bluuebunny/crossref_metadata_2025 huggingface dataset:
Alteration of Colonic Mucosal Permeability during Antibiotic-Induced Dysbiosis
Authors: Ran Ying , Fukui Hirokazu , Xu Xin , Wang Xuan , Ebisutani Nobuhiko , Tanaka Yoshiki , Maeda Ayako , Makizaki Yutaka , Ohno Hiroshi , Kondo Takashi , Kono Tomoaki , Tozawa Katsuyuki , Tomita Toshihiko , Oshima Tadayuki , Miwa Hiroto
Published: August 2020

Although dysbiosis is likely to disturb the mucosal barrier system, the mechanism involved has remained unclear. Here, we investigated alterations of colonic mucosal permeability and tight junction (TJ) molecules in mice with antibiotic-induced dysbiosis. Mice were orally administered vancomycin or polymyxin B for 7 days, and then fecal samples were subjected to microbial 16S rRNA analysis. The colonic mucosal permeability was evaluated by chamber assay. The colonic expression of TJ molecules and cytokines was examined by real-time RT-PCR, Western blotting, and immunohistochemistry. Caco2 cells were stimulated with cytokines and their transepithelial electric resistance (TEER) was measured. Vancomycin-treated mice showed significantly lower gut microbiota diversity than controls, and the same tendency was evident in polymyxin B-treated mice. The colonic mucosal permeability was significantly elevated in both vancomycin- and polymyxin B-treated mice. The expression of claudin 4 in the colonic mucosa was decreased in both vancomycin- and polymyxin B-treated mice. Colonic expression of TNF-α and/or IFN-γ was significantly increased in mice that had been administered antibiotics. TNF-α and IFN-γ stimulation dose-dependently decreased TEER in Caco2 cells. Antibiotic-induced dysbiosis is correlated with the enhancement in colonic tissue permeability, accompanied by a reduction in claudin 4 expression and enhancement in TNF-α and/or IFN-γ expression in mice.
LAMP-2 Is Involved in Surface Expression of RANKL of Osteoblasts In Vitro
Authors: Jansen Ineke D.C. , Tigchelaar-Gutter Wikky , Hogervorst Jolanda M. A. , de Vries Teun J. , Saftig Paul , Everts Vincent
Published: August 2020

Lysosome associated membrane proteins (LAMPs) are involved in several processes, among which is fusion of lysosomes with phagosomes. For the formation of multinucleated osteoclasts, the interaction between receptor activator of nuclear kappa β (RANK) and its ligand RANKL is essential. Osteoclast precursors express RANK on their membrane and RANKL is expressed by cells of the osteoblast lineage. Recently it has been suggested that the transport of RANKL to the plasma membrane is mediated by lysosomal organelles. We wondered whether LAMP-2 might play a role in transportation of RANKL to the plasma membrane of osteoblasts. To elucidate the possible function of LAMP-2 herein and in the formation of osteoclasts, we analyzed these processes in vivo and in vitro using LAMP-2-deficient mice. We found that, in the presence of macrophage colony stimulating factor (M-CSF) and RANKL, active osteoclasts were formed using bone marrow cells from calvaria and long bone mouse bone marrow. Surprisingly, an almost complete absence of osteoclast formation was found when osteoclast precursors were co-cultured with LAMP-2 deficient osteoblasts. Fluorescence-activated cell sorting FACS analysis revealed that plasma membrane-bound RANKL was strongly decreased on LAMP-2 deficient osteoblasts. These results suggest that osteoblastic LAMP-2 is required for osteoblast-induced osteoclast formation in vitro.
Phenotypes of Bronchopulmonary Dysplasia
Authors: Wang Shih-Hsin , Tsao Po-Nien
Published: August 2020

Bronchopulmonary dysplasia (BPD) is the most common chronic morbidity in preterm infants. In the absence of effective interventions, BPD is currently a major therapeutic challenge. Several risk factors are known for this multifactorial disease that results in disrupted lung development. Inflammation plays an important role and leads to persistent airway and pulmonary vascular disease. Since corticosteroids are potent anti-inflammatory agents, postnatal corticosteroids have been used widely for BPD prevention and treatment. However, the clinical responses vary to a great degree across individuals, and steroid-related complications remain major concerns. Emerging studies on the molecular mechanism of lung alveolarization during inflammatory stress will elucidate the complicated pathway and help discover novel therapeutic targets. Moreover, with the advances in metabolomics, there are new opportunities to identify biomarkers for early diagnosis and prognosis prediction of BPD. Pharmacometabolomics is another novel field aiming to identify the metabolomic changes before and after a specific drug treatment. Through this “metabolic signature,” a more precise treatment may be developed, thereby avoiding unnecessary drug exposure in non-responders. In the future, more clinical, genetic, and translational studies would be required to improve the classification of BPD phenotypes and achieve individualized care to enhance the respiratory outcomes in preterm infants.
Diurnal Variation of Urinary Fabry Disease Biomarkers during Enzyme Replacement Therapy Cycles
Authors: Boutin Michel , Lavoie Pamela , Menkovic Iskren , Toupin Amanda , Abaoui Mona , Elidrissi-Elawad Maha , Arthus Marie-Françoise , Fortier Carole , Ménard Claudia , Maranda Bruno , Bichet Daniel G. , Auray-Blais Christiane
Published: August 2020

Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the GLA gene encoding the α-galactosidase A enzyme. This enzyme cleaves the last sugar unit of glycosphingolipids, including globotriaosylceramide (Gb3), globotriaosylsphingosine (lyso-Gb3), and galabiosylceramide (Ga2). Enzyme impairment leads to substrate accumulation in different organs, vascular endothelia, and biological fluids. Enzyme replacement therapy (ERT) is a commonly used treatment. Urinary analysis of Gb3 isoforms (different fatty acid moieties), as well as lyso-Gb3 and its analogues, is a reliable way to monitor treatment. These analogues correspond to lyso-Gb3 with chemical modifications on the sphingosine moiety (−C2H4, −C2H4+O, −H2, −H2+O, +O, +H2O2, and +H2O3). The effects of sample collection time on urinary biomarker levels between ERT cycles were not previously documented. The main objective of this project was to analyze the aforementioned biomarkers in urine samples from seven Fabry disease patients (three treated males, three treated females, and one ERT-naïve male) collected twice a day (morning and evening) for 42 days (three ERT cycles). Except for one participant, our results show that the biomarker levels were generally more elevated in the evening. However, there was less variability in samples collected in the morning. No cyclic variations in biomarker levels were observed between ERT infusions.
Molecular Pharmacology of Synthetic Cannabinoids: Delineating CB1 Receptor-Mediated Cell Signaling
Authors: Walsh Kenneth B. , Andersen Haley K.
Published: August 2020

Synthetic cannabinoids (SCs) are a class of new psychoactive substances (NPSs) that exhibit high affinity binding to the cannabinoid CB1 and CB2 receptors and display a pharmacological profile similar to the phytocannabinoid (-)-trans-Δ9-tetrahydrocannabinol (THC). SCs are marketed under brand names such as K2 and Spice and are popular drugs of abuse among male teenagers and young adults. Since their introduction in the early 2000s, SCs have grown in number and evolved in structural diversity to evade forensic detection and drug scheduling. In addition to their desirable euphoric and antinociceptive effects, SCs can cause severe toxicity including seizures, respiratory depression, cardiac arrhythmias, stroke and psychosis. Binding of SCs to the CB1 receptor, expressed in the central and peripheral nervous systems, stimulates pertussis toxin-sensitive G proteins (Gi/Go) resulting in the inhibition of adenylyl cyclase, a decreased opening of N-type Ca2+ channels and the activation of G protein-gated inward rectifier (GIRK) channels. This combination of signaling effects dampens neuronal activity in both CNS excitatory and inhibitory pathways by decreasing action potential formation and neurotransmitter release. Despite this knowledge, the relationship between the chemical structure of the SCs and their CB1 receptor-mediated molecular actions is not well understood. In addition, the potency and efficacy of newer SC structural groups has not been determined. To address these limitations, various cell-based assay technologies are being utilized to develop structure versus activity relationships (SAR) for the SCs and to explore the effects of these compounds on noncannabinoid receptor targets. This review focuses on describing and evaluating these assays and summarizes our current knowledge of SC molecular pharmacology.
Role of Phosphodiesterase 7 (PDE7) in T Cell Activity. Effects of Selective PDE7 Inhibitors and Dual PDE4/7 Inhibitors on T Cell Functions
Authors: Szczypka Marianna
Published: August 2020

Phosphodiesterase 7 (PDE7), a cAMP-specific PDE family, insensitive to rolipram, is present in many immune cells, including T lymphocytes. Two genes of PDE7 have been identified: PDE7A and PDE7B with three or four splice variants, respectively. Both PDE7A and PDE7B are expressed in T cells, and the predominant splice variant in these cells is PDE7A1. PDE7 is one of several PDE families that terminates biological functions of cAMP—a major regulating intracellular factor. However, the precise role of PDE7 in T cell activation and function is still ambiguous. Some authors reported its crucial role in T cell activation, while according to other studies PDE7 activity was not pivotal to T cells. Several studies showed that inhibition of PDE7 by its selective or dual PDE4/7 inhibitors suppresses T cell activity, and consequently T-mediated immune response. Taken together, it seems quite likely that simultaneous inhibition of PDE4 and PDE7 by dual PDE4/7 inhibitors or a combination of selective PDE4 and PDE7 remains the most interesting therapeutic target for the treatment of some immune-related disorders, such as autoimmune diseases, or selected respiratory diseases. An interesting direction of future studies could also be using a combination of selective PDE7 and PDE3 inhibitors.
Diversity of Parallel Guanine Quadruplexes Induced by Guanine Substitutions
Authors: Bednářová Klára , Vorlíčková Michaela , Renčiuk Daniel
Published: August 2020

Recently, we reported an inhibitory effect of guanine substitutions on the conformational switch from antiparallel to parallel quadruplexes (G4) induced by dehydrating agents. As a possible cause, we proposed a difference in the sensitivity of parallel and antiparallel quadruplexes to the guanine substitutions in the resulting thermodynamic stability. Reports on the influence of guanine substitutions on the biophysical properties of intramolecular parallel quadruplexes are rare. Moreover, such reports are often complicated by the multimerisation tendencies of parallel quadruplexes. To address this incomplete knowledge, we employed circular dichroism spectroscopy (CD), both as stopped-flow-assisted fast kinetics measurements and end-point measurements, accompanied by thermodynamic analyses, based on UV absorption melting profiles, and electrophoretic methods. We showed that parallel quadruplexes are significantly more sensitive towards guanine substitutions than antiparallel ones. Furthermore, guanine-substituted variants, which in principle might correspond to native genomic sequences, distinctly differ in their biophysical properties, indicating that the four guanines in each tetrad of parallel quadruplexes are not equal. In addition, we were able to distinguish by CD an intramolecular G4 from intermolecular ones resulting from multimerisation mediated by terminal tetrad association, but not from intermolecular G4s formed due to inter-strand Hoogsteen hydrogen bond formation. In conclusion, our study indicates significant variability in parallel quadruplex structures, otherwise disregarded without detailed experimental analysis.
Elucidation of Melanogenesis Cascade for Identifying Pathophysiology and Therapeutic Approach of Pigmentary Disorders and Melanoma
Authors: Hida Tokimasa , Kamiya Takafumi , Kawakami Akinori , Ogino Jiro , Sohma Hitoshi , Uhara Hisashi , Jimbow Kowichi
Published: August 2020

Melanogenesis is the biological and biochemical process of melanin and melanosome biosynthesis. Melanin is formed by enzymic reactions of tyrosinase family proteins that convert tyrosine to form brown-black eumelanin and yellow-red pheomelanin within melanosomal compartments in melanocytes, following the cascades of events interacting with a series of autocrine and paracrine signals. Fully melanized melanosomes are delivered to keratinocytes of the skin and hair. The symbiotic relation of a melanocyte and an associated pool of keratinocytes is called epidermal melanin unit (EMU). Microphthalmia-associated transcription factor (MITF) plays a vital role in melanocyte development and differentiation. MITF regulates expression of numerous pigmentation genes for promoting melanocyte differentiation, as well as fundamental genes for maintaining cell homeostasis. Diseases involving alterations of EMU show various forms of pigmentation phenotypes. This review introduces four major topics of melanogenesis cascade that include (1) melanocyte development and differentiation, (2) melanogenesis and intracellular trafficking for melanosome biosynthesis, (3) melanin pigmentation and pigment-type switching, and (4) development of a novel therapeutic approach for malignant melanoma by elucidation of melanogenesis cascade.
Mechanisms of Nutritional Resource Exploitation by Insects
Authors: Leonhardt Sara D. , Lihoreau Mathieu , Spaethe Johannes
Published: August 2020

Insects have evolved an extraordinary range of nutritional adaptations to exploit other animals, plants, bacteria, fungi and soils as resources in terrestrial and aquatic environments. This special issue provides some new insights into the mechanisms underlying these adaptations. Contributions comprise lab and field studies investigating the chemical, physiological, cognitive and behavioral mechanisms that enable resource exploitation and nutrient intake regulation in insects. The collection of papers highlights the need for more studies on the comparative sensory ecology, underlying nutritional quality assessment, cue perception and decision making to fully understand how insects adjust resource selection and exploitation in response to environmental heterogeneity and variability.
Targeting β2-Adrenergic Receptors Shows Therapeutical Benefits in Clear Cell Renal Cell Carcinoma from Von Hippel–Lindau Disease
Authors: Albiñana Virginia , Gallardo-Vara Eunate , de Rojas-P Isabel , Recio-Poveda Lucia , Aguado Tania , Canto-Cano Ana , Aguirre Daniel T. , Serra Marcelo M. , González-Peramato Pilar , Martínez-Piñeiro Luis , Cuesta Angel M. , Botella Luisa Maria
Published: August 2020

Von Hippel–Lindau (VHL), is a rare autosomal dominant inherited cancer in which the lack of VHL protein triggers the development of multisystemic tumors such us retinal hemangioblastomas (HB), CNS-HB, and clear cell renal cell carcinoma (ccRCC). ccRCC ranks third in terms of incidence and first in cause of death. Standard systemic therapies for VHL-ccRCC have shown limited response, with recurrent surgeries being the only effective treatment. Targeting of β2-adrenergic receptor (ADRB) has shown therapeutic antitumor benefits on VHL-retinal HB (clinical trial) and VHL-CNS HB (in vitro). Therefore, the in vitro and in vivo antitumor benefits of propranolol (ADRB-1,2 antagonist) and ICI-118,551 (ADRB-2 antagonist) on VHL−/− ccRCC primary cultures and 786-O tumor cell lines have been addressed. Propranolol and ICI-118,551 activated apoptosis inhibited gene and protein expression of HIF-2α, CAIX, and VEGF, and impaired partially the nuclear internalization of HIF-2α and NFĸB/p65. Moreover, propranolol and ICI-118,551 reduced tumor growth on two in vivo xenografts. Finally, ccRCC patients receiving propranolol as off-label treatment have shown a positive therapeutic response for two years on average. In summary, propranolol and ICI-118,551 have shown antitumor benefits in VHL-derived ccRCC, and since ccRCCs comprise 63% of the total RCCs, targeting ADRB2 becomes a promising drug for VHL and other non-VHL tumors.
Building a Parkinson-Network–Experiences from Germany
Authors: van Munster Marlena , Tönges Lars , Loewenbrück Kai F. , Warnecke Tobias , Eggers Carsten
Published: August 2020

Parkinson’s disease is a complex neurodegenerative disease that can be best treated with a multi-disciplinary care approach. Building care networks has been shown as a useful tool to facilitate the integration of care services and improve outcomes for patients and care providers. However, experiences and practices relating to building a network are very limited in the field of Parkinson’s disease. This paper portrays existing Parkinson networks in Germany. With the help of a standardized template, description of networks and their building-blocks, so-called modules, were collected from all over Germany. Modules were rated in terms of their expected benefit and the required effort when implementing them, with the help of an expert survey. The rating showed that some modules were perceived as more important than others, but all modules were recognized as beneficial for patients and care providers. Overall, the German experience shows that building a Parkinson network facilitates the integration of care and provides a benefit to all stakeholders involved.
Impact of Opioid Analgesia and Inhalation Sedation Kalinox on Pain and Radial Artery Spasm during Transradial Coronary Angiography
Authors: Birgy Caroline , Trimaille Antonin , Messas Nathan , Ristorto Jessica , Kayali Anas , Marchandot Benjamin , Cardi Thomas , Hess Sébastien , Kibler Marion , Jesel Laurence , Ohlmann Patrick , Morel Olivier
Published: August 2020

With respect to the transfemoral approach, transradial procedures enable a drastic reduction of bleeding events and are associated with a reduction of mortality. Radial artery spasm (RAS) is one of the most common complications and may lead to patient discomfort and procedural failure. Currently, there is no consensus on the optimal sedation protocol to avoid RAS. The aim of this study was to investigate the respective impact of opioids analgesia and inhalation sedation with a 50% nitrous oxide/oxygen premix (Kalinox) on pain and occurrence of RAS during transradial coronary procedures. Consecutive patients undergoing transradial coronary angiography were prospectively enrolled in one, single center observational study (Nouvel Hôpital Civil, Strasbourg, France). Patients received opioids analgesia or inhalation sedation with Kalinox. The primary endpoints of the study were the incidence of a pain scale ≥5/10 and the occurrence of RAS. The secondary endpoints were the incidence of side effects. A total of 325 patients were enrolled (185 in the opioids analgesia group, 140 in the Kalinox group). RAS and pain scale ≥5 rates were not significantly different in the opioids analgesia and Kalinox groups (respectively 13.5% vs. 10.0% and 16.2% vs. 11.4%). Headache was more frequently observed in the Kalinox group (6.4% vs. 0.0%; p = 0.002). By multivariate analysis, female gender, BMI <25 kg/m2, puncture difficulty, the use of plastic needle and 6F sheath were identified as independent predictors of RAS. Procedural inhalation sedation by Kalinox is as safe as opioids analgesia during transradial coronary angiography.
The Role of Sense of Voice Presence and Anxiety Reduction in AVATAR Therapy
Authors: Rus-Calafell Mar , Ward Thomas , Zhang Xiao Chi , Edwards Clementine J. , Garety Philippa , Craig Tom
Published: August 2020

AVATAR therapy offers a unique therapeutic context that uses virtual reality technology to create a virtual embodiment of the voice-hearing experience, enabling the person to visualize their persecutory voice and engage in real-time “face-to-face” dialogue. The present study explores, for the first time, the contribution of sense of voice presence, together with session-by-session reduction of anxiety and paranoid attributions about the avatar, to changes in primary outcomes following AVATAR therapy. Data from 39 participants, who completed AVATAR therapy and attended a 12-week follow-up assessment, were analysed. Mid- to high-levels of sense of voice presence were reported across the therapy sessions, along with significant reductions of anxiety levels and paranoid attributions about the avatar. The interaction of sense of voice presence and reduction of anxiety was associated with two of the significant therapy outcomes: PSYRATS total and frequency of voices. The findings suggest that improvements in voice severity and frequency at post AVATAR therapy may be influenced by the combination of feeling less anxious in the context of a realistic simulation of the voice, while voice-related distress may involve additional cognitive and relational processes.
Liquid Biopsy is Instrumental for 3PM Dimensional Solutions in Cancer Management
Authors: Liskova Alena , Samec Marek , Koklesova Lenka , Giordano Frank A. , Kubatka Peter , Golubnitschaja Olga
Published: August 2020

One in every four deaths is due to cancer in Europe. In view of its increasing incidence, cancer became the leading cause of death and disease burden in Denmark, France, the Netherlands, and the UK. Without essential improvements in cancer prevention, an additional 775,000 cases of annual incidence have been prognosed until 2040. Between 1995 and 2018, the direct costs of cancer doubled from EUR 52 billion to EUR 103 billion in Europe, and per capita health spending on cancer increased by 86% from EUR 105 to EUR 195 in general, whereby Austria, Germany, Switzerland, Benelux, and France spend the most on cancer care compared to other European countries. In view of the consequent severe socio-economic burden on society, the paradigm change from a reactive to a predictive, preventive, and personalized medical approach in the overall cancer management is essential. Concepts of predictive, preventive, and personalized medicine (3PM) demonstrate a great potential to revise the above presented trends and to implement cost-effective healthcare that benefits the patient and society as a whole. At any stage, application of early and predictive diagnostics, targeted prevention, and personalization of medical services are basic pillars making 3PM particularly attractive for the patients as well as ethical and cost-effective healthcare. Optimal 3PM approach requires novel instruments such as well-designed liquid biopsy application. This review article highlights current achievements and details liquid biopsy approaches specifically in cancer management. 3PM-relevant expert recommendations are provided.
Children’s Dental Anxiety during the COVID-19 Pandemic: Polish Experience
Authors: Olszewska Aneta , Rzymski Piotr
Published: August 2020

Dental fear and anxiety is a significant issue that affects pediatric patients and creates challenges in oral health management. Considering that the coronavirus disease 2019 (COVID-19) pandemic, along with its associated sanitary regime, social distancing measures and nationwide quarantines, could itself induce public fears, including in children, it is of great interest to explore whether this situation and the necessity of reorganizing dental care could potentially affect the emotional state of pediatric patients facing a need for urgent dental intervention. The present study assessed the emotional state of children ≤ seven years old (n = 25) requiring dental healthcare during a nationwide quarantine in Poland, as well as the anxiety levels of their caregivers. The Faces Anxiety Scale was adopted, and the evaluation was independently performed by the dentist, caregivers and children themselves. The level of anxiety in caregivers was also measured. As demonstrated, children requiring dental intervention during the nationwide quarantine did not reveal a significantly higher anxiety level as compared to the age- and indication-matched pre-pandemic control group (n = 20), regardless of whether their emotional state was evaluated by the dentist, caregivers, or by themselves. However, the share of children scoring the lowest anxiety level in all assessments was smaller in the pandemic group. Boys in the pandemic group had a higher anxiety level, as indicated by a caregiver assessment, and displayed a negative correlation with age in all three types of evaluation. Moreover, caregiver anxiety levels were higher in the pandemic group as compared to the pre-pandemic subset and revealed stronger correlations with the dental anxiety in children. The results suggest that the reorganization of oral healthcare under the pandemic scenario did not have a profound effect on children’s dental anxiety. Nevertheless, findings in young boys highlight that they may be more vulnerable and require special care to mitigate their anxiety and decrease the risk of dentophobia in the future—these observations must be, however, treated with caution due to the small sample size and require further confirmation. Moreover, it is important to reassure caregivers of the safety of the dental visit during the pandemic to minimize the effect of their own anxiety on dental fears in children.
Efficient Deconvolution Architecture for Heterogeneous Systems-on-Chip
Authors: Perri Stefania , Sestito Cristian , Spagnolo Fanny , Corsonello Pasquale
Published: August 2020

Today, convolutional and deconvolutional neural network models are exceptionally popular thanks to the impressive accuracies they have been proven in several computer-vision applications. To speed up the overall tasks of these neural networks, purpose-designed accelerators are highly desirable. Unfortunately, the high computational complexity and the huge memory demand make the design of efficient hardware architectures, as well as their deployment in resource- and power-constrained embedded systems, still quite challenging. This paper presents a novel purpose-designed hardware accelerator to perform 2D deconvolutions. The proposed structure applies a hardware-oriented computational approach that overcomes the issues of traditional deconvolution methods, and it is suitable for being implemented within any virtually system-on-chip based on field-programmable gate array devices. In fact, the novel accelerator is simply scalable to comply with resources available within both high- and low-end devices by adequately scaling the adopted parallelism. As an example, when exploited to accelerate the Deep Convolutional Generative Adversarial Network model, the novel accelerator, running as a standalone unit implemented within the Xilinx Zynq XC7Z020 System-on-Chip (SoC) device, performs up to 72 GOPs. Moreover, it dissipates less than 500mW@200MHz and occupies 5.6%, 4.1%, 17%, and 96%, respectively, of the look-up tables, flip-flops, random access memory, and digital signal processors available on-chip. When accommodated within the same device, the whole embedded system equipped with the novel accelerator performs up to 54 GOPs and dissipates less than 1.8W@150MHz. Thanks to the increased parallelism exploitable, more than 900 GOPs can be executed when the high-end Virtex-7 XC7VX690T device is used as the implementation platform. Moreover, in comparison with state-of-the-art competitors implemented within the Zynq XC7Z045 device, the system proposed here reaches a computational capability up to 20% higher, and saves more than 60% and 80% of power consumption and logic resources requirement, respectively, using 5.7× fewer on-chip memory resources.
Low-Complexity Run-time Management of Concurrent Workloads for Energy-Efficient Multi-Core Systems
Authors: Aalsaud Ali , Xia Fei , Rafiev Ashur , Shafik Rishad , Romanovsky Alexander , Yakovlev Alex
Published: August 2020

Contemporary embedded systems may execute multiple applications, potentially concurrently on heterogeneous platforms, with different system workloads (CPU- or memory-intensive or both) leading to different power signatures. This makes finding the most energy-efficient system configuration for each type of workload scenario extremely challenging. This paper proposes a novel run-time optimization approach aiming for maximum power normalized performance under such circumstances. Based on experimenting with PARSEC applications on an Odroid XU-3 and Intel Core i7 platforms, we model power normalized performance (in terms of instruction per second (IPS)/Watt) through multivariate linear regression (MLR). We derive run-time control methods to exploit the models in different ways, trading off optimization results with control overheads. We demonstrate low-cost and low-complexity run-time algorithms that continuously adapt system configuration to improve the IPS/Watt by up to 139% compared to existing approaches.
Electrical Swath Ships with Underwater Hulls Preventing the Boundary Layer Separation
Authors: Nesteruk Igor , Krile Srecko , Koboevic Zarko
Published: August 2020

The body shapes of aquatic animals can ensure a laminar flow without boundary layer separation at rather high Reynolds numbers. The commercial efficiencies (drag-to-weight ratio) of similar hulls were estimated. The examples of neutrally buoyant vehicles of high commercial efficiency were proposed. It was shown that such hulls can be effectively used both in water and air. In particular, their application for SWATH (Small Water Area Twin Hulls) vehicles is discussed. In particular, the seakeeping characteristics of such ships can be improved due to the use of underwater hulls. In addition, the special shaping of these hulls allows the reducing of total drag, as well as the energetic needs and pollution. The presented estimations show that a weight-to-drag ratio of 165 can be achieved for a yacht with such specially shaped underwater hulls. Thus, a yacht with improved underwater hulls can use electrical engines only, and solar cells to charge the batteries.
Evaluation of Microsatellite Typing, ITS Sequencing, AFLP Fingerprinting, MALDI-TOF MS, and Fourier-Transform Infrared Spectroscopy Analysis of Candida auris
Authors: Vatanshenassan Mansoureh , Boekhout Teun , Mauder Norman , Robert Vincent , Maier Thomas , Meis Jacques F. , Berman Judith , Then Euníce , Kostrzewa Markus , Hagen Ferry
Published: August 2020

Candida auris is an emerging opportunistic yeast species causing nosocomial outbreaks at a global scale. A few studies have focused on the C. auris genotypic structure. Here, we compared five epidemiological typing tools using a set of 96 C. auris isolates from 14 geographical areas. Isolates were analyzed by microsatellite typing, ITS sequencing, amplified fragment length polymorphism (AFLP) fingerprint analysis, matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS), and Fourier-transform infrared (FTIR) spectroscopy methods. Microsatellite typing grouped the isolates into four main clusters, corresponding to the four known clades in concordance with whole genome sequencing studies. The other investigated typing tools showed poor performance compared with microsatellite typing. A comparison between the five methods showed the highest agreement between microsatellite typing and ITS sequencing with 45% similarity, followed by microsatellite typing and the FTIR method with 33% similarity. The lowest agreement was observed between FTIR spectroscopy, MALDI-TOF MS, and ITS sequencing. This study indicates that microsatellite typing is the tool of choice for C. auris outbreak investigations. Additionally, FTIR spectroscopy requires further optimization and evaluation before it can be used as an epidemiological typing method, comparable with microsatellite typing, as a rapid method for tracing nosocomial fungal outbreaks.
Fatal Case of Fungemia by Wickerhamomyces anomalus in a Pediatric Patient Diagnosed in a Teaching Hospital from Brazil
Authors: Dutra Vitor Rodrigues , Silva Leonardo Francisco , Oliveira Adriana Nazaré Miziara , Beirigo Emília Freitas , Arthur Vanessa Mello , Bernardes da Silva Raíssa , Ferreira Thatiana Bragine , Andrade-Silva Leonardo , Silva Marcos Vinícius , Fonseca Fernanda Machado , Silva-Vergara Mario León , Ferreira-Paim Kennio
Published: August 2020

In recent decades, emerging fungal infections have changed the clinical mycology scenario as a consequence of the advances in medical diagnostics and therapeutic procedures, long hospitalization times, and the growing number of individuals with debilitating chronic diseases and impaired immune systems. This report presents a 19 months old Brazilian female patient who developed a severe fungal sepsis by an uncommon yeast. She was admitted at the intensive care unit with severe pneumonia, bronchopulmonary dysplasia, and weight-for-age z score of less than −2. She remained more than 30 days in the intensive care unit where she had a femoral venous catheter placement, enteral nutrition, broad-spectrum antibiotic therapy, and prophylaxis with fluconazole. Moreover, pericardiocentesis was performed due to cardiac tamponade. She had a previous history of prematurity, cardiac surgery due to patent ductus arteriosus, and a long period of hospital stay. Despite the antifungal prophylaxis, two yeast isolates were recovered from blood and then identified by classical mycological methods and internal transcribed spacer (ITS) sequencing as Wickerhamomyces anomalus. Both isolates exhibited susceptibility to amphotericin B, ketoconazole, itraconazole, voriconazole, and fluconazole. Her clinical state worsened, presenting anasarca, epistaxis, and hemorrhagic suffusions in the mouth, sclera, oliguria, and bradycardia. Two days after the first positive culture, she presented a gradual reduction of the white blood cells count, with severe leukopenia and neutropenia. She died five days after.
Seasonal and Daily Activity of Two Zoo-Housed Grizzly Bears (Ursus arctos horribilis)
Authors: Fernandez Eduardo J. , Yoakum Ellen , Andrews Nathan
Published: August 2020

Captive grizzly bears, like their wild counterparts, engage in considerable variability in their seasonal and daily activity. We documented the year-long activity of two grizzly bears located at the Woodland Park Zoo in Seattle, Washington. We found that behaviors emerged in relation to month-to-month, seasonal, and time of day (hour-to-hour) observations, and events that occurred on exhibit, such as daily feedings. Seventeen behaviors split into seven classes of behavior were observed during their on-exhibit time over a 13-month period. Inactivity was the most frequent class of responses recorded, with most inactive behaviors occurring during the winter months. Both stereotypic and non-stereotypic activity emerged during the spring and summer months, with stereotypic activity occurring most frequently in the morning and transitioning to non-stereotypic activity in the latter part of the day. Results are discussed with respect to how captive grizzly bear behaviors relate to their natural seasonal and daily activity, as well as how events, such as feeding times and enrichment deliveries, can be used to optimize overall captive bear welfare.
The Applicability of the Standard DIN EN ISO 3690 for the Analysis of Diffusible Hydrogen Content in Underwater Wet Welding
Authors: Klett Jan , Wolf Thomas , Maier Hans Jürgen , Hassel Thomas
Published: August 2020

The European standard ISO 3690 regulates the measurement of diffusible hydrogen in arc-welded metal. It was designed for different welding methods performed in dry atmosphere (20% humidity). Some details of the standard are not applicable for wet underwater welding. The objective of this study was to extend the applicability of DIN EN ISO 3690:2018-12 to underwater wet-shielded metal arc welding (SMAW). Four different aspects regulated within the standard were accounted for: (1) sample dimensions and number of samples taken simultaneously; (2) time limitations defined by the standard regarding the welding and the cleaning process; (3) time, temperature, and method defined for analysis of the diffusible hydrogen content; (4) normalization of the hydrogen concentration measured. Underwater wet welding was performed using an automated, arc voltage-controlled welding machine. The results are discussed in light of standard DIN EN ISO 3690, and recommendations are provided for the analysis of diffusible hydrogen content upon underwater wet welding.
A Simple and Cost-Effective Method for Producing Stable Surfactant-Coated EGaIn Liquid Metal Nanodroplets
Authors: Xu Bingbing , Ye Feng , Chang Guangtao , Li Ruoxin
Published: August 2020

Liquid metals show unparalleled advantages in printable circuits, flexible wear, drug carriers, and electromagnetic shielding. However, the efficient and large-scale preparation of liquid metal nanodroplets (LM NDs) remains a significant challenge. Here, we propose a simple and efficient method for the large-scale preparation of stable eutectic gallium indium nanodroplets (EGaIn NDs). We compared different preparation methods and found that droplets with smaller particle sizes could quickly be produced using a shaking technique. The size of EGaIn NDs produced using this technique can reach 200 nm in 30 min and 100 nm in 240 min. Benefiting from the simple method, various surfactants can directly modify the surface of the EGaIn NDs to stabilize the prepared droplets. In addition, we discovered that shaking in an ice bath produced spherical nanodroplets, and after shaking for 30 min in a non-ice bath, rod-shaped gallium oxide hydroxide (GaOOH) appeared. Furthermore, the EGaIn NDs we produced have excellent stability—after storage at room temperature for 30 days, the particle size and morphology change little. The excellent stability of the produced EGaIn NDs provides a wider application of liquid metals in the fields of drug delivery, electromagnetic shielding, conductive inks, printed circuits, etc.
Dynamic Characterization of the Biomechanical Behaviour of Bovine Ovarian Cortical Tissue and Its Short-Term Effect on Ovarian Tissue and Follicles
Authors: Pascoletti Giulia , Di Nardo Maddalena , Fragomeni Gionata , Barbato Vincenza , Capriglione Teresa , Gualtieri Roberto , Talevi Riccardo , Catapano Gerardo , Zanetti Elisabetta M.
Published: August 2020

The ovary is a dynamic mechanoresponsive organ. In vitro, tissue biomechanics was reported to affect follicle activation mainly through the Hippo pathway. Only recently, ovary responsiveness to mechanical signals was exploited for reproductive purposes. Unfortunately, poor characterization of ovarian cortex biomechanics and of the mechanical challenge hampers reproducible and effective treatments, and prevention of tissue damages. In this study the biomechanical response of ovarian cortical tissue from abattoir bovines was characterized for the first time. Ovarian cortical tissue fragments were subjected to uniaxial dynamic testing at frequencies up to 30 Hz, and at increasing average stresses. Tissue structure prior to and after testing was characterized by histology, with established fixation and staining protocols, to assess follicle quality and stage. Tissue properties largely varied with the donor. Bovine ovarian cortical tissue consistently exhibited a nonlinear viscoelastic behavior, with dominant elastic characteristics, in the low range of other reproductive tissues, and significant creep. Strain rate was independent of the applied stress. Histological analysis prior to and after mechanical tests showed that the short-term dynamic mechanical test used for the study did not cause significant tissue tear, nor follicle expulsion or cell damage.
Synthesis of Cis-Cisoid or Cis-Transoid Poly(Phenyl-Acetylene)s Having One or Two Carbamate Groups as Oxygen Permeation Membrane Materials
Authors: Zang Yu , Lun Yinghui , Teraguchi Masahiro , Kaneko Takashi , Jia Hongge , Miao Fengjuan , Zhang Xunhai , Aoki Toshiki
Published: August 2020

Three new phenylacetylene monomers having one or two carbamate groups were synthesized and polymerized by using (Rh(norbornadiene)Cl)2 as an initiator. The resulting polymers had very high average molecular weights (Mw) of 1.4–4.8 × 106, with different solubility and membrane-forming abilities. The polymer having two carbamate groups and no hydroxy groups in the monomer unit showed the best solubility and membrane-forming ability among the three polymers. In addition, the oxygen permeability coefficient of the membrane was more than 135 times higher than that of a polymer having no carbamate groups and two hydroxy groups in the monomer unit with maintaining similar oxygen permselectivity. A better performance in membrane-forming ability and oxygen permeability may be caused by a more extended and flexible cis-transoid conformation and lower polarity. On the other hand, the other two new polymers having one carbamate group and two hydroxy groups in the monomer unit showed lower performances in membrane-forming abilities and oxygen permeabilities. It may be caused by a very tight cis-cisoid conformation, which was maintained by intramolecular hydrogen bonds.
Process Development for a Superplastic Hot Tube Gas Forming Process of Titanium (Ti-3Al-2.5V) Hollow Profiles
Authors: Trân Ricardo , Reuther Franz , Winter Sven , Psyk Verena
Published: August 2020

Tube forming technologies based on internal forming pressures, such as hydroforming or hot tube gas forming, are state of the art to manufacture complex closed profile geometries. However, materials with excellent specific strengths and chemical properties, such as titanium alloys, are often challenging to shape due to their limited formability. In this study, the titanium alloy Ti-3Al-2.5V was processed by superplastic hot tube gas forming to manufacture a helically shaped flex tube. The forming process was investigated in terms of process simulation, forming tool technology and process window for the manufacturing of good parts. Within a simulation study, a strain rate optimized forming pressure–time curve was defined. With the newly developed tool design, forming temperatures up to 900 °C and internal forming pressures up to 7 MPa were tested. A process window to manufacture good parts without necking or wrinkling has been successfully identified. The experiment data showed good agreement with the numerical simulations. The detailed study of the process contributes to an in-depth understanding of the superplastic forming of Ti-3Al-2.5V during hot tube gas forming. Furthermore, the study shows the high potential of superplastic hot tube gas forming of titanium alloys for the manufacturing of helical flex tubes and bellows.
Analysis of the Thermal Transfers in a VASM Crucible: Electron Beam Melting Experiment and Numerical Simulation
Authors: Haag Jérémie , Martens Jonathan , Dussoubs Bernard , Jardy Alain , Bellot Jean-Pierre
Published: August 2020

A description of the Vacuum Arc Skull Melting (VASM) process is presented showing its particularly complex features because of the mixing of porous raw materials with the dense remelted metal as well as the very high temperature and the highly transient nature of the process. This paper presents a 3D transient mathematical modelling of the heat transport with the aim of bringing a better understanding of the thermal behavior of the material into the crucible during a melting cycle. The model takes into account the heat input provided by the incoming metal thanks to an adaptive meshing, as well as the latent heat of solidification and the radiative heat transfers. An experimental validation of the model is presented where an electron beam heating source mimics the heat effect of the arc thanks to an excellent guidance of the beam over the melt surface. A comparison between the measured and calculated temperatures of a steel load is reported and reveals a satisfactory agreement. With very few adjustments, concerning mainly heat radiation at the top surface of metal into the crucible, the numerical model appears to be an efficient numerical tool to simulate the VASM process at the industrial scale.
A Metabolomics Workflow for Analyzing Complex Biological Samples Using a Combined Method of Untargeted and Target-List Based Approaches
Authors: Züllig Thomas , Zandl-Lang Martina , Trötzmüller Martin , Hartler Jürgen , Plecko Barbara , Köfeler Harald C.
Published: August 2020

In the highly dynamic field of metabolomics, we have developed a method for the analysis of hydrophilic metabolites in various biological samples. Therefore, we used hydrophilic interaction chromatography (HILIC) for separation, combined with a high-resolution mass spectrometer (MS) with the aim of separating and analyzing a wide range of compounds. We used 41 reference standards with different chemical properties to develop an optimal chromatographic separation. MS analysis was performed with a set of pooled biological samples human cerebrospinal fluid (CSF), and human plasma. The raw data was processed in a first step with Compound Discoverer 3.1 (CD), a software tool for untargeted metabolomics with the aim to create a list of unknown compounds. In a second step, we combined the results obtained with our internally analyzed reference standard list to process the data along with the Lipid Data Analyzer 2.6 (LDA), a software tool for a targeted approach. In order to demonstrate the advantages of this combined target-list based and untargeted approach, we not only compared the relative standard deviation (%RSD) of the technical replicas of pooled plasma samples (n = 5) and pooled CSF samples (n = 3) with the results from CD, but also with XCMS Online, a well-known software tool for untargeted metabolomics studies. As a result of this study we could demonstrate with our HILIC-MS method that all standards could be either separated by chromatography, including isobaric leucine and isoleucine or with MS by different mass. We also showed that this combined approach benefits from improved precision compared to well-known metabolomics software tools such as CD and XCMS online. Within the pooled plasma samples processed by LDA 68% of the detected compounds had a %RSD of less than 25%, compared to CD and XCMS online (57% and 55%). The improvements of precision in the pooled CSF samples were even more pronounced, 83% had a %RSD of less than 25% compared to CD and XCMS online (28% and 8% compounds detected). Particularly for low concentration samples, this method showed a more precise peak area integration with its 3D algorithm and with the benefits of the LDAs graphical user interface for fast and easy manual curation of peak integration. The here-described method has the advantage that manual curation for larger batch measurements remains minimal due to the target list containing the information obtained by an untargeted approach.
Integrating Two-Dimensional Gas and Liquid Chromatography-Mass Spectrometry for Untargeted Colorectal Cancer Metabolomics: A Proof-of-Principle Study
Authors: Yuan Fang , Kim Seongho , Yin Xinmin , Zhang Xiang , Kato Ikuko
Published: August 2020

Untargeted metabolomics is expected to lead to a better mechanistic understanding of diseases and thus applications of precision medicine and personalized intervention. To further increase metabolite coverage and achieve high accuracy of metabolite quantification, the present proof-of-principle study was to explore the applicability of integration of two-dimensional gas and liquid chromatography-mass spectrometry (GC × GC-MS and 2DLC-MS) platforms to characterizing circulating polar metabolome extracted from plasma collected from 29 individuals with colorectal cancer in comparison with 29 who remained cancer-free. After adjustment of multiple comparisons, 20 metabolites were found to be up-regulated and 8 metabolites were found to be down-regulated, which pointed to the dysregulation in energy metabolism and protein synthesis. While integrating the GC × GC-MS and 2DLC-MS data can dramatically increase the metabolite coverage, this study had a limitation in analyzing the non-polar metabolites. Given the small sample size, these results need to be validated with a larger sample size and with samples collected prior to diagnostic and treatment. Nevertheless, this proof-of-principle study demonstrates the potential applicability of integration of these advanced analytical platforms to improve discrimination between colorectal cancer cases and controls based on metabolite profiles in future studies.