bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytomegalovirus-Mediated T Cell Receptor Repertoire Perturbation Is Present in Early Life
Authors: Attaf Meriem , Roider Julia , Malik Amna , Rius Rafael Cristina , Dolton Garry , Prendergast Andrew J. , Leslie Alasdair , Ndung'u Thumbi , Kløverpris Henrik N. , Sewell Andrew K. , Goulder Philip J.
Published: September 2020

Human cytomegalovirus (CMV) is a highly prevalent herpesvirus, particularly in sub-Saharan Africa, where it is endemic from infancy. The T cell response against CMV is important in keeping the virus in check, with CD8 T cells playing a major role in the control of CMV viraemia. Human leukocyte antigen (HLA) B*44:03-positive individuals raise a robust response against the NEGVKAAW (NW8) epitope, derived from the immediate-early-2 (IE-2) protein. We previously showed that the T cell receptor (TCR) repertoire raised against the NW8-HLA-B*44:03 complex was oligoclonal and characterised by superdominant clones, which were shared amongst unrelated individuals (i.e., “public”). Here, we address the question of how stable the CMV-specific TCR repertoire is over the course of infection, and whether substantial differences are evident in TCR repertoires in children, compared with adults. We present a longitudinal study of four HIV/CMV co-infected mother-child pairs, who in each case express HLA-B*44:03 and make responses to the NW8 epitope, and analyse their TCR repertoire over a period spanning more than 10 years. Using high-throughput sequencing, the paediatric CMV-specific repertoire was found to be highly diverse. In addition, paediatric repertoires were remarkably similar to adults, with public TCR responses being shared amongst children and adults alike. The CMV-specific repertoire in both adults and children displayed strong fluctuations in TCR clonality and repertoire architecture over time. Previously characterised superdominant clonotypes were readily identifiable in the children at high frequency, suggesting that the distortion of the CMV-specific repertoire is incurred as a direct result of CMV infection rather than a product of age-related “memory inflation.” Early distortion of the TCR repertoire was particularly apparent in the case of the TCR-β chain, where oligoclonality was low in children and positively correlated with age, a feature we did not observe for TCR-α. This discrepancy between TCR-α and -β chain repertoire may reflect differential contribution to NW8 recognition. Altogether, the results of the present study provide insight into the formation of the TCR repertoire in early life and pave the way to better understanding of CD8 T cell responses to CMV at the molecular level.
Priming Is Dispensable for NLRP3 Inflammasome Activation in Human Monocytes In Vitro
Authors: Gritsenko Anna , Yu Shi , Martin-Sanchez Fatima , Diaz-del-Olmo Ines , Nichols Eva-Maria , Davis Daniel M. , Brough David , Lopez-Castejon Gloria
Published: September 2020

Interleukin (IL)-18 and IL-1β are potent pro-inflammatory cytokines that contribute to inflammatory conditions such as rheumatoid arthritis and Alzheimer’s disease. They are produced as inactive precursors that are activated by large macromolecular complexes called inflammasomes upon sensing damage or pathogenic signals. NLRP3 inflammasome activation is regarded to require a priming step that causes NLRP3 and IL-1β gene upregulation, and also NLRP3 post-translational licencing. A subsequent activation step leads to the assembly of the complex and the cleavage of pro-IL-18 and pro-IL-1β by caspase-1 into their mature forms, allowing their release. Here we show that human monocytes, but not monocyte derived macrophages, are able to form canonical NLRP3 inflammasomes in the absence of priming. NLRP3 activator nigericin caused the processing and release of constitutively expressed IL-18 in an unprimed setting. This was mediated by the canonical NLRP3 inflammasome that was dependent on K+ and Cl− efflux and led to ASC oligomerization, caspase-1 and Gasdermin-D (GSDMD) cleavage. IL-18 release was impaired by the NLRP3 inhibitor MCC950 and by the absence of NLRP3, but also by deficiency of GSDMD, suggesting that pyroptosis is the mechanism of release. This work highlights the readiness of the NLRP3 inflammasome to assemble in the absence of priming in human monocytes and hence contribute to the very early stages of the inflammatory response when IL-1β has not yet been produced. It is important to consider the unprimed setting when researching the mechanisms of NLRP3 activation, as to not overshadow the pathways that occur in the absence of priming stimuli, which might only enhance this response.
Analyses of Climate Variations at Four Meteorological Stations on Remote Islands in the Croatian Part of the Adriatic Sea
Authors: Bonacci Ognjen , Patekar Matko , Pola Marco , Roje-Bonacci Tanja
Published: September 2020

The Mediterranean region is one of the regions in the world that is most vulnerable to the impact of imminent climate change. In particular, climate change has an adverse effect on both the ecosystem and socioeconomic system, influencing water availability for both human and environmental purposes. The most endangered water resources are along the coasts and on islands since they have relatively small volumes and are intensively exploited. We analyzed the time series of air temperature and precipitation measured at four meteorological stations (Komiža, Palagruža, Lastovo, and Biševo) located on small islands in the Croatian part of the Adriatic Sea in this study. The investigated time series extend from the 1950s to the present, being contemporaneous for approximately 50 years. Despite possessing discontinuity, they can be considered as representative for assessing climate change and variability in the scattered environment of the Croatian islands. The results showed increasing trends in the annual air temperature, while the annual cumulative precipitation did not show significant variations. In addition, the analyses of the monthly air temperature showed that statistically significant increasing trends occurred from April to August, suggesting a more severe impact during these months. These results are in accordance with regional and local studies and climate models. Although the climate variability during the analyzed period can be considered as moderate, the impact on water resources could be severe due to the combined effect of the increase in air temperature during warm periods and the intensive exploitation for tourism purposes.
Framing Climate Services: Logics, Actors, and Implications for Policies and Projects
Authors: Lugen Marine
Published: September 2020

This paper explores how climate services are framed in the literature and possible implications for climate services’ policies and projects. By critically exploring the frames around climate services, the wider objective is to encourage more reflexive and responsible research in the field, particularly given the huge challenge that climate change represents. By using a framing analysis based on an extensive literature review, five dominant frames were identified. Climate services are mainly framed (1) as a technological innovation, (2) as a market, (3) as an interface between users and producers, (4) as a risk management tool, and (5) from an ethical angle. The predominant frames influence how we think about climate services, shared assumptions, and the way in which policies and projects are designed. To prevent negative effects of climate services on the ground, such as inequalities, the main recommendations include establishing interdisciplinary and transdisciplinary dialogues between different communities of practice and players, increasing empirical and social science research to improve our understanding of this new field, and finally, re-thinking climate services in terms of adaptation rather than as the mere production of new information products.
Screen-Printed Electrode-Based Sensors for Food Spoilage Control: Bacteria and Biogenic Amines Detection
Authors: Torre Ricarda , Costa-Rama Estefanía , Nouws Henri P. A. , Delerue-Matos Cristina
Published: September 2020

Food spoilage is caused by the development of microorganisms, biogenic amines, and other harmful substances, which, when consumed, can lead to different health problems. Foodborne diseases can be avoided by assessing the safety and freshness of food along the production and supply chains. The routine methods for food analysis usually involve long analysis times and complex instrumentation and are performed in centralized laboratories. In this context, sensors based on screen-printed electrodes (SPEs) have gained increasing importance because of their advantageous characteristics, such as ease of use and portability, which allow fast analysis in point-of-need scenarios. This review provides a comprehensive overview of SPE-based sensors for the evaluation of food safety and freshness, focusing on the determination of bacteria and biogenic amines. After discussing the characteristics of SPEs as transducers, the main bacteria, and biogenic amines responsible for important and common foodborne diseases are described. Then, SPE-based sensors for the analysis of these bacteria and biogenic amines in food samples are discussed, comparing several parameters, such as limit of detection, analysis time, and sample type.
Novel Approaches to Target Mutant FLT3 Leukaemia
Authors: Müller Jörg P. , Schmidt-Arras Dirk
Published: September 2020

Fms-like tyrosine kinase 3 (FLT3) is a member of the class III receptor tyrosine kinases (RTK) and is involved in cell survival, proliferation, and differentiation of haematopoietic progenitors of lymphoid and myeloid lineages. Oncogenic mutations in the FLT3 gene resulting in constitutively active FLT3 variants are frequently found in acute myeloid leukaemia (AML) patients and correlate with patient’s poor survival. Targeting FLT3 mutant leukaemic stem cells (LSC) is a key to efficient treatment of patients with relapsed/refractory AML. It is therefore essential to understand how LSC escape current therapies in order to develop novel therapeutic strategies. Here, we summarize the current knowledge on mechanisms of FLT3 activity regulation and its cellular consequences. Furthermore, we discuss how aberrant FLT3 signalling cooperates with other oncogenic lesions and the microenvironment to drive haematopoietic malignancies and how this can be harnessed for therapeutical purposes.
Detection of EGFR Mutations Using Bronchial Washing-Derived Extracellular Vesicles in Patients with Non-Small-Cell Lung Carcinoma
Authors: Park Juhee , Lee Chaeeun , Eom Jung Seop , Kim Mi-Hyun , Cho Yoon-Kyoung
Published: September 2020

The detection of epidermal growth factor receptor (EGFR) mutation, based on tissue biopsy samples, provides a valuable guideline for the prognosis and precision medicine in patients with lung cancer. In this study, we aimed to examine minimally invasive bronchial washing (BW)-derived extracellular vesicles (EVs) for EGFR mutation analysis in patients with lung cancer. A lab-on-a-disc equipped with a filter with 20-nm pore diameter, Exo-Disc, was used to enrich EVs in BW samples. The overall detection sensitivity of EGFR mutations in 55 BW-derived samples was 89.7% and 31.0% for EV-derived DNA (EV-DNA) and EV-excluded cell free-DNA (EV-X-cfDNA), respectively, with 100% specificity. The detection rate of T790M in 13 matched samples was 61.5%, 10.0%, and 30.8% from BW-derived EV-DNA, plasma-derived cfDNA, and tissue samples, respectively. The acquisition of T790M resistance mutation was detected earlier in BW-derived EVs than plasma or tissue samples. The longitudinal analysis of BW-derived EVs showed excellent correlation with the disease progression measured by CT images. The EGFR mutations can be readily detected in BW-derived EVs, which demonstrates their clinical potential as a liquid-biopsy sample that may aid precise management, including assessment of the treatment response and drug resistance in patients with lung cancer.
Treatment Combinations with DNA Vaccines for the Treatment of Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Authors: Gamat-Huber Melissa , Jeon Donghwan , Johnson Laura E. , Moseman Jena E. , Muralidhar Anusha , Potluri Hemanth K. , Rastogi Ichwaku , Wargowski Ellen , Zahm Christopher D. , McNeel Douglas G.
Published: September 2020

Metastatic castration-resistant prostate cancer (mCRPC) is a challenging disease to treat, with poor outcomes for patients. One antitumor vaccine, sipuleucel-T, has been approved as a treatment for mCRPC. DNA vaccines are another form of immunotherapy under investigation. DNA immunizations elicit antigen-specific T cells that cause tumor cell lysis, which should translate to meaningful clinical responses. They are easily amenable to design alterations, scalable for large-scale manufacturing, and thermo-stable for easy transport and distribution. Hence, they offer advantages over other vaccine formulations. However, clinical trials with DNA vaccines as a monotherapy have shown only modest clinical effects against tumors. Standard therapies for CRPC including androgen-targeted therapies, radiation therapy and chemotherapy all have immunomodulatory effects, which combined with immunotherapies such as DNA vaccines, could potentially improve treatment. In addition, many investigational drugs are being developed which can augment antitumor immunity, and together with DNA vaccines can further enhance antitumor responses in preclinical models. We reviewed the literature available prior to July 2020 exploring the use of DNA vaccines in the treatment of prostate cancer. We also examined various approved and experimental therapies that could be combined with DNA vaccines to potentially improve their antitumor efficacy as treatments for mCRPC.
Transcriptome Profiling Reveals New Insights into the Immune Microenvironment and Upregulation of Novel Biomarkers in Metastatic Uveal Melanoma
Authors: Krishna Yamini , Acha-Sagredo Amelia , Sabat-Pośpiech Dorota , Kipling Natalie , Clarke Kim , Figueiredo Carlos R. , Kalirai Helen , Coupland Sarah E.
Published: September 2020

Metastatic uveal melanoma (mUM) to the liver is incurable. Transcriptome profiling of 40 formalin-fixed paraffin-embedded mUM liver resections and 6 control liver specimens was undertaken. mUMs were assessed for morphology, nuclear BAP1 (nBAP1) expression, and their tumour microenvironments (TME) using an “immunoscore” (absent/altered/high) for tumour-infiltrating lymphocytes (TILs) and macrophages (TAMs). Transcriptomes were compared between mUM and control liver; intersegmental and intratumoural analyses were also undertaken. Most mUM were epithelioid cell-type (75%), amelanotic (55%), and nBAP1-ve (70%). They had intermediate (68%) or absent (15%) immunoscores for TILs and intermediate (53%) or high (45%) immunoscores for TAMs. M2-TAMs were dominant in the mUM-TME, with upregulated expression of ANXA1, CD74, CXCR4, MIF, STAT3, PLA2G6, and TGFB1. Compared to control liver, mUM showed significant (p < 0.01) upregulation of 10 genes: DUSP4, PRAME, CD44, IRF4/MUM1, BCL2, CD146/MCAM/MUC18, IGF1R, PNMA1, MFGE8/lactadherin, and LGALS3/Galectin-3. Protein expression of DUSP4, CD44, IRF4, BCL-2, CD146, and IGF1R was validated in all mUMs, whereas protein expression of PRAME was validated in 10% cases; LGALS3 stained TAMs, and MFGEF8 highlighted bile ducts only. Intersegmental mUMs show differing transcriptomes, whereas those within a single mUM were similar. Our results show that M2-TAMs dominate mUM-TME with upregulation of genes contributing to immunosuppression. mUM significantly overexpress genes with targetable signalling pathways, and yet these may differ between intersegmental lesions.
Development of Colonic Organoids Containing Enteric Nerves or Blood Vessels from Human Embryonic Stem Cells
Authors: Park Chul Soon , Nguyen Le Phuong , Yong Dongeun
Published: September 2020

The increased interest in organoid research in recent years has contributed to an improved understanding of diseases that are currently untreatable. Various organoids, including kidney, brain, retina, liver, and spinal cord, have been successfully developed and serve as potential sources for regenerative medicine studies. However, the application of organoids has been limited by their lack of tissue components such as nerve and blood vessels that are essential to organ physiology. In this study, we used three-dimensional co-culture methods to develop colonic organoids that contained enteric nerves and blood vessels. The development of enteric nerves and blood vessels was confirmed phenotypically and genetically by the use of immunofluorescent staining and Western blotting. Colonic organoids that contain essential tissue components could serve as a useful model for the study of colon diseases and help to overcome current bottlenecks in colon disease research.
Combinatory Treatment of Canavanine and Arginine Deprivation Efficiently Targets Human Glioblastoma Cells via Pleiotropic Mechanisms
Authors: Karatsai Olena , Shliaha Pavel , Jensen Ole N. , Stasyk Oleh , Rędowicz Maria Jolanta
Published: September 2020

Glioblastomas are the most frequent and aggressive form of primary brain tumors with no efficient cure. However, they often exhibit specific metabolic shifts that include deficiency in the biosynthesis of and dependence on certain exogenous amino acids. Here, we evaluated, in vitro, a novel combinatory antiglioblastoma approach based on arginine deprivation and canavanine, an arginine analogue of plant origin, using two human glioblastoma cell models, U251MG and U87MG. The combinatory treatment profoundly affected cell viability, morphology, motility and adhesion, destabilizing the cytoskeleton and mitochondrial network, and induced apoptotic cell death. Importantly, the effects were selective toward glioblastoma cells, as they were not pronounced for primary rat glial cells. At the molecular level, canavanine inhibited prosurvival kinases such as FAK, Akt and AMPK. Its effects on protein synthesis and stress response pathways were more complex and dependent on exposure time. We directly observed canavanine incorporation into nascent proteins by using quantitative proteomics. Although canavanine in the absence of arginine readily incorporated into polypeptides, no motif preference for such incorporation was observed. Our findings provide a strong rationale for further developing the proposed modality based on canavanine and arginine deprivation as a potential antiglioblastoma metabolic therapy independent of the blood–brain barrier.
Fully Inkjet-Printed Short-Channel Metal-Oxide Thin-Film Transistors Based on Semitransparent ITO/Au Source/Drain Electrodes
Authors: Li Yuzhi , Zhang Shengdong
Published: September 2020

In this work, short-channel semitransparent indium-tin-oxide (ITO)/Au electrode pairs were fabricated via inkjet printing and lift-off technology. The printed hydrophobic coffee stripes not only define the channel length of ITO/Au electrode pairs, but also help the realization of uniform short-channel In0.95Ga0.05Ox thin-film transistors (TFTs). The patterned semitransparent ITO/Au films, with the assistance of inkjet printing, exhibit an excellent conductivity compared to that of printed ITO films, and the short-channel In0.95Ga0.05Ox TFTs based on the semitransparent ITO/Au source/drain electrodes exhibit a maximum mobility of 2.9 cm2 V−1 s−1. This work proposes a method to prepare patterned high-conductive electrodes for TFTs with the assistance of inkjet printing.
Strongly Hydrophobic and Superoleophilic PMMA Based Nanocoated Cotton Fabrics
Authors: Wang Hua , Kumar Rajnesh , Memon Hafeezullah
Published: September 2020

Oil–water separation is among the critical issues worldwide due to recent massive oil spills. Moreover, domestic and industrial water pollution due to oil discharge affects marine and aquatic life. Cotton is the most predominant fiber globally because of its use as a principal and popular clothing material. Cotton is also the leading raw material for technical and functional textile applications. In this study, the fabric was cured with poly (methyl methacrylate) (PMMA) nanoparticles to develop hydrophobic and oleophilic cotton fabrics. The dehydrating agents, N,N′-dicyclohexylcarbodiimide (DCC) and dimethyl aminopyridine (DMAP), were used to catalyze the esterification. The results proved that the excellent hydrophobicity of modified cotton fabric provides a water contact angle higher than 140°. In addition, Fourier transforms infrared (FTIR) spectroscopy, as well as X-ray photoelectron spectroscopy (XPS) analysis, confirmed the fabric surface modification. Surface morphological analysis by scanning electron microscope (SEM) revealed the uniform rough surface structure of the modified fabric with nano-coating. The modified fabric resulted in the high separation efficiency of oil and water, suggesting this strategy to be suitable for advanced oil–water separation.
Relationship between Semi-Quantitative Parameters of Thallium-201 Myocardial Perfusion Imaging and Coronary Artery Disease
Authors: Chang Chin-Chuan , Yang Ming-Hui , Liu Chih-Ting , Chu Hsiu-Lan , Lin Chia-Yang , Yen Wei-Jheng , Chung Chao-Yu , Ho Sheng-Yow , Tyan Yu-Chang
Published: September 2020

This study aimed to investigate the diagnostic performance of semi-quantitative parameters of thallium-201 myocardial perfusion imaging (MPI) for coronary artery disease (CAD). From January to December 2017, patients were enrolled who had undergone Tl-201 MPI and received cardiac catheterization for coronary artery disease within three months of MPI. Receiver operating characteristics (ROC) analysis was used to determine the optimal cutoff values of semi-quantitative parameters. A comparison of the sensitivity and specificity of these parameters based on different subgroupings was further performed. A total of 130 patients were enrolled for further analysis. Among the collected parameters, the stress total perfusion deficit (sTPD) had the highest value of the area under curve (0.813) under the optimal cutoff value of 3.5%, with a sensitivity and specificity of 73.5% and 74.5%, respectively (p = 0.0000), for the diagnosis of CAD. With further subgrouping analysis based on history of diabetes or dyslipidemia, the sensitivity and specificity showed similar results. Based on the currently collected data and image acquisition conditions, the sTPD parameter has a clinical role for the diagnosis of CAD with a cutoff value of 3.5%.
Automated Segmentation and Severity Analysis of Subdural Hematoma for Patients with Traumatic Brain Injuries
Authors: Farzaneh Negar , Williamson Craig A. , Jiang Cheng , Srinivasan Ashok , Bapuraj Jayapalli R. , Gryak Jonathan , Najarian Kayvan , Soroushmehr S. M. Reza
Published: September 2020

Detection and severity assessment of subdural hematoma is a major step in the evaluation of traumatic brain injuries. This is a retrospective study of 110 computed tomography (CT) scans from patients admitted to the Michigan Medicine Neurological Intensive Care Unit or Emergency Department. A machine learning pipeline was developed to segment and assess the severity of subdural hematoma. First, the probability of each point belonging to the hematoma region was determined using a combination of hand-crafted and deep features. This probability provided the initial state of the segmentation. Next, a 3D post-processing model was applied to evolve the initial state and delineate the hematoma. The recall, precision, and Dice similarity coefficient of the proposed segmentation method were 78.61%, 76.12%, and 75.35%, respectively, for the entire population. The Dice similarity coefficient was 79.97% for clinically significant hematomas, which compared favorably to an inter-rater Dice similarity coefficient. In volume-based severity analysis, the proposed model yielded an F1, recall, and specificity of 98.22%, 98.81%, and 92.31%, respectively, in detecting moderate and severe subdural hematomas based on hematoma volume. These results show that the combination of classical image processing and deep learning can outperform deep learning only methods to achieve greater average performance and robustness. Such a system can aid critical care physicians in reducing time to intervention and thereby improve long-term patient outcomes.
Peptide Nucleic Acid (PNA)-Enhanced Specificity of a Dual-Target Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) Assay for the Detection and Differentiation of SARS-CoV-2 from Related Viruses
Authors: Choi Won-Suk , Jeong Ju Hwan , Nicolas Halcyon Dawn G. , Oh Sol , Antigua Khristine Joy C. , Park Ji-Hyun , Kim Beomkyu , Yoon Sun-Woo , Shin Kyeong Seob , Choi Young Ki , Baek Yun Hee , Song Min-Suk
Published: September 2020

The threat posed by coronaviruses to human health has necessitated the development of a highly specific and sensitive viral detection method that could differentiate between the currently circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other SARS-related coronaviruses (SARSr-CoVs). In this study, we developed a peptide nucleic acid (PNA)-based real-time quantitative polymerase chain reaction (RT-qPCR) assay targeting the N gene to efficiently discriminate SARS-CoV-2 from other SARSr-CoVs in human clinical samples. Without compromising the sensitivity, this method significantly enhanced the specificity of SARS-CoV-2 detection by 100-fold as compared to conventional RT-qPCR. In addition, we designed an RT-qPCR method for the sensitive and universal detection of ORF3ab-E genes of SARSr-CoV with a limit of detection (LOD) of 3.3 RNA copies per microliter. Thus, the developed assay serves as a confirmative dual-target detection method. Our PNA-mediated dual-target RT-qPCR assay can detect clinical SARS-CoV-2 samples in the range of 18.10–35.19 Ct values with an 82.6–100% detection rate. Furthermore, our assay showed no cross-reactions with other coronaviruses such as human coronaviruses (229E, NL63, and OC43) and Middle East respiratory syndrome coronavirus, influenza viruses (Type B, H1N1, H3N2, HPAI H5Nx, and H7N9), and other respiratory disease-causing viruses (MPV, RSV A, RSV B, PIV, AdV, and HRV). We, thus, developed a PNA-based RT-qPCR assay that differentiates emerging pathogens such as SARS-CoV-2 from closely related viruses such as SARSr-CoV and allows diagnosis of infections related to already identified or new coronavirus strains.
Phishing Attacks Survey: Types, Vectors, and Technical Approaches
Authors: Alabdan Rana
Published: September 2020

Phishing attacks, which have existed for several decades and continue to be a major problem today, constitute a severe threat in the cyber world. Attackers are adopting multiple new and creative methods through which to conduct phishing attacks, which are growing rapidly. Therefore, there is a need to conduct a comprehensive review of past and current phishing approaches. In this paper, a review of the approaches used during phishing attacks is presented. This paper comprises a literature review, followed by a comprehensive examination of the characteristics of the existing classic, modern, and cutting-edge phishing attack techniques. The aims of this paper are to build awareness of phishing techniques, educate individuals about these attacks, and encourage the use of phishing prevention techniques, in addition to encouraging discourse among the professional community about this topic.
Dual Path Attention Net for Remote Sensing Semantic Image Segmentation
Authors: Li Jinglun , Xiu Jiapeng , Yang Zhengqiu , Liu Chen
Published: September 2020

Semantic segmentation plays an important role in being able to understand the content of remote sensing images. In recent years, deep learning methods based on Fully Convolutional Networks (FCNs) have proved to be effective for the sematic segmentation of remote sensing images. However, the rich information and complex content makes the training of networks for segmentation challenging, and the datasets are necessarily constrained. In this paper, we propose a Convolutional Neural Network (CNN) model called Dual Path Attention Network (DPA-Net) that has a simple modular structure and can be added to any segmentation model to enhance its ability to learn features. Two types of attention module are appended to the segmentation model, one focusing on spatial information the other focusing upon the channel. Then, the outputs of these two attention modules are fused to further improve the network’s ability to extract features, thus contributing to more precise segmentation results. Finally, data pre-processing and augmentation strategies are used to compensate for the small number of datasets and uneven distribution. The proposed network was tested on the Gaofen Image Dataset (GID). The results show that the network outperformed U-Net, PSP-Net, and DeepLab V3+ in terms of the mean IoU by 0.84%, 2.54%, and 1.32%, respectively.
Increased Growth Differentiation Factor 15 in Patients with Hypoleptinemia-Associated Lipodystrophy
Authors: Kralisch Susan , Hoffmann Annett , Estrada-Kunz Juliane , Stumvoll Michael , Fasshauer Mathias , Tönjes Anke , Miehle Konstanze
Published: September 2020

Objective. Similar to obesity, lipodystrophy (LD) causes adipose tissue dysfunction and severe metabolic complications. Growth differentiation factor 15 (GDF15) belongs to the transforming growth factor β superfamily and is dysregulated in metabolic disease including obesity and diabetes mellitus. Circulating levels in LD and the impact of leptin treatment have not been investigated so far. Material and Methods. GDF15 serum levels were quantified in 60 LD patients without human immunodeficiency virus infection and 60 controls matched for age, gender, and body mass index. The impact of metreleptin treatment on circulating GDF15 was assessed in a subgroup of patients. GDF15 mRNA expression was determined in metabolic tissues of leptin-deficient lipodystrophic aP2-nSREBP1c-Tg mice, obese ob/ob mice, and control C57Bl6 mice. Results. Median GDF15 serum concentrations were significantly higher in LD patients (819 ng/L) as compared to the control group (415 ng/L) (p < 0.001). In multiple linear regression analysis, an independent and positive association remained between GDF15 on one hand and age, patient group, hemoglobin A1c, triglycerides, and C-reactive protein on the other hand. Moreover, there was an independent negative association between GFD15 and estimated glomerular filtration rate. Circulating GDF15 was not significantly affected by metreleptin treatment in LD patients. Gdf15 was upregulated in leptin-deficient lipodystrophic mice as compared to controls. Moreover, Gdf15 mRNA expression was downregulated by leptin treatment in lipodystrophic and obese animals. Conclusions. Serum concentrations of GDF15 are elevated in LD patients and independently associated with markers of metabolic dysfunction. Gdf15 expression is higher in lipodystrophic mice and downregulated by leptin treatment.
Cardiac Fibroblast-Induced Pluripotent Stem Cell-Derived Exosomes as a Potential Therapeutic Mean for Heart Failure
Authors: Kurtzwald-Josefson Efrat , Zeevi-Levin Naama , Rubchevsky Victor , Bechar Erdman Neta , Schwartz Rohaker Orna , Nahum Ortal , Hochhauser Edith , Ben-Avraham Ben , Itskovitz-Eldor Joseph , Aravot Dan , Barac Yaron
Published: September 2020

The limited regenerative capacity of the injured myocardium leads to remodeling and often heart failure. Novel therapeutic approaches are essential. Induced pluripotent stem cells (iPSC) differentiated into cardiomyocytes are a potential future therapeutics. We hypothesized that organ-specific reprogramed fibroblasts may serve an advantageous source for future cardiomyocytes. Moreover, exosomes secreted from those cells may have a beneficial effect on cardiac differentiation and/or function. We compared RNA from different sources of human iPSC using chip gene expression. Protein expression was evaluated as well as exosome micro-RNA levels and their impact on embryoid bodies (EBs) differentiation. Statistical analysis identified 51 genes that were altered (p ≤ 0.05), and confirmed in the protein level, cardiac fibroblasts-iPSCs (CF-iPSCs) vs. dermal fibroblasts-iPSCs (DF-iPSCs). Several miRs were altered especially miR22, a key regulator of cardiac hypertrophy and remodeling. Lower expression of miR22 in CF-iPSCs vs. DF-iPSCs was observed. EBs treated with these exosomes exhibited more beating EBs p = 0.05. vs. control. We identify CF-iPSC and its exosomes as a potential source for cardiac recovery induction. The decrease in miR22 level points out that our CF-iPSC-exosomes are naïve of congestive heart cell memory, making them a potential biological source for future therapy for the injured heart.
Modular Chimeric Antigen Receptor Systems for Universal CAR T Cell Retargeting
Authors: Sutherland Ashley R. , Owens Madeline N. , Geyer C. Ronald
Published: September 2020

The engineering of T cells through expression of chimeric antigen receptors (CARs) against tumor-associated antigens (TAAs) has shown significant potential for use as an anti-cancer therapeutic. The development of strategies for flexible and modular CAR T systems is accelerating, allowing for multiple antigen targeting, precise programming, and adaptable solutions in the field of cellular immunotherapy. Moving beyond the fixed antigen specificity of traditional CAR T systems, the modular CAR T technology splits the T cell signaling domains and the targeting elements through use of a switch molecule. The activity of CAR T cells depends on the presence of the switch, offering dose-titratable response and precise control over CAR T cells. In this review, we summarize developments in universal or modular CAR T strategies that expand on current CAR T systems and open the door for more customizable T cell activity.
Fatty Acid Synthase Beta Dehydratase in the Lipid Biosynthesis Pathway Is Required for Conidiogenesis, Pigmentation and Appressorium Formation in Magnaporthe oryzae S6
Authors: Sangappillai Vaanee , Nadarajah Kalaivani
Published: September 2020

Lipid biosynthesis produces glycerol, which is important in fueling turgor pressure necessary for germination and penetration of plant host by fungi. As the relationship between pathogenicity and the lipid biosynthetic pathway is not fully understood, we have elucidated the role of the fatty acid synthase beta subunit dehydratase (FAS1) gene in lipid biosynthesis. The FAS1 gene was silenced through homologous double crossover in Magnaporthe oryzae strain S6 to study the effect on lipid biosynthesis. The vegetative growth of Δfas1 mutants show the highest drop on oleic acid (between 10 and 50%), while the mycelial dry weight of mutants dropped significantly on all media. Conidiation of FAS1 mutants show a ~10- and ~5-fold reduction on oatmeal and Potato Dextrose Agar (PDA), respectively. Mutants formed mycelium that were mildly pigmented, indicating that the deletion of FAS1 may have affected melanin biosynthesis. Biochemical and gene expression studies concluded that the fatty acid degradation pathway might have been interrupted by FAS1 deletion. FAS1 mutants showed no enzyme activity on glucose or olive oil, suggesting that the mutants may lack functional peroxisomes and be defective in β-oxidation of fatty acids, hence explaining the reduced lipid deposits in the spores.
Laboratory and Numerical Analysis of Steel Cold-Formed Sigma Beams Retrofitted by Bonded CFRP Tapes
Authors: Szewczak Ilona , Rzeszut Katarzyna , Rozylo Patryk , Samborski Sylwester
Published: September 2020

In this paper, the retrofitting method of thin-walled, cold-formed sigma beams using bonded carbon fibre reinforced polymer (CFRP) tapes is proposed. The effectiveness of the presented strengthening method is investigated by the means of laboratory tests and numerical analysis conducted on simply supported, single-span beams made of 200 × 70 × 2 profile by “Blachy Pruszyński” subjected to a four-point bending scheme. Special attention is paid to the evaluation of possibility to increase the load capacity with simultaneous limitation of beams displacements by appropriate location of CFRP tapes. For this purpose, three beams were reinforced with CFRP tape placed on the inner surface of the upper flange, three with CFRP tape on the inner surface of the web, three beams with reinforcement located on the inner surface of the bottom flange, and two beams were tested as reference beams without reinforcement. CFRP tape with a width of 50 mm and a thickness of 1.2 mm was used as the reinforcement and was bonded to the beams by SikaDur®-30 adhesive. Precise strain measurement was made using electrofusion strain gauges, and displacement measurement was performed using two Aramis coupled devices in combination with the Tritop machine. Numerical models of the considered beams were developed in the Finite Element Method (FEM) program Abaqus®. Experimental and numerical analysis made it possible to obtain a very high agreement of results. Based on the conducted research, it was proved how important is the impact of the applied reinforcement (CFRP tapes) in thin-walled steel structures, with respect to the classic methods of strengthening steel building structures.
Experimental and Analytical Investigations of the Use of Groove-Epoxy Anchorage System for Shear Strengthening of RC Beams Using CFRP Laminates
Authors: Mohamed Khalid , Abdalla Jamal A. , Hawileh Rami A.
Published: September 2020

Reinforced concrete (RC) beams strengthened in shear with carbon fiber reinforced polymer (CFRP) laminates as externally bonded reinforcement (EBR) usually fail due to debonding. This paper presents an experimental and analytical investigation on the use of groove-epoxy as an anchorage system for CFRP plates and sheets bonded on both sides of shear deficient RC beams. The aim of this study is to assess the effectiveness of using groove-epoxy in enhancing the shear capacity of RC beams. Nine rectangular RC beams were strengthened with CFRP plates and sheets with groove-epoxy anchorage systems of different groove widths and tested under four point bending. It is observed that the RC beams strengthened with the groove-epoxy anchorage system showed an increase in the shear-strength over the unstrengthened control beam up to 112 and 141% for plates and sheets, respectively. Also, the increase of shear-strength contribution of the groove-epoxy system to that of CFRP without grooves ranged between 30–190% for CFRP plates and between 40–100% for CFRP sheets. Generally, the contributions of groove-epoxy on shear-strength decreased with the increase of groove width. Moreover, shear strength prediction models, based on modifications of the ACI440.2R-17 shear model, were developed by incorporating groove factors as a modifier to the FRP shear-strength contribution. The developed models predicted the experimental shear-strength of the tested RC beams with a good level of accuracy, with an average mean absolute percent error (MAPE) = 3.31% and 6.68%, normalized mean square error (NMSE) = 0.072, 0.523, and coefficient of determination R2 = 0.964, 0.691, for plates and sheets, respectively.
Interface Shear Strength at Various Joint Types in High-Strength Precast Concrete Structures
Authors: Kim Young-Jin , Chin Won-Jong , Jeon Se-Jin
Published: September 2020

More precast concrete structures have recently been constructed due to their many advantages when compared to conventional cast-in-place construction. Structural behavior at the joints between the precast segments can significantly affect the overall integrity, safety, and serviceability of the structure. In this study, therefore, the interface shear strength of high-strength precast members was investigated by performing push-off tests with the following variables: compressive strength of precast members, dry or wet joint, number and height of shear keys, joint width, filler type, curing temperature, and lateral compressive stress. The test results were analyzed to reveal the effect of each test variable on the joint shear strengths of the specimens. For instance, the failure loads were increased by 14–140%, depending on the lateral compressive stress, as the specified compressive strength of the precast members was increased from 80 to 150 MPa in the dry joints. The failure loads of the wet joints strongly depended on the strength of the filler rather than on that of the precast members and, as a result, the specimen with ultra-high-strength concrete filler was 46–48% stronger than those with high-strength mortar filler. The shear strengths of various joint types obtained from the test were further analyzed in comparison with the predictive equations of Japan Society of Civil Engineers (JSCE) and American Association of State Highway and Transportation Officials (AASHTO) with the aim of validating the appropriateness of these design provisions. In particular, an improved value of a coefficient in the JSCE equation is proposed to cover a range of compressive strengths in various precast members and filling materials.
Liraglutide Increases Serum Levels of MicroRNA-27b, -130a and -210 in Patients with Type 2 Diabetes Mellitus: A Novel Epigenetic Effect
Authors: Giglio Rosaria Vincenza , Nikolic Dragana , Volti Giovanni Li , Stoian Anca Pantea , Banerjee Yajnavalka , Magan-Fernandez Antonio , Castellino Giuseppa , Patti Angelo Maria , Chianetta Roberta , Castracani Carlo Castruccio , Montalto Giuseppe , Rizvi Ali A. , Sesti Giorgio , Rizzo Manfredi
Published: September 2020

Liraglutide has shown favourable effects on several cardiometabolic risk factors, beyond glucose control. MicroRNAs (miRNAs) regulate gene expression, resulting in post-transcriptional modifications of cell response and function. Specific miRNAs, including miRNA-27b, miRNA-130a, and miRNA-210, play a role in cardiometabolic disease. We aimed to determine the effect of liraglutide on the serum levels of miRNA-27b, miRNA-130a and miRNA-210. Twenty-five subjects with type-2 diabetes mellitus (T2DM), naïve to incretin-based therapy, were treated with liraglutide (1.2 mg/day as an add-on to metformin) for 4 months. miRNAs were quantified using real-time polymerase chain reaction. After liraglutide treatment, we found significant reductions in fasting glucose (from 9.8 ± 5.3 to 6.7 ± 1.6 mmol/L, p = 0.0042), glycosylated haemoglobin (HbA1c) (from 8.1 ± 0.8 to 6.6 ± 1.0%, p = 0.0008), total cholesterol (from 5.0 ± 1.0 to 4.0 ± 0.7 mmol/L, p = 0.0011), triglycerides (from 1.9 ± 1.0 to 1.5 ± 0.8 mmol/L, p = 0.0104) and low-density lipoprotein cholesterol (from 2.9 ± 1.2 to 2.2 ± 0.6 mmol/L, p = 0.0125), while the serum levels of miRNA-27b, miRNA-130a and miRNA-210a were significantly increased (median (interquartile range, IQR) changes: 1.73 (7.12) (p = 0.0401), 1.91 (3.64) (p = 0.0401) and 2.09 (11.0) (p = 0.0486), respectively). Since the changes in miRNAs were independent of changes in all the metabolic parameters investigated, liraglutide seems to exert a direct epigenetic effect in T2DM patients, regulating microRNAs involved in the maintenance of endothelial cell homeostasis. These changes might be implicated in liraglutide’s benefits and may represent useful targets for cardiometabolic management.
Probing Changes in Ca2+-Induced Interaction Forces between Calmodulin and Melittin by Atomic Force Microscopy
Authors: Huang Sheng , Wang Jianhua , Sun Heng , Fu Yuna , Wang Yan
Published: September 2020

Mechanobiology studies the means by which physical forces and mechanical properties change intra- or inter- biological macromolecules. Calmodulin (CaM) is involved in physiological activities and various metabolic processes in eukaryotic cells. Although the configuration changes in the interaction between calmodulin and melittin have been studied, the biomechanical relationship of their interaction has rarely been explored. Here, we measured the adhesion forces between calmodulin and melittin in solutions of gradient concentration of calcium ions using atomic force microscopy (AFM). We found that the specific (Fi) and nonspecific (F0) adhesion forces between single melittin and calmodulin in a PBS solution were 69.4 ± 5.0 and 29.3 ± 8.9 pN, respectively. In the presence of 10−7 to 10−3 M Ca2+ PBS solution, the Fi increased significantly to 93.8 ± 5.0, 139.9 ± 9.0, 140.4 ± 9.7, 171.5 ± 9.0, and 213.3 ± 17.8 pN, indicating that the unbinding force between melittin and calmodulin increased in the presence of Ca2+ in a concentration-dependent manner. These findings demonstrated that biomechanical studies based on AFM could help us better understand the melittin/calmodulin-binding processes in the presence of calcium and help us design and screen peptide drugs based on calmodulin.
A Systematic Review of Non-Contact Sensing for Developing a Platform to Contain COVID-19
Authors: Khan Muhammad Bilal , Zhang Zhiya , Li Lin , Zhao Wei , Hababi Mohammed Ali Mohammed Al , Yang Xiaodong , Abbasi Qammer H.
Published: September 2020

The rapid spread of the novel coronavirus disease, COVID-19, and its resulting situation has garnered much effort to contain the virus through scientific research. The tragedy has not yet fully run its course, but it is already clear that the crisis is thoroughly global, and science is at the forefront in the fight against the virus. This includes medical professionals trying to cure the sick at risk to their own health; public health management tracking the virus and guardedly calling on such measures as social distancing to curb its spread; and researchers now engaged in the development of diagnostics, monitoring methods, treatments and vaccines. Recent advances in non-contact sensing to improve health care is the motivation of this study in order to contribute to the containment of the COVID-19 outbreak. The objective of this study is to articulate an innovative solution for early diagnosis of COVID-19 symptoms such as abnormal breathing rate, coughing and other vital health problems. To obtain an effective and feasible solution from existing platforms, this study identifies the existing methods used for human activity and health monitoring in a non-contact manner. This systematic review presents the data collection technology, data preprocessing, data preparation, features extraction, classification algorithms and performance achieved by the various non-contact sensing platforms. This study proposes a non-contact sensing platform for the early diagnosis of COVID-19 symptoms and monitoring of the human activities and health during the isolation or quarantine period. Finally, we highlight challenges in developing non-contact sensing platforms to effectively control the COVID-19 situation.
Effects of Ferrous Sulfate Addition on the Selective Flotation of Scheelite over Calcite and Fluorite
Authors: Jung Moon Young , Park Jay Hyun , Yoo Kyoungkeun
Published: September 2020

The addition of ferrous sulfate as a depressant for Ca-bearing minerals such as calcite and fluorite during scheelite flotation was investigated to recover scheelite from tungsten mine tailings, using Hallimond-tube flotation tests, zeta-potential measurement and Fourier-transform infrared (FT-IR) analyses. The flotation tests indicate that the selectivity of scheelite recovery was the largest over calcite and fluorite under the following conditions: 0.5 g sample, 50 g/ton AF65, 1 × 10−3 M sodium oleate, 1200 g/ton SF2 (sodium silicate and ferrous sulfate) depressant with the 8:2 ratio of sodium silicate and ferrous sulfate, 50 mL/min air injection rate, 5 min flotation time, and pH 8. The selectivity of scheelite flotation increased when the amount of SF2 depressant addition increased to 1200 g/ton, but it decreased by adding 1400 g/ton SF2, which would result from the precipitation of iron components. In the zeta potential results, the zeta potentials of scheelite with the collector show similar results regardless of the addition of SF2, while the change of zeta potentials of calcite and fluorite by adding NaO collector diminished when SF2 was added. In FT-IR analyses, the spectrum of NaO in scheelite results was observed regardless of the addition of SF2, while the spectra of NaO in calcite and fluorite results disappeared when SF2 was added. These results suggest that the addition of SF2 prevents the adsorption of NaO on the surface of calcite and fluorite. Therefore, the addition of SF2 could enhance the selectivity of scheelite flotation over calcite and fluorite.