bluuebunny/crossref_metadata_2025 huggingface dataset:
Emerging Roles of Single-Cell Multi-Omics in Studying Developmental Temporal Patterning
Authors: Lopes Andrea , Magrinelli Elia , Telley Ludovic
Published: October 2020

The complexity of brain structure and function is rooted in the precise spatial and temporal regulation of selective developmental events. During neurogenesis, both vertebrates and invertebrates generate a wide variety of specialized cell types through the expansion and specification of a restricted set of neuronal progenitors. Temporal patterning of neural progenitors rests on fine regulation between cell-intrinsic and cell-extrinsic mechanisms. The rapid emergence of high-throughput single-cell technologies combined with elaborate computational analysis has started to provide us with unprecedented biological insights related to temporal patterning in the developing central nervous system (CNS). Here, we present an overview of recent advances in Drosophila and vertebrates, focusing both on cell-intrinsic mechanisms and environmental influences. We then describe the various multi-omics approaches that have strongly contributed to our current understanding and discuss perspectives on the various -omics approaches that hold great potential for the future of temporal patterning research.
Computer-Aided Estimation of Biological Activity Profiles of Drug-Like Compounds Taking into Account Their Metabolism in Human Body
Authors: Filimonov Dmitry A. , Rudik Anastassia V. , Dmitriev Alexander V. , Poroikov Vladimir V.
Published: October 2020

Most pharmaceutical substances interact with several or even many molecular targets in the organism, determining the complex profiles of their biological activity. Moreover, due to biotransformation in the human body, they form one or several metabolites with different biological activity profiles. Therefore, the development and rational use of novel drugs requires the analysis of their biological activity profiles, taking into account metabolism in the human body. In silico methods are currently widely used for estimating new drug-like compounds’ interactions with pharmacological targets and predicting their metabolic transformations. In this study, we consider the estimation of the biological activity profiles of organic compounds, taking into account the action of both the parent molecule and its metabolites in the human body. We used an external dataset that consists of 864 parent compounds with known metabolites. It is shown that the complex assessment of active pharmaceutical ingredients’ interactions with the human organism increases the quality of computer-aided estimates. The toxic and adverse effects showed the most significant difference: reaching 0.16 for recall and 0.14 for precision.
Mechanism of Albuminuria Reduction by Chymase Inhibition in Diabetic Mice
Authors: Terai Kentaro , Jin Denan , Watase Kenji , Imagawa Akihisa , Takai Shinji
Published: October 2020

Chymase has several functions, such as angiotensin II formation, which can promote diabetic kidney disease (DKD). In this study, we evaluated the effect of the chymase inhibitor TY-51469 on DKD in diabetic db/db mice. Diabetic mice were administered TY-51469 (10 mg/kg/day) or placebo for 4 weeks. No significant difference was observed in body weight and fasting blood glucose between TY-51469- and placebo-treated groups. However, a significant reduction in urinary albumin/creatinine ratio was observed in the TY-51469-treated group compared with the placebo-treated group. In the renal extract, chymase activity was significantly higher in placebo-treated mice than in non-diabetic db/m mice, but it was reduced by treatment with TY-51469. Both NADPH oxidase 4 expression and the oxidative stress marker malondialdehyde were significantly augmented in the placebo-treated group, but they were attenuated in the TY-51469-treated group. Significant increases of tumor necrosis factor-α and transforming growth factor-β mRNA levels in the placebo-treated group were significantly reduced by treatment with TY-51469. Furthermore, the expression of nephrin, which is a podocyte-specific protein, was significantly reduced in the placebo-treated group, but it was restored in the TY-51469-treated group. These findings demonstrated that chymase inhibition reduced albuminuria via attenuation of podocyte injury by oxidative stress.
Toward Drug-Like Multispecific Antibodies by Design
Authors: Sawant Manali S. , Streu Craig N. , Wu Lina , Tessier Peter M.
Published: October 2020

The success of antibody therapeutics is strongly influenced by their multifunctional nature that couples antigen recognition mediated by their variable regions with effector functions and half-life extension mediated by a subset of their constant regions. Nevertheless, the monospecific IgG format is not optimal for many therapeutic applications, and this has led to the design of a vast number of unique multispecific antibody formats that enable targeting of multiple antigens or multiple epitopes on the same antigen. Despite the diversity of these formats, a common challenge in generating multispecific antibodies is that they display suboptimal physical and chemical properties relative to conventional IgGs and are more difficult to develop into therapeutics. Here we review advances in the design and engineering of multispecific antibodies with drug-like properties, including favorable stability, solubility, viscosity, specificity and pharmacokinetic properties. We also highlight emerging experimental and computational methods for improving the next generation of multispecific antibodies, as well as their constituent antibody fragments, with natural IgG-like properties. Finally, we identify several outstanding challenges that need to be addressed to increase the success of multispecific antibodies in the clinic.
How Machine Learning Methods Helped Find Putative Rye Wax Genes Among GBS Data
Authors: Góralska Magdalena , Bińkowski Jan , Lenarczyk Natalia , Bienias Anna , Grądzielewska Agnieszka , Czyczyło-Mysza Ilona , Kapłoniak Kamila , Stojałowski Stefan , Myśków Beata
Published: October 2020

The standard approach to genetic mapping was supplemented by machine learning (ML) to establish the location of the rye gene associated with epicuticular wax formation (glaucous phenotype). Over 180 plants of the biparental F2 population were genotyped with the DArTseq (sequencing-based diversity array technology). A maximum likelihood (MLH) algorithm (JoinMap 5.0) and three ML algorithms: logistic regression (LR), random forest and extreme gradient boosted trees (XGBoost), were used to select markers closely linked to the gene encoding wax layer. The allele conditioning the nonglaucous appearance of plants, derived from the cultivar Karlikovaja Zelenostebelnaja, was mapped at the chromosome 2R, which is the first report on this localization. The DNA sequence of DArT-Silico 3585843, closely linked to wax segregation detected by using ML methods, was indicated as one of the candidates controlling the studied trait. The putative gene encodes the ABCG11 transporter.
Chiral Cyclobutane-Containing Cell-Penetrating Peptides as Selective Vectors for Anti-Leishmania Drug Delivery Systems
Authors: Illa Ona , Olivares José-Antonio , Gaztelumendi Nerea , Martínez-Castro Laura , Ospina Jimena , Abengozar María-Ángeles , Sciortino Giuseppe , Maréchal Jean-Didier , Nogués Carme , Royo Míriam , Rivas Luis , Ortuño Rosa M.
Published: October 2020

Two series of new hybrid γ/γ-peptides, γ-CC and γ-CT, formed by (1S,2R)-3-amino-2,2,dimethylcyclobutane-1-carboxylic acid joined in alternation to a Nα-functionalized cis- or trans-γ-amino-l-proline derivative, respectively, have been synthesized and evaluated as cell penetrating peptides (CPP) and as selective vectors for anti-Leishmania drug delivery systems (DDS). They lacked cytotoxicity on the tumoral human cell line HeLa with a moderate cell-uptake on these cells. In contrast, both γ-CC and γ-CT tetradecamers were microbicidal on the protozoan parasite Leishmania beyond 25 μM, with significant intracellular accumulation. They were conjugated to fluorescent doxorubicin (Dox) as a standard drug showing toxicity beyond 1 μM, while free Dox was not toxic. Intracellular accumulation was 2.5 higher than with Dox-TAT conjugate (TAT = transactivator of transcription, taken as a standard CPP). The conformational structure of the conjugates was approached both by circular dichroism spectroscopy and molecular dynamics simulations. Altogether, computational calculations predict that the drug-γ-peptide conjugates adopt conformations that bury the Dox moiety into a cavity of the folded peptide, while the positively charged guanidinium groups face the solvent. The favorable charge/hydrophobicity balance in these CPP improves the solubility of Dox in aqueous media, as well as translocation across cell membranes, making them promising candidates for DDS.
Platelet Induced Functional Alteration of CD4+ and CD8+ T Cells in HNSCC
Authors: Polasky Christina , Wendt Franziska , Pries Ralph , Wollenberg Barbara
Published: October 2020

Platelets (PLT) are the second most abundant cell type in human blood and exert various immune-regulatory functions under both physiological and pathological conditions. In fact, immune cell regulation via platelets has been demonstrated in several studies within the past decade. However, the exact mechanisms behind T cell regulation remain poorly understood. We questioned whether the formation of aggregates of platelets and T cells has an impact on T-cell functions. In the present study, we stimulated PBMC cultures with anti-CD3 and anti-CD28 mABs and cultured them at a PLT: PBMC ratio of 1:1 or 100:1. After 24, 48, and 72 h, PD-1, PD-L1 expression, and proliferation were analyzed on T cells using flow cytometry. Cytokine production was measured in PHA stimulated CD4 cells after 6 h. We found a significant platelet-mediated decrease in PD-1 and PD-L1 expression, proliferation, as well as IFN-γ and TNF-α production. Perturbations also at least partially remained after spatial separation of PLTs from PBMCs in Transwell-assays. T cell-platelet aggregates showed similar levels of activation markers, proliferation, and secreted cytokines as their non-complexed counterparts. Results indicate a platelet mediated regulation of T cells via direct and indirect contact, but only mediocre effects of the complex formation itself.
Multi-Omics Strategies for Decoding Smoke-Assisted Germination Pathways and Seed Vigour
Authors: Bose Utpal , Juhász Angéla , Broadbent James A. , Komatsu Setsuko , Colgrave Michelle L.
Published: October 2020

The success of seed germination and the successful establishment of seedlings across diverse environmental conditions depends on seed vigour, which is of both economic and ecologic importance. The smoke-derived exogenous compound karrikins (KARs) and the endogenous plant hormone strigolactone (SL) are two classes of butanolide-containing molecules that follow highly similar signalling pathways to control diverse biological activities in plants. Unravelling the precise mode-of-action of these two classes of molecules in model species has been a key research objective. However, the specific and dynamic expression of biomolecules upon stimulation by these signalling molecules remains largely unknown. Genomic and post-genomic profiling approaches have enabled mining and association studies across the vast genetic diversity and phenotypic plasticity. Here, we review the background of smoke-assisted germination and vigour and the current knowledge of how plants perceive KAR and SL signalling and initiate the crosstalk with the germination-associated hormone pathways. The recent advancement of ‘multi-omics’ applications are discussed in the context of KAR signalling and with relevance to their adoption for superior agronomic trait development. The remaining challenges and future opportunities for integrating multi-omics datasets associated with their application in KAR-dependent seed germination and abiotic stress tolerance are also discussed.
Disease-Specific Expression of Conjunctiva Associated Lymphoid Tissue (CALT) in Mouse Models of Dry Eye Disease and Ocular Allergy
Authors: Steven Philipp , Schwab Sebastian , Kiesewetter Anne , Saban Daniel R. , Stern Michael E. , Gehlsen Uta
Published: October 2020

Conjunctiva-associated tissue (CALT) is assumed to play a crucial role in the immune system of the ocular surface. Its function in several ocular surface diseases (OSD) is still not fully understood. This study investigates the function of CALT in mouse models of dry-eye disease and ocular allergy. Since antigen-presentation is the central similarity in the pathologies, this study focuses on antigen-presentation in CALT Morphology and the expression of CALT, which was investigated in mice after induction of dry-eye, ocular allergy, topical antigen-stimulation, and after local depletion of phagocytic cells. Antigen uptake was investigated after the application of fluorescent ovalbumin (OVA). OSD influences the appearance and morphology of CALT in a disease-dependent manner. Ocular allergy leads to an increase and dry-eye disease to a decrease in number and size of CALT. The development of CALT is dependent on the presence of APCs. Professional APCs are present in CALT, and soluble antigen is transported into the follicle. CALT appearance is disease-specific and indicative of differing functions. Although the specific involvement of CALT in OSD needs further study, the existence of functional APCS and antigen-uptake supports the hypothesis that CALT is an immunological key player at the ocular surface.
Luminescence of Cypridina Luciferin in the Presence of Human Plasma Alpha 1-Acid Glycoprotein
Authors: Kanie Shusei , Komatsu Mami , Mitani Yasuo
Published: October 2020

The enzyme Cypridina luciferase (CLase) enables Cypridina luciferin to emit light efficiently through an oxidation reaction. The catalytic mechanism on the substrate of CLase has been studied, but the details remain to be clarified. Here, we examined the luminescence of Cypridina luciferin in the presence of several proteins with drug-binding ability. Luminescence measurements showed that the mixture of human plasma alpha 1-acid glycoprotein (hAGP) and Cypridina luciferin produced light. The total value of the luminescence intensity over 60 s was over 12.6-fold higher than those in the presence of ovalbumin, human serum albumin, or bovine serum albumin. In the presence of heat-treated hAGP, the luminescence intensity of Cypridina luciferin was lower than in the presence of intact hAGP. Chlorpromazine, which binds to hAGP, showed an inhibitory effect on the luminescence of Cypridina luciferin, both in the presence of hAGP and a recombinant CLase. Furthermore, BlastP analysis showed that hAGP had partial amino acid sequence similarity to known CLases in the region including amino acid residues involved in the drug-binding ability of hAGP. These findings indicate enzymological similarity between hAGP and CLase and provide insights into both the enzymological understanding of CLase and development of a luminescence detection method for hAGP.
Advances, Perspectives and Potential Engineering Strategies of Light-Gated Phosphodiesterases for Optogenetic Applications
Authors: Tian Yuehui , Yang Shang , Gao Shiqiang
Published: October 2020

The second messengers, cyclic adenosine 3′-5′-monophosphate (cAMP) and cyclic guanosine 3′-5′-monophosphate (cGMP), play important roles in many animal cells by regulating intracellular signaling pathways and modulating cell physiology. Environmental cues like temperature, light, and chemical compounds can stimulate cell surface receptors and trigger the generation of second messengers and the following regulations. The spread of cAMP and cGMP is further shaped by cyclic nucleotide phosphodiesterases (PDEs) for orchestration of intracellular microdomain signaling. However, localized intracellular cAMP and cGMP signaling requires further investigation. Optogenetic manipulation of cAMP and cGMP offers new opportunities for spatio-temporally precise study of their signaling mechanism. Light-gated nucleotide cyclases are well developed and applied for cAMP/cGMP manipulation. Recently discovered rhodopsin phosphodiesterase genes from protists established a new and direct biological connection between light and PDEs. Light-regulated PDEs are under development, and of demand to complete the toolkit for cAMP/cGMP manipulation. In this review, we summarize the state of the art, pros and cons of artificial and natural light-regulated PDEs, and discuss potential new strategies of developing light-gated PDEs for optogenetic manipulation.
Unconventional Peptide Presentation by Classical MHC Class I and Implications for T and NK Cell Activation
Authors: Zajonc Dirk M.
Published: October 2020

T cell-mediated immune recognition of peptides is initiated upon binding of the antigen receptor on T cells (TCR) to the peptide-MHC complex. TCRs are typically restricted by a particular MHC allele, while polymorphism within the MHC molecule can affect the spectrum of peptides that are bound and presented to the TCR. Classical MHC Class I molecules have a confined binding groove that restricts the length of the presented peptides to typically 8–11 amino acids. Both N- and C-termini of the peptide are bound within binding pockets, allowing the TCR to dock in a diagonal orientation above the MHC-peptide complex. Longer peptides have been observed to bind either in a bulged or zig-zag orientation within the binding groove. More recently, unconventional peptide presentation has been reported for different MHC I molecules. Here, either N- or C-terminal amino acid additions to conventionally presented peptides induced a structural change either within the MHC I molecule that opened the confined binding groove or within the peptide itself, allowing the peptide ends to protrude into the solvent. Since both TCRs on T cells and killer immunoglobulin receptors on Natural Killer (NK) cells contact the MHC I molecule above or at the periphery of the peptide binding groove, unconventionally presented peptides could modulate both T cell and NK cell responses. We will highlight recent advances in our understanding of the functional consequences of unconventional peptide presentation in cellular immunity.
Identification of Viruses and Viroids Infecting Tomato and Pepper Plants in Vietnam by Metatranscriptomics
Authors: Choi Hoseong , Jo Yeonhwa , Cho Won Kyong , Yu Jisuk , Tran Phu-Tri , Salaipeth Lakha , Kwak Hae-Ryun , Choi Hong-Soo , Kim Kook-Hyung
Published: October 2020

Tomato (Lycopersicum esculentum L.) and pepper (Capsicum annuum L.) plants belonging to the family Solanaceae are cultivated worldwide. The rapid development of next-generation sequencing (NGS) technology facilitates the identification of viruses and viroids infecting plants. In this study, we carried out metatranscriptomics using RNA sequencing followed by bioinformatics analyses to identify viruses and viroids infecting tomato and pepper plants in Vietnam. We prepared a total of 16 libraries, including eight tomato and eight pepper libraries derived from different geographical regions in Vietnam. We identified a total of 602 virus-associated contigs, which were assigned to 18 different virus species belonging to nine different viral genera. We identified 13 different viruses and two viroids infecting tomato plants and 12 viruses and two viroids infecting pepper plants with viruses as dominantly observed pathogens. Our results showed that multiple infection of different viral pathogens was common in both plants. Moreover, geographical region and host plant were two major factors to determine viral populations. Taken together, our results provide the comprehensive overview of viral pathogens infecting two important plants in the family Solanaceae grown in Vietnam.
Proteomic Characterization of Urinary Extracellular Vesicles from Kidney-Transplanted Patients Treated with Calcineurin Inhibitors
Authors: Carreras-Planella Laura , Juega Javier , Taco Omar , Cañas Laura , Franquesa Marcella , Lauzurica Ricardo , Borràs Francesc Enric
Published: October 2020

Use of immunosuppressive drugs is still unavoidable in kidney-transplanted patients. Since their discovery, calcineurin inhibitors (CNI) have been considered the first-line immunosuppressive agents, in spite of their known nephrotoxicity. Chronic CNI toxicity (CNIT) may lead to kidney fibrosis, a threatening scenario for graft survival. However, there is still controversy regarding CNIT diagnosis, monitoring and therapeutic management, and their specific effects at the molecular level are not fully known. Aiming to better characterize CNIT patients, in the present study, we collected urine from kidney-transplanted patients treated with CNI who (i) had a normal kidney function, (ii) suffered CNIT, or (iii) presented interstitial fibrosis and tubular atrophy (IFTA). Urinary extracellular vesicles (uEV) were enriched and the proteome was analyzed to get insight into changes happening during CNI. Members of the uroplakin and plakin families were significantly upregulated in the CNIT group, suggesting an important role in CNIT processes. Although biomarkers cannot be asserted from this single pilot study, our results evidence the potential of uEV as a source of non-invasive protein biomarkers for a better detection and monitoring of this renal alteration in kidney-transplanted patients.
Looking for Targets to Restore the Contractile Function in Congenital Myopathy Caused by Gln147Pro Tropomyosin
Authors: Karpicheva Olga E. , Simonyan Armen O. , Rysev Nikita A. , Redwood Charles S. , Borovikov Yurii S.
Published: October 2020

We have used the technique of polarized microfluorimetry to obtain new insight into the pathogenesis of skeletal muscle disease caused by the Gln147Pro substitution in β-tropomyosin (Tpm2.2). The spatial rearrangements of actin, myosin and tropomyosin in the single muscle fiber containing reconstituted thin filaments were studied during simulation of several stages of ATP hydrolysis cycle. The angular orientation of the fluorescence probes bound to tropomyosin was found to be changed by the substitution and was characteristic for a shift of tropomyosin strands closer to the inner actin domains. It was observed both in the absence and in the presence of troponin, Ca2+ and myosin heads at all simulated stages of the ATPase cycle. The mutant showed higher flexibility. Moreover, the Gln147Pro substitution disrupted the myosin-induced displacement of tropomyosin over actin. The irregular positioning of the mutant tropomyosin caused premature activation of actin monomers and a tendency to increase the number of myosin cross-bridges in a state of strong binding with actin at low Ca2+.
On the Calculation of Propulsive Characteristics of a Bulk-Carrier Moving in Head Seas
Authors: Polyzos S. , Tzabiras G.
Published: October 2020

The present work describes a simplified Computational Fluid Dynamics (CFD) approach in order to calculate the propulsive performance of a ship moving at steady forward speed in head seas. The proposed method combines experimental data concerning the added resistance at model scale with full scale Reynolds Averages Navier–Stokes (RANS) computations, using an in-house solver. In order to simulate the propeller performance, the actuator disk concept is employed. The propeller thrust is calculated in the time domain, assuming that the total resistance of the ship is the sum of the still water resistance and the added component derived by the towing tank data. The unsteady RANS equations are solved until self-propulsion is achieved at a given time step. Then, the computed values of both the flow rate through the propeller and the thrust are stored and, after the end of the examined time period, they are processed for calculating the variation of Shaft Horsepower (SHP) and RPM of the ship’s engine. The method is applied for a bulk carrier which has been tested in model scale at the towing tank of the Laboratory for Ship and Marine Hydrodynamics (LSMH) of the National Technical University of Athens (NTUA).
Typhoon-Triggered Phytoplankton Bloom and Associated Upper-Ocean Conditions in the Northwestern Pacific: Evidence from Satellite Remote Sensing, Argo Profile, and an Ocean Circulation Model
Authors: Lee Joon-Ho , Moon Jae-Hong , Kim Taekyun
Published: October 2020

A long-lasting phytoplankton bloom, characterized by high chlorophyll-a (Chl-a) concentrations in an eddy-like feature, was detected in MODIS satellite imagery of the northwestern Pacific following the passage of Typhoon Krosa in August 2019. Satellite datasets, Argo measurements, and regional ocean models were analyzed to determine the occurrence and abundance of high-Chl-a concentrations and the upper-ocean conditions associated with them before and after the passage of the typhoon. Remote sensing data revealed that the typhoon triggered sharp increases in surface Chl-a concentrations more than five times the pre-typhoon average, which lasted for two weeks. The elevated post-typhoon concentrations coincided with a pre-existing oceanic cyclone that was detected as an altimetry-based sea surface height anomaly. The typhoon looped around the oceanic cyclone and lingered for two days at slow speeds (less than 2 m/s), producing an unusual sea-surface cooling of up to approximately 9 °C in the cyclonic eddy region. Our model successfully captured the typhoon-induced cold-core cyclonic circulation, which corresponded to the region of high Chl-a concentration. Model–data comparisons revealed that the looping motion of the slow-moving typhoon enhanced the pre-existing cyclonic circulation, resulting in strong vertical mixing and upwelling, consequently initiating a phytoplankton bloom due to increased nutrient supply to the euphotic zone.
Comparative Proteomic Profiling of Marine and Freshwater Synechocystis Strains Using Liquid Chromatography-Tandem Mass Spectrometry
Authors: Kwon Dami , Park Jong-Moon , Duong Van-An , Hong Seong-Joo , Cho Byung-Kwan , Lee Choul-Gyun , Choi Hyung-Kyoon , Kim Dong-Myung , Lee Hookeun
Published: October 2020

Freshwater Synechocystis sp. PCC 6803 has been considered to be a platform for the production of the next generation of biofuels and is used as a model organism in various fields. Various genomics, transcriptomics, metabolomics, and proteomics studies have been performed on this strain, whereas marine Synechocystis sp. PCC 7338 has not been widely studied despite its wide distribution. This study analyzed the proteome profiles of two Synechocystis strains using a liquid chromatography–tandem mass spectrometry-based bottom-up proteomic approach. Proteomic profiling of Synechocystis sp. PCC 7338 was performed for the first time with a data-dependent acquisition method, revealing 18,779 unique peptides and 1794 protein groups. A data-independent acquisition method was carried out for the comparative quantitation of Synechocystis sp. PCC 6803 and 7338. Among 2049 quantified proteins, 185 up- and 211 down-regulated proteins were defined in Synechocystis sp. PCC 7338. Some characteristics in the proteome of Synechocystis sp. PCC 7338 were revealed, such as its adaptation to living conditions, including the down-regulation of some photosynthesis proteins, the up-regulation of kdpB, and the use of osmolyte glycine as a substrate in C1 metabolism for the regulation of carbon flow. This study will facilitate further studies on Synechocystis 7338 to define in depth the proteomic differences between it and other Synechocystis strains.
The Effect of Stochasticity of Waves on Coastal Flood and Its Variations with Sea-level Rise
Authors: Idier Déborah , Pedreros Rodrigo , Rohmer Jérémy , Le Cozannet Gonéri
Published: October 2020

Coastal floods are driven by many hydro-meteorological forcing factors, among which are mean sea levels, tides, atmospheric storm surges, and waves. Depending on these conditions, wave overtopping may occur and, in some cases, lead to a significant flood. In the present study, we investigate the effect of the stochastic character of waves on the flood itself using a phase-resolving wave model (SWASH). We focus on the macro-tidal site of Gâvres (France), consider two past flood events (both resulting from wave overtopping), and investigate how the effect of randomness of waves on the flood is changing with the forcing conditions and the time span (minutes to hours). We clearly show that the effect of waves’ stochasticity on the flood itself is far from being negligible and, especially on a short time scale (~15 min), generates an uncertainty comparable to that induced by the sea-level rise scenarios, as long as the still water level remains smaller than the critical level above which overflow occurs. This implies that lower confidence should be assigned to flood projection on sites where wave overtopping is the main process leading to flood.
Primary Care Physician Experiences with Integrated Population-Scale Genetic Testing: A Mixed-Methods Assessment
Authors: Lemke Amy A. , Amendola Laura M. , Kuchta Kristine , Dunnenberger Henry M. , Thompson Jennifer , Johnson Christian , Ilbawi Nadim , Oshman Lauren , Hulick Peter J.
Published: October 2020

The scalable delivery of genomic medicine requires collaboration between genetics and non-genetics providers. Thus, it is essential to investigate and address the perceived value of and barriers to incorporating genetic testing into the clinical practice of primary care providers (PCPs). We used a mixed-methods approach of qualitative interviews and surveys to explore the experience of PCPs involved in the pilot DNA-10K population genetic testing program. Similar to previous research, PCPs reported low confidence with tasks related to ordering, interpreting and managing the results of genetic tests, and identified the need for additional education. PCPs endorsed high levels of utility for patients and their families but noted logistical challenges to incorporating genetic testing into their practice. Overall PCPs were not familiar with the United States’ Genetic Information Nondiscrimination Act and they expressed high levels of concern for patient data privacy and potential insurance discrimination. This PCP feedback led to the development and implementation of several processes to improve the PCP experience with the DNA-10K program. These results contribute to the knowledge base regarding genomic implementation using a mixed provider model and may be beneficial for institutions developing similar clinical programs.
Association between Sarcopenia and Physical Function among Preoperative Lung Cancer Patients
Authors: Kong Sunga , Shin Sumin , Lee Jae Kyung , Lee Genehee , Kang Danbee , Cho Juhee , Kim Hong Kwan , Zo Jae Ill , Shim Young Mog , Park Hye Yun , Shin Dong Wook
Published: October 2020

We aimed to investigate the prevalence of sarcopenia using new diagnostic criteria and association of sarcopenia with cardiopulmonary function and physical activity (PA) in preoperative lung cancer patients. The data of 614 patients were obtained from the CATCH-LUNG cohort study. Patients were classified into three groups—normal (n = 520), pre-sarcopenia (n = 60, low skeletal muscle mass index only), and sarcopenia (n = 34, low SMI and strength). Cardiopulmonary function was measured using the 6-min walk test (6MWT), and PA was objectively measured using a wearable device. The adjusted odds ratio (aOR) for a <400-m distance in 6MWT was 3.52 (95% confidence interval (CI) 1.34–9.21) and 6.63 (95% CI 2.25–19.60) in the pre-sarcopenia and sarcopenia groups, respectively, compared to that in the normal group. The aOR (95% CI) for <5000 steps/day was 1.64 (0.65–4.16) and 4.20 (1.55–11.38) in the pre-sarcopenia and sarcopenia groups, respectively, compared to that in the normal group. In conclusion, the prevalence of pre-sarcopenia and sarcopenia was 9.8% and 5.5%, respectively, among preoperative lung cancer patients. Cardiopulmonary function and physical activity were significantly lower in the pre-sarcopenia and sarcopenia groups than in the normal group. Patients with sarcopenia had more robust findings, suggesting the importance of muscle strength and mass.
Colon Cancer Biomarkers: Implications for Personalized Medicine
Authors: Pritzker Kenneth P.H.
Published: October 2020

The heterogeneity of colon cancers and their reactions presents both a challenge and promise for personalized medicine. The challenge is to develop effective biologically personalized therapeutics guided by predictive and prognostic biomarkers. Presently, there are several classes of candidate biomarkers, including genomic probes, inhibitory RNAs, assays for immunity dysfunction and, not to be forgotten, specific histopathologic and histochemical features. To develop effective therapeutics, candidate biomarkers must be qualified and validated in comparable independent cohorts, no small undertaking. This process and subsequent deployment in clinical practice involves not only the strong association of the biomarker with the treatment but also careful attention to the prosaic aspects of representative tumor site selection, obtaining a fully adequate sample which is preserved and prepared to optimize high quality analysis. In the future, the clinical utility of biomarker analytical results will benefit from associated clinical and basic science data with the assistance of artificial intelligence techniques. By application of an individualized, selected suite of biomarkers, comprehensively interpreted, individualized, more effective and less toxic therapy for colon cancer will be enabled, thereby fulfilling the promise of personalized medicine.
GWAS of Post-Orthodontic Aggressive External Apical Root Resorption Identified Multiple Putative Loci at X-Y Chromosomes
Authors: Iber-Díaz Paula , Senen-Carramolino Raquel , Iglesias-Linares Alejandro , Fernández-Navarro Pablo , Flores-Mir Carlos , Yañez-Vico Rosa
Published: October 2020

Personalized dental medicine requires from precise and customized genomic diagnostic. To conduct an association analysis over multiple putative loci and genes located at chromosomes 2, 4, 8, 12, 18, X, and Y, potentially implicated in an extreme type of external apical root resorption secondary to orthodontic forces (aEARR). A genome-wide association study of aEARR was conducted with 480 patients [ratio~1:3 case/control]. Genomic DNA was extracted and analyzed using the high-throughput Axiom platform with the GeneTitan® MC Instrument. Up to 14,377 single nucleotide polymorphisms (SNPs) were selected at candidate regions and clinical/diagnostic data were recorded. A descriptive analysis of the data along with a backward conditional binary logistic regression was used to calculate odds ratios, with 95% confidence intervals [p < 0.05]. To select the best SNP candidates, a logistic regression model was fitted assuming a log-additive genetic model using R software [p < 0.0001]. In this sample the top lead genetic variants associated with aEARR were two novel putative genes located in the X chromosome, specifically, STAG 2 gene, rs151184635 and RP1-30E17.2 gene, rs55839915. These variants were found to be associated with an increased risk of aEARR, particularly restricted to men [OR: 6.09; 95%CI: 2.6–14.23 and OR: 6.86; 95%CI: 2.65–17.81, respectively]. Marginal associations were found at previously studied variants such as SSP1: rs11730582 [OR: 0.54; 95%CI: 0.34–0.86; p = 0.008], P2RX7: rs1718119 [OR: 0.6; 95%CI: 0.36–1.01; p = 0.047], and TNFRSF11A: rs8086340 [OR: 0.6; 95%CI: 0.38–0.95; p = 0.024]), found solely in females. Multiple putative genetic variants located at chromosomes X and Y are potentially implicated in an extreme phenotype of aEARR. A gender-linked association was noted.
Sensor Networks in Structural Health Monitoring: From Theory to Practice
Authors: Dertimanis Vasilis , Chatzi Eleni
Published: October 2020

The growing attention that structural health monitoring (SHM) has enjoyed in recent years can be attributed, amongst other factors, to the advent of low-cost and easily deployable sensors [...]
Effects of Agroforestry and Other Sustainable Practices in the Kenya Agricultural Carbon Project (KACP)
Authors: Nyberg Ylva , Musee Caroline , Wachiye Emmanuel , Jonsson Mattias , Wetterlind Johanna , Öborn Ingrid
Published: October 2020

With growing global demand for food, unsustainable farming practices and large greenhouse gas emissions, farming systems need to sequester more carbon than they emit, while also increasing productivity and food production. The Kenya Agricultural Carbon Project (KACP) recruited farmer groups committed to more Sustainable Agricultural Land Management (SALM) practices and provided these groups with initial advisory services on SALM, farm enterprise development and village savings and loan associations. Recommended SALM practices included agroforestry, cover crops, mulching, composting manure, terracing, reduced tillage and water harvesting. The effects of the KACP on the uptake of SALM practices, maize yield, perceived food self-sufficiency and savings during the initial four years were assessed comparing control and project farmers using interviews, field visits and measurements. Farmers participating in the KACP seemed to have increased uptake of most SALM practices and decreased the use of practices to be avoided under the KACP recommendations. Agroforestry and terraces showed positive effects on maize yield. During all four years, the KACP farms had higher maize yield than control farms, but yield differences were similar in 2009 and 2012 and there was no overall significant effect of the KACP. In 2012, the KACP farms had higher food self-sufficiency and tended to have higher monetary savings than control farms.
Cathodoluminescence Spectroscopic Stress Analysis for Silicon Oxide Film and Its Damage Evaluation
Authors: Kammachi Shingo , Goshima Yoshiharu , Goami Nobutaka , Yamashita Naoaki , Kakinuma Shigeru , Nishikata Kentaro , Naka Nobuyuki , Inoue Shozo , Namazu Takahiro
Published: October 2020

We describe the stress analysis of silicon oxide (SiO2) thin film using cathodoluminescence (CL) spectroscopy and discuss its availability in this paper. To directly measure the CL spectra of the film under uniaxial tensile stresses, specially developed uniaxial tensile test equipment is used in a scanning electron microscope (SEM) equipped with a CL system. As tensile stress increases, the peak position and intensity proportionally increase. This indicates that CL spectroscopy is available as a stress measurement tool for SiO2 film. However, the electron beam (EB) irradiation time influences the intensity and full width at half maximum (FWHM), which implies that some damage originating from EB irradiation accumulates in the film. The analyses using Raman spectroscopy and transmission electron microscopy (TEM) demonstrate that EB irradiation for stress measurement with CL induces the formation of silicon (Si) nanocrystals into SiO2 film, indicating that CL stress analysis of the film is not nondestructive, but destructive inspection.
Recession of Environmental Barrier Coatings under High-Temperature Water Vapour Conditions: A Theoretical Model
Authors: Jiang Peng , Ye Cheng
Published: October 2020

Rare-earth disilicates are the major material used on the top layer of environmental barrier coating (EBC) systems. Although rare-earth disilicates are highly resistant to water vapour, corrosion due to water vapour at high temperature is still one of the main reasons of failure of EBC systems. In this study, a corrosion model of ytterbium disilicates in water vapour at high temperature was derived, based on the gas diffusion theory. Using this theoretical model, we studied the evolution rule of the corroded area on the top layer of the EBC under gas flow at high temperature. The influence of the various parameters of the external gas on the corrosion process and the corrosion kinetics curve were also discussed. The theoretical model shows that the increase in gas temperature, gas flow velocity, water partial pressure, and total gas pressure accelerate coating corrosion. Among these factors, the influence of total gas pressure on the corrosion process is relatively weak, and the effect of the continuous increase of the gas velocity on the corrosion process is limited. The shape of the corrosion kinetics curve is either a straight or parabolic, and it was determined by a combination of external gas parameters.
Hierarchical Microstructure of Laser Powder Bed Fusion Produced Face-Centered-Cubic-Structured Equiatomic CrFeNiMn Multicomponent Alloy
Authors: Yang Xuan , Ge Yanling , Lehtonen Joonas , Hannula Simo-Pekka
Published: October 2020

A cobalt-free equiatomic CrFeNiMn multicomponent alloy was fabricated from gas-atomized powder using laser powder bed fusion (L-PBF), also known as selective laser melting (SLM). The as-built specimens had a single face-centered cubic (FCC) structure, relative density of 98%, and hardness up to 248 HV0.5 for both the scanning speeds applied. In this work, we report the hierarchical microstructural features observed in the as-built specimens. These are comprised of melt pools, grains, cell structures including dendritic cells, elongated cells, equiaxed cells (~500 nm), and sub-cells (150–300 nm). The cell and sub-cell walls are composed of a notably high density of dislocations. In addition, segregation of Mn and Ni was detected at the cell walls, but only occasionally at the sub-cell walls. SLM exhibits the capability to produce FCC-structured equiatomic CrFeNiMn multicomponent alloy with the refined and hierarchical microstructure.
Lifetime Prediction Methods for Degradable Polymeric Materials—A Short Review
Authors: Plota Angelika , Masek Anna
Published: October 2020

The determination of the secure working life of polymeric materials is essential for their successful application in the packaging, medicine, engineering and consumer goods industries. An understanding of the chemical and physical changes in the structure of different polymers when exposed to long-term external factors (e.g., heat, ozone, oxygen, UV radiation, light radiation, chemical substances, water vapour) has provided a model for examining their ultimate lifetime by not only stabilization of the polymer, but also accelerating the degradation reactions. This paper presents an overview of the latest accounts on the impact of the most common environmental factors on the degradation processes of polymeric materials, and some examples of shelf life of rubber products are given. Additionally, the methods of lifetime prediction of degradable polymers using accelerated ageing tests and methods for extrapolation of data from induced thermal degradation are described: the Arrhenius model, time–temperature superposition (TTSP), the Williams–Landel–Ferry (WLF) model and 5 isoconversional approaches: Friedman’s, Ozawa–Flynn–Wall (OFW), the OFW method corrected by N. Sbirrazzuoli et al., the Kissinger–Akahira–Sunose (KAS) algorithm, and the advanced isoconversional method by S. Vyazovkin. Examples of applications in recent years are given.
Research on the Flame Retardancy Properties and Mechanism of Modified Asphalt with Halloysite Nanotubes and Conventional Flame Retardant
Authors: Tan Yangwei , He Zhaoyi , Li Xiang , Jiang Bin , Li Jiaqi , Zhang Yonggang
Published: October 2020

The inflammability of asphalt road will promote fire spread in the tunnel and produce lots of toxic smoke. To improve the fire resistance of asphalt pavement, mineral powder flame retardants are generally replaced by flame retardants in equal amounts. In this study, the effects of the synergistic flame retardancy system of halloysite nanotubes (HNTs) and conventional flame retardants (CFR) on the flame retardancy performance and mechanism of asphalt were investigated. Firstly, the flame retardancy properties of the HNTs and CFR composite modified asphalt were investigated based on the Cleveland open cup method (COC), Limiting oxygen index meter (LOI), and Cone calorimeter tests (CCTs). Then, the flame retardancy mechanism of the modified asphalt was studied based on Thermogravimetric analyzer (TGA), Fourier-transform infrared (FTIR), and Scanning electron microscopy (SEM). The results show that adding HNTs could improve the flame retardancy of the CFR modified asphalt binder. When 1 wt % HNTs and 8 wt % CFR were used, the limiting oxygen index of asphalt increased by 40.1%, the ignition temperature increased by 40 °C, while the heat release rate, total heat release, the smoke production rate, total smoke release, and other parameters decreased with varying degrees. Based on TG, FTIR, and SEM, the targeted flame retardancy mechanism and synergistic effect of HNTs/CFR flame retardancy system were revealed and summarized as three stages: (1) Stage 1, aluminum hydroxide (ATH) absorbs heat through thermal decomposition and inhibits the decomposition of lightweight components in asphalt; (2) Stage 2, aluminum diethyl phosphate (ADP) decomposes and produces organic phosphoric acid, which catalyzes crosslinking and ring thickening of asphalt and the quenching effect of phosphorus free radicals to block the combustion; and (3) Stage 3, HNTs plays an important role in increasing the integrity and density of the barrier layer. In addition, the Al2O3 produced by the decomposition of ATH, the carbon layer formed by the ADP catalyzed pitch, and HNTs play a significant synergistic effect in the formation of the barrier layer. Thus, the combination of HNTs and CFR has been proved to be a prospective flame retardancy system for asphalt.
Influence of Metallic Oxide Nanoparticles on the Mechanical Properties of an A-TIG Welded 304L Austenitic Stainless Steel
Authors: Balos Sebastian , Dramicanin Miroslav , Janjatovic Petar , Kulundzic Nenad , Zabunov Ivan , Pilic Branka , Klobčar Damjan
Published: October 2020

Austenitic stainless steels represent a significant aerospace material, being used for various castings, structural components, landing gear components, afterburners, exhaust components, engine parts, and fuel tanks. The most common joining process is tungsten inert gas (TIG) welding, which possesses many advantages such as suitability to weld a wide range of ferrous and non-ferrous metals and alloys, providing high quality welds with good mechanical properties. Its major disadvantage is low productivity due to low penetration and welding speed. This can be overcome by introducing an activating flux before welding. The activating flux reverses the material flow of the weld pool, significantly increasing penetration. Therefore, shielding gas consumption is reduced and welding without a consumable is enabled. However, the consumable in conventional TIG also enables the conditioning of the mechanical properties of welds. In this study, Si and Ti metallic oxide nanoparticles were used to increase the weld penetration depth, while bend testing, tensile, and impact toughness were determined to evaluate the mechanical properties of welds. Furthermore, optical emission spectroscopy, light, and scanning electron microscope were used to determine the chemical compositions and microstructures of the welds. Chemical compositions and weld mechanical properties were similar in all specimens. The highest tensile and impact properties were obtained with the specimen welded with the flux containing 20% TiO2 and 80% SiO2 nanoparticles. Although lower than those of the base metal, they were well within the nominal base metal mechanical properties.