bluuebunny/crossref_metadata_2025 huggingface dataset:
High-Temperature Corrosion Behaviors of Structural Materials for Lead-Alloy-Cooled Fast Reactor Application
Authors: Lee Seung Gi , Shin Yong-Hoon , Park Jaeyeong , Hwang Il Soon
Published: March 2021

The corrosion of nuclear-grade steels in lead–bismuth eutectic (LBE) complicates the realization of high coolant temperatures. Corrosion tests of T91, HT9, and SS316L were performed in static cells at 600 °C for 2000 h at an oxygen level of 10−6 wt.%. The obtained corrosion surfaces of post-processed samples were characterized by several microscopy methods. Up to 1000 h, all the alloys exhibited an evolution of duplex oxide layers, which were spalled until 2000 h due to their increased thickness and decreased integrity. Following the spallation, a thin internal Cr-rich oxide layer was formed above the Cr-depleted zone for T91 and HT9. SS316L was penetrated by LBE down to 300 μm in severe cases. A comparison on the corrosion depths of the materials with regard to the parabolic oxidation law with abundant literature data suggests that it may lose its validity once the duplex layer is destroyed as it allows LBE to penetrate the metal substrate.
Effect of Muscle Action on the Kinetic and Kinematic Behavior of the Barbell during Isoinertial Strength Assessment
Authors: Garnacho-Castaño Manuel Vicente , Hernández-Lougedo Juan , García-Fernández Pablo , Maté-Muñoz José Luis
Published: March 2021

An isoinertial strength assessment was performed to examine the kinetic and kinematic behavior of the barbell during several muscle actions. Velocity–time characteristics, force–time relationship, one repetition maximum (1RM), power output, and acceleration were compared in eccentric–concentric (EC) versus concentric only (C) sequences of the bench press (BP) and military press (MP). In two separate sessions, 28 and 29 resistance-trained athletes executed EC or C sequences in random order of the BP and MP, respectively, in an incremental load test up to their 1RM. Higher values were recorded in BP-EC than in BP-C, MP-EC, or MP-C (p < 0.01) for peak acceleration, peak rate of force development, peak rate of velocity development, and power output. Significant differences were detected between exercises in terms of the portion of the concentric phase (%) at which peak acceleration was detected, or acceleration up until peak velocity was observed (p < 0.05). No differences were observed between exercises in the portion of the concentric phase where acceleration up to the braking phase took place. The eccentric muscle action prior to concentric movement was a key factor to enhance the kinematic and kinetic performance in BP exercise. No such effects of the countermovement were produced in MP.
The Effects of External Loads and Muscle Forces on the Knee Joint Ligaments during Walking: A Musculoskeletal Model Study
Authors: Frigo Carlo Albino , Donno Lucia
Published: March 2021

A musculoskeletal model was developed to analyze the tensions of the knee joint ligaments during walking and to understand how they change with changes in the muscle forces. The model included the femur, tibia, patella and all components of cruciate and collateral ligaments, quadriceps, hamstrings and gastrocnemius muscles. Inputs to the model were the muscle forces, estimated by a static optimization approach, the external loads (ground reaction forces and moments) and the knee flexion/extension movement corresponding to natural walking. The remaining rotational and translational movements were obtained as a result of the dynamic equilibrium of forces. The validation of the model was done by comparing our results with literature data. Several simulations were carried out by sequentially removing the forces of the different muscle groups. Deactivation of the quadriceps produced a decrease of tension in the anterior cruciate ligament (ACL) and an increase in the posterior cruciate ligament (PCL). By removing the hamstrings, the tension of ACL increased at the late swing phase, while the PCL force dropped to zero. Specific effects were observed also at the medial and lateral collateral ligaments. The removal of gastrocnemius muscles produced an increase of tension only on PCL and lateral collateral ligaments. These results demonstrate how musculoskeletal models can contribute to knowledge about complex biomechanical systems as the knee joint.
Conformational Transitions of Double-Stranded DNA in Thin Films
Authors: Serec Kristina , Šegedin Nikola , Krajačić Maria , Dolanski Babić Sanja
Published: March 2021

Conformational transitions of double-stranded DNA in different environments have long been studied as vital parts of both in vitro and in vivo processes. In this study, utilizing Fourier transform infrared spectroscopy (FTIR), we provide detailed analysis of dynamics of A- to B-form transitions in DNA thin films of different hydrated states based on a statistical analysis of a substantial number of spectra and band shape analysis (peak fitting) in both the phosphate (1150–1000 cm−1) and sugar–phosphate (900–750 cm−1) region. Hydration of DNA thin films is systematically controlled by the time spent in the desiccator chamber (from 3 min to 40 min) allowing conformation and hydration signatures, in addition to variations due to ambient conditions, to be resolved in the spectra. Conformation transition from A-form to more ordered B-form is observed if sufficient time in the desiccator chamber is allowed and is confirmed by changes on the bands at ≈890, 860, 837, and 805 cm−1. Phosphate vibrations at ≈1230 cm−1 and 1089 cm−1, and backbone vibrations at ≈1030 cm−1 and 765 cm−1 were found to be sensitive to changes in hydration rather than conformation. Additionally, we found that spectral variations caused by ambient conditions can be significantly reduced without inducing conformational changes, which serves as a good basis for quality assurance.
Analytical Solutions of Model Problems for Large-Deformation Micromorphic Approach to Gradient Plasticity
Authors: Aslan Ozgur , Bayraktar Emin
Published: March 2021

The objective of this work is to present analytical solutions for several 2D model problems to demonstrate the unique plastic fields generated by the implementation of micromorphic approach for gradient plasticity. The approach is presented for finite deformations and several macroscopic and nonstandard microscopic boundary conditions are applied to a gliding plate to illustrate the capability to predict the size effects and inhomogeneous plastic fields promoted by the gradient terms. The constitutive behavior of the material undergoing plastic deformation is analyzed for softening, hardening and perfect plastic response and corresponding solutions are provided. The analytical solutions are also shown to match with the numerical results obtained by implementing a user element subroutine (UEL) to the commercial finite element software Abaqus/Standard.
Effect of Unit-Cell Size on the Barely Visible Impact Damage in Woven Composites
Authors: El-Dessouky Hassan M. , Saleh Mohamed Nasr , Wang Ying , Alotaibi Mohamed S.
Published: March 2021

The effect of the weaving architecture and the z-binding yarns, for 2D and 3D woven composites on the low-velocity impact resistance of carbon fibre reinforced composites, is investigated and benchmarked against noncrimp fabric (NCF). Four architectures, namely: NCF, 2D plain weave (2D-PW), 3D orthogonal: plain (ORT-PW) and twill (ORT-TW), were subjected to 15 J impact using a 16 mm-diameter, 6.7 kg hemispherical impactor. Nondestructive techniques, including ultrasonic C-scanning, Digital Image Correlation (DIC) and X-ray computed tomography (CT) were used to map and quantify the size of the induced barely visible impact damage (BVID). The energy absorption of each architecture was correlated to the damage size: both in-plane and in-depth directions. The 3D architectures, regardless of their unit-cell size, demonstrated the highest impact resistance as opposed to 2D-PW and the NCF. X-ray CT segmentation showed the effect of the higher frequency of the z-binding yarns, in the ORT-PW case, in delamination and crack arresting even when compared to the other 3D architecture (ORT-TW). Among all the architectures, ORT-PW exhibited the highest damage resistance with the least damage size. This suggests that accurate design of the z-binding yarns’ path and more importantly its frequency in 3D woven architectures is essential for impact-resistant composite structures.
Optimization of Aging Time for Improved Antioxidant Activity and Bacteriostatic Capacity of Fresh and Black Garlic
Authors: Chang Tsan-Chang , Jang Hung-Der
Published: March 2021

To determine the optimization of aging time for improved antioxidant activity and bacteriostatic capacity of garlic during its aging, garlic produced in Yunlin region, Taiwan, was employed as the test material in an analysis of the allicin content, total phenol content, antioxidant activity, and bacteriostatic capacity of fresh and aged garlic extracts. Allicin content of the aging garlic decreased to a minor level, whereas total phenol content increased to 16.96 mg gallic acid equivalent (GAE)/mL after 35 days of the aging process. The results of antioxidant testing demonstrated favorable positive correlations among IC50 of DPPH scavenging capacity, Trolox equivalent antioxidant activity, and superoxide dismutase activity for both the fresh and aged garlic extracts. The analytical results showed that aging of garlic at 70 °C and 85% relative humidity for 40 days substantially increased the quantity of phenolics, DPPH scavenging capacity, Trolox equivalent antioxidant activity, and superoxide dismutase activity and enhanced the antioxidant activity. The extracts exhibited higher bacteriostatic capacity against Gram-positive bacteria such as Bacillus subtilis and Staphylococcus aureus than against Gram-negative bacteria such as Escherichia coli and Pseudomonas aeruginosa. In conclusion, black garlic aged under the optimum conditions exhibited favorable antioxidant activity and bacteriostatic ability.
Memory and Cache Contention Denial-of-Service Attack in Mobile Edge Devices
Authors: Cho Won , Kong Joonho
Published: March 2021

In this paper, we introduce a memory and cache contention denial-of-service attack and its hardware-based countermeasure. Our attack can significantly degrade the performance of the benign programs by hindering the shared resource accesses of the benign programs. It can be achieved by a simple C-based malicious code while degrading the performance of the benign programs by 47.6% on average. As another side-effect, our attack also leads to greater energy consumption of the system by 2.1× on average, which may cause shorter battery life in the mobile edge devices. We also propose detection and mitigation techniques for thwarting our attack. By analyzing L1 data cache miss request patterns, we effectively detect the malicious program for the memory and cache contention denial-of-service attack. For mitigation, we propose using instruction fetch width throttling techniques to restrict the malicious accesses to the shared resources. When employing our malicious program detection with the instruction fetch width throttling technique, we recover the system performance and energy by 92.4% and 94.7%, respectively, which means that the adverse impacts from the malicious programs are almost removed.
Application of Long-Short-Term-Memory Recurrent Neural Networks to Forecast Wind Speed
Authors: Elsaraiti Meftah , Merabet Adel
Published: March 2021

Forecasting wind speed is one of the most important and challenging problems in the wind power prediction for electricity generation. Long short-term memory was used as a solution to short-term memory to address the problem of the disappearance or explosion of gradient information during the training process experienced by the recurrent neural network (RNN) when used to study time series. In this study, this problem is addressed by proposing a prediction model based on long short-term memory and a deep neural network developed to forecast the wind speed values of multiple time steps in the future. The weather database in Halifax, Canada was used as a source for two series of wind speeds per hour. Two different seasons spring (March 2015) and summer (July 2015) were used for training and testing the forecasting model. The results showed that the use of the proposed model can effectively improve the accuracy of wind speed prediction.
Hot Days and Heat Waves in Poland in the Period 1951–2019 and the Circulation Factors Favoring the Most Extreme of Them
Authors: Wibig Joanna
Published: March 2021

The aim of the study is to analyze the occurrence of hot days and heat waves in Poland, their intra-annual distribution, and their long-term variability, and to present the circulation factors favoring the appearance of extensive waves in the country. Hot days were days with Tmax not lower than the threshold value defined by the 95th percentile of summer Tmax in the period 1961–1990. Atmospheric circulation was described using sea level pressure, geopotential of 700 and 500 hPa level, and horizontal and vertical wind on these levels. A statistically significant increase in the number of hot days in the entire study period and a significant acceleration in growth after 1980 were shown. In the entire analyzed period, only 11 waves were found covering at least 25% of the country area and lasting no less than a week. Among them, only one occurred before 1990, and more than half were observed in the last decade. Four circulation patterns favoring the extensive heat waves were distinguished differing the location of main baric center location. Spatial and temporal distribution of vertical velocity anomalies allows distinguishing clear phases of strengthening, stabilization, and weakening of anticyclone accompanying the occurrence of a heat wave.
Severity-Mapped Vibrotactile Cues to Support Interruption Management with Weather Messaging in the General Aviation Cockpit
Authors: Rodriguez-Paras Carolina , McKenzie Johnathan T. , Choterungruengkorn Pasakorn , Ferris Thomas K.
Published: March 2021

Despite the increasing availability of technologies that provide access to aviation weather information in the cockpit, weather remains a prominent contributor to general aviation (GA) accidents. Pilots fail to detect the presence of new weather information, misinterpret it, or otherwise fail to act appropriately on it. When cognitive demands imposed by concurrent flight tasks are high, the risks increase for each of these failure modes. Previous research shows how introducing vibrotactile cues can help ease or redistribute some of these demands, but there is untapped potential in exploring how vibratory cues can facilitate “interruption management”, i.e., fitting the processing of available weather information into flight task workflow. In the current study, GA pilots flew a mountainous terrain scenario in a flight training device while receiving, processing, and acting on various weather information messages that were displayed visually, in graphical and text formats, on an experimental weather display. Half of the participants additionally received vibrotactile cues via a connected smartwatch with patterns that conveyed the “severity” of the message, allowing pilots to make informed decisions about when to fully attend to and process the message. Results indicate that weather messages were acknowledged more often and faster when accompanied by the vibrotactile cues, but the time after acknowledgment to fully process the messages was not significantly affected by vibrotactile cuing, nor was overall situation awareness. These findings illustrate that severity-encoded vibrotactile cues can support pilot awareness of updated weather as well as task management in processing weather messages while managing concurrent flight demands.
Impact of COVID-19 Lockdown on Air Pollutants in a Coastal Area of the Yangtze River Delta, China, Measured by a Low-Cost Sensor Package
Authors: Chen Lang , Li Jingjing , Pang Xiaobing , Shi Kangli , Chen Jianmeng , Wang Junliang , Xu Meng
Published: March 2021

Ningbo is a major coastal city in the Yangtze River Delta region, China, with the largest cargo capacity in the world. We conducted a field campaign in Ningbo to measure the impact of the COVID-19 lockdown on air pollutants including NO2, O3 and CO from 21 January to 23 March 2020, using a home-made low-cost sensor package. The average concentrations of NO2, O3 and CO were observed to be 7.2, 37.5 and 648.5 ppb, respectively, during the lockdown. Compared with the previous year, the concentrations of NO2 and CO decreased by 63.1% and 6.9%, while the concentration of O3 increased by 37.9%. The significant reduction of NO2 concentration may be attributed to the reduced emissions of freighters and heavy trucks with lower port cargo throughput, which led to a decrease of NO concentration. The increase of O3 concentration was probably due to the lower titration of O3 by NO. After the lockdown, the concentrations of O3 and NO2 increased by 15.5% and 143.1%, respectively, compared with those during the lockdown. The temporal variations of the concentrations of NO2, O3 and CO measured by the sensor package were coincident with those obtained by the reference apparatus, which proves the sensor package to be suitable for air quality monitoring in field campaigns. This is the first time that a dramatic decrease in NO2 concentration in a coastal city due to a lockdown has been reported.
Introducing a New Detailed Long-Term COSMO-CLM Hindcast for the Russian Arctic and the First Results of Its Evaluation
Authors: Platonov Vladimir , Varentsov Mikhail
Published: March 2021

Diverse and severe weather conditions and rapid climate change rates in the Arctic emphasize the need for high-resolution climatic and environmental data that cannot be obtained from the scarce observational networks. This study presents a new detailed hydrometeorological dataset for the Russian Arctic region, obtained as a long-term hindcast with the nonhydrostatic atmospheric model COSMO-CLM for the 1980–2016 period. The modeling workflow, evaluation techniques, and preliminary analysis of the obtained dataset are discussed. The model domain included the Barents, Kara, and Laptev Seas with ≈12-km grid spacing. The optimal model setup was chosen based on preliminary simulations for several summer and winter periods with varied options, and included the usage of ERA-Interim reanalysis data as forcing data, the new model version 5.05 with so-called ICON-based physics, and a spectral nudging technique. The wind speed and temperature climatology in the new COSMO-CLM dataset closely agreed with the ERA-Interim reanalysis, but with detailed spatial patterns. The added value of the higher-resolution COSMO-CLM data with respect to the ERA-Interim was most pronounced for higher wind speeds during downslope windstorms with the influence of mountain ranges on the temperature patterns, including surface temperature inversions. The potential applications and plans of further product development are also discussed.
The Value of a Decrease in Temperature by One Degree Celsius of the Regional Microclimate—The Cooling Effect of the Paddy Field
Authors: Chiueh Ya-Wen , Tan Chih-Hung , Hsu Hsiang-Yi
Published: March 2021

In the face of climate change, extreme climates are becoming more frequent. There were severe droughts in Taiwan in 2020, 2014–2015, and 2002. In these years, the paddy fields were kept fallow to save water and transfer agricultural water to non-agricultural use. On the other hand, with global warming, the existence of paddy fields may be one of the natural solutions to regional temperature mitigation. This study used remote sensing to quantify the difference in temperature between paddy fields and urban areas. The result of overall surface temperature deductive analysis revealed that the temperature in the whole Taoyuan research area was 1.2 °C higher in 2002 than in 2003 because of fallowing of the paddy field, while in the Hsinchu research area, it was 1.5 °C higher in 2002 than in 2003, due to the same reason described above. In terms of the difference in land use, for the Hsinchu research area, the surface temperature deductive result showed that the average paddy field temperature in 2002 was 22.3 °C (sample area average), which was 7.7 °C lower than that of the building and road point and 4.3 °C lower than that of the bare land point. The average paddy field temperature in 2003 was 19.2 °C (sample area average), which was 10.1 °C lower than that of the building and road point and 8.3 °C lower than that of the bare land point. Then this study evaluated the economic valuation of the paddy field cooling effect using the contingent valuation method. Through the paddy field cooling effect and in the face of worsening extreme global climate, the willingness to pay (WTP) of the respondents in Taiwan for a decrease of 1 °C with regard to the regional microclimate was evaluated. It was found that people in Taiwan are willing to pay an extra 8.89 USD/per kg rice/year for the paddy for a decrease in temperature by 1 °C in the regional microclimate due to the paddy field. Furthermore, this study applied the benefits transfer method to evaluate the value of a decrease of 1 °C in the regional microclimate in Taiwan. The value of a decrease of 1 °C in the regional microclimate in Taiwan is 9,693,144,279 USD/year. In this regard, the economic value of 1 °C must not be underestimated. In conclusion, more caution is needed while making decisions to change the land use of paddy fields to other land uses.
The Micrometeorology of the Haifa Bay Area and Mount Carmel during the Summer
Authors: Klausner Ziv , Ben-Efraim Mattya , Arav Yehuda , Tas Eran , Fattal Eyal
Published: March 2021

The Haifa bay area (HBA), which includes Mount Carmel and the Zevulun valley is the third largest metropolitan area in Israel. It is also a centre of heavy industry and an important transportation hub which serve as sources of local anthropogenic pollution. Such sources are associated with adverse health effects. In order to estimate the possible exposure of the inhabitants in such heterogeneous orographic area, a detailed atmospheric transport and dispersion modelling study is required, which in turn must take into account the local micrometeorology. The aim of this study is to conduct a spatio-temporal analysis of the flow field in the HBA in order to identify the common patterns of the average wind and characterize the statistical parameters of turbulence in this area, essential for detailed pollutants dispersion modelling. This study analyses data collected during four months of summer in a network of 16 weather stations which extend across Mount Carmel and the Zevulun valley. It was found that, during the evening and night time on Mount Carmel, different flow patterns may develop on each side, separated by the watershed line. When such conditions do not develop, as well as during the daytime, the wind field, both on Mount Carmel and the Zevulun valley is approximately homogenous. The analysis of the Monin–Obukhov similarity theory functions for the velocity standard deviations show a distinct difference between Mount Carmel and the Zevulun valley, as well as between strong and weak winds. This difference can be clearly seen also in the diurnal hourly distribution of atmospheric stabilities which exhibit higher proportions of unstable conditions in the Zevulun valley during day time and higher proportion of stable stratifications at the Mount Carmel during night-time.
Supramolecular Structuring of Hyaluronan-Lactose-Modified Chitosan Matrix: Towards High-Performance Biopolymers with Excellent Biodegradation
Authors: Ladiè Riccardo , Cosentino Cesare , Tagliaro Irene , Antonini Carlo , Bianchini Giulio , Bertini Sabrina
Published: March 2021

Non-covalent interactions in supramolecular chemistry provide useful systems to understand biological processes, and self-assembly systems are suitable assets to build-up innovative products for biomedical applications. In this field, polyelectrolyte complexes are interesting, especially when polysaccharides are involved, due to their non-toxicity and bio-absorbability. In this work, we investigated a polyelectrolyte formed by hyaluronic acid (HA), a negatively charged linear polysaccharide, with Chitlac (Ch), a positively charged lactose-modified chitosan. The aim of the study was the investigation of a novel Ch–HA polyelectrolyte complex, to understand the interaction between the two polysaccharides and the stability towards enzymatic activity. By means of gel permeation chromatography–triple detector array (GPC–TDA), nuclear magnetic resonance (NMR), dynamic viscosity, Zeta Potential and scanning electron microscopy (SEM), the polyelectrolyte complex properties were identified and compared to individual polysaccharides. The complex showed monodisperse molecular weight distribution, high viscosity, negative charge, and could be degraded by specific enzymes, such as hyaluronidase and lysozyme. The results suggest a close interaction between the two polysaccharides in the complex, which could be considered a self-assembly system.
Glatiramer Acetate Treatment in Multiple Sclerosis-Associated Fatigue—Beneficial Effects on Self-Assessment Scales But Not on Molecular Markers
Authors: Neuhaus Oliver , Köhler Wolfgang , Then Bergh Florian , Kristoferitsch Wolfgang , Faiss Jürgen , Rosenkranz Thorsten , Reske Dirk , Patejdl Robert , Hartung Hans-Peter , Zettl Uwe K.
Published: March 2021

Although fatigue is a common symptom in multiple sclerosis (MS), its pathomechanisms are incompletely understood. Glatiramer acetate (GA), an immunomodulatory agent approved for treatment of relapsing-remitting MS (RRMS), possesses unique mechanisms of action and has been shown to exhibit beneficial effects on MS fatigue. The objective of this study was to correlate clinical, neuropsychological, and immunological parameters in RRMS patients with fatigue before and during treatment with GA. In a prospective, open-label, multicenter trial, 30 patients with RRMS and fatigue were treated with GA for 12 months. Inclusion criterion was the presence of fatigue as one of the most frequent and disabling symptoms. Before and during treatment, fatigue was assessed using the Fatigue Severity Scale (FSS), the MS-FSS, and the Modified Fatigue Impact Scale (MFIS). In addition, fatigue and quality of life were assessed using the Visual Analog Scales (VAS). Laboratory assessments included screening of 188 parameters using real-time PCR microarrays followed by further analysis of several cytokines, chemokines, and neurotrophic factors. Fatigue self-assessments were completed in 25 patients. After 12 months of treatment with GA, 13 of these patients improved in all three scales (with the most prominent effects on the MFIS), whereas 5 patients had deteriorated. The remaining 7 patients exhibited inconsistent effects within the three scales. Fatigue and overall quality of life had improved, as assessed via VAS. Laboratory assessments revealed heterogeneous mRNA levels of cytokines, chemokines, and neurotrophic factors. In conclusion, we were not able to correlate clinical and molecular effects of GA in patients with RRMS and fatigue.
Recent Insights into Anthocyanin Pigmentation, Synthesis, Trafficking, and Regulatory Mechanisms in Rice (Oryza sativa L.) Caryopsis
Authors: Mackon Enerand , Jeazet Dongho Epse Mackon Guibeline Charlie , Ma Yafei , Haneef Kashif Muhammad , Ali Niyaz , Usman Babar , Liu Piqing
Published: March 2021

Anthocyanins are antioxidants used as natural colorants and are beneficial to human health. Anthocyanins contribute to reactive oxygen species detoxification and sustain plant growth and development under different environmental stresses. They are phenolic compounds that are broadly distributed in nature and are responsible for a wide range of attractive coloration in many plant organs. Anthocyanins are found in various parts of plants such as flowers, leaves, stems, shoots, and grains. Considering their nutritional and health attributes, anthocyanin-enriched rice or pigmented rice cultivars are a possible alternative to reduce malnutrition around the globe. Anthocyanin biosynthesis and storage in rice are complex processes in which several structural and regulatory genes are involved. In recent years, significant progress has been achieved in the molecular and genetic mechanism of anthocyanins, and their synthesis is of great interest to researchers and the scientific community. However, limited studies have reported anthocyanin synthesis, transportation, and environmental conditions that can hinder anthocyanin production in rice. Rice is a staple food around the globe, and further research on anthocyanin in rice warrants more attention. In this review, metabolic and pre-biotic activities, the underlying transportation, and storage mechanisms of anthocyanins in rice are discussed in detail. This review provides potential information for the food industry and clues for rice breeding and genetic engineering of rice.
An Analysis of the External Validity of EEG Spectral Power in an Uncontrolled Outdoor Environment during Default and Complex Neurocognitive States
Authors: Edwards Dalton J. , Trujillo Logan T.
Published: March 2021

Traditionally, quantitative electroencephalography (QEEG) studies collect data within controlled laboratory environments that limit the external validity of scientific conclusions. To probe these validity limits, we used a mobile EEG system to record electrophysiological signals from human participants while they were located within a controlled laboratory environment and an uncontrolled outdoor environment exhibiting several moderate background influences. Participants performed two tasks during these recordings, one engaging brain activity related to several complex cognitive functions (number sense, attention, memory, executive function) and the other engaging two default brain states. We computed EEG spectral power over three frequency bands (theta: 4–7 Hz, alpha: 8–13 Hz, low beta: 14–20 Hz) where EEG oscillatory activity is known to correlate with the neurocognitive states engaged by these tasks. Null hypothesis significance testing yielded significant EEG power effects typical of the neurocognitive states engaged by each task, but only a beta-band power difference between the two background recording environments during the default brain state. Bayesian analysis showed that the remaining environment null effects were unlikely to reflect measurement insensitivities. This overall pattern of results supports the external validity of laboratory EEG power findings for complex and default neurocognitive states engaged within moderately uncontrolled environments.
Searching the Dark Genome for Alzheimer’s Disease Risk Variants
Authors: Raybould Rachel , Sims Rebecca
Published: March 2021

Sporadic Alzheimer’s disease (AD) is a complex genetic disease, and the leading cause of dementia worldwide. Over the past 3 decades, extensive pioneering research has discovered more than 70 common and rare genetic risk variants. These discoveries have contributed massively to our understanding of the pathogenesis of AD but approximately half of the heritability for AD remains unaccounted for. There are regions of the genome that are not assayed by mainstream genotype and sequencing technology. These regions, known as the Dark Genome, often harbour large structural DNA variants that are likely relevant to disease risk. Here, we describe the dark genome and review current technological and bioinformatics advances that will enable researchers to shed light on these hidden regions of the genome. We highlight the potential importance of the hidden genome in complex disease and how these strategies will assist in identifying the missing heritability of AD. Identification of novel protein-coding structural variation that increases risk of AD will open new avenues for translational research and new drug targets that have the potential for clinical benefit to delay or even prevent clinical symptoms of disease.
The Role of Vitamin D as a Biomarker in Alzheimer’s Disease
Authors: Bivona Giulia , Lo Sasso Bruna , Gambino Caterina Maria , Giglio Rosaria Vincenza , Scazzone Concetta , Agnello Luisa , Ciaccio Marcello
Published: March 2021

Vitamin D and cognition is a popular association, which led to a remarkable body of literature data in the past 50 years. The brain can synthesize, catabolize, and receive Vitamin D, which has been proved to regulate many cellular processes in neurons and microglia. Vitamin D helps synaptic plasticity and neurotransmission in dopaminergic neural circuits and exerts anti-inflammatory and neuroprotective activities within the brain by reducing the synthesis of pro-inflammatory cytokines and the oxidative stress load. Further, Vitamin D action in the brain has been related to the clearance of amyloid plaques, which represent a feature of Alzheimer Disease (AD), by the immune cell. Based on these considerations, many studies have investigated the role of circulating Vitamin D levels in patients affected by a cognitive decline to assess Vitamin D’s eventual role as a biomarker or a risk factor in AD. An association between low Vitamin D levels and the onset and progression of AD has been reported, and some interventional studies to evaluate the role of Vitamin D in preventing AD onset have been performed. However, many pitfalls affected the studies available, including substantial discrepancies in the methods used and the lack of standardized data. Despite many studies, it remains unclear whether Vitamin D can have a role in cognitive decline and AD. This narrative review aims to answer two key questions: whether Vitamin D can be used as a reliable tool for diagnosing, predicting prognosis and response to treatment in AD patients, and whether it is a modifiable risk factor for preventing AD onset.
Normatively Irrelevant Affective Cues Affect Risk-Taking under Uncertainty: Insights from the Iowa Gambling Task (IGT), Skin Conductance Response, and Heart Rate Variability
Authors: Priolo Giulia , D’Alessandro Marco , Bizzego Andrea , Bonini Nicolao
Published: March 2021

Being able to distinguish between safe and risky options is paramount in making functional choices. However, deliberate manipulation of decision-makers emotions can lead to risky behaviors. This study aims at understanding how affective reactions driven by normatively irrelevant affective cues can interfere with risk-taking. Good and Bad decks of the Iowa Gambling Task have been manipulated to make them unpleasant through a negative auditory manipulation. Anticipatory skin conductance response (SCR) and heart rate variability (HRV) have been investigated in line with the somatic marker hypothesis. Results showed fewer selections from Good decks when they were negatively manipulated (i.e., Incongruent condition). No effect of the manipulation was detected when Bad decks were negatively manipulated (i.e., Congruent condition). Higher anticipatory SCR was associated with Bad decks in Congruent condition. Slower heart rate was found before selections from Good decks in Control and Congruent condition and from Bad decks in Incongruent condition. Differences in heart rate between Bad and Good decks were also detected in Congruent condition. Results shed light on how normatively irrelevant affective cues can interfere with risk-taking.
Optimizing Multi-Family Building Massing for Affordability and Envelope Performance: An Investigation of the Trade-Offs Implicit in Low Rise Residential Buildings
Authors: Mosey Grant , Deal Brian
Published: March 2021

The United States faces twin crises of housing affordability and environmental degradation. Under these clouds, the nation is experiencing an explosive growth in new construction multi-family housing. This paper seeks to evaluate how designers might optimize the organization of such projects to minimize cost and maximize environmental performance. A method is developed for evaluating the construction costs and environmental performance of multifamily developments across four variables: building height, number of buildings, building width, and building floor area. Our analysis suggests that buildings with deeper floor plates are preferable for both economic and environmental reasons. We also suggest that taller buildings have more performative envelopes while shorter buildings are more economical to construct. Finally, we offer a method of finding a compromise between economic and environmental objectives for projects of a given square footage. Most commonly, this “compromise” takes the form of a moderate number of mid-rise buildings with deep floor plates. This investigation adds nuance to the existing literature on the effects of building shape on building cost and envelope performance. It also provides designers with a method of potentially constructing multifamily buildings in a less expensive and more environmentally conscious way.
Fatty Acid Synthase Confers Tamoxifen Resistance to ER+/HER2+ Breast Cancer
Authors: Menendez Javier A. , Papadimitropoulou Adriana , Vander Steen Travis , Cuyàs Elisabet , Oza-Gajera Bharvi P. , Verdura Sara , Espinoza Ingrid , Vellon Luciano , Mehmi Inderjit , Lupu Ruth
Published: March 2021

The identification of clinically important molecular mechanisms driving endocrine resistance is a priority in estrogen receptor-positive (ER+) breast cancer. Although both genomic and non-genomic cross-talk between the ER and growth factor receptors such as human epidermal growth factor receptor 2 (HER2) has frequently been associated with both experimental and clinical endocrine therapy resistance, combined targeting of ER and HER2 has failed to improve overall survival in endocrine non-responsive disease. Herein, we questioned the role of fatty acid synthase (FASN), a lipogenic enzyme linked to HER2-driven breast cancer aggressiveness, in the development and maintenance of hormone-independent growth and resistance to anti-estrogens in ER/HER2-positive (ER+/HER2+) breast cancer. The stimulatory effects of estradiol on FASN gene promoter activity and protein expression were blunted by anti-estrogens in endocrine-responsive breast cancer cells. Conversely, an AKT/MAPK-related constitutive hyperactivation of FASN gene promoter activity was unaltered in response to estradiol in non-endocrine responsive ER+/HER2+ breast cancer cells, and could be further enhanced by tamoxifen. Pharmacological blockade with structurally and mechanistically unrelated FASN inhibitors fully impeded the strong stimulatory activity of tamoxifen on the soft-agar colony forming capacity—an in vitro metric of tumorigenicity—of ER+/HER2+ breast cancer cells. In vivo treatment with a FASN inhibitor completely prevented the agonistic tumor-promoting activity of tamoxifen and fully restored its estrogen antagonist properties against ER/HER2-positive xenograft tumors in mice. Functional cancer proteomic data from The Cancer Proteome Atlas (TCPA) revealed that the ER+/HER2+ subtype was the highest FASN protein expressor compared to basal-like, HER2-enriched, and ER+/HER2-negative breast cancer groups. FASN is a biological determinant of HER2-driven endocrine resistance in ER+ breast cancer. Next-generation, clinical-grade FASN inhibitors may be therapeutically relevant to countering resistance to tamoxifen in FASN-overexpressing ER+/HER2+ breast carcinomas.
Dinaciclib, a Bimodal Agent Effective against Endometrial Cancer
Authors: Howard David , James David , Murphy Kate , Garcia-Parra Jezabel , Pan-Castillo Belen , Rex Stuart , Moul Annemarie , Jones Eilir , Bilbao-Asensio Marc , Michue-Seijas Saul , Lutchman-Singh Kerryn , Margarit Lavinia , Francis Lewis W. , Rees Paul , Gonzalez Deyarina , Conlan R. Steven
Published: March 2021

Endometrial cancer (EC) is the sixth most prevalent female cancer globally and although high rates of success are achieved when diagnosed at an early stage, the 5-year survival rate for cancers diagnosed at Stages II–IV is below 50%. Improving patient outcomes will necessitate the introduction of novel therapies to the clinic. Pan-cyclin-dependent kinase inhibitors (CDKis) have been explored as therapies for a range of cancers due to their ability to simultaneously target multiple key cellular processes, such as cell cycle progression, transcription, and DNA repair. Few studies, however, have reported on their potential for the treatment of EC. Herein, we examined the effects of the pan-CDKi dinaciclib in primary cells isolated directly from tumors and EC cell lines. Dinaciclib was shown to elicit a bimodal action in EC cell lines, disrupting both cell cycle progression and phosphorylation of the RNA polymerase carboxy terminal domain, with a concomitant reduction in Bcl-2 expression. Furthermore, the therapeutic potential of combining dinaciclib and cisplatin was explored, with the drugs demonstrating synergy at specific doses in Type I and Type II EC cell lines. Together, these results highlight the potential of dinaciclib for use as an effective EC therapy.
Transitioning the Molecular Tumor Board from Proof of Concept to Clinical Routine: A German Single-Center Analysis
Authors: Hoefflin Rouven , Lazarou Adriana , Hess Maria Elena , Reiser Meike , Wehrle Julius , Metzger Patrick , Frey Anna Verena , Becker Heiko , Aumann Konrad , Berner Kai , Boeker Martin , Buettner Nico , Dierks Christine , Duque-Afonso Jesus , Eisenblaetter Michel , Erbes Thalia , Fritsch Ralph , Ge Isabell Xiang , Geißler Anna-Lena , Grabbert Markus , Heeg Steffen , Heiland Dieter Henrik , Hettmer Simone , Kayser Gian , Keller Alexander , Kleiber Anita , Kutilina Alexandra , Mehmed Leman , Meiss Frank , Poxleitner Philipp , Rawluk Justyna , Ruf Juri , Schäfer Henning , Scherer Florian , Shoumariyeh Khalid , Tzschach Andreas , Peters Christoph , Brummer Tilman , Werner Martin , Duyster Justus , Lassmann Silke , Miething Cornelius , Boerries Melanie , Illert Anna L. , von Bubnoff Nikolas
Published: March 2021

Molecular precision oncology faces two major challenges: first, to identify relevant and actionable molecular variants in a rapidly changing field and second, to provide access to a broad patient population. Here, we report a four-year experience of the Molecular Tumor Board (MTB) of the Comprehensive Cancer Center Freiburg (Germany) including workflows and process optimizations. This retrospective single-center study includes data on 488 patients enrolled in the MTB from February 2015 through December 2018. Recommendations include individual molecular diagnostics, molecular stratified therapies, assessment of treatment adherence and patient outcomes including overall survival. The majority of MTB patients presented with stage IV oncologic malignancies (90.6%) and underwent an average of 2.1 previous lines of therapy. Individual diagnostic recommendations were given to 487 patients (99.8%). A treatment recommendation was given in 264 of all cases (54.1%) which included a molecularly matched treatment in 212 patients (43.4%). The 264 treatment recommendations were implemented in 76 patients (28.8%). Stable disease was observed in 19 patients (25.0%), 17 had partial response (22.4%) and five showed a complete remission (6.6%). An objective response was achieved in 28.9% of cases with implemented recommendations and for 4.5% of the total population (22 of 488 patients). By optimizing the MTB workflow, case-discussions per session increased significantly while treatment adherence and outcome remained stable over time. Our data demonstrate the feasibility and effectiveness of molecular-guided personalized therapy for cancer patients in a clinical routine setting showing a low but robust and durable disease control rate over time.
The Two-Faced Role of SIRT6 in Cancer
Authors: Fiorentino Francesco , Carafa Vincenzo , Favale Gregorio , Altucci Lucia , Mai Antonello , Rotili Dante
Published: March 2021

Sirtuin 6 (SIRT6) is a NAD+-dependent nuclear deacylase and mono-ADP-ribosylase with a wide spectrum of substrates. Through its pleiotropic activities, SIRT6 modulates either directly or indirectly key processes linked to cell fate determination and oncogenesis such as DNA damage repair, metabolic homeostasis, and apoptosis. SIRT6 regulates the expression and activity of both pro-apoptotic (e.g., Bax) and anti-apoptotic factors (e.g., Bcl-2, survivin) in a context-depending manner. Mounting evidence points towards a double-faced involvement of SIRT6 in tumor onset and progression since the block or induction of apoptosis lead to opposite outcomes in cancer. Here, we discuss the features and roles of SIRT6 in the regulation of cell death and cancer, also focusing on recently discovered small molecule modulators that can be used as chemical probes to shed further light on SIRT6 cancer biology and proposed as potential new generation anticancer therapeutics.
The Impact of Pressure and Hydrocarbons on NOx Abatement over Cu- and Fe-Zeolites at Pre-Turbocharger Position
Authors: Zengel Deniz , Barth Simon , Casapu Maria , Grunwaldt Jan-Dierk
Published: March 2021

Positioning the catalysts in front of the turbocharger has gained interest over recent years due to the earlier onset temperature and positive effect of elevated pressure. However, several challenges must be overcome, like presence of higher pollutant concentrations due to the absence or insufficient diesel oxidation catalyst volume at this location. In this context, our study reports a systematic investigation on the effect of pressure and various hydrocarbons during selective catalytic reduction (SCR) of NOx with NH3 over the zeolite-based catalysts Fe-ZSM-5 and Cu-SSZ-13. Using a high-pressure catalyst test bench, the catalytic activity of both zeolite catalysts was measured in the presence and absence of a variety of hydrocarbons under pressures and temperatures resembling the conditions upstream of the turbocharger. The results obtained showed that the hydrocarbons are incompletely converted over both catalysts, resulting in numerous byproducts. The emission of hydrogen cyanide seems to be particularly problematic. Although the increase in pressure was able to improve the oxidation of hydrocarbons and significantly reduce the formation of HCN, sufficiently low emissions could only be achieved at high temperatures. Regarding the NOx conversion, a boost in activity was obtained by increasing the pressure compared to atmospheric reaction conditions, which compensated the negative effect of hydrocarbons on the SCR activity.
Cerebral Insulin Bolus Revokes the Changes in Hepatic Lipid Metabolism Induced by Chronic Central Leptin Infusion
Authors: Barrios Vicente , López-Villar Elena , Frago Laura M. , Canelles Sandra , Díaz-González Francisca , Burgos-Ramos Emma , Frühbeck Gema , Chowen Julie A. , Argente Jesús
Published: March 2021

Central actions of leptin and insulin on hepatic lipid metabolism can be opposing and the mechanism underlying this phenomenon remains unclear. Both hormones can modulate the central somatostatinergic system that has an inhibitory effect on growth hormone (GH) expression, which plays an important role in hepatic metabolism. Using a model of chronic central leptin infusion, we evaluated whether an increase in central leptin bioavailability modifies the serum lipid pattern through changes in hepatic lipid metabolism in male rats in response to an increase in central insulin and the possible involvement of the GH axis in these effects. We found a rise in serum GH in leptin plus insulin-treated rats, due to an increase in pituitary GH mRNA levels associated with lower hypothalamic somatostatin and pituitary somatostatin receptor-2 mRNA levels. An augment in hepatic lipolysis and a reduction in serum levels of non-esterified fatty acids (NEFA) and triglycerides were found in leptin-treated rats. These rats experienced a rise in lipogenic-related factors and normalization of serum levels of NEFA and triglycerides after insulin treatment. These results suggest that an increase in insulin in leptin-treated rats can act on the hepatic lipid metabolism through activation of the GH axis.