bluuebunny/crossref_metadata_2025 huggingface dataset:
Revision of COVID in China: a thorough analysis of epidemic situations and Chinese strategies during the pandemic
Authors: Deng Yawen , Tian Yushun , Wang Yintong , Xing Yuan
Published: September 2021

COVID-19, the disease caused by SARS-CoV-2, emerged in December 2019 in Wuhan, China, when Chinese authorities confirmed several patients with fever, difficulty breathing, and invasive lesions on the lungs. The virus then spread quickly across the globe, and by May 17, there were a total of 18,151,717 cases worldwide. While some countries still have an exponentially increasing rate of new cases, China has stabilized the spread of the virus. In the review of COVID-19 in this paper, we used sources from Google Scholar, PubMed, Research Gate, etc. In addition, when investigating public policy data and the number of infections, we also used the statements and relevant data from the official websites of the governments of Dalian and Beijing. Our investigation is based on the summary and analysis of the above data to reach our conclusion. We investigated the basic characteristics of COVID-19, the corresponding Sinovac vaccine and mRNA vaccine, the first round of outbreaks in Wuhan, Beijing, and Dalian, and the warning role of COVID-19 in the future. We demonstrated that keeping social distance and isolating infected patients in time can effectively block the transmission of the virus. This paper exposes the necessary public health measures during the pandemic, providing experiences and lessons for a potential future pandemic.
A comprehensive review on COVID-19: What we know and how to treat against the novel coronavirus
Authors: Wang Jiacheng , Xu Xianhao , Xu Zihan
Published: September 2021

COVID-19 emerged in Wuhan, China, at the end of 2019 and then soon evolved into a global pandemic. The novel coronavirus inducing this pandemic is under extensive study held by researchers all over the world. We give out a comprehensive review of what we have known about this novel coronavirus, including the pathogenesis. Passive immunity, different strategies, and targets for vaccine development and antiviral drugs are introduced as therapeutic strategies. At last, many other properties of SARS-Cov-2 are discussed.
Experimental-numerical method for evaluation of energy consumption in percussive drilling of granite
Authors: Yao Wei , Hokka Mikko
Published: September 2021

Most geothermal energy is found in hot and dry rock (HDR), and the total resources distributed at depths of 3-10 km are 20.9×106 EJ. Most HDR projects are developed in granite formations and understanding and control of the energy consumption in percussive drilling of granite is essential. Thus, the impact energy is dissipated in various processes including fracture of the granite, kinetic energy of the particles, and heat. This study presents a numerical-experimental method to evaluate the energy consumption in percussive drilling process. The method uses particle flow code (PFC2D) and experiments using a modified Hopkinson pressure bar system. Optical high-speed and infrared cameras were used to record the impact process during the dynamic drilling process. The velocity of fragments was estimated by the high-speed images and the instantaneous temperature change during the impact was observed from infrared images. Preliminary results are given in this study indicating that the proposed numerical and experimental methodologies can be used to investigate the energy consumption during percussive drilling. The preliminary results presented in this paper are part of a larger work in progress, and more work needs be carried out to obtain the energy consumption of the drilling process under different loading and boundary conditions.
Investigation of the Specific Energy Absorption of Triply Periodic Minimal Surfaces Subjected to Impact Loading
Authors: AlMahri Sara , Santiago Rafael , Lee Dong-wook , Ramos Henrique , Alabdouli Haleimah , Alteneiji Mohamed , Guan Zhongwei , Alves Marcilio
Published: September 2021

Triply periodic minimal surfaces (TPMS) have attracted tremendous research interest due to their lightweight and superior mechanical properties. In this study, two TPMS sheet-based structures (FRD and Neovius) are designed, fabricated, and tested under dynamic and quasistatic loading conditions. Selective laser melting (SLM) is employed to facilitate the fabrication of such complex structures out of stainless steel (SS316L). Scanning electron microscopy (SEM) is utilized to assess the quality of the printed structures. The dynamic compressive behaviour is investigated through performing a direct impact compression test via a Direct Impact Hopkinson Bar (DIHB) at a strain rate of 2000 s-1. Quasi-static tests are also performed at a strain rate of 0.005 s-1. The specific energy absorption (SEA) is compared under both loading conditions to investigate the performance of such structures under dynamic loading. Results show that both structures exhibit higher SEA values under high deformation rates. In fact, Neovius structures outperform FRD structures in terms of specific energy absorption as it exhibits a SEA value of 22.11 J/g and 24.8 J/g SEA in quasi-static and dynamic conditions, respectively.
Use of a Shock Tube Platform in the Replication of Blast Lung Injury
Authors: Butler Benjamin , Nguyen Thuy-Tien , Williams Alun , Tucker Andrew , Proud William G. , Brown Katherine A.
Published: September 2021

War and asymmetrical conflicts are becoming increasingly prevalent in the modern world. Due to improvements in conflict medicine, survivable injuries are now more severe than they once were. Therefore, it is now more important than ever that there exist scientific and engineering methods for replicating wartime injuries in the context of the laboratory. We have developed one such method: a shock tube platform for testing ex vivo samples of the porcine respiratory system. Using this platform, we can, to some extent, simulate the pathophysiological consequences of blast lung. This is a condition commonly present in victims of explosive blasts, both those due to typical armaments and Improvised Explosive Devices (IEDs). Presented here are the results of experiments conducted using porcine bronchiole tissue as ex vivo organ cultures. Data presented show epithelial damage, consistent with known trauma-induced cell injury that can lead to acute respiratory distress syndrome (ARDS).
The effect of strain history on dynamic necking in titanium alloys, experimental and numerical analysis
Authors: Gour Govind , Thomson Daniel , Nik Petrinic Julian Reed , Pellegrino Antonio
Published: September 2021

The determination of the dynamic response of titanium alloys is vital for aerospace industrial applications. The present research investigates the effect of strain history and temperature on the dynamic strain localization in Ti-6Al-4V grade-5 alloy. The experimental campaign was conducted using a Split Hopkinson Tensile Bar (SHTB) equipped with an ultra-highspeed camera. The characterization of the material is highly affected once necking occurs. The true dynamic response is compared for various loading conditions. Furthermore, in order to provide insights about on the local dynamic behavior, a numerical model is established using LSDYNAExplicit solver for monotonic loading conditions. Different constitutive material models are compared, including the phenomenological material model Johnson-Cook, and physically based model, Modified BammanChiesa-Johnson (BCJ).
Modelling the influence of strain and strain rate on the thermal softening during dynamic loading of ductile metals
Authors: Mirone Giuseppe , Barbagallo Raffaele
Published: September 2021

Although the combined effect of strain rate and temperature on the behaviour of metals is widely recognized, no universally accepted viewpoints are available about the physical phenomena. Experiments on a highly ductile A2-70 steel, performed at moderate dynamic rates (10 s-1) and different initial temperatures (20 to 150 °C), are firstly aimed here at assessing whether the thermal softening previously verified at static rates on the same steel is also suitable for describing now the mixed effect of dynamic rates and consequent variable temperatures, or further contributions to the thermal softening are necessary for describing such mixed effects. A general multiplicative model of the dynamic hardening is proposed, based on a static flow curve at room temperature to be increased by the dynamic amplification and to be decreased by the thermal softening, the latter incorporating the known “static component” depending on both strain and constant temperatures, together with a new “dynamic component” incorporating the dependence on the temperature variation and promoted by fast straining. The dynamic amplification of the stress is then obtained from another series of dynamic tests ran at initial room temperature and four nominal strain rates between 1 and 1800 s-1. The trend obtained is compatible with the seizing of the strain rate effect beyond necking onset, already found for other metals in previous works. All the experiments are based on the acquisition of the current load (by load cells for the testing machine and by strain gauges for the Hopkinson bar) and of the current cross section through optical diameter measurements by a fast camera; then, the effective current values of true stress-true strain-true strain rate are measured on a semi-local basis over the neck section at different instants during the test.
An alternative method for the measurement of mechanical properties at intermediate strain rates: a numerical study
Authors: Farotti Emanuele , Mancini Edoardo , Sasso Marco
Published: September 2021

A feasibility study of an innovative apparatus for dynamic characterization of materials at intermediate strain rates is presented. The working principle is based on the Split Hopkinson bar, but the wave propagation occurs through properly sized springs. The system is designed to generate and transmit tension or compression waves having a low propagation speed, in order to reduce the specimen strain rate at the impact. At first, a simplified theory is presented for the estimation of longitudinal wave speed in springs as a function of the main engineering parameters of the coil dimensioning. Then, a preliminary sizing of the apparatus is proposed based on basic considerations of wave propagation theory. Finally, a numerical model of a compression test is presented as a proof-of-concept.
Transient SH Wave Propagation of Elastic Plate
Authors: Miura Kotaro , Sakamoto Makoto , Tanabe Yuji
Published: September 2021

We consider the transient wave propagation problem of linear, isotropic and elastic plate applied SH impact loading on the surface. Analytical solution of half-space obtained by the inverse Fourier-Laplace double transform using Cagniard-De Hoop method. The wave propagation problem of plate was considered by using a half-space exact solution and reflect wave from the boundary of plate are expressed using the image method. Some numerical results of stress and displacement components are presented. The mathematical technique appear in the basic problem can apply to the transient P wave propagation and more advanced problems.
Influence of material properties on the performance of blast-loaded steel plates with pre-cut defects
Authors: Elveli Benjamin S. , Børvik Tore , Aune Vegard
Published: September 2021

Experimental and numerical investigations are carried out to determine how thin steel plates with pre-cut defects behave under blast loading. The defects considered in this study are represented by four square holes, symmetrically distributed around the centre of the target plates. The target plates were manufactured from two types of steel, i.e., a dual-phase medium strength steel and a high-strength martensitic steel. A shock tube facility was used to expose the plates to blast-like loading conditions. The experiments showed that both the blast resistance and the corresponding fracture mode changed with material properties. Numerical simulations were performed using the finite element code LS-DYNA, where the numerical results were found to be in good agreement with the experimental data in predicting the ductile fracture during the blast-structure interaction. The numerical simulations confirmed that significant work hardening will distribute the plasticity throughout the plate material during deformation, while limited work hardening will tend to localize the plasticity that results in earlier fracture.
Strain Rate Dependent Constitutive Modelling of 3D Printed Polymers
Authors: Lißner Maria , Thomson Daniel , Petrinic Nik , Bergmann Jeroen
Published: September 2021

Experimental results from 3D printed TPC (thermoplastic copolyester) compression specimens were used to develop a combined experimental-numerical framework to support the design of e.g. 3D printed mouthguards. First, a commercially available material model capable of representing the strain-rate dependent behaviour of materials undergoing large deformations is identified. Second, experimental results from solid 3D printed compression specimens are used to calibrate the identified material models. Third, 3D printed compression specimens with two different cavity geometries are used to assess the ability of the material model to accurately reproduce the experimental observations. The numerical investigation indicates a good representation of the strain rate dependent experimental results of 3D printed specimens.
Structure of a shell made from uranium alloyed with iron and germanium after explosive loading
Authors: Belyaev D.A. , Aleksandrov A.S. , Zuev Yu.N. , Kozlov E.A. , Shestakov A.E. , Lekomtsev S.A. , Nedosviti A.S. , Svyatov I.L. , Levi E.A.
Published: September 2021

This paper presents results of metallographic examination of a thick-wall spherical shell from uranium alloyed with iron and germanium. This shell is recovered after low-level explosive loading. Light microscopy, hardness measurement, scanning electron microscopy and X-Ray diffraction study were used to investigate the meridional section of the test shell as this section most completely exhibits the whole variety of structural features associated with explosive loading of the material. Processing, presentation, and analysis of experimental data on volumetric distribution of studied physical quantities were performed with the help of digital panning and color mapping.
Localization of plastic deformation in stretching plates: effect of crystalline structure
Authors: Dequiedt Jean-Lin , Denoual Christophe
Published: September 2021

The integration of the polycrystalline structure in the simulation of stretching plates, performed by the random generation of a grain aggregate and a set of lattice orientations, gives new insights into the phenomenon of plastic strain localization in the form of necking, albeit well predicted at the scale of continuum by instability analysis. A transition is displayed from initial grain scale heterogeneity, with some connection to crystal lattice orientation towards stress axes, to the onset of macroscopic localization patterns. Depending on the number of grains and on the stretching rate, it seems that a competition emerges between a “weakest link” process for which the final necks are located in places where initial deformation is high and an instable mode controlled process during which larger patterns emerge driving the location of the final necks. At high stretching rates, it seems that the second effect is enhanced with, accordingly, a pattern size almost insensitive to the grain size and a limited variability with the grain structure occurrence.
Thermomechanical tensile properties of deposited Inconel 718 superalloy over a wide range of strain rate and temperature
Authors: Scapin Martina , Peroni Lorenzo , Yuan Kangbo , Guo Weiguo
Published: September 2021

Nickel-based superalloys show high strength retained also at high temperature and they are widespread used for structural components exposed during services to high temperature combined with high strain rate or impact loading conditions. The objective of this study was the investigation of the plastic flow behaviour of Laser Metal Deposited Nickel-based superalloy Inconel718. The material was manufactured at Northwestern Polytechnical University in China. Specimens with three different heat treatment conditions were investigated: as-deposited, directly aged and aged after homogenization and solution. High strain rate tensile tests were performed on the direct Hopkinson bar setup developed at DYNLab laboratory at Politecnico di Torino. At a nominal strain rate of 1500 s-1the temperature sensitivity was investigated between 20 and 1000°C. An induction heating system was adopted, and the temperature was monitored by thermocouples and infrared pyrometer and high-speed camera. The results showed the materials strength decreases as a function of temperature with a significant drop starting from 800 °C. An asymmetric tension-compression behaviour was found by comparing the results with data in compression. The strain rate influence was investigated at room temperature and very limited or negligible sensitivity was found covering six orders of magnitude in strain rate.
A multispecies investigation of the strain rate sensitivity of the modulus of cortical bone
Authors: Rampersadh Claire Victoria , Welgemoed Lee-Anne , Cloete Trevor John
Published: September 2021

The stiffness of cortical bone shows both inter- and intra-species variation. Currently, it is unclear whether this variation is due to differing testing protocols or an inherent feature of the material. Additionally, there is a lack of literature dealing with species other than human and bovine, particularly in the intermediate strain rate regime. In this study, cortical bone specimens were machined from the femurs of four species: baboon, crocodile, sheep and ostrich. Specimens were tested in the quasi-static and intermediate strain rate regimes using consistent testing protocols implemented by a single researcher. The results show a similar strain rate dependence for all species, i.e. the modulus shows negligible rate effects in the quasi-static regime, but a significant increase when moving to intermediate strain rates. This suggests that while the stiffness of the bone is species dependent, the effect of strain rate may be species independent. The observed intra- and inter-species variation is less than that reported in literature, highlighting the importance of a consistent testing protocol in multi-species studies.
Investigation on interface charges in SiN/AlxGa1−xN/GaN heterostructures by analyzing the gate-to-channel capacitance and the drain current behaviors
Authors: Rrustemi Bledion , Jaud Marie-Anne , Triozon François , Piotrowicz Clémentine , Vandendaele William , Leroux Charles , Le Royer Cyrille , Biscarrat Jérôme , Ghibaudo Gérard
Published: September 2021

In SiN/AlGaN/GaN heterostructures, the evaluation of interface charges at the SiN/AlGaN and AlGaN/GaN interfaces is crucial since they both rule the formation of the two-dimensional electron gas (2DEG) at the AlGaN/GaN interface. In this paper, we conducted a thorough analysis of the gate-to-channel capacitance CGC(VG) and of the drain current ID(VG) over a gate voltage VG range enabling the depletion of the 2DEG and the formation of the electron channel at the SiN/AlGaN interface. This work includes the establishment of analytical equations for VTH1 (formation of the 2DEG) and VTH2 (formation of the electron channel at the SiN/AlGaN interface) as a function of interface charges and of the p-doping below the 2DEG. The inclusion of the p-doped layer below the 2DEG and the use we made of VTH2 have not been reported in previous studies. Our analysis allows a reliable estimate of the interface charges at the AlxGa1−xN/GaN and SiN/AlxGa1−xN interfaces for various Al concentrations x as well as to demonstrate that the polarization charge at the SiN/AlxGa1−xN interface is compensated, which confirms previous findings. Moreover, this compensation is found to be induced by the AlGaN layer rather than the SiN layer.
Ultrafast demagnetization in NiCo2O4 thin films probed by time-resolved microscopy
Authors: Takahashi Ryunosuke , Tani Yoshiki , Abe Hirotaka , Yamasaki Minato , Suzuki Ikumi , Kan Daisuke , Shimakawa Yuichi , Wadati Hiroki
Published: September 2021

Using a time-resolved magneto-optical Kerr effect microscope, we observed ultrafast demagnetization of inverse-spinel-type ferrimagnet NiCo2O4 (NCO) epitaxial thin films with perpendicular magnetic anisotropy. This microscope uses a pump-probe method, where the sample is pumped at 1030 nm, and magnetic domain images are acquired via magneto-optical Kerr effect microscopy at 515 nm (the second harmonic). We observed the dynamics of the magnetic domain of the NCO thin film via laser irradiation and obtained a demagnetization time constant of approximately 0.4 ps. This time constant was significantly smaller than the large time constants reported for other half-metallic oxides. This timescale of ∼0.4 ps agrees with the spin polarization of ∼0.7 determined by tunnel magnetoresistance [Shen et al., Appl. Phys. Lett. 117, 042408 (2020)].
Measuring the probe Stark shift by frequency modulation spectroscopy in an 87Sr optical lattice clock
Authors: Xu Qinfang , Lu Xiaotong , Xia Jingjing , Wang Yebing , Chang Hong
Published: September 2021

In this paper, we demonstrate a frequency modulation technique to accurately measure the probe Stark shift of optical clocks. The effective coupling strength of the probe laser to the clock transition is precisely controlled by this frequency modulation technique, which is different from the traditional method by controlling the effective coupling strength via changing the probe light power. In an 87Sr optical lattice clock, the probe Stark shifts are measured as a function of the square of the bare state coupling strength. The probe Stark shift coefficient of 87Sr is experimentally determined as −6.0(5)×10−7/Hz using this frequency modulation technique. With the help of frequency modulation, the probe light power can be as large as possible without decreasing the measurement precision and the achieved measurement lever arm is improved by more than one order of magnitude compared with previous results.
Monte Carlo analysis of the influence of surface charges on GaN asymmetric nanochannels: Bias and temperature dependence
Authors: Pérez-Martín E. , Íñiguez-de-la-Torre I. , Gaquière C. , González T. , Mateos J.
Published: September 2021

In this paper, the occupancy of sidewall surface states having a clear signature in the performance of AlGaN/GaN-based self-switching diodes (SSDs) is analyzed using a semi-classical Monte Carlo (MC) simulator in a wide temperature (T) range, from 100 to 300 K. Experimental I–V curves show an unusual current decrease at low temperature attributed to surface trapping. The dependence on T of the negative surface charge density σ at the etched sidewalls of the SSDs is essential to explain the measurements. Two devices with different widths (80 and 150 nm) have been characterized and simulated in detail paying especial attention to the modeling of the surface states. At room temperature, MC simulations with a position-independent value of σ are able to qualitatively reproduce the I–V curves. However, a more complex approach is required to correctly replicate the values and shape of the DC experimental curves at low temperature, below 220 K. An algorithm where σ depends not only on T but also on the applied bias V is proposed to successfully fit the current values at every bias point. The model is able to explain the physics of the unexpected dependence of the resistance with the channel width and the sign change in the bowing coefficient, the parameters that govern the detection capabilities of the diodes.
Ladder operators and coherent states for the Rosen–Morse system and its rational extensions
Authors: Garneau-Desroches S , Hussin V
Published: September 2021

Ladder operators for the hyperbolic Rosen–Morse (RMII) potential are realized using the shape invariance property appearing, in particular, using supersymmetric quantum mechanics. The extension of the ladder operators to a specific class of rational extensions of the RMII potential is presented and discussed. Coherent states are then constructed as almost eigenstates of the lowering operators. Some properties are analyzed and compared. The ladder operators and coherent states constructions presented are extended to the case of the trigonometric Rosen–Morse (RMI) potential using a point canonical transformation.
Visible Light Photocatalytic Degradation of Sunset Yellow Dye and Industrial Textile Wastewater Using Pd-BiFeO3 Composite
Authors: Jaffari Z H , Lam S M , Ng D Q , Sin J C
Published: September 2021

Herein, pristine BiFeO3 and Pd-incorporated BiFeO3 (Pd-BiFeO3) composite were synthesized using hydrothermal synthesis method. The physiochemical and optical properties of the synthesized materials were investigated using numerous techniques. The Pd-BiFeO3 composite significantly enhanced the photocatalytic degradation of sunset yellow (SSY) dye in comparison with the pristine BiFeO3 under visible light irradiation. The enhanced photoactivity was credited to the improved photogenerated charge carrier separation, which was in accordance with the photoelectrochemical measurements. Moreover, the Pd-BiFeO3 composite can be recycled for seven consecutive runs without sufficient loss of photocatalytic activity. Radical trapping studies suggested that the hydroxyl radical (•OH), hydrogen peroxide (H2O2) and hole (h+) were the key reactive oxidizing species. A possible photocatalytic enhancement mechanism of Pd-BiFeO3 composite was stated. Finally, for the first time, the Pd-BiFeO3 composite was also applied towards the effective degradation of industrial textile wastewater.
Detection of the Carbaryl in Wastewater by HPLC-DAD
Authors: Xiaona JI , Lin Fanglong , Ren Zhimin , Tian Xi , Zuo Yan , Bian Dejun
Published: September 2021

A method for determination of the carbaryl pesticide residue in wastewater by high performance liquid chromatography (HPLC). HPLC using Agilent ZORBAX SB-C18 column as a separate column; the use of volume ratio(55:45) of methanol: water as the mobile phase; the use of a diode array detector(DAD) detection at 268 nm at carbaryl residues; pretreatment of water samples using the extraction method is simple and feasible method of operation; laboratory water samples from wastewater, test results show: accuracy relative standard deviation(RSD) was 0.67%, and the recovery rates were in the range of 102 to 112%.
Research on Sustainable Development Path of Ecological Agriculture Industry in Beijing Suburbs—Taking Xibaidian Village, Daxingzhuang Town, Pinggu District as an Example
Authors: Wu Siqi , Wang Zhi , Tan Yarong
Published: September 2021

With the vigorous advancement of rural revitalization policies, industrial prosperity has put forward new requirements for the ecological agriculture industry. Not only requires the provision of higher quality agricultural products, but also promotes the adjustment of the agricultural industry structure. It is necessary to meet the continuous increase in farmers’ income and the people’s demand for a better life. In recent years, Beijing suburban agriculture has achieved good results in green production, rural energy and agricultural leisure construction. However, there are still problems such as being greatly affected by raw materials, low operating economic income, and insufficient technical equipment. In this paper, the three development models of eco agriculture in Xibaidian village are analyzed. Construct a sustainable development path for the ecological agriculture industry in the suburbs of Beijing from the development concept, development mechanism and new industrial formats. Promote diversification to build a rural complex in Beijing, and realize the harmonious unity of ecological protection and farmers’ income increase.
Techno-economic Analysis and Comparative Study for the Sustainability of Private Motor Vehicles in China
Authors: Lu Chuyue
Published: September 2021

This article discusses the life cycle energy consumption and cost of three new energy vehicles (NEVs) through life cycle analysis (LCA) and techno-economic analysis, and compares them with a conventional vehicle (CV). In ideal, average, and extreme scenarios, new energy vehicles are more sustainable than CV, especially in terms of greenhouse gas emissions, but are not as economical as CV. To be concise, electric vehicles have the best environmental sustainability, but the total cost is higher than CVs. The total cost of hybrid electric vehicles is slightly lower than conventional vehicles, but the environmental sustainability is poor.
Supervised machine learning applied to gas leak detection in air conditioner cooling system
Authors: Moreira S. F. , Shah V. , Varela M. L. R. , Monteiro A. C. , Putnik G. D.
Published: September 2021

This paper aims to present a concept test for an alternative refrigerant gas leak detection method, to be used in air conditioning manufacturing processes, in order to increase confidence in retaining products with gas leak in the factory, minimizing human interference in the test. To analyse the proposed solution, experimentation cycles were conducted, involving variables of industrial environment, product, and a thermographic camera with infrared technology, responsible for collecting the thermal image of the leak study area. Supervised machine learning method was used to train algorithms on temperature dataset to classify an area either as “Gas leakage” or “Normal”. The regression logistic algorithm had the best performance in the predictions, showing that it is possible to detect “Gas leakage” area in automatic decision-making in an industrial environmental.
New results for witnesses of Robin’s criterion
Authors: Saouter Yannick
Published: September 2021

In a seminal paper, Robin proved that the Riemann hypothesis holds if and only if the inequality

σ
(
n
)
=

∑

d

|

n

d
>

e
γ

n
log
⁡
log
⁡
n

\sigma (n)=\sum _{d|n} d > e^\gamma n \log \log n

holds for all integers greater than 5040, where

γ
\gamma

is the Euler-Mascheroni constant. In this article, we prove new results on putative violations of Robin’s criterion.
Ketogenic dietary interventions in autosomal dominant polycystic kidney disease—a retrospective case series study: first insights into feasibility, safety and effects
Authors: Strubl Sebastian , Oehm Simon , Torres Jacob A , Grundmann Franziska , Haratani Jazmine , Decker Morgan , Vuong Sabrina , Kaur Bhandal Amrit , Methot Nils , Haynie-Cion Rhianna , Meyer Franziska , Siedek Florian , Korst Uwe , Müller Roman-Ulrich , Weimbs Thomas
Published: September 2021

Background

Our laboratory published the first evidence that nutritional ketosis, induced by a ketogenic diet (KD) or time-restricted diet (TRD), ameliorates disease progression in polycystic kidney disease (PKD) animal models. We reasoned that, due to their frequent use for numerous health benefits, some autosomal dominant PKD (ADPKD) patients may already have had experience with ketogenic dietary interventions (KDIs). This retrospective case series study is designed to collect the first real-life observations of ADPKD patients about safety, feasibility and possible benefits of KDIs in ADPKD as part of a translational project pipeline.

Methods

Patients with ADPKD who had already used KDIs were recruited to retrospectively collect observational and medical data about beneficial or adverse effects and the feasibility and safety of KDIs in questionnaire-based interviews.

Results

A total of 131 ADPKD patients took part in this study. About 74 executed a KD and 52 a TRD for 6 months on average. A total of 86% of participants reported that KDIs had improved their overall health, 67% described improvements in ADPKD-associated health issues, 90% observed significant weight loss, 64% of participants with hypertension reported improvements in blood pressure, 66% noticed adverse effects that are frequently observed with KDIs, 22 participants reported safety concerns like hyperlipidemia, 45 participants reported slight improvements in estimated glomerular filtration rate and 92% experienced KDIs as feasible while 53% reported breaks during their diet.

Conclusions

Our preliminary data indicate that KDIs may be safe, feasible and potentially beneficial for ADPKD patients, highlighting that prospective clinical trials are warranted to confirm these results in a controlled setting and elucidate the impact of KDIs specifically on kidney function and cyst progression.
Matrix metalloproteinase-2 on activated platelets triggers endothelial PAR-1 initiating atherosclerosis
Authors: Momi Stefania , Falcinelli Emanuela , Petito Eleonora , Ciarrocca Taranta Giulia , Ossoli Alice , Gresele Paolo
Published: September 2021

Aims 

Platelets participate in atherogenesis with mechanisms not yet fully clarified. Vascular wall MMP-2 is involved in the arterial remodelling accompanying atherosclerosis. Platelets contain and release MMP-2 but no informations are available on its role in atherosclerotic lesion formation.

Methods and results 

We generated double knockout mice lacking the LDL receptor and MMP-2 only in circulating blood cells showing that they develop significantly lesser femoral intima thickening after photochemical-induced arterial damage and atherosclerotic lesions in the aorta, measured by the en face method, after 4 months of atherogenic diet. Moreover, repeated transfusions of autologous-activated platelets in LDLR−/− mice on atherogenic diet significantly enhanced the extension of aortic atherosclerotic lesions while transfusion of activated platelets from MMP-2−/− mice did not. In vitro coincubation studies showed that platelet-derived MMP-2 plays a pivotal role in the development and progression of atherosclerosis through a complex cross-talk between activated platelets, monocyte/macrophages, and endothelial cells. Translational studies in patients with CAD and chronic HIV infection showed that platelet surface expression of MMP-2 highly significantly correlated with the degree of carotid artery stenosis.

Conclusion 

We show a previously unknown mechanism of the pathway through which platelets expressing MMP-2 trigger the initial phases of atherosclerosis and provide a mechanism showing that they activate endothelial PAR-1 triggering endothelial p38MAPK signalling and the expression of adhesion molecules. The development of drugs blocking selectively platelet MMP-2 or its expression may represent a new approach to the prevention of atherosclerosis.
Pipeline for generating stable large genomic deletions in zebrafish, from small domains to whole gene excisions
Authors: Tromp Alisha , Robinson Kate , Hall Thomas E , Mowry Bryan , Giacomotto Jean
Published: September 2021

Here we describe a short feasibility study and methodological framework for the production of stable, CRISPR/Cas9-based, large genomic deletions in zebrafish, ranging from several base pairs (bp) to hundreds of kilobases (kb). Using a cocktail of four single guide RNAs (sgRNAs) targeting a single genomic region mixed with a marker-sgRNA against the pigmentation gene tyrosinase, we demonstrate that one can easily and accurately excise genomic regions such as promoters, protein domains, specific exons, or whole genes. We exemplify this technique with a complex gene family, neurexins, composed of three duplicated genes with multiple promoters and intricate splicing processes leading to thousands of isoforms. We precisely deleted small regions such as their transmembrane domains (150 bp deletion in average) to their entire genomic locus (300 kb deletion for nrxn1a for instance). We find that both the concentration and ratio of Cas9/sgRNAs are critical for the successful generation of these large deletions and, interestingly, that in our study, their transmission frequency does not seem to decrease with increasing distance between sgRNA target sites. Considering the growing reports and debate about genetically compensated small indel mutants, the use of large-deletion approaches is likely to be widely adopted in studies of gene function. This strategy will also be key to the study of non-coding genomic regions. Note that we are also describing here a custom method to produce the sgRNAs, which proved to be faster and more robust than the ones traditionally used in the community to date.
Changes in the Hierarchy of Functional Impairment From Middle Age to Older Age
Authors: Brown Rebecca T , Diaz-Ramirez L Grisell , Boscardin W John , Cappola Anne R , Lee Sei J , Steinman Michael A
Published: September 2021

Background

Understanding the hierarchy of functional impairment in older adults has helped illuminate mechanisms of impairment and inform interventions, but little is known about whether hierarchies vary by age. We compared the pattern of new-onset impairments in activities of daily living (ADLs) and instrumental ADLs (IADLs) from middle age through older age.

Methods

We conducted a cohort study using nationally representative data from 32 486 individuals enrolled in the Health and Retirement Study. The outcomes were new-onset impairment in each ADL and IADL, defined as self-reported difficulty performing each task, assessed yearly for 9 years. We used multistate models and competing risks survival analysis to estimate the cumulative incidence of impairment in each task by age group (ages 50–64, 65–74, 75–84, and 85 or older).

Results

The pattern of incident ADL impairments differed by age group. Among individuals ages 50–64 and 65–74 who were independent at baseline, over 9 years’ follow-up, difficulties dressing and transferring were the most common impairments to develop. In individuals ages 75–84 and 85 or older who were independent at baseline, difficulties bathing, dressing, and walking were most common. For IADLs, the pattern of impairments was similar across age groups; difficulty shopping was most common followed by difficulty managing money and preparing meals. Complementary analyses demonstrated a similar pattern.

Conclusions

These findings suggest that the hierarchy of ADL impairment differs by age. These findings have implications for the development of age-specific interventions to prevent or delay functional impairment.
Frequency filter for elastic bending waves: Poincaré map method and experiment
Authors: Torres-Guzmán J C , Arreola-Lucas A , Quintana-Moreno M , Zamora-Romero N , Flores-Olmedo E , Báez G , Méndez-Sánchez R A
Published: September 2021

In this work, the Poincaré map numerical method was successfully developed to solve the fourth-order differential equation that describes the flexural vibrations of a beam, within the Timoshenko beam theory. The Euler-Bernoulli continuity conditions were considered, which are valid for frequencies smaller than the critical frequency. As an example, this method was used to design a complex elastic structure, characterized by a flexural frequency spectrum with a broad band gap. Such structure consists of two coupled phononic crystals, which were designed with filling factor values in such a way that in their bending frequency spectra, an allowed band of the first part, overlaps with a band gap of the second one and vice versa. The resulting composed system has a much wider effective gap than its original components, between 4 and 10.5 kHz. This system works as an elastic bending wave filter. Finally, these three structured elastic systems were constructed, and characterized by the acoustic resonance spectroscopy technique. The natural flexural frequencies as well as the corresponding wave amplitudes of each structured beam were measured. The experimental measurements show excellent agreement with the numerical simulation.
BioSeq-BLM: a platform for analyzing DNA, RNA and protein sequences based on biological language models
Authors: Li Hong-Liang , Pang Yi-He , Liu Bin
Published: September 2021

In order to uncover the meanings of ‘book of life’, 155 different biological language models (BLMs) for DNA, RNA and protein sequence analysis are discussed in this study, which are able to extract the linguistic properties of ‘book of life’. We also extend the BLMs into a system called BioSeq-BLM for automatically representing and analyzing the sequence data. Experimental results show that the predictors generated by BioSeq-BLM achieve comparable or even obviously better performance than the exiting state-of-the-art predictors published in literatures, indicating that BioSeq-BLM will provide new approaches for biological sequence analysis based on natural language processing technologies, and contribute to the development of this very important field. In order to help the readers to use BioSeq-BLM for their own experiments, the corresponding web server and stand-alone package are established and released, which can be freely accessed at http://bliulab.net/BioSeq-BLM/.
OS02.4.A Molecular characterization of adult cerebellar glioblastomas identifies distinct prognosis subgroups
Authors: Picart T , Poncet D , Barritault M , Pallud J , Metellus P , Zouaoui S , Bauchet L , Guyotat J , Gabut M , Honnorat J , Ducray F , Meyronet D
Published: September 2021

BACKGROUND

Adult cerebellar glioblastomas (cGBM) are very rare and recent studies have shown that they constitute a heterogeneous group of gliomas. The aim of the present study was to characterize the prevalence and prognostic significance of major driver molecular alterations in a large series of cGBM.

MATERIAL AND METHODS

Adults with histologically proven cGBM diagnosed between 2003 and 2017 were identified from the French brain tumor database and the Club de Neuro-Oncologie of the Société Française de Neurochirurgie. Tumors were reviewed and reclassified according to WHO 2016. Targeted sequencing was performed, including determination of H3F3A, TERTp, IDH1/2, FGFR1, BRAF and EGFR status.

RESULTS

A total of 83 adult patients (median age 57 years) with cGBM (hemispheric n= 47, vermian n=14 or both n=22) were identified. Median overall survival was 10 months. Main molecular alterations observed were TERT promoter, H3F3A K27M, hotspot FGFR1 (N546 and K656), BRAF mutations, EGFR amplification and ATRX loss of expression in 19.2%, 18.8%, 10.9%, 2.6%, 19.5% and 22.7% of patients, respectively. cGBM could be classified into 6 mutually exclusive subgroups associated with age at diagnosis and prognosis: pTERT and/or EGFR amplified tumors (n=22, 26.5%, median age = 62 years, median OS = 4 months), H3K27M-mutant tumors (n=15, 18.1%, median age = 48 years, median OS =8 months), tumors with MAPK pathway activating mutations (FGFR1, BRAF) or occurring in NF1 patients (n=15, 18.1%, median age = 41 years, median OS = 57 months), radiation-induced tumors (n=5, 6%, median age = 47 years, median OS = 5 months), IDH-mutant tumors (n=1) and unclassified tumors (n=25, 30.1%, median age = 63 years, median OS = 17 months). In multivariate analysis, MAPK activating mutations and ATRX loss of expression were independently associated with a better outcome and pTERT/EGFR alterations with a worse outcome.

CONCLUSION

About 18% of tumors diagnosed as cGBM harbor actionable MAPK activating genetic alterations. Targeted sequencing enables to classify these tumors into clinically relevant subgroups.
OS03.3.A Characterization of long-term metabolic changes of irradiated brain metastases using serial dynamic FET PET imaging
Authors: Galldiks N , Stoffels G , Werner J , Bauer E K , Baues C , Celik E , Ruge M I , Fink G R , Langen K , Lohmann P
Published: September 2021

BACKGROUND

In the present study, we characterized the long-term metabolic changes of brain metastases irradiated with stereotactic radiosurgery (SRS) by sequential dynamic PET imaging using the radiolabeled amino acid O-(2-[18F]-fluoroethyl)-L-tyrosine (FET). We hypothesized that this approach is of considerable clinical value to diagnose delayed radiation-induced changes.

MATERIAL AND METHODS

From 2010–2021, we retrospectively identified patients with brain metastases from solid extracranial primary tumors who (i) were treated with SRS with or without concurrent immunotherapy using checkpoint inhibitors, (ii) had equivocal or progressive MRI findings after SRS, and (iii) subsequently underwent at least two additional dynamic FET PET scans during follow-up for long-term evaluation. Mean tumor-to-brain ratios (TBR) and the dynamic FET PET parameter time-to-peak were obtained. Diagnostic performances were calculated using receiver operating characteristic curve analyses. Diagnoses were confirmed histologically or clinicoradiologically.

RESULTS

We identified 36 patients with 98 FET PET scans (median number, 3; range, 2–6). Concurrent to SRS, 8 patients (22%) were treated with checkpoint inhibitors. Following SRS, suspicious MRI findings occurred after a median time of 11 months (range, 2–64 months). Subsequently, FET PET scans were acquired over a median period of 13 months (range, 5–60 months). The overall median follow-up time was 26 months (range, 8–101 months). Twenty-one patients (58%) had delayed radiation-induced changes. TBRs calculated from the last available FET PET scan showed the highest accuracy (92%) to identify delayed radiation-induced changes (threshold, 1.95; P<0.001).

CONCLUSION

FET PET has a high diagnostic accuracy for characterizing the long-term changes of irradiated brain metastases.
OS06.9A Diversity of cellular communication in glioblastoma
Authors: Joseph K , Vollmer L , Ravi V M , Beck J , Hofmann U G , Schnell O , Heiland D H
Published: September 2021

BACKGROUND

Owing to recent advances in understanding of the active functional states exhibited within glioblastoma (GBM), intra-tumoral cellular signaling has moved into focus of neuro-oncological research. In our study, we aim to explore the diversity of transcellular signaling and investigate correlations to transcriptional dynamics and cellular behavior.

MATERIAL AND METHODS

Electrophysiological mapping of primary GBM cultures was performed by planar microelectrodes, in conjunction with calcium imaging in a human neocortical section based GBM model. Exposure to conditions that are physiologically present within the tumor was carried out to identify specific signaling cells of interest and signaling diversity presented as response to specific environmental conditions. Transcriptional dynamics and plasticity were examined by means of scRNA-sequencing with CRISPR based perturbation, spatial transcriptomics and deep long-read RNA-sequencing.

RESULTS

Electrophysiological profiles of primary GBM cell lines revealed highly variable network activity. Despite these different characteristics, all profiled primary cell-lines exhibited characteristics of scale-free networks, confirmed in a human neocortical GBM model. When the GBM was allowed to grow in “in-vivo” like environment, basal activity was significantly increased, owing to interactions with elements within the neural environment. Cellular signaling was directly correlated to changes in the environment, like hypoxia or glutamatergic activation, and total inhibition of electrical signaling was achieved only with a combination of both gap junction and synaptic inhibitors. Using single-cell sequencing and proteomics, we identified several genes related to synaptogenesis that plays a crucial role in network formation and consequently transcellular signaling. CRISPR based perturbation of these genes resulted in alterations in cellular morphology and decreased cellular connectivity, with electrical signaling being significantly attenuated. Single-cell sequencing of perturbed tumor cells in the GBM model revealed a loss of developmental lineages and significant reduction of cellular stress response state.

CONCLUSION

Our findings highlight the role of electrical signaling in glioblastoma. Cellular stressors induce intercellular signaling, leading to transcriptional adaptation suggesting that there exists a highly complex and powerful mechanism for dynamic transcriptional state adaptation.