bluuebunny/crossref_metadata_2025 huggingface dataset:
Thymine-Functionalized Gold Nanoparticles (Au NPs) for a Highly Sensitive Fiber-Optic Surface Plasmon Resonance Mercury Ion Nanosensor
Authors: Yuan Huizhen , Sun Guangyi , Peng Wei , Ji Wei , Chu Shuwen , Liu Qiang , Liang Yuzhang
Published: February 2021

Mercury ion (Hg2+) is considered to be one of the most toxic heavy metal ions. Once the content of Hg2+ exceeds the quality standard in drinking water, the living environment and health of human beings will be threatened and destroyed. Therefore, the establishment of simple and efficient methods for Hg2+ ion detection has important practical significance. In this paper, we present a highly sensitive and selective fiber-optic surface plasmon resonance (SPR) Hg2+ ion chemical nanosensor by designing thymine (T)-modified gold nanoparticles (Au NPs/T) as the signal amplification tags. Thymine-1-acetic acid (T-COOH) was covalently coupled to the surface of 2-aminoethanethiol (AET)-modified Au NPs and Au film by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride/N-Hydroxysuccinimide (EDC/NHS) activation effect, respectively. In the presence of Hg2+ ions, the immobilized thymine combines specifically with Hg2+ ions, and forms an Au/thymine-Hg2+-thymine/Au (Au/T-Hg2+-T/Au) complex structure, leading to a shift in SPR wavelength due to the strong electromagnetic couple between Au NPs and Au film. Under optimal conditions, the proposed sensor was found to be highly sensitive to Hg2+ in the range of 80 nM–20 µM and the limit of detection (LOD) for Hg2+ was as low as 9.98 nM. This fiber-optic SPR sensor afforded excellent selectivity for Hg2+ ions against other heavy metal ions such as Fe3+, Cu2+, Ni2+, Ba2+, K+, Na+, Pb2+, Co2+, and Zn2+. In addition, the proposed sensor was successfully applied to Hg2+ assay in real environmental samples with excellent recovery. Accordingly, considering its simple advantages, this novel strategy provides a potential platform for on-site determination of Hg2+ ions by SPR sensor.
Nanopatterning of Weak Links in Superconducting Oxide Interfaces
Authors: Singh Gyanendra , Lesne Edouard , Winkler Dag , Claeson Tord , Bauch Thilo , Lombardi Floriana , Caviglia Andrea D. , Kalaboukhov Alexei
Published: February 2021

The interface between two wide band-gap insulators, LaAlO3 and SrTiO3 (LAO/STO), hosts a quasi-two-dimensional electron gas (q2DEG), two-dimensional superconductivity, ferromagnetism, and giant Rashba spin-orbit coupling. The co-existence of two-dimensional superconductivity with gate-tunable spin-orbit coupling and multiband occupation is of particular interest for the realization of unconventional superconducting pairing. To investigate the symmetry of the superconducting order parameter, phase sensitive measurements of the Josephson effect are required. We describe an approach for the fabrication of artificial superconducting weak links at the LAO/STO interface using direct high-resolution electron beam lithography and low-energy argon ion beam irradiation. The method does not require lift-off steps or sacrificial layers. Therefore, resolution is only limited by the electron beam lithography and pattern transfer. We have realized superconducting weak links with a barrier thickness of 30–100 nm. The barrier transparency of the weak links can be controlled by the irradiation dose and further tuned by a gate voltage. Our results open up new possibilities for the realization of quantum devices in oxide interfaces.
Novel PVDF-PVP Hollow Fiber Membrane Augmented with TiO2 Nanoparticles: Preparation, Characterization and Application for Copper Removal from Leachate
Authors: Abba Mohammed Umar , Man Hasfalina Che , Azis Raba’ah Syahidah , Isma Idris Aida , Hazwan Hamzah Muhammad , Yunos Khairul Faezah , Katibi Kamil Kayode
Published: February 2021

High proportion of copper has become a global challenge owing to its negative impact on the environment and public health complications. The present study focuses on the fabrication of a polyvinylidene fluoride (PVDF)-polyvinyl pyrrolidone (PVP) fiber membrane incorporated with varying loading (0, 0.5, 1.0, 1.5, and 2.0 wt%) of titanium dioxide (TiO2) nanoparticles via phase inversion technique to achieve hydrophilicity along with high selectivity for copper removal. The developed fibers were characterized based on scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), permeability, porosity, zeta potential, and contact angle. The improved membrane (with 1.0 wt% TiO2) concentration recorded the maximum flux (223 L/m2·h) and copper rejection (98.18%). Similarly, 1.0 wt% concentration of TiO2 nanoparticles made the membrane matrix more hydrophilic with the least contact angle of 50.01°. The maximum copper adsorption capacity of 69.68 mg/g was attained at 1.0 wt% TiO2 concentration. The experimental data of adsorption capacity were best fitted to the Freundlich isotherm model with R2 value of 0.99573. The hybrid membrane developed in this study has considerably eliminated copper from leachate and the concentration of copper in the permeate was substantially reduced to 0.044 mg/L, which is below standard discharge threshold.
TiO2-Based Nanocomposites Thin Film Having Boosted Photocatalytic Activity for Xenobiotics Water Pollution Remediation
Authors: Nicosia Angelo , Vento Fabiana , Di Mari Gisella Maria , D’Urso Luisa , Mineo Placido G.
Published: February 2021

Photocatalytic remediation represents a potential sustainable solution to the abatement of xenobiotic pollutants released within the water environment. Aeroxide® P25 titanium dioxide nanoparticles (TiO2 NPs) are well-known as one of the most efficient photocatalysts in several applications, and have also been investigated in water remediation as suspended powder. Recently, their application in the form of thin films has been revealed as a potential alternative to avoid time-consuming filtration processes. Polymers represent suitable substrates to immobilize TiO2 NPs, allowing further production of thin films that can be exploited as a photoactive coating for environmental remediation. Nevertheless, the methods adopted to immobilize TiO2 NPs on polymer matrix involve time-consuming procedures and the use of several reactants. Here, titanium dioxide-based nanocomposites (NCx) were obtained through a new approach based on Methyl Methacrylate in situ bulk polymerization and were compared with a blended mixture (BL). Their morphology and chemical–physical properties were investigated through Thermogravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), UV–Vis, and Raman spectroscopies. It was revealed that the in situ approach deeply influences the chemical–physical interactions between the polymer matrix and TiO2 NPs. Photocatalytic experiments revealed the boosted photodegradation activity of NCx thin films, induced by the in situ approach. The photodegradation of paraquat and acetaminophen was also ascertained.
The Role of Hypothalamic Inflammation in Diet-Induced Obesity and Its Association with Cognitive and Mood Disorders
Authors: Dionysopoulou Sofia , Charmandari Evangelia , Bargiota Alexandra , Vlahos Nikolaos F , Mastorakos George , Valsamakis Georgios
Published: February 2021

Obesity is often associated with cognitive and mood disorders. Recent evidence suggests that obesity may cause hypothalamic inflammation. Our aim was to investigate the hypothesis that there is a causal link between obesity-induced hypothalamic inflammation and cognitive and mood disorders. Inflammation may influence hypothalamic inter-connections with regions important for cognition and mood, while it may cause dysregulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis and influence monoaminergic systems. Exercise, healthy diet, and glucagon-like peptide receptor agonists, which can reduce hypothalamic inflammation in obese models, could improve the deleterious effects on cognition and mood.
Does the High Prevalence of Vitamin D Deficiency in African Americans Contribute to Health Disparities?
Authors: Ames Bruce N. , Grant William B. , Willett Walter C.
Published: February 2021

African Americans have higher incidence of, and mortality from, many health-related problems than European Americans. They also have a 15 to 20-fold higher prevalence of severe vitamin D deficiency. Here we summarize evidence that: (i) this health disparity is partly due to insufficient vitamin D production, caused by melanin in the skin blocking the UVB solar radiation necessary for its synthesis; (ii) the vitamin D insufficiency is exacerbated at high latitudes because of the combination of dark skin color with lower UVB radiation levels; and (iii) the health of individuals with dark skin can be markedly improved by correcting deficiency and achieving an optimal vitamin D status, as could be obtained by supplementation and/or fortification. Moderate-to-strong evidence exists that high 25-hydroxyvitamin D levels and/or vitamin D supplementation reduces risk for many adverse health outcomes including all-cause mortality rate, adverse pregnancy and birth outcomes, cancer, diabetes mellitus, Alzheimer’s disease and dementia, multiple sclerosis, acute respiratory tract infections, COVID-19, asthma exacerbations, rickets, and osteomalacia. We suggest that people with low vitamin D status, which would include most people with dark skin living at high latitudes, along with their health care provider, consider taking vitamin D3 supplements to raise serum 25-hydroxyvitamin D levels to 30 ng/mL (75 nmol/L) or possibly higher.
The Impact of Obesity and a High-Fat Diet on Clinical and Immunological Features in Systemic Lupus Erythematosus
Authors: Kono Masanori , Nagafuchi Yasuo , Shoda Hirofumi , Fujio Keishi
Published: February 2021

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with multiple organ involvement predominantly affecting women of childbearing age. Environmental factors, as well as genetic predisposition, can cause immunological disturbances that manifest as SLE. A habitual high-fat diet and obesity have recently been reported to play a role in the pathogenesis of autoimmune diseases. The frequency of obesity is higher in patients with SLE than in general populations. Vitamin D and adipokines, such as leptin and adiponectin, are possible mediators connecting obesity and SLE. Serum leptin and adiponectin levels are elevated in patients with SLE and can impact innate and adaptive immunity. Vitamin D deficiency is commonly observed in SLE. Because vitamin D can modulate the functionality of various immune cells, we review vitamin D supplementation and its effects on the course of clinical disease in this work. We also discuss high-fat diets coinciding with alterations of the gut microbiome, or dysbiosis. Contingent upon dietary habits, microbiota can be conducive to the maintenance of immune homeostasis. A high-fat diet can give rise to dysbiosis, and patients who are affected by obesity and/or have SLE possess less diverse microbiota. Interestingly, a hypothesis about dysbiosis and the development of SLE has been suggested and reviewed here.
The Contribution of Dietary Magnesium in Farm Animals and Human Nutrition
Authors: Pinotti Luciano , Manoni Michele , Ferrari Luca , Tretola Marco , Cazzola Roberta , Givens Ian
Published: February 2021

Magnesium (Mg) is a mineral that plays an essential role as cofactor of more than 300 enzymes. Mg in farm animals’ and human nutrition is recommended to avoid Mg deficiency, ensure adequate growth and health maintenance. Mg supplementation above the estimated minimum requirements is the best practice to improve farm animals’ performances (fertility and yield) and food products’ quality, since the performance of farm animals has grown in recent decades. Mg supplementation in pigs increases meat quality and sows’ fertility; in poultry, it helps to avoid deficiency-related health conditions and to improve meat quality and egg production by laying hens; in dairy cows, it serves to avoid grass tetany and milk fever, two conditions related to hypomagnesaemia, and to support their growth. Thus, Mg supplementation increases food products’ quality and prevents Mg deficiency in farm animals, ensuring an adequate Mg content in animal-source food. These latter are excellent Mg sources in human diets. Sub-optimal Mg intake by humans has several implications in bone development, muscle function, and health maintenance. This review summarizes the main knowledge about Mg in farm animals and in human nutrition.
Towards an Optimized Fetal DHA Accretion: Differences on Maternal DHA Supplementation Using Phospholipids vs. Triglycerides during Pregnancy in Different Models
Authors: Gázquez Antonio , Larqué Elvira
Published: February 2021

Docosahexaenoic acid (DHA) supplementation during pregnancy has been recommended by several health organizations due to its role in neural, visual, and cognitive development. There are several fat sources available on the market for the manufacture of these dietary supplements with DHA. These fat sources differ in the lipid structure in which DHA is esterified, mainly phospholipids (PL) and triglycerides (TG) molecules. The supplementation of DHA in the form of PL or TG during pregnancy can lead to controversial results depending on the animal model, physiological status and the fat sources utilized. The intestinal digestion, placental uptake, and fetal accretion of DHA may vary depending on the lipid source of DHA ingested by the mother. The form of DHA used in maternal supplementation that would provide an optimal DHA accretion for fetal brain development, based on the available data obtained most of them from different animal models, indicates no consistent differences in fetal accretion when DHA is provided as TG or PL. Other related lipid species are under evaluation, e.g., lyso-phospholipids, with promising results to improve DHA bioavailability although more studies are needed. In this review, the evidence on DHA bioavailability and accumulation in both maternal and fetal tissues after the administration of DHA supplementation during pregnancy in the form of PL or TG in different models is summarized.
Tick-Borne Hemoparasites of Sheep: A Molecular Research in Turkey
Authors: Ceylan Onur , Byamukama Benedicto , Ceylan Ceylan , Galon Eloiza May , Liu Mingming , Masatani Tatsunori , Xuan Xuenan , Sevinc Ferda
Published: February 2021

Tick-borne diseases (TBDs) indulge in severe economic losses in the livestock industry by adversely affecting the small ruminant breeding in tropical and subtropical zone countries, including Turkey. Turkey encompasses a wide land area representing diverse climatic conditions. The present study explored the presence and distribution of Babesia ovis, Theileria ovis, Theileria lestoquardi, Anaplasma ovis, Anaplasma phagocytophilum and the co-occurrence status of these pathogens. A total of 299 sheep blood samples were collected from fifteen provinces located in six different geographical regions in Turkey. PCR analyses were executed using species-specific primers based on Babesia ovis BoSSU rRNA, Theileria ovis ToSSU rRNA, Theileria lestoquardi 18S rRNA, Anaplasma ovis Major Surface Protein (AoMSP4), and Anaplasma phagocytophilum 16S rRNA genes. Overall, 219 (73.24%) sheep were found to be infected with at least one of the following protozoan and rickettsial pathogens; B. ovis, A. ovis,T. ovis, and A. phagocytophilum. Theileria lestoquardi was not detected in any blood sample. The global prevalence of B. ovis, A. ovis, T. ovis, and A. phagocytophilum was estimated to be 2.68%, 16.05%, 41.47%, and 57.19%, respectively. Besides this, dual (24.41%), triple (9.03%), and quadruple (0.67%) co-infections were detected in the study. Phylogenetic analysis revealed significant nucleotide sequence identities between the sequences obtained in this study and the sequences registered in the GenBank. This study provides relevant data regarding the predominance of ovine tick-borne protozoan and rickettsial agents in Turkey. A high molecular prevalence of tick-borne pathogens (TBPs) was identified in the study. This situation indicates that TBPs should be screened continuously, and necessary control measures should be taken to prevent diseases caused by tick-borne protozoan and rickettsial agents.
Distribution of Virulence Factors and Resistance Determinants in Three Genotypes of Staphylococcus argenteus Clinical Isolates in Japan
Authors: Aung Meiji Soe , Urushibara Noriko , Kawaguchiya Mitsuyo , Hirose Mina , Ike Miyo , Ito Masahiko , Kobayashi Nobumichi
Published: February 2021

Staphylococcus argenteus, a novel staphylococcal species independent of S. aureus, causes a wide spectrum of infectious diseases. As detection of this species from humans and animals has been increasingly reported worldwide, its growing virulence and drug resistance via external genetic determinants has become concerning. In this study, the prevalence and genetic characteristics of virulence factors and drug resistance determinants were investigated for 82 S. argenteus clinical isolates in Hokkaido, Japan, for a one-year period starting in August 2019. These S. argenteus isolates corresponded to 0.66% of the total number of S. aureus isolates collected in the same period. The most prevalent genotype was sequence type (ST) 2250 and staphylocoagulase (coa) genotype XId (45.1%, n = 37), followed by ST1223-coa XV (30.5%, n = 25) and ST2198-coa XIV (24.4%, n = 20). Panton-Valentine leukocidin genes (lukS-PV-lukF-PV) were identified in a single ST2250 isolate. Only ST1223 isolates had the enterotoxin gene cluster (egc-2), seb, and selw (detection rate; 100%, 60%, and 84%, respectively), while sec, sey, sel26-sel27, tst-1 were only detected in ST2250 isolates (detection rate; 10.8%, 100%, 67.6%, and 10.8%, respectively). ST2198 isolates harbored selx at a significantly higher rate (60%) than isolates of other STs. Although most of S. argenteus isolates were susceptible to antimicrobials examined, ST2198 showed higher resistance rates to penicillin, macrolides, and aminoglycosides than other STs, and it harbored various resistance genes such as blaZ, erm(C), msr(A), lnuA, and aac(6′)-Ie-aph(2″)-Ia. Only one ST2250 isolate possessed SCCmec-IVc, showing resistance to oxacillin. blaZ was the most prevalent determinant of resistance in the three STs and belonged to two plasmid groups and a chromosomal group, suggesting its diverse origin. lnu(A) in ST2198 isolates was assigned to a major cluster with various staphylococcal species. The present study indicates that the prevalence of virulence factors and drug resistance profile/determinants differ depending on the lineage (ST) of S. argenteus.
Comparison of Cytokine Expression Profile in Chikungunya and Dengue Co-Infected and Mono-Infected Patients’ Samples
Authors: Krishnan Saravana Murali , Mahalingam Jayashri , Sabarimurugan Shanthi , Muthu Thiruvengadam , Venkidasamy Baskar , Krishnasamy Kaveri , Sharma Ashutosh , Ramalingam Sathishkumar
Published: February 2021

Chikungunya (CHIKV) and Dengue (DENV) viruses cause an acute febrile illness which is hard to clinically differentiate and treat since both exhibit similar symptoms. Hence, this study was aimed at identifying the expression profiles of cytokines on co-infected samples and compare with CHIKV and DENV mono-infected samples. Serum samples of 292 suspected patients during 2009–2011 were analyzed. The presence of primary (IgM)/secondary (IgG) antibodies and early NS1 Dengue antigens were confirmed by capture ELISA. Molecular diagnosis and serotypes were discriminated by RT-PCR, confirmed by sequencing. All the plasma samples were assayed for cytokine expression by BDTM cytometry bead array (CBA) and compared with independent mono-infection viral load. Among the tested samples, 82 were confirmed as Dengue positive; 52 through IgM (17.8%), and 30 through IgG (10.2%). Additionally, 186 samples were confirmed as Chikungunya, 96 through IgM (32.6%) and 92 through IgG (31.5%) ELISA, respectively. Interestingly, 19 patients were co-infection positive in which, only 6 were confirmed for CHIKV and 7 for DENV by RT-PCR. Among 8 cytokines, IL-2, IL-8, IFNα, IFN γ, and IL-12 were found to be significantly different between co-infected and CHIKV mono-infected patients and correlated with viral load. DENV viral load was correlated with cytokine expression and a significant difference in IL-2 and IL-12 was observed between DENV mono-infected and DENV and CHIKV co-infected patients. Results indicated that apart from serological and molecular confirmation, cytokines could be used as a specific biomarker for the diagnosis of DENV and CHIKV. In the future, the role of independent cytokines can be determined to understand the pathogenesis and etiology of these dreadful diseases.
Alterations of Fucosyltransferase Genes and Fucosylated Glycans in Gastric Epithelial Cells Infected with Helicobacter pylori
Authors: Fan Ruyue , Han Xiurui , Gong Yanan , He Lihua , Xue Zhijing , Yang Yaming , Sun Lu , Fan Dongjie , You Yuanhai , Meng Fanliang , Yan Xiaomei , Zhang Maojun , Zhang Jianzhong
Published: February 2021

Helicobacter pylori (H. pylori) adhesion to human gastric epithelial cells is closely linked with fucosylated glycans. Therefore, investigation of fucosylation in the interaction of gastric epithelial cells with H. pylori is critical. In this study we used lectin microarrays to detect the expression of fucosylated glycans in gastric epithelial cells (GES-1) infected with H. pylori strains isolated from patients with different diseases including chronic gastritis, duodenal ulcers, and gastric cancer (each containing two strains) at 4 h. In addition, we investigated the time-course expression of fucosyltransferase (FUT) 1–6 genes in GES-1 cells stimulated with H. pylori strains at 0.5–8 h. At 4 h post-infection, Lotus, AAA, BC2LCN, PA-IIL, CNL and ACG lectins had increased signals in H. pylori-infected GES-1 cells compared to uninfected cells. Higher expression of FUT1 and FUT2 was detected in all H. pylori-infected GES-1 cells within 2 h, regardless of the H. pylori strain. In particular, the expression of FUT2 was higher in H. pylori-infected GES-1 cells with a higher fold change in levels of BC2LCN lectin specific to α1-2 linked fucose (Fuc) at 4 h. The results suggest that the high levels of α1, 2-linked Fuc synthesized by FUT1/2, might play a role in the preliminary stage of H. pylori infection. This provides us with pivotal information to understand the adhesion of H. pylori to human gastric epithelial cells.
Intestinal Viral Loads and Inactivation Kinetics of Livestock Viruses Relevant for Natural Casing Production: A Systematic Review and Meta-Analysis
Authors: Jelsma Tinka , Wijnker Joris J. , van der Poel Wim H. M. , Wisselink Henk J.
Published: February 2021

Animal intestines are the source of edible sausage casings, which are traded worldwide and may come from areas where notifiable infectious animal diseases are prevalent. To estimate the risks of virus contamination, knowledge about the quantity of virus and decimal reduction values of the standard preservation method by salting is of great importance. A literature search, based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, was performed in search engine CAB Abstracts to determine the viral load of 14 relevant animal viruses in natural casings or intestines. Only a very limited number of scientific publications per virus were found and viral loads in the intestines varied from high for ASFV (five publications), BVDV (3), CSFV (6), PPRV (3), RPV (2) and TGEV (3) to moderate for PEDV (2) and SVDV (3), low for HEV (2) and FMDV (5), very low for VESV (1) and negative for PrV (2) and VSV (1). PRRSV was found in intestines, however, viral titers were not published. Three viruses (BVDV, CSFV and PPRV) with high viral loads were selected to search for their inactivation kinetics. For casings, no inactivation data were found, however, thermal inactivation data of these viruses were available, but differed in quantity, quality and matrices. In conclusion, important data gaps still exist when it comes to the quantitative inactivation of viruses in sausage casings or livestock intestines.
Informing Patients about Biosimilar Medicines: The Role of European Patient Associations
Authors: Vandenplas Yannick , Simoens Steven , Van Wilder Philippe , Vulto Arnold G. , Huys Isabelle
Published: February 2021

Biosimilar medicines support the sustainability of national healthcare systems, by reducing costs of biological therapies through increased competition. However, their adoption into clinical practice largely depends on the acceptance of healthcare providers and patients. Patients are different from health care professionals (HCPs), who are informing themselves professionally. For patients, the biosimilar debate only becomes actual when they are confronted with disease and drug choices. This paper provides a literature review on how patients are and should be informed about biosimilars, searching in scientific databases (i.e., Medline, Embase). Several large surveys have shown a lack of knowledge and trust in biosimilars among European patients in recent years. This review identified five main strategies to inform patients about biosimilars: (1) provide understandable information, (2) in a positive and transparent way, (3) tailored to the individual’s needs, (4) with one voice, and (5) supported by audiovisual material. Moreover, the importance of a multistakeholder approach was underlined by describing the role of each stakeholder. Patients are a large and diffuse target group to be reached by educational programs. Therefore, patient associations have become increasingly important in correctly informing patients about biosimilar medicines. This has led to widespread biosimilar information for patients among European patient associations. Therefore, a web-based screening of European Patients’ Forum (EPF) and International Alliance of Patients’ Organizations (IAPO) member organizations on publicly available information about biosimilars was performed. We found that the level of detail, correctness, and the tone of the provided information varied. In conclusion, it is paramount to set up a close collaboration between all stakeholders to communicate, develop, and disseminate factual information about biosimilars for patients.
Live Vaccinia Virus-Coated Microneedle Array Patches for Smallpox Vaccination and Stockpiling
Authors: Choi In-Jeong , Cha Hye-Ran , Hwang Su Jin , Baek Seung-Ki , Lee Jae Myun , Choi Seong-O
Published: February 2021

Although smallpox has been eradicated globally, the potential use of the smallpox virus in bioterrorism indicates the importance of stockpiling smallpox vaccines. Considering the advantages of microneedle-based vaccination over conventional needle injections, in this study, we examined the feasibility of microneedle-based smallpox vaccination as an alternative approach for stockpiling smallpox vaccines. We prepared polylactic acid (PLA) microneedle array patches by micromolding and loaded a second-generation smallpox vaccine on the microneedle tips via dip coating. We evaluated the effect of excipients and drying conditions on vaccine stability in vitro and examined immune responses in female BALB/c mice by measuring neutralizing antibodies and interferon (IFN)-γ-secreting cells. Approximately 40% of the virus titer was reduced during the vaccine-coating process, with or without excipients. At −20 °C, the smallpox vaccine coated on the microneedles was stable up to 6 months. Compared to natural evaporation, vacuum drying was more efficient in improving the smallpox vaccine stability. Microneedle-based vaccination of the mice elicited neutralizing antibodies beginning 3 weeks after immunization; the levels were maintained for 12 weeks. It significantly increased IFN-γ-secreting cells 12 weeks after priming, indicating the induction of cellular immune responses. The smallpox-vaccine-coated microneedles could serve as an alternative delivery system for vaccination and stockpiling.
Formulation and In Vitro and In Silico Characterization of “Nano-in-Micro” Dry Powder Inhalers Containing Meloxicam
Authors: Party Petra , Bartos Csilla , Farkas Árpád , Szabó-Révész Piroska , Ambrus Rita
Published: February 2021

Pulmonary delivery has high bioavailability, a large surface area for absorption, and limited drug degradation. Particle engineering is important to develop inhalable formulations to improve the therapeutic effect. In our work, the poorly water-soluble meloxicam (MX) was used as an active ingredient, which could be useful for the treatment of non-small cell lung cancer, cystic fibrosis, and chronic obstructive pulmonary disease. We aimed to produce inhalable “nano-in-micro” dry powder inhalers (DPIs) containing MX and additives (poly-vinyl-alcohol, leucine). We targeted the respiratory zone with the microcomposites and reached a higher drug concentration with the nanonized active ingredient. We did the following investigations: particle size analysis, morphology, density, interparticular interactions, crystallinity, in vitro dissolution, in vitro permeability, in vitro aerodynamics (Andersen cascade impactor), and in silico aerodynamics (stochastic lung model). We worked out a preparation method by combining wet milling and spray-drying. We produced spherical, 3–4 µm sized particles built up by MX nanoparticles. The increased surface area and amorphization improved the dissolution and diffusion of the MX. The formulations showed appropriate aerodynamical properties: 1.5–2.4 µm MMAD and 72–76% fine particle fraction (FPF) values. The in silico measurements proved the deposition in the deeper airways. The samples were suitable for the treatment of local lung diseases.
Utilizing Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) to Analyze Interstitial Fluid Flow and Transport in Glioblastoma and the Surrounding Parenchyma in Human Patients
Authors: Chatterjee Krishnashis , Atay Naciye , Abler Daniel , Bhargava Saloni , Sahoo Prativa , Rockne Russell C. , Munson Jennifer M.
Published: February 2021

Background: Glioblastoma (GBM) is the deadliest and most common brain tumor in adults, with poor survival and response to aggressive therapy. Limited access of drugs to tumor cells is one reason for such grim clinical outcomes. A driving force for therapeutic delivery is interstitial fluid flow (IFF), both within the tumor and in the surrounding brain parenchyma. However, convective and diffusive transport mechanisms are understudied. In this study, we examined the application of a novel image analysis method to measure fluid flow and diffusion in GBM patients. Methods: Here, we applied an imaging methodology that had been previously tested and validated in vitro, in silico, and in preclinical models of disease to archival patient data from the Ivy Glioblastoma Atlas Project (GAP) dataset. The analysis required the use of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), which is readily available in the database. The analysis results, which consisted of IFF flow velocity and diffusion coefficients, were then compared to patient outcomes such as survival. Results: We characterized IFF and diffusion patterns in patients. We found strong correlations between flow rates measured within tumors and in the surrounding parenchymal space, where we hypothesized that velocities would be higher. Analyzing overall magnitudes indicated a significant correlation with both age and survival in this patient cohort. Additionally, we found that neither tumor size nor resection significantly altered the velocity magnitude. Lastly, we mapped the flow pathways in patient tumors and found a variability in the degree of directionality that we hypothesize may lead to information concerning treatment, invasive spread, and progression in future studies. Conclusions: An analysis of standard DCE-MRI in patients with GBM offers more information regarding IFF and transport within and around the tumor, shows that IFF is still detected post-resection, and indicates that velocity magnitudes correlate with patient prognosis.
Accurate Power-Efficient Format-Scalable Multi-Parallel Optical Digital-to-Analogue Conversion
Authors: Nazarathy Moshe , Tomkos Ioannis
Published: February 2021

In optical transmitters generating multi-level constellations, optical modulators are preceded by Electronic Digital-to-Analog-Converters (eDAC). It is advantageous to use eDAC-free Optical Analog to Digital Converters (oDAC) to directly convert digital bitstreams into multilevel PAM/QAM optical signals. State-of-the-art oDACs are based on Segmented Mach-Zehnder-Modulators (SEMZM) using multiple modulation segments strung along the MZM waveguides to serially accumulate binary-modulated optical phases. Here we aim to assess performance limits of the Serial oDACs (SEMZM) and introduce an alternative improved Multi-Parallel oDAC (MPoDAC) architecture, in particular based on arraying multiple binary-driven MZMs in parallel: Multi-parallel MZM (MPMZM) oDAC. We develop generic methodologies of oDAC specification and optimization encompassing both SEMZM and MPMZM options in Direct-Detection (DD) and Coherent-Detection (COH) implementations. We quantify and compare intrinsic performance limits of the various serial/parallel DD/COH subclasses for general constellation orders, comparing with the scant prior-work on the multi-parallel option. A key finding: COH-MPMZM is the only class synthesizing ‘perfect’ (equi-spaced max-full-scale) constellations while maximizing energy-efficiency-SEMZM/MPMZM for DD are less accurate when maximal energy-efficiency is required. In particular, we introduce multiple variants of PAM4|8 DD and QAM16|64 COH MPMZMs, working out their accuracy vs. energy-efficiency-and-complexity tradeoffs, establishing their format-reconfigurability (format-flexible switching of constellation order and/or DD/COH).
Effects of Lacto-Fermented Agricultural By-Products as a Natural Disinfectant against Post-Harvest Diseases of Mango (Mangifera indica L.)
Authors: Ranjith Fernando H. , Muhialdin Belal J. , Yusof Noor L. , Mohammed Nameer K. , Miskandar Muhammad H. , Hussin Anis Shobirin Meor
Published: February 2021

Background: the antagonism activity of lactic acid bacteria metabolites has the potential to prevent fungal growth on mango. Methods: the potential of developing natural disinfectant while using watermelon rinds (WR), pineapple (PP), orange peels (OP), palm kernel cake (PKC), and rice bran (RB), via lacto-fermentation was investigated. The obtained lactic acid bacteria (LAB) metabolites were then employed and the in vitro antifungal activity toward five spoilage fungi of mango was tested through liquid and solid systems. Besides, the effect of the produced disinfectant on the fungal growth inhibition and quality of mango was investigated. Results: the strains Lactobacillus plantarum ATCC8014 and Lactobacillus fermentum ATCC9338 growing in the substrates PKC and PP exhibited significantly higher in vitro antifungal activity against Colletotrichum gloeosporioides and Botryodiplodia theobromae as compared to other tested LAB strains and substrates. The in-situ results demonstrated that mango samples that were treated with the disinfectant produced from PKC fermented with L. plantarum and L. fermentum had the lowest disease incidence and disease severity index after 16 days shelf life, as well as the lowest conidial concentration. Furthermore, PKC that was fermented by L. fermentum highly maintained the quality of the mango. Conclusions: lactic acid fermentation of PKC by L. fermentum demonstrated a high potential for use as a natural disinfectant to control C. gloeosporioides and B. theobromae on mango.
Effects of Extra Virgin Olive Oil Polyphenols on Beta-Cell Function and Survival
Authors: Marrano Nicola , Spagnuolo Rosaria , Biondi Giuseppina , Cignarelli Angelo , Perrini Sebastio , Vincenti Leonardo , Laviola Luigi , Giorgino Francesco , Natalicchio Annalisa
Published: February 2021

Extra virgin olive oil (EVOO) is a major component of the Mediterranean diet and is appreciated worldwide because of its nutritional benefits in metabolic diseases, including type 2 diabetes (T2D). EVOO contains significant amounts of secondary metabolites, such as phenolic compounds (PCs), that may positively influence the metabolic status. In this study, we investigated for the first time the effects of several PCs on beta-cell function and survival. To this aim, INS-1E cells were exposed to 10 μM of the main EVOO PCs for up to 24 h. Under these conditions, survival, insulin biosynthesis, glucose-stimulated insulin secretion (GSIS), and intracellular signaling activation (protein kinase B (AKT) and cAMP response element-binding protein (CREB)) were evaluated. Hydroxytyrosol, tyrosol, and apigenin augmented beta-cell proliferation and insulin biosynthesis, and apigenin and luteolin enhanced the GSIS. Conversely, vanillic acid and vanillin were pro-apoptotic for beta-cells, even if they increased the GSIS. In addition, oleuropein, p-coumaric, ferulic and sinapic acids significantly worsened the GSIS. Finally, a mixture of hydroxytyrosol, tyrosol, and apigenin promoted the GSIS in human pancreatic islets. Apigenin was the most effective compound and was also able to activate beneficial intracellular signaling. In conclusion, this study shows that hydroxytyrosol, tyrosol, and apigenin foster beta-cells’ health, suggesting that EVOO or supplements enriched with these compounds may improve insulin secretion and promote glycemic control in T2D patients.
A Quarter Century History of ATML1 Gene Research
Authors: Iida Hiroyuki , Takada Shinobu
Published: February 2021

The cloning of the ATML1 gene, encoding an HD-ZIP class IV transcription factor, was first reported in 1996. Because ATML1 mRNA was preferentially detected in the shoot epidermis, cis-regulatory sequences of ATML1 have been used to drive gene expression in the outermost cells of the shoot apical meristem and leaves, even before the function of ATML1 was understood. Later studies revealed that ATML1 is required for developmental processes related to shoot epidermal specification and differentiation. Consistent with its central role in epidermal development, ATML1 activity has been revealed to be restricted to the outermost cells via several regulatory mechanisms. In this review, we look back on the history of ATML1 research and provide a perspective for future studies.
A Quality Integrated Fuzzy Inference System for the Reliability Estimating of Fluorochemical Engineering Processes
Authors: Xue Feng , Li Xintong , Zhou Kun , Ge Xiaoxia , Deng Weiping , Chen Xu , Song Kai
Published: February 2021

Hypertoxic materials make it critical to ensure the safety of the fluorochemical engineering processes. This mainly depends on the over maintenance or the manual operations due to the lack of precise models and mechanism knowledge. To quantify the deviations of the operating variables and the product quality from their target values at the same time and to overcome the measurement delay of the product quality, a novel quality integrated fuzzy inference system (QFIS) was proposed to estimate the reliability of the operation status as well as the product quality to enhance the performance of the safety monitoring system. To this end, a novel quality-weighted multivariate inverted normal loss function was proposed to quantify the deviation of the product quality from the target value to overcome the measurement delay. Vital safety process variables were identified according to the expert knowledge. Afterward, the quality loss and the vital variables were inputs to an elaborate fuzzy inference system to estimate the process reliability of the fluorochemical engineering processes. By integrating the abundant expert knowledge and a data-driven quality prediction model to design the fuzzy rules of QFIS, not only the operation reliability but also the product quality can be monitored on-line. Its superiority in estimating system reliability has been strongly proved by the application of a real fluorochemical engineering process located in East China. Moreover, the application of the Tennessee Eastman process also confirmed its generalization performance for other complicated black-box chemical processes.
Steganography and Steganalysis in Voice over IP: A Review
Authors: Wu Zhijun , Guo Junjun , Zhang Chenlei , Li Changliang
Published: February 2021

The rapid advance and popularization of VoIP (Voice over IP) has also brought security issues. VoIP-based secure voice communication has two sides: first, for legitimate users, the secret voice can be embedded in the carrier and transmitted safely in the channel to prevent privacy leakage and ensure data security; second, for illegal users, the use of VoIP Voice communication hides and transmits illegal information, leading to security incidents. Therefore, in recent years, steganography and steganography analysis based on VoIP have gradually become research hotspots in the field of information security. Steganography and steganalysis based on VoIP can be divided into two categories, depending on where the secret information is embedded: steganography and steganalysis based on voice payload or protocol. The former mainly regards voice payload as the carrier, and steganography or steganalysis is performed with respect to the payload. It can be subdivided into steganography and steganalysis based on FBC (fixed codebook), LPC (linear prediction coefficient), and ACB (adaptive codebook). The latter uses various protocols as the carrier and performs steganography or steganalysis with respect to some fields of the protocol header and the timing of the voice packet. It can be divided into steganography and steganalysis based on the network layer, the transport layer, and the application layer. Recent research results of steganography and steganalysis based on protocol and voice payload are classified in this paper, and the paper also summarizes their characteristics, advantages, and disadvantages. The development direction of future research is analyzed. Therefore, this research can provide good help and guidance for researchers in related fields.
Simultaneous Hand–Eye and Intrinsic Calibration of a Laser Profilometer Mounted on a Robot Arm
Authors: Pavlovčič Urban , Arko Peter , Jezeršek Matija
Published: February 2021

A method for simultaneous laser profilometer and hand–eye calibration in relation to an industrial robot as well as its implementation is presented. In contrast to other methods, the new calibration procedure requires the measurement of only one reference geometry to calculate all the transformation parameters. The reference geometry is measured with a laser profilometer from 15 different poses. The intrinsic parameters of the profilometer, as well as the extrinsic (hand–eye) parameters, are then numerically optimized to achieve the minimum deviation between the reference and the measured geometry. The method was characterized with experiments that revealed a standard deviation of the displacements between the reference geometry after the calibration of less than 0.105 mm in the case of using the robot-arm actuator and 0.046 mm in case of using a 5-axis CNC milling machine. The entire procedure, including measurement and calculation, can be completely automated and lasts less than 10 min. This opens up possibilities for regular on-site recalibration of the entire system.
Multi-Task End-to-End Self-Driving Architecture for CAV Platoons
Authors: Huch Sebastian , Ongel Aybike , Betz Johannes , Lienkamp Markus
Published: February 2021

Connected and autonomous vehicles (CAVs) could reduce emissions, increase road safety, and enhance ride comfort. Multiple CAVs can form a CAV platoon with a close inter-vehicle distance, which can further improve energy efficiency, save space, and reduce travel time. To date, there have been few detailed studies of self-driving algorithms for CAV platoons in urban areas. In this paper, we therefore propose a self-driving architecture combining the sensing, planning, and control for CAV platoons in an end-to-end fashion. Our multi-task model can switch between two tasks to drive either the leading or following vehicle in the platoon. The architecture is based on an end-to-end deep learning approach and predicts the control commands, i.e., steering and throttle/brake, with a single neural network. The inputs for this network are images from a front-facing camera, enhanced by information transmitted via vehicle-to-vehicle (V2V) communication. The model is trained with data captured in a simulated urban environment with dynamic traffic. We compare our approach with different concepts used in the state-of-the-art end-to-end self-driving research, such as the implementation of recurrent neural networks or transfer learning. Experiments in the simulation were conducted to test the model in different urban environments. A CAV platoon consisting of two vehicles, each controlled by an instance of the network, completed on average 67% of the predefined point-to-point routes in the training environment and 40% in a never-seen-before environment. Using V2V communication, our approach eliminates casual confusion for the following vehicle, which is a known limitation of end-to-end self-driving.
The Lessons of Public–Private Collaboration for Energy Regeneration in a Spanish City. The Case of Txantrea Neighbourhood (Pamplona)
Authors: López Rodríguez Ramón , Durán Villa Francisco R. , Piñeira Mantiñán María José
Published: February 2021

Although the transformation of the energy model is a global problem, cities take on a leading role in the process as they are important consumers of energy resources. For years, local authorities have been implementing various energy saving initiatives. The transport and equipment renovation sectors, as well as the residential renovation sector, are the focus of the objectives of local strategies to reduce greenhouse gas (GHG) emissions. In this article we analyse the role of local government in the energy transition, its relationship with other public–private territorial agents, and the involvement of citizens in the design and implementation of their initiatives. To this end, we will focus on the case of Pamplona, a city in the north of Spain with a policy aimed at low-energy, renewable, decentralised, and sustainable restructuring. We will analyse the heating districts of its Txantrea neighbourhood. By means of qualitative information obtained through interviews, we will see how the project has been carried out, which actors participated, the problems encountered, and how it has impacted savings, the improvement of quality of life of the residents, and urban and energetic regeneration processes.
Renewable Energy Use and Ecological Footprints Mitigation: Evidence from Selected South Asian Economies
Authors: Xue Lian , Haseeb Mohammad , Mahmood Haider , Alkhateeb Tarek Tawfik Yousef , Murshed Muntasir
Published: February 2021

Fossil fuel-dependency has induced a trade-off between economic growth and environmental degradation across the developing nations in particular. Against this backdrop, this study aims to evaluate the impacts of renewable energy use on the ecological footprints in the context of four South Asian fossil fuel-dependent nations: Bangladesh, India, Pakistan, and Sri Lanka. The econometric analysis involves the use of recently developed methods that account for cross-sectional dependency, slope heterogeneity, and structural break issues in the data. The results reveal that renewable energy consumption reduces the ecological footprints while nonrenewable energy use boosts the ecological footprints. The results also confirm the validity of the environmental Kuznets curve and pollution haven hypotheses for the panel of the South Asian nations. Besides, foreign direct investment inflows are found to degrade the environment while higher institutional quality improves it. Furthermore, unidirectional causalities are run from overall energy use, economic growth, and institutional quality to ecological footprints. At the same time, bidirectional associations between foreign direct investment inflows and ecological footprints are also ascertained. The overall findings highlight the pertinence of reducing fossil fuel-dependency, enhancing economic growth, restricting dirty foreign direct investment inflows, and improving institutional quality to ensure environmental sustainability across South Asia.