bluuebunny/crossref_metadata_2025 huggingface dataset:
Introduction of business continuity plan for small and medium-sized local construction companies and restoration activities in Japan in the event of natural disasters
Authors: Okuno I
Published: June 2023

In recent years, Japan has suffered significant damage due to natural disasters such as major earthquakes and flood Construction companies are expected to play an important role during natural disasters and respond quickly and restore infrastructure. The first author runs a small local construction company in Okayama, Japan. During a flood in 2011 at Okayama, the embankment restoring site turned extremely dangerous for workers. At this juncture, the first author, in the capacity of a company manager, identified the safety and administrative issues, and in 2013, the company began to implement BCP. When there was heavy flooding in Okayama in 2017, they supported the administration in recovery operations based on their BCP. The impact of BCP is to be acknowledged as the emergency operations were safer and timelier. BCP of the company has been continuously improved, and they were invited to join infrastructure recovery activities in the disaster area of Great East Japan Earthquake in 2019. The area is not the usual business region of the company, but 1,000 km away. There is a high requirement for human resources and equipment for emergency and recovery activities immediately after a disaster. Most of the construction companies are small and locally based in Japan, and several resources available at the construction site itself for initial recovery activities. It is desirable to prepare a plan so that the affected companies themselves can respond. The main tasks are the training of personnel to provide guidance and support for BCP, and the development of systems and laws that can actively support activities. By capturing accurate information on resources of local construction companies, their capability and response speed during an emergency can be improved. It is also necessary to create a system to receive support from other companies or organizations in case self-help is difficult or insufficient.
Analysis capacity of U-turn movement at median opening using microsimulation PTV Vissim (case study: median opening Jl. Prof. Soedarto, SH. Tembalang, Semarang, Indonesia)
Authors: Karimi M B U Al , Haryadi B , Setiadji B H
Published: June 2023

The median opening is a facility for turning vehicles, but when traffic flow is too high can become a congestion point. Congestion due to the volume of turning vehicles turning over capacity. Based on these problems, it is necessary to know the U-turn movement capacity of the median opening. In addition, analytical capacity calculations have limitations in practical simulations similar to traffic conditions in the field. The purpose of this study was to compare the capacity of U-turn movement of light vehicle (LV) at median opening using two methods, that is, Harder model and PTV Vissim microsimulation which was validated by the capacity of field measurements. Two median opening located on Jl. Prof. Soedarto, S.H., Tembalang, Semarang, that is, Polines and Tembalang exit toll median opening, were selected as case studies. The results showed that the PTV Vissim microsimulation could outperform the Harder model in estimating the capacity of U-turn movement for LV vehicles at median opening. The inconsistent behavior of the drivers when they make U-turn, together with the geometry of the median openings, contributed to the significant errors produced by Harder model.
Process chain for forming and consolidating fiber-reinforced thermoplastics and metallic sheets in a two-stage isothermal tool
Authors: Behrens B-A , Raatz A , Hübner S , Farahmand E , Albracht L , Fünfkirchler T , Yarcu S , Schumann C , Wehmeyer J
Published: June 2023

Due to their good mechanical properties and low structural weight, multi-material structures are a promising approach in the automotive industry to lightweight design, body construction and functionalization. Especially metal and plastic are mainly combined to achieve improved properties of the final component compared to mono-material structures. This paper describes the development of a manufacturing cell for the joint forming and heat-assisted press joining of steels and continuous fiber-reinforced thermoplastics in the form of unidirectional carbon-fiber tapes. In order to achieve shorter cycle times and to ensure economical production, a manufacturing cell, supplemented with automated handling by means of two robots and an isothermal, two forming stages tool concept was developed and tested. The composite components produced were tested with regard to their mechanical performance. The feasibility of the production was demonstrated. All composite components had a higher specific load capacity than a pure steel component. Cycle times of well under 60 seconds were achieved. An enormous reduction in process time compared to variothermal tool concepts could be achieved with the new manufacturing cell.
Investigation on evolution of microstructure and mechanical properties of heat-treatable 6010-S aluminium alloy during gas-based hot sheet metal forming process
Authors: Teeuwen T , Baru N K , Bailly D , Hirt G
Published: June 2023

Modern hot sheet metal forming processes offer the opportunity, especially in the automotive sector, to meet current demands for ultra-lightweight design. Due to the increased formability at the high process temperatures, high-strength aluminium alloys are increasingly coming into the focus of the industry. However, the complex thermo-mechanical interactions within these processes can lead to undesirable microstructural changes that could have a negative impact on the final mechanical properties. The purpose of this work is therefore to investigate the microstructural evolution of age-hardenable EN AW 6010-S alloy in the course of a modern gas-based sheet metal forming process and to quantify its influence on the resulting mechanical T6 properties. For this purpose, two different components were first formed at laboratory scale and the areas of microstructural interest were identified. Metallographic examinations and EBSD measurements were performed to visualize the influence of process temperature and deformation on the microstructure. EDX analysis helped to identify non-metallic phases. In the next step, artificial aging of the components was performed to increase the mechanical properties. Tensile tests and hardness measurements showed that the deformation and temperature have no negative influence on the final mechanical properties of the alloy.
Numerical and experimental investigation of hole flangeability of AA6061 alloy
Authors: Kumar V , Ravi Kumar D
Published: June 2023

Hole flangeability is a measure of edge formability or local formability, and it is important for forming processes like stretch flanging. Hole flangeability of sheet metals is evaluated by determination of hole expansion ratio (HER) using a standard hole expansion test (HET). In the present work, numerical and experimental investigation of hole flangeability has been carried out on 1.6mm thick AA6061 alloy sheets. The material model plays an important role in the accuracy of predicted results in numerical simulations. The simulations have been carried out using two different work hardening laws (Swift and Voce). The failure has been predicted using the experimentally determined forming limit curve (FLC) of AA6061 alloy sheets. HER and thickness have been predicted along the edge of the expanded hole by simulation. The predicted HER and thinning from FE simulation have been validated experimentally by performing hole expansion tests according to ISO 16630-2009 using a conical punch. The predicted results have been found to be in good agreement with the experimental results.
Study on the ultrasonic-assisted spinning of thin-walled cylindrical parts with longitudinal and transverse ribs
Authors: Li Shuangli , Zhao Yixi , Yu Zhongqi , Li Shuhui
Published: June 2023

Current studies have shown that the application of composite energy fields in the plastic forming process can help reduce the forming load and promote material flow. In this paper, a new method of ultrasonic-assisted spinning integral forming for thin-walled cylindrical parts with outer ribs was proposed, which could not only improve the manufacturing efficiency of ribbed cylindrical parts, but also further improve the forming height of outer ribs. A simulation model of ultrasonic-assisted spinning for thin-walled cylindrical parts with longitudinal and transverse outer ribs was established, the influence of ultrasonic amplitude on the forming accuracy of longitudinal and transverse outer ribs was obtained, and the mechanism of ultrasonic vibration improving the forming accuracy of ribs was revealed. On this basis, ultrasonic-assisted spinning equipment was built to verify the feasibility of this process. The results showed that with the increase of ultrasonic amplitude, the forming height of longitudinal and transverse outer ribs gradually increases, and the effect of raising the forming height of transverse ribs is higher than that of longitudinal ribs. In addition, as the ultrasonic amplitude increases, the uniformity of the forming morphology of the outer rib is not obviously improved. The spinning of the outer rib is mainly realized by the material in the form of integral filling into the groove. The ultrasonic vibration improves the material flow properties, and promotes the filling of the material into the rib groove, thereby increasing the spinning forming height of the outer ribs. The forming height of the outer rib was measured with or without ultrasonic vibration. When the rolling reduction is 1 mm, the average forming height of the outer ribs is increased by 50% compared with that without ultrasound, which provides a new research idea for the integral forming of the spinning of thin-walled cylindrical parts with longitudinal and transverse ribs.
Partial resistance tempering of hot-stamped components made of 22MnB5 for subsequent bending
Authors: Behrens B A , Hübner S , Herbst S , Albracht L , Wehmeyer J , Yarcu S , Müller P , Farahmand E
Published: June 2023

The manganese-boron alloy 22MnB5 is particularly used for structural and safety-relevant parts in the automotive industry. Parts made from this alloy are usually produced using the hot forming process. Here, the sheet is heated to over 950 °C using an industrial roller hearth furnace. The heated sheet is then simultaneously formed and quenched in a cooled tool with a temperature gradient of more than 27 K/s. This leads to the formation of a martensitic microstructure with a hardness value of over 450 HV10 and an elongation at break of less than 6%. The small strain potential of such components makes them difficult to form after hot-stamping. Due to the high temperature gradients of resistance heating, a sheet can be heat-treated locally without a large temperature transition zone. This can be used to locally soften already hot-stamped components for subsequent operations such as bending. Within the scope of this paper, resistance heating is used to soften a hot-stamped 22MnB5+AlSi sheet stripe of 3 mm width. The sheet could consequently be bent over an angle of 90° without cracking the substrate.
Measurement and prediction methods for forming limit strain of stretch bending deformation in sheet metal forming
Authors: Taguchi Y , Maeda Y , Maeda Y
Published: June 2023

In this study, a new test method using protruding punch was proposed, that can separate bending and stretching deformations. In this test, the blank makes simultaneous contact with the punch head and shoulder to ensure a constant bending angle during the test. After the simultaneous contact, increasing the punch stroke increases the amount of stretch deformation without changing the bending deformation. In addition, this test method can control the inflow of materials by controlling the BHF, and it is possible to evaluate cracks during stretch bending deformation even for materials with low forming limits. This test can control the distribution of strain through the thickness. As a result, the measurable surface formation limit strain in this test was higher than FLC with uniform strain along the thickness. It is suggested that this is because the strain gradient through the thickness delayed the timing of necking occurrence. There is a linear relationship between this strain gradient and the maximum principal strain on the sheet surface, which can be applied to the prediction of stretch-bending cracks in FEM analysis.
Development of a new cyclic shear test setup for characterizing thin metallic foils
Authors: Karadogan C , Beck M , Cyron P , Riedmüller K R , Liewald M
Published: June 2023

Recent developments aimed at reducing cumulative CO2emissions in the energy sector and e-mobility are leading to an increase in the production volumes of formed components made from thin metallic foils used for alternative energy supply concepts. Thus, components such as bipolar plates in fuel cells and a variety of parts in e-motors and batteries are being manufactured in ever higher quantities and thinner material thicknesses. As a consequence, this leads to increased challenges regarding the feasibility and robustness of required production processes. Finite Element Analysis in fact do represent a useful tool in this context to predict and to optimize expected outcome of forming processes virtually at an early stage of development. The prediction accuracy of such simulation codes thereby significantly depends on the precision of modelling the sheet metal material behavior, which is derived from special characterization methods. However, classical approaches to mechanical characterization usually tend to fail in case of thin metallic foils, especially when the structural stability of the specimen becomes an important factor for the validity of the characterization test. The cyclic shear test, for example, is used to determine the hardening behavior of the material to be characterized, but appear unsuitable for metallic foil investigations unless a special anti-wrinkling device is used. Current anti-wrinkling devices proposed in literature must be attached directly to the deforming area of the specimen and cause further weaknesses. Attaching such devices to prevent the specimen from wrinkling requires remarkable skills of the operator to avoid deforming of the specimen even before testing. Against this background, this paper presents a novel experimental setup, which increases the structural stability of the cyclic shear specimen and thus prevents wrinkling. Structural stability of specimen is enhanced by curving the gauge area of the specimen to drastically suppress the tendency to wrinkle. As a proof of concept FE-simulations with LS-Dyna were performed in this study to verify this novel idea and to design a suitable experimental setup.
Process optimisation and robustness analysis for HFQ process
Authors: Mohamed M , Szegda D , Swift J , Gaines O , Ling D , Sonntag M , Güner A
Published: June 2023

Lightweight materials and lightweight technologies have gained significant attention from all EV vehicle manufacturers. Aluminium has been commonly used as a lightweight replacement for steel in the automotive industry for many years. High-strength aluminium alloys have high specific strength, and their formability increases significantly at elevated temperatures. New manufacturing technologies incorporating elevated temperature forming have emerged recently, allowing forming of high and ultrahigh-strength aluminium alloys. One such technology is Hot Form Quench (HFQ)® which is a process that combines high formability with virtually no springback for (ultra)-high-strength aluminium alloys. The thermal expansion of aluminium alloys is approximately twice that of steel, leading to significant material contraction during in-die quenching. This is especially pronounced for large or long components. Therefore, robustness analysis of the process parameters can be used to optimise the process parameters and enable a capable production of parts meeting dimensional specification requirements. Such analysis can be performed using AutoForm-Sigma solver and this paper presents a simulation methodology developed in AutoForm and its use to verify the accuracy of the thermal distortion prediction for one of the safety cell structure components. A sensitivity analysis has been implemented to optimise the process parameters to improve manufacturing robustness.
Optimization of the physical scaling approach through the adaption of the inverted membrane stresses
Authors: Zimmermann P , Birkert A , Nowack M , Kraft T
Published: June 2023

Dimensional deviations of stamped car body components caused by elastic springback still represent a significant problem for the development of the stamping tools. First, the springback causes deviations of the part in vertical direction to the part surface due to bending stresses. Second, the surface area of the part contracts (and also bends) due to elastic membrane stresses. The precise manifestation of the contraction depends both on the part stiffness and on the – usually heterogeneous – distribution of the membrane stresses. Usually, the resulting deformations cannot adequately be compensated by globally homogeneous scaling approaches. In order to carry out a locally correct compensation of the stamping tools, Birkert et al. have recently presented a physical scaling approach based on the inverted membrane stresses gained from the part in the closed die to compensate the active die surfaces. This approach delivered significantly better results but left potential for improvement. It is shown in the present paper how the existing approach and thus the scaling values can further be improved by adapting the inverted membrane stresses in an appropriate way. This is done by comparing the amount of strain changes during spring-back with those of the scaling process in a first step and adjusting the compensation stresses, in a second step, in such a way that the considered strain amounts are approximately identical.
Pressure Distributions in Deep Drawing with a Passive Cardanic Blank Holder
Authors: Breunig A , Groche P
Published: June 2023

Deep drawing processes are strongly influenced by the blank holder forces, as well as their local distribution. In current deep drawing tools, this pressure distribution is dominated by the compliance of the specific machine the tool is mounted on. Therefore, each tool must be manually polished to enable the desired distribution of the blank holder pressure. This regularly causes problems when transferring tools from one machine to another, for example from a try-out press to a regular press line. As both machines have unique compliances, the pressure distribution on the flange of the drawn part changes. Additional manual spot grinding is needed to achieve the desired pressure distribution on the flange. To counteract this problem, the use of a passive cardanic blank holder is proposed in this paper. The cardanic blank holder can freely tilt around two axes, which leads to an auto-leveling effect of the blank holder on the sheet, resulting in a more uniform blank holder pressure. This effect is demonstrated experimentally using pressure sensitive film on the same tool with two different blank holders, one equipped with a conventional blank holder, the other with a cardanic blank holder. To demonstrate transferability, the experiments are repeated on multiple single acting presses. The contribution will present and discuss the resulting pressure distributions.
Novel tool steel for application in hot stamping
Authors: Knippenberg J , Niederhofer P , Krull H-G , Richert S
Published: June 2023

Hot stamping is a commonly used procedure to manufacture components from high strength steels, which are used for parts of car bodies. Against the background of production efficiency and costs, there is a number of factors which determine the performance of tools used in hot stamping, e.g. cycle time in production and lifetime of the tools. Main requirement is a high wear resistance, while additional properties such as high thermal conductivity can be considered being beneficial. Many steel grades, which are currently applied in hot stamping tools (e.g. hot work tool steel 1.2367) contain high amounts of alloying elements which gives them good mechanical properties, particularly at high temperatures. However, these steels in turn suffer from a rather low thermal conductivity and only moderate wear resistance. Optimization of the balance of mechanical properties, wear resistance, and thermal conductivity can lead to a better general performance of hot working tool steels used in hot stamping applications. In this study, a novel tool steel is characterized with special focus on properties relevant for hot stamping tools. Results are compared to those of reference hot work tool steels. Wear tests that were conducted in the framework of this paper include laboratory setups like ASTM G65 / G75 and high-temperature strip-drawing test setups to simulate the conditions of the process closer to reality. Results show that the novel tool steel is characterized by an increased wear resistance in combination with a higher thermal conductivity compared with common hot work tool steels. Furthermore it is approved that a wide range of desired properties can be adjusted in this alloy via heat treatment. The favourable combination of properties makes the novel tool steel suitable for application in hot stamping tools.
Experimental investigation of the effect of lubricant change on automotive component
Authors: Carvalho L A , Zsolt L
Published: June 2023

Manufacturing problems resulting from lubricant supplier changes are relatively common in automotive press shops. Simulations using computer-aided design (process and tool) detect a significant proportion of manufacturing problems before tools are physically produced. In modern forming codes, an enhanced Coulomb model is used to numerically model the friction phenomena associated with lubrication. In the laboratory condition, determining model parameters through physical measurement is challenging. As a result, it became necessary to design a device that could be utilized in industrial environments. In this study, we present the prediction of a manufacturing problem resulting from a change in the lubricant of an industrial sheet metal part. The measuring device has been developed based on the parameters of the friction model of the lubricant materials. The developed measuring device may be used to determine the pressure and velocity dependent friction model parameters. The measuring device can only measure a limited range of pressures and velocities, so the results are extended to a wider range using a mathematical method. The results are used to demonstrate the effect of lubricant material changes on the forming process using the AutoForm code.
Structural, spectroscopic and morphology studies on green synthesized ZnO nanoparticles
Authors: Sarkar Toton , Kundu Sani , Ghorai Gurupada , Sahoo Pratap Kumar , Bhattacharjee Ashis
Published: June 2023

Zinc oxide nanoparticles (ZnO NPs) were synthesised using Tabernaemontana divaricata flower extract (TFE) in different weight percentages by facile, eco-friendly and cost-effective green synthesis method. Formation and structure of the ZnO NPs were studied by powder XRD, FT−IR, Raman and TEM studies. The crystals formed are of hexagonal wurtzite structure with biological functional groups attached. Average crystallite size of the ZnO NPs (17.5−23.3 nm) was obtained from the analysis of powder XRD data which increased with increase of TFE amount while the estimated values of dislocation density and micro-strain exhibited an opposite behaviour. The optical (direct and indirect) energy band gap values estimated using UV–vis DRS spectral data decreased with increasing amount of TFE. The photoluminescence spectra for the ZnO NPs exhibited multiple peaks spread over the visible region with one peak in the NIR region indicating the existence of various defect levels of Zn and O. Position of these defect levels within the band gap was assigned which is significantly modulated by TFE. TFE amount-dependent peak shift and/or peak broadening were observed in the Raman spectra of the ZnO NPs which were correlated with the growing disorder in the crystals induced by the extract molecules. FESEM study showed the agglomerated NPs with quasi-spherical morphology. Particle size of the ZnO NPs was estimated from FESEM images. EDX study indicated that increased presence of TFE in ZnO decreased the oxygen content in the synthesised material. HRTEM study revealed the agglomeration of nanoparticles with single crystalline nature. Present study convincingly established that flower extract used for the green synthesis efficiently modified the structure and optical property, defect levels and morphology of the potentially useful ZnO nanoparticles.
Impact of nitrogen annealing on the electrical properties of HgCdTe epitaxial films
Authors: Jin Dapeng , Zhou Songmin , Chen Lu , Lin Chun , He Li
Published: June 2023

The nitrogen annealing of HgCdTe materials grown by molecular beam epitaxy (MBE) was carried out to manipulate their electrical properties. The results show that the annealing temperature, annealing time and cooling process all have significant influences on the electrical properties of HgCdTe materials. Excessive annealing temperature or long annealing time can make voids emerge on the surface of the CdTe passivation layer. Carrier concentration and mobility vary exponentially with annealing time and they reach an equilibrium value determined by annealing temperature over a long annealing duration. Moreover, time constants are given and a longer time is needed for mobility to reach an equilibrium value than carrier concentration. The relationship between equilibrium carrier concentration and annealing temperature is given and the activation energy under nitrogen annealing is calculated as 0.63 eV. For a long cooling duration, Hg vacancies are annihilated by Hg atoms diffusion, which makes carrier concentration lower and mobility higher. In addition, some outlier data were found in this experiment and explained by the combination between Te antisites and Hg vacancies.
Towards control of the chirality sign at ultrathin metal films: Bi at 2Ni/Co
Authors: Gallego Silvia
Published: June 2023

Proximity effects can be used to introduce spin–orbit interactions in magnetic metallic layers in contact to a heavy metal (HM). This well known phenomenon has been exploited to induce chiral spin textures at Co ultrathin films, where the left- or right- handedness can be tuned by the HM layer position, based on the broken inversion symmetry of the film and the existence of an additive interface effect. Here we show that structural and chemical features introducing further symmetry reductions can be added to this scenario ultimately enabling control over the definition of a unique winding sense. We focus on 2Ni/Co heterostructures and Bi, a scarcely explored HM metal of large size, to combine a chemically inhomogeneous ferromagnetic stack along the normal to the surface with in-plane asymmetries. Our results are contrasted to 2Co layers combined with Ir.
Performance evaluation of a novel synchronously interdigitated/winded lithium-ion battery configuration enabled by 3D printing through numerical simulations
Authors: Li Yide , Li Jie , Liu Zhiyuan , Chen Zhangwei , Liu Changyong
Published: June 2023

Thick electrodes with higher energy density are highly desirable for lithium-ion batteries (LIBs). However, the sluggish transport of Li-ions in thick electrodes is a critical challenge. In this study, a novel synchronously interdigitated/winded battery configuration enabled by 3D printing is proposed. The cathode, separator, and anode are synchronously interdigitated in the core and synchronously winded in the outer-rings to form an integrated full battery. With this novel battery configuration, Li-ions can transport between neighboring cathode and anode, thereby significantly reduce the transport distance of Li-ions, and improve the electrochemical reaction kinetics. To evaluate the electrochemical performance of this battery configuration, this study investigates the effects of various parameters including the electronic conductivity, electrode porosity, electrode line width, separator thickness, and number of winded outer-rings on the electrochemical performance through numerical simulations. Results showed that electronic conductivity is the most crucial factor in determining the electrochemical performance. In combination with multi-material 3D printing, the battery configuration proposed in this study may be utilized to build LIBs with higher energy density.
Climatology and decadal changes of Arctic atmospheric rivers based on ERA5 and MERRA-2
Authors: Zhang Chen , Tung Wen-wen , Cleveland William S
Published: June 2023

We present the Arctic atmospheric river (AR) climatology based on twelve sets of labels derived from ERA5 and MERRA-2 reanalyses for 1980–2019. The ARs were identified and tracked in the 3-hourly reanalysis data with a multifactorial approach based on either atmospheric column-integrated water vapor (IWV) or integrated water vapor transport (IVT) exceeding one of the three climate thresholds (75th, 85th, and 95th percentiles). Time series analysis of the AR event counts from the AR labels showed overall upward trends from the mid-1990s to 2019. The 75th IVT- and IWV-based labels, as well as the 85th IWV-based labels, are likely more sensitive to Arctic surface warming, therefore, detected some broadening of AR-affected areas over time, while the rest of the labels did not. Spatial exploratory analysis of these labels revealed that the AR frequency of occurrence maxima shifted poleward from over-land in 1980–1999 to over the Arctic Ocean and its outlying Seas in 2000–2019. Regions across the Atlantic, the Arctic, to the Pacific Oceans trended higher AR occurrence, surface temperature, and column-integrated moisture. Meanwhile, ARs were increasingly responsible for the rising moisture transport into the Arctic. Even though the increase of Arctic AR occurrence was primarily associated with long-term Arctic surface warming and moistening, the effects of changing atmospheric circulation could stand out locally, such as on the Pacific side over the Chukchi Sea. The changing teleconnection patterns strongly modulated AR activities in time and space, with prominent anomalies in the Arctic-Pacific sector during the latest decade. Besides, the extreme events identified by the 95th-percentile labels displayed the most significant changes and were most influenced by the teleconnection patterns. The twelve Arctic AR labels and the detailed graphics in the atlas can help navigate the uncertainty of detecting and quantifying Arctic ARs and their associated effects in current and future studies.
Managing small populations—using genetic data and trial translocations to help inform suitable conservation measures for the alpine blue-sowthistle (Cicerbita alpina) in Scotland
Authors: Finger A , Smedley M , Halley D , Frachon N , Ahrends A
Published: June 2023

Habitat fragmentation is causing an increasing amount of species loss around the world and creates problems at the population level. Many species are left as only small and isolated populations, which are vulnerable to genetic erosion and inbreeding depression. Here we present a study on the alpine blue-sowthistle (Cicerbita alpina). Due to intensive grazing the species is very rare in Scotland, where it occurs at only four small, montane sites, has never been reported to reproduce and is in need of conservation interventions. As the species can grow clonally it is unknown how many individuals remain and whether populations are affected by genetic isolation. We (1) quantified genetic diversity, inbreeding and between-population differentiation in Scotland and Norway using 15 microsatellite loci, and (2) experimentally translocated plants to new sites. Genetic diversity in Scotland was low (H
E: 0.35; Allelic Richness: 1.84; 4 sites) compared to Norway (H
E: 0.52; Allelic Richness: 2.56; 5 sites). The transplants were able to grow at new sites and are therefore not restricted to steep, montane ledges. While grazing is likely to be the main factor preventing range expansion, long-term genetic isolation has possibly further lowered population viability. To avoid local extinction of this species, conservation translocations and genetic rescue might be appropriate conservation interventions, but this needs to be further tested in a controlled environment and away from wild sites to avoid potential risks of outbreeding depression.
A Closer Look at Practice Effects in Mild Cognitive Impairment and Alzheimer’s Disease
Authors: Duff Kevin , Dixon Ava , Embree Lindsay
Published: June 2023

Practice effects have become a potentially important variable regarding the diagnosis, prognosis, and treatment recommendations in mild cognitive impairment (MCI) and Alzheimer’s disease (AD). However, the understanding of these short-term changes in test scores remains unclear. The current observational study sought to examine variables that influence the magnitude of short-term practice effects in MCI and AD, including demographic information, cognitive performance, daily functioning, and medical comorbidities. One hundred sixty-six older adults classified as cognitively intact, amnestic MCI, or mild AD were tested twice across 1 week with a brief battery of neuropsychological tests. Correlational and regression analyses examined the relationship of practice effects with demographic and clinical variables. Results indicated that practice effects were minimally related to demographic variables and medical comorbidities, but they were significantly related to cognitive variables, depressive symptoms, and daily functioning. These findings expand our understanding of practice effects in MCI and AD, and they may allow a better appreciation of how they could affect clinical care and research.
Biologically informed variational autoencoders allow predictive modeling of genetic and drug-induced perturbations
Authors: Doncevic Daria , Herrmann Carl
Published: June 2023

Motivation

Variational autoencoders (VAEs) have rapidly increased in popularity in biological applications and have already successfully been used on many omic datasets. Their latent space provides a low-dimensional representation of input data, and VAEs have been applied, e.g. for clustering of single-cell transcriptomic data. However, due to their non-linear nature, the patterns that VAEs learn in the latent space remain obscure. Hence, the lower-dimensional data embedding cannot directly be related to input features.

Results

To shed light on the inner workings of VAE and enable direct interpretability of the model through its structure, we designed a novel VAE, OntoVAE (Ontology guided VAE) that can incorporate any ontology in its latent space and decoder part and, thus, provide pathway or phenotype activities for the ontology terms. In this work, we demonstrate that OntoVAE can be applied in the context of predictive modeling and show its ability to predict the effects of genetic or drug-induced perturbations using different ontologies and both, bulk and single-cell transcriptomic datasets. Finally, we provide a flexible framework, which can be easily adapted to any ontology and dataset.

Availability and implementation

OntoVAE is available as a python package under https://github.com/hdsu-bioquant/onto-vae.
WarpSTR: determining tandem repeat lengths using raw nanopore signals
Authors: Sitarčík Jozef , Vinař Tomáš , Brejová Broňa , Krampl Werner , Budiš Jaroslav , Radvánszky Ján , Lucká Mária
Published: June 2023

Motivation

Short tandem repeats (STRs) are regions of a genome containing many consecutive copies of the same short motif, possibly with small variations. Analysis of STRs has many clinical uses but is limited by technology mainly due to STRs surpassing the used read length. Nanopore sequencing, as one of long-read sequencing technologies, produces very long reads, thus offering more possibilities to study and analyze STRs. Basecalling of nanopore reads is however particularly unreliable in repeating regions, and therefore direct analysis from raw nanopore data is required.

Results

Here, we present WarpSTR, a novel method for characterizing both simple and complex tandem repeats directly from raw nanopore signals using a finite-state automaton and a search algorithm analogous to dynamic time warping. By applying this approach to determine the lengths of 241 STRs, we demonstrate that our approach decreases the mean absolute error of the STR length estimate compared to basecalling and STRique.

Availability and implementation

WarpSTR is freely available at https://github.com/fmfi-compbio/warpstr
Interpretable deep learning architectures for improving drug response prediction performance: myth or reality?
Authors: Li Yihui , Hostallero David Earl , Emad Amin
Published: June 2023

Motivation

Interpretable deep learning (DL) models that can provide biological insights, in addition to accurate predictions, are of great interest to the biomedical community. Recently, interpretable DL models that incorporate signaling pathways have been proposed for drug response prediction (DRP). While these models improve interpretability, it is unclear whether this comes at the cost of less accurate DRPs, or a prediction improvement can also be obtained.

Results

We comprehensively and systematically assessed four state-of-the-art interpretable DL models using three pathway collections to assess their ability in making accurate predictions on unseen samples from the same dataset, as well as their generalizability to an independent dataset. Our results showed that models that explicitly incorporate pathway information in the form of a latent layer perform worse compared to models that incorporate this information implicitly. However, in most evaluation setups, the best performance was achieved using a black-box multilayer perceptron, and the performance of a random forests baseline was comparable to those of the interpretable models. Replacing the signaling pathways with randomly generated pathways showed a comparable performance for the majority of the models. Finally, the performance of all models deteriorated when applied to an independent dataset. These results highlight the importance of systematic evaluation of newly proposed models using carefully selected baselines. We provide different evaluation setups and baseline models that can be used to achieve this goal.

Availability and implementation

Implemented models and datasets are provided at https://doi.org/10.5281/zenodo.7787178 and https://doi.org/10.5281/zenodo.7101665, respectively.
Fluid treatment in acute pancreatitis: a careful balancing act
Authors: Strand Kristian , Møller Jannicke H
Published: June 2023

Administration of intravenous fluids remains important in acute pancreatitis, but there is still equipose regarding the amount of fluids needed to reduce further organ failure and death. In this paper the damaging effects of fluid overload are discussed and we suggest an approach to fluid therapy incorporating recent evidence from randomized controlled trials.
Architectural traits underlie growth form diversity and polycarpic versus monocarpic life histories inCerberiopsis(Apocynaceae)
Authors: Salmon Camille , Isnard Sandrine , Caraglio Yves , Heuret Patrick
Published: June 2023

Plant architecture strongly influences plant growth habits, as it determines the arrangement, function and fate of meristems. How architecture could be involved in the monocarpic life history, i.e. dying after flowering, remains poorly investigated. Monocarpy is evident in some species since they are annual or because their single stem flowers apically. However, monocarpy in long-lived branched trees is rare and remains poorly understood. We aim to highlight the architectural features involved in the monocarpic strategy of Cerberiopsis candelabra, a rainforest tree endemic to New Caledonia. We conducted a comparative analysis of the genus, which comprises three species with different growth habits. Twenty plants of each species were studied at different ontogenic stages. We compared their developmental sequence and analysed their processes of growth, branching, flowering and reiteration. We identified a combination of traits that distinguish the species, and we found a syndrome of two architectural features that support the monocarpic strategy in C. candelabra: the synchronous flowering of all terminal meristems and the absence of delayed branching. Flowering in C. candelabra preferentially occurs when the complete architectural sequence is developed, but the plant never shows signs of senescence, suggesting that environmental stresses, such as wind disturbance, could be the main trigger for flowering. The architecture of C. candelabra is suggested to be the most derived in the genus.
Optimizing the Design of Clinical Trials to Evaluate the Efficacy of Function-Promoting Therapies
Authors: Bhasin Shalender , Cawthon Peggy M , Correa-de-Araujo Rosaly , Storer Thomas W , Volpi Elena , Newman Anne B , Dioh Waly , Tourette Cendrine , Evans William J , Fielding Roger A
Published: June 2023

Background

Several candidate molecules that may have application in treating physical limitations associated with aging and chronic diseases are in development. Challenges in the framing of indications, eligibility criteria, and endpoints and the lack of regulatory guidance have hindered the development of function-promoting therapies.

Methods

Experts from academia, pharmaceutical industry, National Institutes of Health (NIH), and Food and Drug Administration (FDA) discussed optimization of trial design including the framing of indications, eligibility criteria, and endpoints.

Results

Mobility disability associated with aging and chronic diseases is an attractive indication because it is recognized by geriatricians as a common condition associated with adverse outcomes, and it can be ascertained reliably. Other conditions associated with functional limitation in older adults include hospitalization for acute illnesses, cancer cachexia, and fall injuries. Efforts are underway to harmonize definitions of sarcopenia and frailty. Eligibility criteria should reconcile the goals of selecting participants with the condition and ensuring generalizability and ease of recruitment. An accurate measure of muscle mass (eg, D3 creatine dilution) could be a good biomarker in early-phase trials. Performance-based and patient-reported measures of physical function are needed to demonstrate whether treatment improves how a person lives, functions, or feels. Multicomponent functional training that integrates training in balance, stability, strength, and functional tasks with cognitive and behavioral strategies may be needed to translate drug-induced muscle mass gains into functional improvements.

Conclusions

Collaborations among academic investigators, NIH, FDA, pharmaceutical industry, patients, and professional societies are needed to conduct well-designed trials of function-promoting pharmacological agents with and without multicomponent functional training.
Drugs Targeting Mechanisms of Aging to Delay Age-Related Disease and Promote Healthspan: Proceedings of a National Institute on Aging Workshop
Authors: Espinoza Sara E , Khosla Sundeep , Baur Joseph A , de Cabo Rafael , Musi Nicolas
Published: June 2023

The geroscience hypothesis posits that by targeting key hallmarks of aging we may simultaneously prevent or delay several age-related diseases and thereby increase healthspan, or life span spent free of significant disease and disability. Studies are underway to examine several possible pharmacological interventions for this purpose. As part of a National Institute on Aging workshop on the development of function-promoting therapies, scientific content experts provided literature reviews and state-of-the-field assessments for the studies of senolytics, nicotinamide adenine dinucleotide (NAD+) boosters, and metformin. Cellular senescence increases with age, and preclinical studies demonstrate that the use of senolytic drugs improves healthspan in rodents. Human studies using senolytics are in progress. NAD+ and its phosphorylated form, NADP+, play vital roles in metabolism and cellular signaling. Increasing NAD+ by supplementation with precursors including nicotinamide riboside and nicotinamide mononucleotide appears to extend healthspan in model organisms, but human studies are limited and results are mixed. Metformin is a biguanide widely used for glucose lowering, which is believed to have pleiotropic effects targeting several hallmarks of aging. Preclinical studies suggest it improves life span and healthspan, and observational studies suggest benefits for the prevention of several age-related diseases. Clinical trials are underway to examine metformin for healthspan and frailty prevention. Preclinical and emerging clinical studies suggest there is potential to improve healthspan through the use of pharmacologic agents reviewed. However, much further research is needed to demonstrate benefits and general safety for wider use, the appropriate target populations, and longer-term outcomes.
Weight Gain and Metabolic Changes in Patients With First-Episode Psychosis or Early-Phase Schizophrenia Treated With Olanzapine: A Meta-Analysis
Authors: Correll Christoph U , Højlund Mikkel , Graham Christine , Todtenkopf Mark S , McDonnell David , Simmons Adam
Published: June 2023

Background

Patients with first-episode psychosis or early-phase schizophrenia are susceptible to olanzapine-associated weight gain and cardiometabolic dysregulation. This meta-analysis characterized weight and metabolic effects observed during olanzapine treatment in randomized clinical trials in this vulnerable patient population.

Methods

PubMed, EMBASE, and Dialog were searched for randomized controlled trials (RCTs) reporting weight or cardiometabolic outcomes associated with olanzapine treatment in first-episode psychosis or early-phase schizophrenia. Random-effects meta-analysis and meta-regression were conducted using R v4.0.5.

Results

Of 1203 records identified, 26 RCTs informed the analyses. The meta-analytic mean (95% CI) weight gain was 7.53 (6.42–8.63) kg in studies (n = 19) that reported weight gain with olanzapine treatment. Stratified by duration, the mean (95% CI) weight gain was significantly higher in studies >13 weeks in duration than in those lasting ≤13 weeks: 11.35 (10.05–12.65) vs 5.51 (4.73–6.28) kg, respectively. Despite between-study variability, increases from baseline in most glycemic and lipid parameters were generally small in studies of both ≤13 and >13 weeks. There were no correlations, however, between weight gain and metabolic parameter changes when stratified by study duration.

Conclusions

In RCTs enrolling patients with first-episode psychosis or early-phase schizophrenia, olanzapine was consistently associated with weight gain that was greater in studies lasting >13 weeks compared with those of ≤13 weeks. Metabolic changes observed across studies suggest that RCTs may underestimate metabolic sequelae vs real-world treatment observations. Patients with first-episode psychosis or early-phase schizophrenia are vulnerable to olanzapine-associated weight gain; strategies minimizing olanzapine-associated weight gain should be carefully considered.
Polynomial Relations Among Kappa Classes on the Moduli Space of Curves
Authors: Kazarian Maxim , Norbury Paul
Published: June 2023

We construct an infinite collection of universal—independent of $(g,n)$—polynomials in the Miller–Morita–Mumford classes $\kappa _m\in H^{2m}( \overline{\mathcal{M}}_{g,n},{\mathbb{Q}})$, defined over the moduli space of genus $g$ stable curves with $n$ labeled points. We conjecture vanishing of these polynomials in a range depending on $g$ and $n$.