bluuebunny/crossref_metadata_2025 huggingface dataset:
The Venom of the Ectoparasitoid Wasp Pachycrepoideus vindemiae (Hymenoptera: Pteromalidae) Induces Apoptosis of Drosophila melanogaster Hemocytes
Authors: Wan Bin , Yang Lei , Zhang Jiao , Qiu Liming , Fang Qi , Yao Hongwei , Poirié Marylène , Gatti Jean-Luc , Ye Gongyin
Published: June 2020

The pupal ectoparasitoid Pachycrepoideus vindemiae injects venom into its fly hosts prior to oviposition. We have shown that this venom causes immune suppression in Drosophila melanogaster pupa but the mechanism involved remained unclear. Here, we show using transgenic D. melanogaster with fluorescent hemocytes that the in vivo number of plasmatocytes and lamellocytes decreases after envenomation while it has a limited effect on crystal cells. After in vitro incubation with venom, the cytoskeleton of plasmatocytes underwent rearrangement with actin aggregation around the internal vacuoles, which increased with incubation time and venom concentration. The venom also decreased the lamellocytes adhesion capacity and induced nucleus fragmentation. Electron microscopy observation revealed that the shape of the nucleus and mitochondria became irregular after in vivo incubation with venom and confirmed the increased vacuolization with the formation of autophagosomes-like structures. Almost all venom-treated hemocytes became positive for TUNEL assays, indicating massive induced apoptosis. In support, the caspase inhibitor Z-VAD-FMK attenuated the venom-induced morphological changes suggesting an involvement of caspases. Our data indicate that P. vindemiae venom inhibits D. melanogaster host immunity by inducing strong apoptosis in hemocytes. These assays will help identify the individual venom component(s) responsible and the precise mechanism(s)/pathway(s) involved.
Deep Multimodal Learning for the Diagnosis of Autism Spectrum Disorder
Authors: Tang Michelle , Kumar Pulkit , Chen Hao , Shrivastava Abhinav
Published: June 2020

Recent medical imaging technologies, specifically functional magnetic resonance imaging (fMRI), have advanced the diagnosis of neurological and neurodevelopmental disorders by allowing scientists and physicians to observe the activity within and between different regions of the brain. Deep learning methods have frequently been implemented to analyze images produced by such technologies and perform disease classification tasks; however, current state-of-the-art approaches do not take advantage of all the information offered by fMRI scans. In this paper, we propose a deep multimodal model that learns a joint representation from two types of connectomic data offered by fMRI scans. Incorporating two functional imaging modalities in an automated end-to-end autism diagnosis system will offer a more comprehensive picture of the neural activity, and thus allow for more accurate diagnoses. Our multimodal training strategy achieves a classification accuracy of 74% and a recall of 95%, as well as an F1 score of 0.805, and its overall performance is superior to using only one type of functional data.
Perception of Ecosystem Services in Constituting Multi-Functional Landscapes in Slovakia
Authors: Bezák Peter , Mederly Peter , Izakovičová Zita , Moyzeová Milena , Bezáková Magdaléna
Published: June 2020

Landscape provides many services for human wellbeing through its mosaic of ecosystems. Although different landscape spatial structures limit some access to these services for local residents, their demand for landscape benefits creates a crucial component in landscape planning. Herein, we evaluate the ecosystem service supply from landscape structures in four different areas of Slovakia and we identify the public preferences for these services. This evaluation was assisted by expert-based ecosystem services (ES) matrix assessment and feedback from experts and key local stakeholders. The associated land cover assessment revealed that although forests are the most important for ES delivery, followed by extensive agricultural mosaics, cultural services have the highest average supply value. In contrast, the experts and local stakeholders considered that provisioning services were the most important of all ES groups because of products available from arable land. The overall public awareness of benefits provided by nature proved relatively high, and this is a good sign for the development of multi-functional landscapes. The comparison of study sites revealed that even stakeholders living in intensively used land, with its overall low ES supply, assessed ES as very important in general. The general public could therefore be included in environmental planning to promote a more multi-functional landscape. In addition, the analysis herein will communicate gained insights to the local planners and decision-makers and confirm the importance of this ES participatory approach using top-down methodology. This may require the following measures in Slovakia: establishing an interdisciplinary group of experts for regular assessment of strategic landscape planning documents and regulatory instruments, developing key directives which establish well-balanced participatory procedures, improving open local government, and supporting down-scaled implementation of integrated landscape planning in cooperation with local action groups.
A Review for Consistent Analysis of Hydrogen Permeability through Dense Metallic Membranes
Authors: Suzuki Asuka , Yukawa Hiroshi
Published: June 2020

The hydrogen permeation coefficient (ϕ) is generally used as a measure to show hydrogen permeation ability through dense metallic membranes, which is the product of the Fick’s diffusion coefficient (D) and the Sieverts’ solubility constant (K). However, the hydrogen permeability of metal membranes cannot be analyzed consistently with this conventional description. In this paper, various methods for consistent analysis of hydrogen permeability are reviewed. The derivations of the descriptions are explained in detail and four applications of the consistent descriptions of hydrogen permeability are introduced: (1) prediction of hydrogen flux under given conditions, (2) comparability of hydrogen permeability, (3) understanding of the anomalous temperature dependence of hydrogen permeability of Pd-Ag alloy membrane, and (4) design of alloy composition of non-Pd-based alloy membranes to satisfy both high hydrogen permeability together with strong resistance to hydrogen embrittlement.
Benchmarks for Accelerated Cyclic Plasticity Models with Finite Elements
Authors: Srnec Novak Jelena , De Bona Francesco , Benasciutti Denis
Published: June 2020

In numerical simulations of components subjected to low-cycle fatigue loading, the material cyclic plasticity behavior must be modelled until complete stabilization, which occurs approximately at half the number of cycles to failure. If the plastic strain per cycle is small, a huge number of cycles must be simulated, which results into a huge and thus unaffordable simulation time. Acceleration techniques for shortening this time are useful, although their accuracy needs to be checked. This work aims to compare different approaches (nonlinear kinematic with “initial” and “stabilized” parameters and combined nonlinear kinematic and isotropic with the speed of stabilization fictitiously increased). It considers two benchmarks taken from the literature, in which the material has opposite cyclic behaviors (hardening, softening). A plane finite element model can be used in both benchmarks, thus permitting a simulation up to complete stabilization. Results confirm that the common approach of considering only the kinematic model (calibrated on “initial” or “stabilized” material state) from the very first cycle could lead to relevant errors. The acceleration technique based on a fictitious increase in the speed of stabilization leads to accurate results. Guidelines for calibrating this technique on a material’s hardening or softening behavior are, finally, proposed.
High-Performance Pure Sine Wave Inverter with Robust Intelligent Sliding Mode Maximum Power Point Tracking for Photovoltaic Applications
Authors: Chang En-Chih
Published: June 2020

Photovoltaic (PV) power generation has been extensively used as a result of the limited petrochemical resources and the rise of environmental awareness. Nevertheless, PV arrays have a widespread range of voltage changes in a variety of solar radiation, load, and temperature circumstances, so a maximum power point tracking (MPPT) method must be applied to get maximum power from PV systems. Sliding mode control (SMC) is effectively used in PV power generation due to its robustness, design simplicity, and superior interference suppression. When the PV array is subject to large parameter changes/highly uncertain conditions, the SMC leads to degraded steady-state performance, poor transient tracking speed, and unwanted flutter. Therefore, this paper proposes a robust intelligent sliding mode MPPT-based high-performance pure sine wave inverter for PV applications. The robust SMC is designed through fast sliding regime, which provides fixed time convergence and a non-singularity that allows better response in steady-state and transience. To avoid the flutter caused by system unmodeled dynamics, an enhanced cuckoo optimization algorithm (ECOA) with automatically adjustable step factor and detection probability is used to search control parameters of the robust sliding mode, thus finding global optimal solutions. The coalescence of both robust SMC and ECOA can control the converter to obtain MPPT with faster convergence rate and without untimely trapping at local optimal solutions. Then the pure sine wave inverter with robust intelligent sliding mode MPPT of the PV system delivers a high-quality and stable sinusoidal wave voltage to the load. The efficacy of the proposed method is validated on a MPPT pure sine wave inverter system by using numerical simulations and experiments. The results show that the output of the proposed PV system can improve steady-state performance and transient tracking speed.
A Novel Miniature and Selective CMOS Gas Sensor for Gas Mixture Analysis—Part 2: Emphasis on Physical Aspects
Authors: Avraham Moshe , Stolyarova Sara , Blank Tanya , Bar-Lev Sharon , Golan Gady , Nemirovsky Yael
Published: June 2020

This is a second part of the paper presenting a miniature, combustion-type gas sensor (dubbed GMOS) based on a novel thermal sensor (dubbed TMOS). The TMOS is a micromachined CMOS-SOI transistor, which acts as the sensing element and is integrated with a catalytic reaction plate, where ignition of the gas takes place. Part 1 focused on the chemical and technological aspects of the sensor. In part 2, the emphasis is on the physical aspects of the reaction micro-hot plate on which the catalytic layer is deposited. The three main challenges in designing the hot plate are addressed: (i) How to design a hot plate operating in air, with a low thermal conductivity; (ii) how to measure the temperature of the hot plate during operation; (iii) how to reduce the total consumed power during operation. Reported simulated as well as analytical models and measured results are in good agreement.
How Important Is Eating Rate in the Physiological Response to Food Intake, Control of Body Weight, and Glycemia?
Authors: Argyrakopoulou Georgia , Simati Stamatia , Dimitriadis George , Kokkinos Alexander
Published: June 2020

The link between eating rate and energy intake has long been a matter of extensive research. A better understanding of the effect of food intake speed on body weight and glycemia in the long term could serve as a means to prevent weight gain and/or dysglycemia. Whether a fast eating rate plays an important role in increased energy intake and body weight depends on various factors related to the studied food such as texture, viscosity and taste, but seems to be also influenced by the habitual characteristics of the studied subjects as well. Hunger and satiety quantified via test meals in acute experiments with subsequent energy intake measurements and their association with anorexigenic and orexigenic regulating peptides provide further insight to the complicated pathogenesis of obesity. The present review examines data from the abundant literature on the subject of eating rate, and highlights the main findings in people with normal weight, obesity, and type 2 diabetes, with the aim of clarifying the association between rate of food intake and hunger, satiety, glycemia, and energy intake in the short and long term.
Inadequacy of Immune Health Nutrients: Intakes in US Adults, the 2005–2016 NHANES
Authors: Reider Carroll A. , Chung Ray-Yuan , Devarshi Prasad P. , Grant Ryan W. , Hazels Mitmesser Susan
Published: June 2020

A well-functioning immune system is essential for human health and well-being. Micronutrients such as vitamins A, C, D, E, and zinc have several functions throughout the immune system, yet inadequate nutrient intakes are pervasive in the US population. A large body of research shows that nutrient inadequacies can impair immune function and weaken the immune response. Here, we present a new analysis of micronutrient usual intake estimates based on nationally representative data in 26,282 adults (>19 years) from the 2005–2016 National Health and Nutrition Examination Surveys (NHANES). Overall, the prevalence of inadequacy (% of population below estimated average requirement [EAR]) in four out of five key immune nutrients is substantial. Specifically, 45% of the U.S. population had a prevalence of inadequacy for vitamin A, 46% for vitamin C, 95% for vitamin D, 84% for vitamin E, and 15% for zinc. Dietary supplements can help address nutrient inadequacy for these immune-support nutrients, demonstrated by a lower prevalence of individuals below the EAR. Given the long-term presence and widening of nutrient gaps in the U.S.—specifically in critical nutrients that support immune health—public health measures should adopt guidelines to ensure an adequate intake of these micronutrients. Future research is needed to better understand the interactions and complexities of multiple nutrient shortfalls on immune health and assess and identify optimal levels of intake in at-risk populations.
Attenuation of Lipopolysaccharide-Induced Acute Lung Injury by Hispolon in Mice, Through Regulating the TLR4/PI3K/Akt/mTOR and Keap1/Nrf2/HO-1 Pathways, and Suppressing Oxidative Stress-Mediated ER Stress-Induced Apoptosis and Autophagy
Authors: Huang Ching-Ying , Deng Jeng-Shyan , Huang Wen-Chin , Jiang Wen-Ping , Huang Guan-Jhong
Published: June 2020

The anti-inflammatory effect of hispolon has identified it as one of the most important compounds from Sanghuangporus sanghuang. The research objectives were to study this compound using an animal model by lipopolysaccharide (LPS)-induced acute lung injury. Hispolon treatment reduced the production of the pro-inflammatory mediator NO, TNF-α, IL-1β, and IL-6 induced by LPS challenge in the lung tissues, as well as decreasing their histological alterations and protein content. Total cell number was also reduced in the bronchoalveolar lavage fluid (BALF). Moreover, hispolon inhibited iNOS, COX-2 and IκB-α and phosphorylated IKK and MAPK, while increasing catalase, SOD, GPx, TLR4, AKT, HO-1, Nrf-2, Keap1 and PPARγ expression, after LPS challenge. It also regulated apoptosis, ER stress and the autophagy signal transduction pathway. The results of this study show that hispolon regulates LPS-induced ER stress (increasing CHOP, PERK, IRE1, ATF6 and GRP78 protein expression), apoptosis (decreasing caspase-3 and Bax and increasing Bcl-2 expression) and autophagy (reducing LC3 I/II and Beclin-1 expression). This in vivo experimental study suggests that hispolon suppresses the LPS-induced activation of inflammatory pathways, oxidative injury, ER stress, apoptosis and autophagy and has the potential to be used therapeutically in major anterior segment lung diseases.
Polyphenolic Maqui Extract as a Potential Nutraceutical to Treat TNBS-Induced Crohn’s Disease by the Regulation of Antioxidant and Anti-Inflammatory Pathways
Authors: Ortiz Tamara , Argüelles-Arias Federico , Illanes Matilde , García-Montes Josefa-María , Talero Elena , Macías-García Laura , Alcudia Ana , Vázquez-Román Victoria , Motilva Virginia , De-Miguel Manuel
Published: June 2020

Nutraceuticals include a wide variety of bioactive compounds, such as polyphenols, which have been highlighted for their remarkable health benefits. Specially, maqui berries have shown great antioxidant activity and anti-inflammatory effects on some inflammatory diseases. The objectives of the present study were to explore the therapeutic effects of maqui berries on acute-phase inflammation in Crohn’s disease. Balb/c mice were exposed to 2,4,6-trinitrobenzene sulfonic acid (TNBS) via intracolonic administration. Polyphenolic maqui extract (Ach) was administered orally daily for 4 days after TNBS induction (Curative Group), and for 7 days prior to the TNBS induction until sacrifice (Preventive Group). Our results showed that both preventive and curative Ach administration inhibited body weight loss and colon shortening, and attenuated the macroscopic and microscopic damage signs, as well as significantly reducing transmural inflammation and boosting the recovery of the mucosal architecture and its muco-secretory function. Additionally, Ach promotes macrophage polarization to the M2 phenotype and was capable of down-regulating significantly the expression of inflammatory proteins COX-2 and iNOS, and at the same time it regulates the antioxidant Nrf-2/HO-1 pathway. In conclusion, this is the first study in which it is demonstrated that the properties of Ach as could be used as a preventive and curative treatment in Crohn’s disease.
Raspberry Ketone [4-(4-Hydroxyphenyl)-2-Butanone] Differentially Effects Meal Patterns and Cardiovascular Parameters in Mice
Authors: Kshatriya Dushyant , Hao Lihong , Li Xinyi , Bello Nicholas T.
Published: June 2020

Raspberry ketone (RK; [4-(4-hydroxyphenyl)-2-butanone]) is a popular nutraceutical used for weight management and appetite control. We sought to determine the physiological benefits of RK on the meal patterns and cardiovascular changes associated with an obesogenic diet. In addition, we explored whether the physiological benefits of RK promoted anxiety-related behaviors. Male and female C57BL/6J mice were administered a daily oral gavage of RK 200 mg/kg, RK 400 mg/kg, or vehicle for 14 days. Commencing with dosing, mice were placed on a high-fat diet (45% fat) or low-fat diet (10% fat). Our results indicated that RK 200 mg/kg had a differential influence on meal patterns in males and females. In contrast, RK 400 mg/kg reduced body weight gain, open-field total distance travelled, hemodynamic measures (i.e., reduced systolic blood pressure (BP), diastolic BP and mean BP), and increased nocturnal satiety ratios in males and females. In addition, RK 400 mg/kg increased neural activation in the nucleus of the solitary tract, compared with vehicle. RK actions were not influenced by diet, nor resulted in an anxiety-like phenotype. Our findings suggest that RK has dose-differential feeding and cardiovascular actions, which needs consideration as it is used as a nutraceutical for weight control for obesity.
Antiproliferative and Apoptotic Effects of Cardamonin against Hepatocellular Carcinoma HepG2 Cells
Authors: Badroon Nassrin A. , Abdul Majid Nazia , Alshawsh Mohammed A.
Published: June 2020

Liver cancer is the sixth most common cancer in terms of incidence and the fourth in terms of mortality. Hepatocellular carcinoma (HCC) represents almost 90% of primary liver cancer and has become a major health problem globally. Cardamonin (CADMN) is a natural bioactive chalcone found in several edible plants such as cardamom and Alpinia species. Previous studies have shown that CADMN possesses anticancer activities against breast, lung, prostate and colorectal cancer. In the present study, the mechanisms underlying the anti-hepatocellular carcinoma effects of CADMN were investigated against HepG2 cells. The results demonstrated that CADMN has anti-proliferative effects and apoptotic action on HepG2 cells. CADMN showed potent cytotoxicity against HepG2 cells with an IC50 of 17.1 ± 0.592 μM at 72 h. Flow cytometry analysis demonstrated that CADMN arrests HepG2 cells in G1 phase and induces a significant increase in early and late apoptosis in a time-dependent manner. The mechanism by which CADMN induces apoptotic action was via activation of both extrinsic and intrinsic pathways. Moreover, the findings of this study showed the involvement of reactive oxygen species (ROS), which inhibit the NF-κB pathway and further enhance the apoptotic process. Together, our findings further support the potential anticancer activity of CADMN as an alternative therapeutic agent against HCC.
Effects of Cocoa-Rich Chocolate on Blood Pressure, Cardiovascular Risk Factors, and Arterial Stiffness in Postmenopausal Women: A Randomized Clinical Trial
Authors: Garcia-Yu Irene A. , Garcia-Ortiz Luis , Gomez-Marcos Manuel A. , Rodriguez-Sanchez Emiliano , Agudo-Conde Cristina , Gonzalez-Sanchez Jesus , Maderuelo-Fernandez Jose A. , Recio-Rodriguez Jose I.
Published: June 2020

This study aimed to evaluate the effects of the intake of 10 g of cocoa-rich chocolate on blood pressure, other cardiovascular risk factors, and vascular structure and function in postmenopausal women. A total of 140 postmenopausal women participated in this randomized and controlled parallel clinical trial. For six months, the intervention group (IG; n = 73) consumed daily 10 g of chocolate (99% cocoa) added to their usual food intake, whereas the control group (CG; n = 67) did not receive any intervention. Blood pressure, pulse pressure (PP), cardio-ankle vascular index (CAVI), ankle-brachial index (ABI), brachial-ankle pulse wave velocity (baPWV), augmentation index, and laboratory variables were measured at baseline and six months. ANCOVA analyses adjusted for baseline values revealed no significant differences for systolic blood pressure (−1.45 mm Hg; 95% confidence interval (CI): −4.79, 1.88; p = 0.391) or baPWV (0.18 m/s; 95% CI: −0.14, 0.50; p = 0.263) between groups. A decrease in PP was observed in the IG compared to the CG (−2.05 mm Hg; 95% CI: −4.08, −0.02; p = 0.048). The rest of the vascular structure and function parameters and other measured variables remained unchanged. The daily intake of 10 g of cocoa-rich chocolate seems to provide little improvement to cardiovascular health, but neither does it cause any adverse effects on the parameters evaluated in postmenopausal women in the long term.
Assessment of the Potential Skin Application of Plectranthus ecklonii Benth.
Authors: Nicolai Marisa , Mota Joana , Fernandes Ana S. , Pereira Filipe , Pereira Paula , P. Reis Catarina , Robles Velasco Maria Valéria , Baby André Rolim , Rosado Catarina , Rijo Patrícia
Published: June 2020

Plectranthus ecklonii Benth. has widespread ethnobotanical use in African folk medicine for its medicinal properties in skin conditions. In this study, two different basic formulations containing P. ecklonii extracts were prepared, one in an organic solvent and the other using water. The aqueous extract only contained rosmarinic acid (RA) at 2.02 mM, and the organic extract contained RA and parvifloron D at 0.29 and 3.13 mM, respectively. RA in aqueous solution permeated skin; however, in P. ecklonii organic extract, this was not detected. Thus, P. ecklonii aqueous extract was further studied and combined with benzophenone-4, which elevated the sun protection factor (SPF) by 19.49%. No significant cytotoxic effects were observed from the aqueous extract. The Staphylococcus epidermidis strain was used to determine a minimum inhibitory concentration (MIC) value of 10 µg·mL−1. The aqueous extract inhibited the activity of acetylcholinesterase by 59.14 ± 4.97%, and the IC50 value was 12.9 µg·mL−1. The association of the P. ecklonii extract with a UV filter substantially elevated its SPF efficacy. Following the multiple bioactivities of the extract and its active substances, a finished product could be claimed as a multifunctional cosmeceutical with broad skin valuable effects, from UV protection to antiaging action.
Copolymeric Micelles Overcome the Oral Delivery Challenges of Amphotericin B
Authors: Nimtrakul Pataranapa , Williams Desmond B. , Tiyaboonchai Waree , Prestidge Clive A.
Published: June 2020

Classified as a Biopharmaceutical Classification System (BCS) class IV drug, amphotericin B (AmB) has low aqueous solubility and low permeability leading to low oral bioavailability. To improve these limitations, this study investigated the potential of AmB-loaded polymeric micelles (AmB-PM) to increase intestinal absorption. AmB-PM were prepared with polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol copolymer (Soluplus®) as a polymeric carrier and used a modified solvent diffusion and microfluidics (NanoAssemblr®) method. AmB-PM have a mean particle size of ~80 nm and are mono-disperse with a polydispersity index <0.2. The entrapment efficiency of AmB was up to 95% and achieved with a high drug loading up to ~20% (w/w) with a total amount of incorporated drug of 1.08 ± 0.01 mg/mL. Importantly, compared to free drug, AmB-PM protected AmB from degradation in an acidic (simulated gastric) environment. Viability studies in Caco-2 cells confirmed the safety/low toxicity of AmB-PM. In vitro cellular absorption studies confirmed that AmB-PM increased AmB uptake in Caco-2 cells 6-fold more than free AmB (i.e., 25% compared with 4% within 30 min). Furthermore, the permeability of AmB across Caco-2 monolayers was significantly faster (2-fold) and more pronounced for AmB-PM in comparison to free drug (3.5-fold increase). Thus, the developed AmB-PM show promise as a novel oral delivery system for AmB and justifies further investigation.
A Comparative Survey Study on Meaning-Making Coping among Cancer Patients in Turkey
Authors: Cetrez Önver A. , Ahmadi Fereshteh , Erbil Pelin
Published: June 2020

(1) Background: The role of culture in secular, spiritual, and religious coping methods is important, but needs more attention in research. The aim has been to (1) investigate the meaning-making coping methods among cancer patients in Turkey and (2) whether there were differences in two separate samples (compared to Study 2, Study 1 had a younger age group, was more educated, and grew up in a big city), (3) paying specific attention to gender, age, education, and area of residence. (2) Methods: Quantitative study using a convenience sampling in two time periods, Study 1 (n = 94) and Study 2 (n = 57). (3) Results: In Study 2, there is a significant increase in several religious and spiritual coping strategies. Additionally, there is a positive correlation between being a woman and using more religious or spiritual coping strategies. Secular meaning-making coping strategies also increase significantly in Study 2. The results confirmed the hypotheses for gender, educational, and age differences in seeking support from religious leaders. The results also confirmed the hypotheses for gender and educational level in a punishing God reappraisal and demonic reappraisal. (4) Conclusions: As Turkey is a country at the junction of strong religiosity and deep-rooted secularism, dividing up the meaning-making coping methods into the religious and spiritual, on one hand, and the secular, on the other, reveals interesting results.
The Anticoagulant Nafamostat Potently Inhibits SARS-CoV-2 S Protein-Mediated Fusion in a Cell Fusion Assay System and Viral Infection In Vitro in a Cell-Type-Dependent Manner
Authors: Yamamoto Mizuki , Kiso Maki , Sakai-Tagawa Yuko , Iwatsuki-Horimoto Kiyoko , Imai Masaki , Takeda Makoto , Kinoshita Noriko , Ohmagari Norio , Gohda Jin , Semba Kentaro , Matsuda Zene , Kawaguchi Yasushi , Kawaoka Yoshihiro , Inoue Jun-ichiro
Published: June 2020

Although infection by SARS-CoV-2, the causative agent of coronavirus pneumonia disease (COVID-19), is spreading rapidly worldwide, no drug has been shown to be sufficiently effective for treating COVID-19. We previously found that nafamostat mesylate, an existing drug used for disseminated intravascular coagulation (DIC), effectively blocked Middle East respiratory syndrome coronavirus (MERS-CoV) S protein-mediated cell fusion by targeting transmembrane serine protease 2 (TMPRSS2), and inhibited MERS-CoV infection of human lung epithelium-derived Calu-3 cells. Here we established a quantitative fusion assay dependent on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S protein, angiotensin I converting enzyme 2 (ACE2) and TMPRSS2, and found that nafamostat mesylate potently inhibited the fusion while camostat mesylate was about 10-fold less active. Furthermore, nafamostat mesylate blocked SARS-CoV-2 infection of Calu-3 cells with an effective concentration (EC)50 around 10 nM, which is below its average blood concentration after intravenous administration through continuous infusion. On the other hand, a significantly higher dose (EC50 around 30 μM) was required for VeroE6/TMPRSS2 cells, where the TMPRSS2-independent but cathepsin-dependent endosomal infection pathway likely predominates. Together, our study shows that nafamostat mesylate potently inhibits SARS-CoV-2 S protein-mediated fusion in a cell fusion assay system and also inhibits SARS-CoV-2 infection in vitro in a cell-type-dependent manner. These findings, together with accumulated clinical data regarding nafamostat’s safety, make it a likely candidate drug to treat COVID-19.
Development and Evaluation of a Sensitive Bacteriophage-Based MRSA Diagnostic Screen
Authors: Brown Matthew , Hahn Wendy , Bailey Bryant , Hall Alex , Rodriguez Gema , Zahn Henriett , Eisenberg Marcia , Erickson Stephen
Published: June 2020

Engineered luciferase reporter bacteriophages provide specific, sensitive, rapid and low-cost detection of target bacteria and address growing diagnostic needs in multiple industries. Detection of methicillin-resistant Staphylococcus aureus (MRSA) nasal colonization and antibiotic susceptibility play a critical supportive role in preventing hospital-acquired infections and facilitating antibiotic stewardship. We describe the development and evaluation of a novel phage-based MRSA diagnostic screen for nasal swab specimens. The screen utilizes two luciferase reporter phages capable of recognizing genetically-diverse Staphylococcus aureus. The beta-lactam antibiotic cefoxitin is included to differentiate between resistant (MRSA) and susceptible organisms. The screen positively identified 97.7% of 390 clinical MRSA isolates at low bacterial concentrations. At higher inoculums, 93.5% of 123 clinical non-MRSA Staphylococcus aureus yielded appropriate negative results. Although cross-reactivity of the phage cocktail was observed with other staphylococcal and bacillus species, these false positives were absent under selective conditions. MRSA remained detectable in the presence of 38 distinct competing species and was accurately identified in 100% of 40 spiked nasal specimens. Thus, this six-hour screen sensitively detected MRSA both in vitro and in human nasal matrix.
Persistent Innate Immune Stimulation Results in IRF3-Mediated but Caspase-Independent Cytostasis
Authors: Urban Christian , Welsch Hendrik , Heine Katharina , Wüst Sandra , Haas Darya A. , Dächert Christopher , Pandey Aparna , Pichlmair Andreas , Binder Marco
Published: June 2020

Persistent virus infection continuously produces non-self nucleic acids that activate cell-intrinsic immune responses. However, the antiviral defense evolved as a transient, acute phase response and the effects of persistently ongoing stimulation onto cellular homeostasis are not well understood. To study the consequences of long-term innate immune activation, we expressed the NS5B polymerase of Hepatitis C virus (HCV), which in absence of viral genomes continuously produces immune-stimulatory RNAs. Surprisingly, within 3 weeks, NS5B expression declined and the innate immune response ceased. Proteomics and functional analyses indicated a reduced proliferation of those cells most strongly stimulated, which was independent of interferon signaling but required mitochondrial antiviral signaling protein (MAVS) and interferon regulatory factor 3 (IRF3). Depletion of MAVS or IRF3, or overexpression of the MAVS-inactivating HCV NS3/4A protease not only blocked interferon responses but also restored cell growth in NS5B expressing cells. However, pan-caspase inhibition could not rescue the NS5B-induced cytostasis. Our results underline an active counter selection of cells with prolonged innate immune activation, which likely constitutes a cellular strategy to prevent persistent virus infections.
Innate Immune Components That Regulate the Pathogenesis and Resolution of hRSV and hMPV Infections
Authors: Andrade Catalina A. , Pacheco Gaspar A. , Gálvez Nicolas M. S. , Soto Jorge A. , Bueno Susan M. , Kalergis Alexis M.
Published: June 2020

The human respiratory syncytial virus (hRSV) and human Metapneumovirus (hMPV) are two of the leading etiological agents of acute lower respiratory tract infections, which constitute the main cause of mortality in infants. However, there are currently approved vaccines for neither hRSV nor hMPV. Moreover, despite the similarity between the pathology caused by both viruses, the immune response elicited by the host is different in each case. In this review, we discuss how dendritic cells, alveolar macrophages, neutrophils, eosinophils, natural killer cells, innate lymphoid cells, and the complement system regulate both pathogenesis and the resolution of hRSV and hMPV infections. The roles that these cells play during infections by either of these viruses will help us to better understand the illnesses they cause. We also discuss several controversial findings, relative to some of these innate immune components. To better understand the inflammation in the lungs, the role of the respiratory epithelium in the recruitment of innate immune cells is briefly discussed. Finally, we review the main prophylactic strategies and current vaccine candidates against both hRSV and hMPV.
n-3 Polyunsaturated Fatty Acids Impede the TCR Mobility and the TCR–pMHC Interaction of Anti-Viral CD8+ T Cells
Authors: Lim Younghyun , Kim Seyoung , Kim Sehoon , Kim Dong-In , Kang Kyung Won , Hong So-Hee , Lee Sang-Myeong , Koh Hye Ran , Seo Young-Jin
Published: June 2020

The immune-suppressive effects of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) on T cells have been observed via multiple in vitro and in vivo models. However, the precise mechanism that causes these effects is still undefined. In this study, we investigated whether n-3 PUFAs regulated T cell receptor (TCR) and peptide-major histocompatibility complex (pMHC) interactions. The expansion of anti-viral CD8+ T cells that endogenously synthesize n-3 PUFAs (FAT-1) dramatically decreased upon lymphocytic choriomeningitis virus (LCMV) infection in vivo. This decrease was not caused by the considerable reduction of TCR expression or the impaired chemotactic activity of T cells. Interestingly, a highly inclined and laminated optical sheet (HILO) microscopic analysis revealed that the TCR motility was notably reduced on the surface of the FAT-1 CD8+ T cells compared to the wild type (WT) CD8+ T cells. Importantly, the adhesion strength of the FAT-1 CD8+ T cells to the peptide-MHC was significantly lower than that of the WT CD8+T cells. Consistent with this result, treatment with docosahexaenoic acid (DHA), one type of n-3 PUFA, significantly decreased CD8+ T cell adhesion to the pMHC. Collectively, our results reveal a novel mechanism through which n-3 PUFAs decrease TCR-pMHC interactions by modulating TCR mobility on CD8+ T cell surfaces.
MODERASI ISLAM (WASATHIYAH ISLAM) PERSPEKTIF AL-QUR’AN, AS-SUNNAH SERTA PANDANGAN PARA ULAMA DAN FUQAHA
Authors: Arif Muhammad Khairan
Published: June 2020

Konsep Wasathiyah Islam atau moderasi Islam saat ini telah menjadi arah atau aliran pemikiran Islam yang telah menjadi diskursus penting dalam dunia Islam dewasa ini, melihat kondisi umat Islam yang selalu menjadi tertuduh dalam setiap peristiwa kekerasan yang dilakukan oleh personal muslim yang tidak memahami karakter dan ini ajaran Islam. Oleh karenanya penilitian literatif ini bertujuan memberikan pemahaman dan konsep orisinil tentang aliran pemikiran moderasi islam, agar setiap muslim modern dapat memahami dan mengimplementasikannya dengan benar dan komprehensif dalam kehidupannya sehari-hari. Penelitian ini menggunakan metode kepustakaan dan kajian literasi Islam klasik maupun modern dari Al-Qur’an, As-Sunnah dan kitab-kitab klasik dan modern dari para Ulama dan Fuqaha yang kompeten dibidangnya. Literatur tersebut dikaji dan dianalisa oleh peneliti dengan teliti untuk menghasilkan kesimpulan yang tepat dan teruji. Hasil penelitian ini adalah; diketahuinya secara pasti makna dan konsep moderasi Islam menurut Al-Qur’an, As-Sunnah dan para Ulama serta menjawab keraguan sebagian muslim terhadap konsep moderasi Islam

 

The concept of Wasathiyah Islam or the current Islamic moderation has become the direction or the flow of Islamic thought that has become an important discourse in the Islamic world today, see the condition of Muslims who have always become accused in every event Violence committed by personal Muslims who do not understand the character and this teachings of Islam. Therefore, this literative study aims to provide an original understanding and concept of the flow of Islamic moderation thinking, so that every modern Muslim can understand and implement it properly and comprehensively in its life.This research uses a method of literature and study of classical and modern Islamic literacy from the Qur'an, As-Sunnah and the classical and modern books of scholars and Fuqaha who are competent in their field. The literature is examined and analysed by researchers carefully to produce precise and proven conclusions.The results of this research are; To be sure the meaning and concept of moderation of Islam according to the Qur'an, As-Sunnah and scholars and answer the doubt of some Muslims on the concept of moderation Islam
DAKWAH DALAM KELUARGA
Authors: Munajah Neneng
Published: June 2020

Artikel ini membahas keluarga sebagai objek prioritas dalam berdakwah. Hal ini dikarenakan setiap manusia, pasti menyerap pemikiran, ajaran, dan nilai-nilai agama yang hidup dalam keluarganya; keluarga adalah miniatur dari komunitas dan masyarakat Islam. Keluarga juga merupakan kelanjutan logis dari kedua fungsi keluarga di atas, maka institusi keluarga dengan sendirinya menjadi salah satu faktor penentu bagi kekuatan dan kelemahan umat Islam secara keseluruhan. Adanya globalisasi telah memberikan dampak yang signifikan terhadap masyarakat, termasuk dakwah. Seperti: melonggarnya ikatan keluarga, melemahnya ikatan-ikatan moral akibat dari paham serba halal, permissivenisme (al-ibahiyyah) dan paham hedonisme yang menyertai modernisme, serta kegoncangan jiwa yang mengganggu ketenangan dan kedamaian keluarga dan rumah tangga. Sehingga dakwah dalam keluarga menuntut aktualisasi sistem dan nilai-nilai Islam dalam kehidupan keluarga. Di samping itu, dalam artikel ini penulis mencoba mengemukakan hal-hal pokok yang perlu diperhatikan dalam pembinaan keluarga Islam sebagai pilar utama dakwah. Pertama, soal pembentukan keluarga melalui pernikahan. Kedua, soal pendidikan dan penanaman nilai-nilai agama dalam keluarga. Ketiga, soal penegakan keadilan dan kesetaraan gender. Karena ketiga hal ini berpengaruh terhadap kekuatan dan ketahanan keluarga Islam.

This article discusses the family as a priority object in da'wah. This is because every human being, must absorb the thoughts, teachings, and religious values ​​that live in his/her family; the family is a miniature of the Islamic community and society. The family is also a logical continuation of the two family functions above, so the family institution itself is one of the determining factors for the strengths and weaknesses of the Muslim community as a whole. The existence of globalization has had a significant impact on society, including propaganda. Such as: loosening of family ties, weakening of moral ties as a result of all-round understanding, permissivenism (al-ibahiyyah) and understanding of hedonism that accompany modernism, and the shock of the soul that disturbs the peace and peace of family and household. So preaching in the family demands the actualization of Islamic systems and values ​​in family life. In addition, in this article the author tries to put forward the main things that need to be considered in fostering Islamic families as the main pillars of da'wah. First, a matter of forming a family through marriage. Second, the education and the inculcation of religious values ​​in the family. Third, the matter of upholding justice and gender equality. Because these three things affect the strength and resilience of Islamic families.
AGAMA DAN FILSAFAT
Authors: Faqihuddin Ahmad
Published: June 2020

Ibnu Khaldun adalah salah satu pemikir yang teguh beriman kepada Allah dan orang yang teguh berpegang pada ajaran Islam. Dalam kitabnya Al-Muqaddimah selalu diselingi dengan nama Allah dan ayat-ayat Al-Qur’an yang sesuai dengan pokok pembahasannya dan pada setiap penutup pasal selalu diakhiri dengan doa dan ayat-ayat Al-Qur’an. Jjika berbicara tentang agama, Ibnu Khaldun tidak lupa selalu mengutip ayat-ayat Al-Qur’an dan hadits-hadits Nabi. Dalam berbicara tentang filsafat, Ibnu Khaldun terlebih dahulu menguraikan perkembangan filsafat Yunani terutama mengenai Plato dan Aristoteles yang membicarakan konsep Tuhan. Ibnu Khaldun juga mengkritik Plato dan Aristoteles, dikatakan bahwa keduanya memiliki konsep yang tidak jelas tentang Tuhan. Ibnu Khaldun juga mengkritik para filsafat dan filosof yang berusaha menjadikan filsafat sebagai sarana menjaga masalah keimanan, akan tetapi Ia tetap menghargai filsafat. Ibnu Khaldun adalah orang pertama yang telah membuat studi kritis terhadap filsafat karena keterbatasan pengetahuan manusia. Sedikit sekali ia menyinggung cara-cara spekulatif yang pernah dikemukakan Al-Farabi, Ibnu Sina, Ibnu Rusyd, dan filosof-filosof lain. Ibnu Khaldun lebih cenderung kepada pendirian Ibnu Rusyd dalam pemikiran ketika berhadapan dengan Al-Ghazali, tapi sebagian para ahli mengatakan bahwa Ibnu Khaldun sedikit banyak dipengaruhi oleh pemikiran Al-Ghazali.

Ibn Khaldun was one of the thinkers who firmly believed in Allah and firmly adhered to the teachings of Islam. In his book Al-Muqaddimah,he has always interspersed with the name of Allah and the verses of the Qur'an in accordance with the subject matter. And even at each closing the chapter, he always ends with prayer and verses of the Qur'an. Whenever talking about the religion Ibn Khaldun always quote the verses of the Qur'an and the hadiths of the Prophet. In talking about philosophy, he first described the development of Greek philosophy, especially about Plato and Aristotle who talked about the concept of God. Ibn Khaldun criticized Plato and Aristotle, saying that the two concepts about God were unclear. Ibn Khaldun also criticized philosophers and philosophers who tried to make philosophy a means of guarding the problem of faith. However he still respected the philosophy. Ibn Khaldun was the first to make a critical study of philosophy because of the limitations of human knowledge. He mentioned very little about the speculative ways that Al-Farabi, Ibn Sina, Ibn Rushd, and other philosophers have suggested. Ibn Khaldun was more inclined towards the establishment of Ibn Rushd in thought when dealing with Al-Ghazali, but some experts say that Ibn Khaldun was more or less influenced by Al-Ghazali.
KRITIK ATAS METODE HERMENEUTIKA DALAM TAFSIR ALQURÁN
Authors: Uyuni Badrah
Published: June 2020

Hermeneutika sebagai metodologi yang diprakarsai sebagai alternative metode penafsiran Al-Qurán telah ditawarkan oleh Ilmuwan Barat dan Ilmuwan Muslim Moderat dan Liberal. Hanya saja hal ini menjadi perdebatan dalam internal kalangan ummat Islam dikarenakan hermenuetika berbeda dengan Tafsir maupun Ta’wil yang merupakan ilmu yang sudah disepakati dalam metodologi memehami Al-Qurán dan dengan hermenuetika semua hasil tafsir dan ta’wil yang dilakukan oleh ulama itu hanyalah penafsiran, dan karenanya bergantung pada subyektivitas orangnya. Ada 3 aliran utama dalam tubuh ummat ketika menyikapi metode hermeneutika untuk tafsir Al-Qurán. Yaitu: menerima, menolak sepenuhnya, dan menerima sebagian dengan beberapa alasan. Produk yang dihasilkan dari hermeneutika mengarah kepada suatu paham relativisme yang menganggap tidak adanya tafsir yang tetap. Dan akhirnya membuat konklusi general bahwa semua tafsir dianggap produk akal manusia yang relatif, kontekstual, temporal, dan personal. Akibat yang ditampilkan oleh metode ini pun tidak sesederhana yang diperkirakan namun berdampak tidak hanya pada hukum syariat Islam dan juga kepada factor ideology, sosial, psikologi, dan budaya Ummat Islam.
Design of Pneumatic Gripper for Pick and Place Operation (Four Jaw)
Authors: Velineni Poornesh , Suresh Jayasuriya , C Naveen Kumar , M Suresh
Published: June 2020

Grippers are attached at the end of an industrial arm robot for material handling purpose. Grippers plays a major role in all pick and place application industries. Those are connected as end effectors to realize and develop a task in an industrial work floor. Pneumatic gripper works with the principle of compressed air. The gripper is connected to a compressed air supply. When air pressure is applied on the piston, the gripper gets opened while the air gets exist from the piston it gets closed. It is possible to control the force acting on the gripper by controlling the air pressure with the help of the valve. The objective is to design an effective, simple, and economic gripper for pick and place application.
A New Family of Archimedean Copula via Trigonometric Generator Function
Authors: SUSAM Selim Orhun
Published: June 2020

In this paper, new type of Archimedean copula based on cotangent generator function, and dependence characteristics are investigated. Also, the estimation procedure of the dependence parameter is given. A Monte Carlo study is performed to measure the performance of estimators. To demonstrate the goodness of fit performance of the new family, a real data analysis is performed.
Approximate Bound State Solutions of the Hellmann Plus Kratzer Potential in N-dimensional Space
Authors: ÖZFİDAN Aysel
Published: June 2020

We have examined the approximate l_(N-1)-state solutions of the N-dimensional Schrödinger equation for a particle interacting with the Hellmann plus Kratzer potential. In hyperspherical coordinate system, we have constructed the bound state energy equation and the wavefunctions expressed by the hypergeometric function via the asymptotic iteration approach in detail. When considered the special cases of parameters in Hellmann plus Kratzer potential, this potential turns into several potential models. In this connection, the non-relativistic energy spectra for the modified Kratzer, Yukawa, Coulomb and Hellmann potentials in approximate analytic form have been obtained in hyperspherical coordinates. We have presented the numerical energy eigenvalues for the Hellmann, Yukawa and Coulomb potentials in N=3 dimensions. Our present results provide an appropriate test of the accuracy of asymptotic iteration formalism.