricular hypertrophy (LVH) due to systematic training (athlete’s heart, AH) from morphologic assessment remains challenging. The purpose of this study was to examine the role of T2 mapping and deformation imaging obtained by cardiovascular magnetic resonance (CMR) to discriminate AH from HCM with (HOCM) or without outflow tract obstruction (HNCM).

Methods

Thirty-three patients with HOCM, 9 with HNCM, 13 strength-trained athletes as well as individual age- and gender-matched controls received CMR. For T2 mapping, GRASE-derived multi-echo images were obtained and analyzed using dedicated software. Besides T2 mapping analyses, left ventricular (LV) dimensional and functional parameters were obtained including LV mass per body surface area (LVMi), interventricular septum thickness (IVS), and global longitudinal strain (GLS).

Results

While LVMi was not significantly different, IVS was thickened in HOCM patients compared to athlete’s. Absolute values of GLS were significantly increased in patients with HOCM/HNCM compared to AH. Median T2 values were elevated compared to controls except in athlete’s heart. ROC analysis revealed T2 values (AUC 0.78) and GLS (AUC 0.91) as good parameters to discriminate AH from overall HNCM/HOCM.

Conclusion

Discrimination of pathologic from non-pathologic LVH has implications for risk assessment of competitive sports in athletes. Multiparametric CMR with parametric T2 mapping and deformation imaging may add information to distinguish AH from LVH due to HCM.

Key Points

• Structural analyses using T2 mapping cardiovascular magnetic resonance imaging (CMR) may help to further distinguish myocardial diseases.

• To differentiate pathologic from non-pathologic left ventricular hypertrophy, CMR including T2 mapping was obtained in patients with hypertrophic obstructive/non-obstructive cardiomyopathy (HOCM/HNCM) as well as in strength-trained athletes.

• Elevated median T2 values in HOCM/HNCM compared with athlete’s may add information to distinguish athlete’s heart from pathologic left ventricular hypertrophy.