Lemon balm extracts by dry plant material of Melissa officinalis were tested against their efficacy against for different fungal species Alternaria alternata, Fusarium oxysporum, Aspergillus flavus and Beauveria bassiana. The aqueous phase of the extract was evaluated for antioxidant, antifungal and also anti-aflatoxigenic activity. A synergism evaluation was also performed concerning, the small quantity of lemon balm polar essential oil compounds extracted into the infusion and the water soluble compounds in the extract. The experiments were conducted in solid cultures and the growth inhibition was demonstrated by measuring mycelial diameter. Additionally, the effect on conidia production was also demonstrated. Lemon balm was also used for in situ test on Pistachia vera seed against Aspergillus flavus growth and aflatoxin production. Results revealed enhancement of fungal growth by lemon balm extracts however total inhibition of aflatoxins production on Pistachia vera seeds was observed, and both actions were tried to attributed to volatile and water soluble compounds identified based on GC/MS, HPLC/DAD and LC/MS, and the observed antioxidant activity. Volatile and water - soluble compounds found to be in absolute synergism in mycelium growth enhancement and the observed anti-aflatoxigenic activity addressed to the high antioxidant activity observed and synergistic action between the other water soluble phenolic compounds identified in the extract. The findings of this study underline the high biological active potential of lemon balm extracts under various screening test since for the first time full phytochemical analysis of lemon balm extracts.

The feasibility of using full ion kinetics, instead of gyrokinetics, in simulating low-frequency Ion-Temperature-Gradient (ITG) instabilities in tokamaks has recently been demonstrated by Sturdevant et al. [Physics of Plasmas 24, 081207 (2017)]. In that work, a variational integrator was developed to integrate the full orbits of ions in toroidal geometry, which proved to be accurate in capturing both the short-time scale cyclotron motion and long time scale drift motion. The present work extends that work in three aspects. First, we implement a relatively simple full orbit integrator, the Boris integrator, and demonstrate that the accuracy of this integrator is also sufficient for simulation of ITG instabilities. Second, the equilibrium magnetic configuration is extended to general toroidal configuration specified numerically, enabling simulation of realistic equilibria reconstructed from tokamak experiments. Third, we extend that work to the nonlinear regime and investigate the nonlinear saturation of ITG instabilities. To verify the new numerical implementation of the orbit integrator and magnetic configuration, the linear electrostatic ITG frequency and growth rate are compared with those given in Sturdevant's work and good agreement is found.

The mitigation of NLOS (non-line-of-sight) propagation conditions is one of main challenges in wireless signals based indoor localization. When RFID localization technology is applied in applications, RSS fluctuates frequently due to the shade and multipath effect of RF signal, which could result in localization inaccuracy. In particularly, when tags carriers are walking in LOS (line-of-sight) and NLOS hybrid environment, great attenuation of RSS will happen, which would result in great location deviation. The paper proposes an IMU-assisted (Inertial Measurement Unit) RFID based indoor localization in LOS/NLOS hybrid environment. The proposed method includes three improvements over previous RSS based positioning methods: IMU aided RSS filtering, IMU aided LOS/NLOS distinguishing and IMU aided LOS/NLOS environment switching. Also, CRLB (Cramér-Rao Low Bound) is calculated to prove theoretically that indoor positioning accuracy for proposed method in LOS/NLOS mixed environment is higher than position precision of only use RSS information. Simulation and experiments are conducted to show that proposed method can reduce the mean positioning error to around 3 meters without site survey.

Document deskewing is a fundamental problem in document image processing. While existing methods have limitations, such as Hough Line Transformation that can deskew images upside down, and Deep Learning models that require huge amounts of human labour and computational resources and still fail to deskew while taking care of orientation, OCR-based methods also struggle to read text when it is tilted. In this paper, we propose a novel, simple, cost-effective deep learning method for fixing the skew and orientation of documents. Our approach reduces the search space for the machine learning model to predict whether an image is upside down or not, avoiding the huge search space of predicting an angle between 0 and 360. We finetuned a MobileNetV2 model, which was pre-trained on imagenet, using only 200 images and achieve good results. This method is useful for automation-based tasks, such as data extraction using OCR technology, and can greatly reduce manual labour.

Multiferroics, showing both ferroelectric and magnetic order, are promising candidates for future electronic devices. Especially, the fundamental understanding of ferroelectric switching is of key relevance for further improvements, which however is rarely reported in literature. On a prime example for a spin-driven multiferroic, LiCuVO₄, we present an extensive study of the ferroelectric order and the switching behavior as function of external electric and magnetic fields. From frequency-dependent polarization switching and using the Ishibashi-Orihara theory, we deduce the existence of ferroelectric domains and domain-walls. These have to be related to counterclockwise and clockwise spin-spirals leading to the formation of multiferroic domains. A novel measurement – multiferroic hysteresis loop – is established to analyze the electrical polarization simultaneously as a function of electrical and magnetic fields. This technique allows characterizing the complex coupling between ferroelectric and magnetic order in multiferroic LiCuVO₄.

Engineering of drug nanocarriers combining fine-tuned mucoadhesive/mucopenetrating properties is currently being investigated to ensure more efficient mucosal drug delivery. Aiming to improve the transmucosal delivery of hydrophobic drugs, we designed a novel kind nanogel produced by the self-assembly of amphiphilic chitosan graft copolymers ionotropically crosslinked with sodium tripolyphosphate. In this work, we synthesized for the first time chitosan-g-poly(methyl methacrylate) nanoparticles thiolated by the conjugation of N-acetyl cysteine. First, we confirmed that both non-crosslinked and crosslinked nanoparticles in the 0.05-0.1% w/v concentration range display very good cell compatibility in two cell lines that are relevant to oral delivery, Caco2 cells that mimic the intestinal epithelium and HT29-MTX cells that produce mucin. Then, we evaluated the effect of crosslinking, nanoparticle concentration and thiolation on the permeability in vitro utilizing monolayers of (i) Caco2 and (ii) Caco2:HT29-MTX cells (9:1 cell number ratio). Results confirmed that the ability of the nanoparticles to cross Caco2 monolayer was affected by the crosslinking. In addition, thiolated nanoparticles interact more strongly with mucin, resulting in a decrease of the apparent permeability coefficient (Papp) compared to the pristine nanoparticles. Moreover, for all the nanoparticles, higher concentration resulted in lower Papp suggesting indicating that the transport pathways could undergo saturation.

The sustainable development of our world has gain particular attention of a wide range of decisional factors, civil society, business sector, and scientific community, seeing that the prosperity of people and society is possible with the aid of sustained and inclusive economic growth of all countries and regions. Educational environment has a decisive impact on changes in the way that societies are coping with national, regional, and global challenges and opportunities brought by sustainable development. Looking at the implications of HE on the progress of society, the paper addressed the lack of HE institutional capacity to integrate the principles and practices of sustainable development into all aspects of education and learning. The scope of research problem was bounded on the capability of HEI as organization and school to act as entrepreneurial university by combining the scope of its responsibility within the value chain through a practical and effective mechanism needed to align the strategy with sustainable development goals (SDGs). Embarking on the path of SDGs requires HEI to design, launch, implement, and customize specific processes architectures to govern the advance of sustainability approach. The authors applied the process scoping diagram to capture and conceptualize the educational model needed to guide the HEI through the process of change to embrace sustainability into organizational culture and daily operations. It has been used the SIPOC method (Supplier, Input, Process, Output, Customer) with Visio software tool to articulate processes relationships embedded in the educational model of HEI. The benefits relied on the organized view of the work processes needed to be performed to incorporate SDGs into the strategy of any entrepreneurial HEI. Finally, the authors shared their views on the scalability of the model which may be customized and harmonized in accordance with different HE circumstances and priorities. Implementing the proposed educational model requires long-term institutional commitment, transparency, continuous performance improvement, and communicating the strategy for SDGs and its achievements to wider stakeholders.

This study is designed to assess and improve apparel sewing section efficiency and productivity throughout line balancing. Apparel industry is one of the oldest and among the most global industry, being primarily concerned with the design and production of cloth and their supply. The central process in apparel manufacturing is the joining together of components which is known as the sewing process , which is the most labour intensive type of manufacturing process .Proper utilization of resources in garment sewing section is more critical to enhance the performance of the apparel industry by reducing production cost and minimizing wastage. For effective utilization of resources in the sewing section, good line balancing is important to increase productivity and production efficiency. This research was a design to analyse and improve the assembling line in the case of Telaje garment manufacturing and sales plc. The study was first conduct observations in the production floor and start work with the selection of sewing line in the garment production process. Among the nine lines of the factory select one on the production floor and one garment ordered product known as five pocket men’s jeans trousers are selected. For this study, both qualitative and quantitative research approaches were employed. Both primary and secondary data sources are used to detail the collected relevant data to understand the current efficiency scenario of the factory. The main challenges to minimizing line efficiency and productivity with the expected performance measurement are improper utilization of resources and improper implementation of line balancing in sewing section, therefore this thesis work shows that the bottleneck process and consequence solution will be searched, and finally significantly improving the productivity by 418 unit products/ day and, hence the efficiency will increase from 28.83% to 50.04% of the line

The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was isolated in 2012 and is well known to cause the respiratory syndrome. The orf1ab gene is known to mediate MERS-CoV replication. In this study, we have discussed the in silico prediction of potential siRNAs targeting MERS-CoV-orf1ab gene for antiviral therapeutics. To identify the potential siRNAs, various factors were considered. We have excluded the siRNAs with off-target effects and potential binding with human mRNAs. By using available softwares, total twenty-one functional, off-target reduced potential siRNA were selected from four hundred and sixty-two siRNAs based on greater potency and specificity. We have tested only seven siRNAs initially to evaluate their performance by reverse transfection approach by lipofectamine mediated delivery in Vero cells. The evaluation results showed no cytotoxicity at various concentrations of siRNAs used. The results obtained in this study provided preliminary information about the cytotoxicity which will help us to further evaluate siRNAs in other cell cultures to find out the replication inhibition efficiency of MERS-CoV. Finally, it is concluded that the in silico prediction and designing resulted in filtration and selection of potential siRNAs with high accuracy, efficiency, and strength which can be further utilized for the development of oligonucleotide-based therapeutics.

Patient-derived xenograft (PDX) models are created by engraftment of patients’ tumor tissues into immunocompetent mice. Since PDX model keep the characteristics of primary patient’s tumor such as gene expression profiles and drug sensitivity, it now becomes most reliable in vivo human cancer model. The engraftment rate are increased with the introduction of NOD/Scid based immunocompromised mice, especially, NK cell defective NOD strains such as NOD/Scid/IL2Rγnu (NOG/ NSG) mice and NOD/Scid/Jak3null (NOJ) mice. Success ratio differs from the origin of tumor: Gastrointestinal tumors tend to higher success rate and breast cancer is lower. Subcutaneous transplantation is most popular method to establish PDX, but some tumor needs orthotropic or renal capsule transplantation, and human hormone treatment is needed to establish hormone dependent cancers such as prostate and breast cancer. PDX library with patient’s clinical data, gene-expression patterns, mutational status, drug responsiveness and tumor architecture will be the powerful tool for developing specific biomarker and novel individualized therapy and establishing precision cancer medicine.

This paper presents findings of a study on continuous feed-in management and continuous synthetic inertia contribution with wind turbines. A realistic case study, based on real measurements, is outlined. A wind turbine feeds into a weak feeder, such that its power has to be adapted to the permissible loading of this feeder. At the same time the wind turbine is to provide inertia to the grid by applying the previously published variable inertia constant controller. It is discussed that optimal grid utilisation and simultaneous inertia contribution are mandatory for the frequency control in power systems that are heavily penetrated with renewable energies. The study shows that continuous feed-in management can be combined well with continuous inertia provision. There are hardly any negative consequences for the wind turbine. The benefits for the grid are convincing, both in terms of increased system utilisation and in terms of provided inertia. It is concluded that wind turbines can enhance angular stability in a power system to a larger extent than conventional power plants.

The protection of electronics against environmental influences and mechanical loads is important for integration of conventional electronics in textile conductive tapes. For this purpose, the sensors on the tapes are molded with plastic locally. This process step is recognized in the injection molding process. The molding compound is then later selected depending on: The field of application, the parameters of the manufacturing process and the textile tape properties. We have designed a mould for liquid silicone (LSR) as well as for the textile and electronic insertions. The cavities are sealed by a local compression of the textile and the two inserts are positioned with position pins representing the main aspect of the mould design. The sampling tool and the process parameter optimization are mainly based on the material properties of the silicone and the mechanical sensitivity of the inserts. To reduce the deformation of the circuit boards by the melt front and ensuring the functionality of the electronics a low-pressure process is used.

Inorganic nanoparticles are utilized for therapeutic, diagnostic, or in combination, theranostic purposes. The latter involves simultaneous sensing, imaging, or tracking of drug delivery. Furthermore, these nanoparticles can differ in their morphologies, which affect outcomes such as the effectiveness of hyperthermia, induction, drug loading, circulation time by escaping the body's immune system, imaging modality clarity, and biosensing. However, design of these theranostics is limited by the lack of a method to predict their therapeutic efficacy. Herein, we report a simple and novel computational approach via algebraic and geometric calculations of surface area (SA) to volume (V) ratios (SA:V) which can help predict the efficacy of the inorganic nanoparticles of the investigated morphologies. The approach comprises a coding platform for the program and uses Python 3 on a Windows 10 operating system. Analyses of 29 polyhedral morphologies that inorganic nanoparticles could assume ex silico showed that only particular concave and convex morphologies in this size regime are more productive over the standard sizes as well as a few noted in literature for baseline comparison. Our results provide a method that can aid in predicting the efficacy of inorganic nanoparticles with certain morphology giving rise to their fundamental basis and eventual implementation ex silico.

In an effort to discover an effective and selective antitumour agent, synthesis and anti-cancer potential of 4-(pyridin-4-yl)-6-(thiophen-2-yl)pyrimidin-2(1H)-one (SK-25), which has been reported earlier by us with significant cytotoxicity towards MiaPaCa-2 malignant cells, with an IC₅₀ value of 1.95 μM and was found to instigate apoptosis. In the present study, the antitumour efficacy of SK-25 was investigated on Ehrlich ascites tumour (solid), Sarcoma 180 (solid) tumour and Ehrlich ascites carcinoma. The compound was found to inhibit tumour development by 94.71% in Ehrlich ascites carcinoma (EAC), 59.06% in Ehrlich tumour (ET, solid) and 45.68% in Sarcoma-180 (solid) at 30 mg/kg dose. Additionally, SK-25 was established to be non-toxic at a maximum tolerated dose of 1000 mg/kg in acute oral toxicity in Swiss-albino mice. Computer-based predictions also show that the compounds could have an interesting DMPK profile. The current study provides insight for further investigation of the antitumour potential of the molecule.

The estrogen hormone receptor (ER) mediated gene expression mainly regulate the development and physiology of primary and secondary reproductive system alongside bone-forming, metabolism and behaviour. Over-expressed ER is associated with several pathological conditions and play a key role in breast cancer occurrence, progression and metastasis. Hibiscus sabdariffa L. or roselle is a rich source of naturally occurring polyphenolic compounds including anthocyanins and reportedly have strong estrogenic activity. To validate these findings, we have investigated the estrogen receptor binding affinity and safety of some previously recorded polyphenols using a suite of computational methods. Our investigation showed the estrogen-receptor binding potential of Pelargonidin, Delphinidin, Cyanidin, and Hibiscetin are more efficient than popular breast cancer drugs, Tamoxifen and Raloxifene, with favourable toxicological parameters and low half maximal inhibitory concentration. This is the first report to investigate the phytochemical basis of estrogenic activity of Hibiscus sabdariffa L.

Based on the kinematic approach of the limit analysis and slip-line theories, this paper proposes a new 2D analytical model to evaluate the collapse support pressure to ensure the face stability of a circular tunnel in purely cohesive soils driven by a shield. The normality conditions, the yield criterion and the vertical soil arching effect are considered in the analytical model. Two upper bound solutions corresponding to the ratio of the cover to the diameter (C/D) are derived from considering the mechanisms based on the motion of rigid multi-blocks. Comparisons are made with existing upper and lower bound solutions published in previous articles. The results are close to the solutions of practical engineering. The failure mechanisms proposed in this study provide a better explanation for the failure process in the heading of the tunnel face.

Recent emergence of novel coronavirus (SARS-CoV-2) all over the world has resulted more than 33,106 global deaths. To date well-established therapeutics modules for infected patients are unknown. In this present initiative, molecular interactions between FDA-approved antiviral drugs against the Hepatitis-C virus (HCV) have been investigated theoretically against the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2. HCV and SARS-CoV-2 are both +ssRNA viruses. At 25^o C beclabuvir, a non-nucleoside inhibitor of the RdRp_HCV can efficiently bind to RdRp _SARS-CoV-2 (ΔG_AutoDock = -9.95 kcal mol^-1) with an inhibition constant of 51.03 nM. Both the ΔG_London and ΔG_{GBVI / WSA} values were - 9.06 and - 6.67 kcal mol^-1, respectively for binding of beclabuvir to RdRp_SARS-CoV-2. In addition, beclabuvir has also shown better binding free energy with RdRp_SARS-CoV-2 (ΔG_vina = -8.0 kcal mol^-1) than that observed with the Thumb 1 domain of RdRp_HCV (ΔG_vina = -7.1 kcal mol^-1). InterProScan has suggested the RNA-directed 5'-3' polymerase activity exists within 549^th to 776^th amino acid residues of RdRp_SARS-CoV, where the major amino acid residues interacting being I591, Y621, C624, D625, A690, N693, L760, D762, D763, and E813-N817. Molecular interaction suggests occupancy of beclabuvir inside the active site environment of the RdRp_SARS-CoV-2, the enzyme essential for viral RNA synthesis. In conclusion, results suggest beclabuvir may serve as an anti-SARS-CoV-2 drug.

The COVID-19 infections in Pakistan are spreading at an exponential rate and a point may soon be reached where rigorous prevention measures would need to be adopted. Mathematical models can help define the scale of an epidemic and the rate at which an infection can spread in a community. I used ARIMA Model, Diffusion Model, SIRD Model and Prophet Model to forecast the magnitude of the COVID-19 pandemic in Pakistan and compared the numbers with the reported cases on the national database. Results depicts that Pakistan could hit peak number of infectious cases between June 2020 and July, 2020.

Chilli leaf curl virus (ChiLCV) is a severe threat to the successful cultivation of the chilli peppers. Besides, the genetics and heterosis for important traits under the influence of ChiLCV infestation is not well studied. Therefore here, were crossed seven genotypes (lines) with high yield and quality attributes with four highly resistant genotypes (testers) in a line (L) × tester (T) mating design to produce 28 F1 hybrids. Parents and their hybrids were evaluated for yield attributes and ChiLCV resistance. All the four testers were symptomless and among seven lines, two were moderately resistant and five were moderately susceptible to the ChiLCV. Among 28 F1 hybrids, 12 showed a moderate resistant reaction, 11 were moderately susceptible and five susceptible to the ChiLCV disease. Based on per se performance, most promising hybrid combinations were L3 × T2, L6 × T1, and L3 × T1 for yield attributes. Whereas the superior crosses for ChiLCV resistance based on heterobeltosis, standard heterosis and specific combining ability test (SCA) effects were L6 × T1 and L7 × T3. Lines and testers showed significant differences for all the characters except for the plant height. The general combining ability (GCA) effects for testers were significant for all the traits except for days to first harvest. The ratio of σ2GCA/σ2SCA indicated the predominance of non-additive gene effects in the inheritance of traits studied in this experiment. The contribution of lines was more compared to testers for all the characters except for primary branches plant-1. Overall, this study provides valuable information regarding the genetics and heterosis in chilli with respect to ChiLCV infestation

Backward electromagnetic waves are extraordinary waves with contra-directed phase velocity and energy flux. Unusual properties of the coherent nonlinear optical coupling of the phase-matched ordinary and backward electromagnetic waves with contra-directed energy fluxes are described which enable greatly-enhanced frequency and propagation direction conversion, parametrical amplification, as well as control of shape of the light pulses. Extraordinary transient processes that emerge in such metamaterials in pulsed regimes are described. The results of the numerical simulation of particular plasmonic metamaterials with hyperbolic dispersion are presented, which prove the possibility to match phases of such coupled guided ordinary and backward electromagnetic waves. Particular properties of the outlined processes in the proposed metamaterial are demonstrated through numerical simulations. Potential applications include ultra-miniature amplifiers, frequency changing reflectors, modulators, pulse shapers, and remotely actuated sensors.

The world is currently, subjected to the worst health crisis documented in modern history; an epidemic led by the novel coronavirus disease 2019 (COVID-19). At the epicenter of this crisis, healthcare professionals continue working to safeguard our well-being. To the regular high levels of stress, COVID new heights even more to healthcare professionals so depending on the area, specialty, and type of work. Here we investigated what are the tendencies, or areas most affected. Through an adaptation of the original COVID-stress scale, we developed a remote, fast test designed for healthcare professionals of the Northeastern part of Mexico, an important part of the country with economic and cultural ties to the US. Our results showed 4 key correlations as highly dependent: Work area – Xenophobia (p < 0.045), Work with COVID patients - Traumatic stress (p < 0.001) and Total number of COVID patients per day – Traumatic stress (p < 0.027), and Total number of COVID patients - Compulsive checking and reassurance. Overall concluding that normal levels of stress have increased (mild – moderate). Additionally, we further determine that the fear of being an asymptomatic patient (potential to spread without knowing) continues being a concern.

Abstract Antibacterial activities can be improved using mixed ligands. Mixed ligands involved in this research are sodium sulfadiazine (Na-sfz) and dithiocarbamate (ai-dtc). One-pot synthesis was used to synthesize ligand of aniline dithiocarbamate (ai-dtc) and the corresponding coordination compounds of [VO(sfz)(ai-dtc)] and [Zn(sfz)(ai-dtc)]. Crystals of ai-dtc, which grew from the solution when refrigerated after five days, were diffracted with technique of single crystal x-ray crystallography to reveal the structure. Other characterization techniques involving physicochemical parameters, FT-IR, UV-Vis and NMR (1H NMR and 13C NMR) were carried out on ligands of ai-dtc, sfz and corresponding coordination compounds. Differences in results of FT-IR, UV-Vis and NMR between ligands and their respective metal ions confirmed the coordination. The in vitro antibacterial studies showed that the ligands (not the metal complexes) had modest activity against Gram negative bacteria: Staphylococcus aureus, whereas, the coordination compounds had modest activities against the Gram negative bacteria: Escherichia coli and Pseudomonas aeruginosa.

Nowadays, there are several electric vehicle (EV) on the market, due to the innovation of technology that promotes the new components such as battery, transmission, electric motors. This paper proposes a design approach for the configuration synthesis and simulation of the in-wheel-hub motor transmissions with the six-link mechanisms. The synthesis process shows 6 mechanisms with six members and eight joints, 15 new clutchless motor transmissions and 16 new clutched motor transmissions. A novel motor transmission in the feasibility of the synthesized configurations is selected as an example to analyze the working principle with operation modes and power flow paths. And, this design is modeled for the simulation process that generates the results of operation mode transition and energy regulation.

Far-red fluorescent reporter genes can be used for tracking cells non-invasively in vivo using fluorescence imaging. Here, we investigate the effectiveness of the far-red fluorescent protein, E2-Crimson (E2C), for tracking mouse embryonic cells (mESCs) in vivo following subcutaneous administration into mice. Using a knock-in strategy, we introduced E2C into the Rosa26 locus of an E14-Bra-GFP mESC line, and after confirming that the E2C had no obvious effect on the phenotype of the mESCs, we injected them into mice and imaged them over 9 days. The results showed that fluorescence intensity was weak, and cells could only be detected when injected at high densities. Furthermore, intensity peaked on day 4 and then started to decrease, despite the fact that tumour volume continued to increase beyond day 4. Histopathological analysis showed that although E2C fluorescence could barely be detected in vivo at day 9, analysis of frozen sections indicated that all mESCs within the tumours continued to express E2C. We hypothesise that the decrease in fluorescence intensity in vivo was probably due to the fact that the mESC tumours became more vascular with time, thus leading to increased absorbance of E2C fluorescence by haemoglobin. We conclude that the E2C reporter has limited use for tracking cells in vivo, at least when introduced as a single copy into the Rosa26 locus.

As renewed interest in human space-exploration intensifies, a coherent and modernized strategy for mission-design and planning has become increasingly crucial. Biotechnology has emerged as a promising approach to increase mission resilience, flexibility, and efficiency by virtue of its ability to efficiently utilize in situ resources and reclaim resources from waste streams. Since its infancy during the Apollo years, biotechnology, and specifically biomanufacturing, have witnessed significant expansions of scope and scale. Here we outline four primary mission classes, on Luna and Mars, that drive a staged and accretive biomanufacturing strategy. Each class requires a unique approach to integrate biomanufacturing into the existing mission architecture and so faces unique challenges in technology development.These challenges stem directly from the resources available in a given mission class – the degree to which feedstocks are derived from cargo and in situ resources – and the degree to which loop-closure is necessary. We see that as mission duration and distance from Earth increase, the benefits of specialized sustainable biomanufacturing processes increases. Here we present a strategic approach, guided by technoeconomics, to development, testing, and deployment of these technologies serves to nucleate the larger effort of supporting a sustained human presence in space. The processes needed for each scenario spans the technical breadth of synthetic biology to design engineering, from sophisticated genetic tailoring of chassis-organisms to building scalable, automated, easily operable bioreactors and processing systems. As space-related technology development often does, these advancements are likely to have profound implications for the creation of a stable, resilient bioeconomy on Earth.

The present work evaluates the food effect on the absorption of rivaroxaban (Riva), a BCS II drug, from the orally administered commercial immediate-release tablet (Xarelto IR) using physiologically based pharmacokinetic (PBPK) and conventional in vitro- in vivo correlation (IVIVC) models. The bioavailability of Riva upon oral administration of Xarelto IR tablet is reported to exhibit a positive food effect. The PBPK model for Riva was developed and verified using the previously reported in vivo data for oral solution (5 and 10 mg) and Xarelto IR tablet (5 and 10 mg dose strength). Once the PBPK model was established, the in vivo performance of the tablet formulation with the higher dose strength (Xarelto IR tablet 20 mg in fasted and fed state) was predicted using the experimentally obtained data of in vitro permeability, biorelevant solubility and in vitro dynamic dissolution data using United States Pharmacopeia (USP) IV flow-through cell apparatus. In addition, the mathematical IVIVC model was developed using the in vitro dissolution and in vivo profile of 20 mg strength Xarelto IR tablet in fasted condition. Using the developed IVIVC model, the pharmacokinetic (PK) profile of the Xarelto IR tablet in fed condition was predicted and compared with the PK parameters obtained via the PBPK model. A virtual in vivo PK study was designed using a single-dose, 3-treatment cross-over trial in 50 subjects to predict the PK profile of the Xarelto® IR tablet in the fed state. Overall, the results obtained from the IVIVC model were found to be comparable with that from the PBPK model. The outcome from both the model pointed to the positive food effect on the in vivo profile of the Riva. The developed models thus can be effectively extended to establish bioequivalence for the marketed and novel complex formulations of Riva such as amorphous solid dispersions.

In this paper the authors describe the architecture of a multidisciplinary data acquisition and visualization platform devoted to the management of coastal environments. The platform integrates heterogeneous data acquisition sub-systems that can be roughly divided in two main categories: remote sensing systems and in-situ sensing systems. Remote sensing solutions include aerial and underwater remote data acquisition while in-situ sensing solutions include the use of RFID tracers, Wireless Sensor Networks and imaging techniques. All the data collected by these subsystems are stored, integrated and fused on a single platform that is also in charge of data visualization. This last task is carried out according to the paradigm of Augmented Virtuality which foresees the augmentation of a virtually reconstructed environment with data collected in the real world. The described solution proposes a novel holistic approach where different disciplines concur, with different data acquisition techniques, to a large scale definition of coastal dynamics, in order to better describe and face the coastal erosion phenomenon. The overall framework has been conceived by the so-called Team COSTE, a joint research team between the Universities of Pisa, Siena and Florence.

Matiyasevich's theorem states that there is no algorithm to decide whether or not a given Diophantine equation has a solution in non-negative integers. Smorynski's theorem states that the set of all Diophantine equations which have at most finitely many solutions in non-negative integers is not recursively enumerable. We prove: (1) Smorynski's theorem easily follows from Matiyasevich's theorem, (2 ) Hilbert's Tenth Problem for Q has a negative solution if and only if the set of all Diophantine equations with a finite number of rational solutions is not recursively enumerable.

Women have been leading organizations and communities for centuries, but their journeys in leadership have sometimes been challenging. This paper aims to reflect on women's positive and negative experiences in leadership roles and understand the factors contributing to their successes and challenges.To explore these issues, we will draw on various academic literature, including studies on gender and leadership and case studies of women in leadership positions. We will also examine the cultural and social factors that affect women's experiences in leadership, including bias and discrimination, societal expectations, and work-life balance challenges.One key theme from this analysis is the importance of role models and support networks in helping women succeed in leadership roles. Women with access to mentorship, sponsorship, and peer networks are more likely to thrive in their roles and overcome the challenges they may face. However, lacking female role models and mentors can make it difficult for women to advance in their careers and contribute to feelings of isolation and imposter syndrome.Another important theme is the need for organizations and society to address systemic biases and discrimination that prevent women from reaching their full potential. This can include initiatives such as unconscious bias training, flexible work arrangements, and policies that support gender diversity and inclusion.In conclusion, this paper highlights women's positive and negative experiences in leadership roles and emphasizes the need for ongoing efforts to support and empower women in leadership. By addressing the challenges women face and building a culture of inclusion and support, organizations and society can help unlock the full potential of women leaders and create a more equitable and just world.

This work focuses on the study of the microstructure, hardening and stiffening effect caused by the secondary phases formed in titanium matrices. These secondary phases were originated from reactions between the matrix and boron particles added in the starting mixtures of the composites. Not only was the composite composition studied as an influencing factor in the behaviour of the composites, but also different operational temperatures. Three volume percentages of boron content were tested (0.9, 2.5 and 5 vol % of amorphous boron). The manufacturing process used to produce the composites was inductive hot pressing, which operational temperatures were between 1000 °C to 1300 °C. Specimens showed optimal densification. Moreover, microstructural study revealed the formation of TiB in various shapes and proportions. Mechanical testing confirmed that the secondary phases had a positive influence on the properties of the composites. In general, adding boron particles increased the hardness and stiffness of the composites; however rising temperatures resulted in greater increases in stiffness than in hardness.

The microstructure of Al-5Fe-1.5Er alloy was characterized and analyzed by using XRD, SEM, TEM and EDS. The effect of microstructure on the behavior of crack initiation and propagation was investigated by in situ tensile testing. Results show that the microstructure consists of α-Al matrix, Al₃Fe, Al₄Er, eutectic phase Al₃Fe + Al₄Er, while the 1.5 wt.% Er was added in Al-5Fe alloy. The twin structure of the Al₃Fe phase was observed, and the twin plane is {001}. Moreover, a continuous concave and convex interface structure of the Al₄Er has been found. Al₃Fe is in the form of a sheet with a clear gap inside.In situ tensile tests of the alloy at room temperature show that the crack initiation occured mainly in the Al₃Fe phase, and that the crack propagation modes include intergranular and transgranular expansion. Crack transgranular expansion is due to the strong binding ability between Al₄Er phases and surrounding organization, and the continuous concave and convex interface structure of the Al₄Er provides a significant meshing effect on the matrix and eutectic structure.

In plants and animals, endogenous biological molecules, termed damage-associated molecular patterns (DAMPs) or alarmins, are released by damaged, stressed or dying cells following abiotic stress such as radiation and drought stress. In turn, a cascade of downstream signaling events is initiated leading to the up-regulation of defense-related genes. In the present study, in an effort to investigate the conservation status of the molecular mechanisms implicated in the danger signaling, thorough in silico phylogenetic and structural analyses of the effector biomolecules were performed in taxonomically diverse plant species. On the basis of our results, the defense mechanisms appear to be largely conserved within the plant kingdom. Of note is our finding that the sequence and/or function of several components of these mechanisms were found to be conserved in animals, as well.

In this paper, we use three different experimental methods (particle method, grid method and hybrid method) to model and simulate the smoke from the perspective of fluid dynamics. Through the comparison of different methods, we conclude: The particle method can avoid the numerical dissipation problem caused by grid calculation, but it also brings problems such as the distortion of the trajectory of the example. The grid method is accurate in calculation, but it is prone to numerical dissipation and loss of details. Finally, we choose the hybrid method to store the vorticity in the form of particles in vortex particles, avoiding the numerical dissipation problem caused by the use of grids, and including rich turbulence, which perfectly shows the simulation effect of smoke.

Shipbreaking research has not been in the forefront until the last decade in which environmental and occupational hazards have been highlighted while economic sustainability and contextual conditions were not equally considered. The adoption of a triple bottom line approach across core business issues (environmental impacts, workplace safety ) as well as peripheral stakeholders expectation (environmental sustainability focus) has been retarded due to the less attention on the latter. Based on the findings of the 128 review papers, the study suggests that organizational learning and economic sustainability needs to prioritize through the formation of strange alliance among the stakeholders. The study argues that the dialogue and discussion on the peripheral stakeholders (NGOs, yard managers, national and international policy organizations) would lead to a more sustainable shipbreaking industry in the south Asian regions.

During the last decades, the production systems have developed different strategies to increase their competitiveness in the global market. In a manufacturing and services systems, Lean Manufacturing has been consolidated through the correct implementation of its tools. The present paper presents a case study developed in a Food Packer company where a Simulation Model was considered as an alternative to reduce the waste time generated by the poor distribution of operations and transportation areas for a product within the factory. As a matter of fact, the company has detected problems on the layout distribution that prevents to fulfill the market demand. In addition, the principal aim was to create a simulation model to test different hypothetical scenarios and alternative designs for the layout distribution without modifying its facilities. Moreover, the implemented methodology was based on classical models of simulation projects and a compendium of the manufacturing systems optimization by simulation process used during the last ten years. Also, a mathematic model supported by the Promodel ® simulation software was developed considering the company characteristics; along with the model development, it was possible to compare the production system performance from the percentage of used locations, the percentage of resources utilization, the number of finished products, and the level of Work in Process (WIP). Finally, the verification and validation stages were performed before running the scenarios in the real production area. The results generated by the implementation of the project represent an increase of 68% in the production capacity and a reduction of 5% in the WIP. In addition, both outcomes are associated with the resources management, which were reassigned to other production areas.

Legumes develop root nodules that harbour endosymbiotic bacteria, rhizobia. These rhizobia convert nitrogen to ammonia by biological nitrogen fixation. A thorough understanding of the biological nitrogen fixation in legumes and its regulation is key to develop sustainable agriculture. It is well known that plant hormones affect nodule formation; however, most studies are limited to model legumes due to their suitability for in vitro, plate-based assays. Specifically, it is almost impossible to measure the effects of exogenous hormones or other additives during nodule development in crop legumes such as soybean as they have huge root system in soil. To circumvent this issue, the present research develops suitable media and growth conditions for efficient nodule development under in vitro, soil free conditions in an important legume crop, soybean. Moreover, we also evaluate the effects of all major phytohormones during soybean nodulation under identical conditions. This versatile, inexpensive, scalable and simple protocol provides several advantages over previously established methods. It is extremely time-and resource-efficient, does not require special training or equipment, and produces highly reproducible results. The approach is expandable to other large legumes as well as for other exogenous additives.

The deep neural network - BERT model (Bidirectional Encoder Representations from Transformers) and the stocks cumulative abnormal return is used in this article to analyze the sentiment of financial texts. The proposed approach, unlike those used so far, does not require the creation of dictionaries, takes into account the broad context of words and their meaning in financial texts, eliminates the problem of ambiguity of words in various contexts, does not require manual labelling of data and is free from the subjective assessment of the researcher. The sentiment of financial texts in the meaning presented in this paper is directly related to the market reaction to the information contained in these texts. For texts belonging to one of the two classes (positive or negative) with the highest probability the BERT model gives the results of predictions with a precision level of 62.38% for the positive class and 55% for the negative class. The results at this level can be used in event study, market efficiency research, investment strategy development or support of investment analysts using fundamental analysis.

The concept of geostationary VHTS (Very High Throughput Satellites) is based on multibeam coverage with intensive frequency and polarization reuse in addition to the use of larger bandwidths in the feeder links, in order to provide high capacity satellite links at a reduced cost per Gbps in orbit. The dimensioning and design of satellite networks based on VHTS imposes the analysis of multiple trade-offs to achieve an optimal solution in terms of cost, capacity and figure of merit of the user terminal. In this paper, we propose a new method for sizing VHTS satellite networks based on an analytical expression of the forward link CINR (Carrier-to-Interference-plus-Noise Ratio) that is used to evaluate the trade-off of different combinations of system parameters. The proposed method considers both technical and commercial requirements as inputs including the constraints to achieve the optimum solution in terms of the user G/T, the number of beams and the system cost. The cost model includes both satellite and ground segments. Exemplary results are presented with feeder links using Q/V bands, DVB-S2X and transmission methods based on CCM and VCM (Constant and Variable Coding and Modulation, respectively) in two scenarios with different service areas.

Synthesis of new series of 1-phenyl-3-(4-(pyridin-3-yl) phenyl) urea derivatives and its in vitro antiproliferative activities against NCI-60 human cancer cell lines of nine different cancer types are described. Fourteen compounds 5a-n have been synthesized with three different hydrogen bondable moieties (4-hydroxylmethylpiperidinyl and trimethoxyphenyloxy and 4-hydroxyethylpiperazine) attached to the core structure 1-phenyl-3-(4-(pyridin-3-yl) phenyl) urea. Different substituents with different π and σ values were added on the terminal phenyl group. Compounds with 4-hydroxymethylpiperidine moiety showed higher mean percentage inhibition values over the 60-cell line panel at 10-µM concentration. They showed broad-spectrum antiproliferative activity over many cell lines of different cancer types. For instance, compound 5a elicited some lethal rather than inhibition effects on SK-MEL-5 melanoma cell line, 786-0, A498, RXF 393 renal cancer cell lines, and MDA-MB-468 breast cancer cell line by 146.1, 108.7, 136.2, 134.8, 116.6 % at 10 µM, respectively. Compounds 5a-e exhibited superior antiproliferative activity than Paclitaxel and Gefitinib against the most sensitive cell lines. Two compounds, 5a and 5d showed promising mean growth inhibitions and thus were further tested at five-dose testing mode to determine their IC₅₀ values. The data revealed that 5a and 5d urea compounds are the most active derivatives with significant efficacies and superior potencies than Paclitaxel in 21 different cancer cell lines, belonging particularly to renal cancer and melanoma cell lines. Moreover, 5a and 5d had superior potencies than Gefitinib in 38 and 34 cancer cell lines, respectively; belonging particularly to colon cancer, breast cancer and melanoma cell lines.

Flushing tap water is often promoted as a simple and low cost approach to reducing water lead exposures. This study evaluated lead reduction when prevailing flush guidelines (30 seconds-2 minutes) are implemented in a city compliant with lead-associated water regulations (New Orleans, LA). Water samples (n=1,497) collected from a convenience sample of 376 residential sites (2015-2017) were analyzed for lead in samples collected: at 1) first draw (n=375), and after incremental flushes of 2) 30-45 seconds (n=375), 3) 2.5-3 minutes (n=373), and 4) 5.5-6 minutes (n=218). There was no significant reduction when compared to the first draw lead level, until the 6 minute flush (p<0.05); but most sites (52%) still had detectable lead (≥1 ppb) after 6 minutes. Older homes (pre-1950) and low occupancy sites had significantly higher WLLs (p<0.05).Each sample type had health-based standard exceedances at over 50% of sites sampled (max: 58 ppb). While flushing is an effective short-term approach to remediate high lead, prevailing flush recommendations are an inconsistently effective exposure prevention measure that can often inadvertently increase exposures. Public health messages should be modified to ensure appropriate application of flushing for specific cities, while acknowledging its short-comings and practical limitations.

Three kinds of hydrophobic groups grafted starches of maleic anhydride grafted starch (MAH-g-starch), lactic acid grafted starch (LA-g-starch), and methyl acrylate grafted starch (MA-g-starch) were prepared by in-situ solid phase polymerization. The results of Fourier transform infrared spectroscopy (FT-IR) and X-ray photoelectron spectroscopy (XPS) were confirmed successful grafting. The grafting ratios of MAH-g-starch, LA-g-starch and MA-g-starch were 6.50%, 12.45%, and 0.57%, respectively. Influenced by the grafting ratio, LA-g-starch had the best hydrophobic properties and the largest molecular weight, and those for MA-g-starch was the worst. The surfaces of grafted starches were covered with graft polymer, with obvious surface roughness and bond degree of MAH-g-starch and LA-g-starch. The crystalline structure of grafted starches showed some damage, with LA-g-starch exhibiting the greatest decrease in crystallinity, and less of a change for MA-g-starch. Overall, the grafting reaction improved thermoplasticity, with LA-g-starch the most improved, followed by MAH-g-starch, and then MA-g-starch.

This article makes a general analysis of the supply chain of photovoltaic systems in Colombia, taking as a starting point a conceptual base and the current situation of the country in this sector. This article especially will contemplate the non-interconnected areas (ZNI) to the electricity grid in the national, due to its complexity in the logistics issues. Likewise, the work performs a graphical representation of the stages and processes of the supply chain using a powerful-modeled tool such as the Petri Nets (PNs). Finally, it identifies some of the flaws in the operation and the joint of all the links of the logistic part and from there it is based the importance of the strategy of orientation to the supply chain (SCO) as a possible alternative to improve and to enhance the logistic processes of this type of systems.

Cancer cell lines are widely used as in vitro models of tumorigenesis, facilitating fundamental discoveries in cancer biology and translational medicine. Currently, there are few options for glioblastoma (GBM) treatment and limited in vitro models with accurate genomic and transcriptomic characterization. Here, a detailed characterization of a new GBM cell line, namely AHOL1, was conducted in order to fully characterize its molecular composition based on its copy number alteration (CNA) and transcriptome profiling, followed by the validation of key elements associated with GBM tumorigenesis. Large numbers of CNAs and differentially expressed genes (DEGs) were identified. CNAs were distributed throughout the genome, including gains at Xq11.1-q28, Xp22.33-p11.1, Xq21.1-q21.33, 4p15.1-p14, 8q23.2-q23.3 and losses at Yq11.21-q12, Yp11.31-p11.2 and 12p13.31 positions. Nine druggable genes were identified, including HCRTR2, ETV1, PTPRD, PRKX, STS, RPS6KA6, ZFY, USP9Y and KDM5D. By integrating DEGs and CNAs, we identified 57 overlapping genes enriched in fourteen pathways. Altered expression of several cancer-related candidates found in the DEGs-CNA dataset was confirmed by RT-qPCR. Taken together, this first comprehensive genomic and transcriptomic landscape of AHOL1 provides unique resources for further studies and identifies several druggable targets that may be useful for therapeutics and biologic and molecular investigation of GBM.

The current study sets out to develop an empirical line method (ELM) radiometric calibration framework for reducing atmospheric contributions in UAS imagery and for producing scaled remote sensing reflectance imagery. Using a MicaSense RedEdge camera flown on a custom-built octocopter, the research reported herein finds that atmospheric contributions have an important impact on UAS imagery. Data collected over the Lower Pearl River Estuary in Mississippi during five week-long missions covering a wide range of environmental conditions was used to develop and test a simplified ELM radiometric calibration framework designed specifically for the reduction of atmospheric contributions to UAS imagery in studies with limited site accessibility or data acquisition time constraints. The framework was effective in reducing atmospheric and other external contributions to UAS imagery. Unique to the proposed radiometric calibration framework is the radiance to reflectance conversion conducted externally from the calibration equations which allows for the normalization of illumination independent from the time of UAS image acquisition and from the time of calibration equations development. This paper presents the simplified ELM radiometric calibration framework that can be used as a time-effective calibration technique to reduce errors in the UAS imagery.

The terms 'open' and 'openness' are widely used across the current higher education environment particularly in the areas of repository services and scholarly communications. Open-access licensing and open-source licensing are two prevalent manifestations of open culture within higher education research environments. As theoretical ideals, open-licensing models aim at openness and academic freedom. But operating as they do within the context of global neoliberalism, to what extent are these models constructed by, sustained by, and co-opted by neoliberalism? In this paper, we interrogate the use of open-licensing within scholarly communications and within the larger societal context of neoliberalism. Through synthesis of various sources, we will examine how open access licensing models have been constrained by neoliberal or otherwise corporate agendas, how open access and open scholarship have been reframed within discourses of compliance, how open-source software models and software are co-opted by politico-economic forces, and how the language of 'openness' is widely misused in higher education and repository services circles to drive agendas that run counter to actually increasing openness. We will finish by suggesting ways to resist this trend and use open-licensing models to resist neoliberal agendas in open scholarship.

Thai basil is a renowned medicinal plant and a rich source of bioactive antioxidant compounds having several health benefits, with actions to prevent of cancer, diabetes and cardiovascular disease. Plant cell and tissue culture technologies can be routinely established as an important, sustainable and low-cost biomass source for the production of high-value phytochemicals. The current study aimed at developing an effective protocol for the production of Thai basil leaf derived callus cultures with sustainable and high production of biomass and antioxidants as an alternative of leaves production. MS basal medium with various concentrations of plant growth regulators (PGRs) compatible with nutraceutical applications (i.e., gibberellic acid (GA3) and 6-benzylaminopurine (BAP) either alone or in combination with naphthalene acetic acid (NAA)) were evaluated. Among all tested PGRs, the combination BAP:NAA (5 mg/L:1 mg/L) yield maximum biomass accumulation (fresh weight (FW): 190 g/L and dry weight (DW): 13.05 g/L) as well as enhanced phenolic (346.08 mg/L) production. HPLC quantification analysis indicated high productions of chicoric acid (35.77 mg/g DW) and rosmarinic acid (7.35 mg/g DW) under optimized callus culture conditions. Antioxidant potential was assessed using both in vitro cell free and in vivo cellular antioxidant assays. Maximum in vitro antioxidant activity DPPH (93.2 % of radical scavenging activity) and ABTS (1322 µM Trolox equivalent antioxidant capacity) was also observed for the extracts from callus cultures grown on optimal conditions. In vivo cellular antioxidant activity assay confirmed the effective protection against oxidative stress of the corresponding extract by the maximum inhibition of ROS and RNS production. Compared to commercial leaves, callus extracts showed higher production of chicoric acid and rosmarinic acid associated with higher antioxidant capacity. In addition, this biological system also has a large capacity for continuous biomass production, thus demonstrating its high potential for possible nutraceutical applications.

The RAINBOW Phase III study established the efficacy of the combination of paclitaxel and ramucirumab, a monoclonal antibody targeting VEGF receptor-2 (VEGF-R2), as second-line therapy. We retrospectively analyzed the data of patients treated with ramucirumab plus paclitaxel at our Institution to evaluate the impact of clinical heterogeneous figures on the efficacy and safety of this combination paclitaxel/ramucirumab in a real- life cohort of patients. After a median follow-up of 10.74 months, the median progression-free survival (PFS) was 5.8 months (95% CI: 3.04 - 5,63). Disease control rate (DCR) was 61% and the median duration of response (DOR) was 5.8 months. Median overall survival (OS) was 8.3 months. A trend toward better outcome was observed in HER2 positive patients. In multivariate analysis, nutritional status (p = 0.0001) and number of metastatic sites (p = 0.0266) resulted significantly related with longer PFS. Our analysis confirmed the efficacy and safety of the combination of ramucirumab with paclitaxel also in the real-life practice and the median PFS is significantly longer than that reported for Western population in previous studies. Subgroup analysis confirms the key-role of nutritional status as prognostic factor and suggests a possible interaction between EGF and angiogenesis pathways that deserves further investigations.

Temporary pavilions play an important role as experimental fields for architects, designers and engineers, apart from providing exhibition spaces. Novel structural and formal solutions applied in pavilions also can give them unusual appearance that attracts eyesight of spectators. In this article authors explore the possibility of combination of structural novelty, visual attractiveness and low-cost by a design and construction of a temporary pavilion. For that purpose, an innovative structural system and design approach was applied, i.e. membrane structure designed in Rhino and Grasshopper environments with the use of Kiwi!3D IsoGeometric analysis tool. The designed pavilion, named Obverse/Reverse, was built in Opole, Poland, for the occasion of World Architecture Day in July 2019. Design and construction was performed by the authors in cooperation with students’ organisation Humanisation of Urban Environment from the Faculty of Architecture Wroclaw University of Science and Technology. The Rresultant pavilion proved the possibility of obtaining a low-budgets but visually attractive architectural solution with the adaption of parametrical design tools and some scientific background with innovative structural systems.

The human capital index is a multivariate variable used to measure the assessment of human resource productivity in the future. Human capital has a connection with economic development. Moreover, the study looks to analyses the relationship between Human Capital and Economic Growth indicators such as HCI and GDP. Human Capital relates to the development of individual skills to make them function more profitable for the national economy. The study was aimed at investigating the effect of population, the number of people engaged and the average annual hours worked by engaged persons on the human capital index. The analysis was in SPSS for the findings. Correlation tests were used for analysis. The study revealed that population, the number of people engaged and the average annual hours worked by engaged persons had a significant positive effect on the human capital index.

Local binary pattern is one of the visual descriptors and can be used as a powerful feature extractor for texture classification. In this paper, a novel representation for face recognition is proposed, called it Bilateral Line Local Binary Patterns (BL-LBP). This scheme is an extension of Line Local Binary Patterns descriptors in the statistical learning subspace. The present bilateral descriptors are fused with an ensemble learning of calibrated SVM models. The performance of this scheme is evaluated using 5 standard face databases. It is found that it is robust against illumination variation, diverse facial expressions and head pose variations and its recognition accuracy reaches 98 percent, running on a mobile device with a processing speed of 63 ms per face. Results suggest that our proposed method can be very useful for the vision systems that have limited resources where the computational cost is critical.

Single nucleotide polymorphisms (SNP) are associated with diseases and drug response variabilities in humans. Elucidating the damaging and disease-associated SNPs using wet-laboratory approaches can be challenging and resource-demanding due to the large number of SNPs in the human genome. Due to the growth in the field of computational biology and bioinformatics, algorithms have been developed to help screen and filter out the most deleterious SNPs that are worth considering for wet-laboratory studies. Here we review the existing in-silico based methods used to predict and characterize the effects of SNPs on protein structure and function. This cutting-edge approach will facilitate the search for novel therapeutics, help understand the etiology of diseases and fast-track the personalized medicine agenda.

Here, we report on ZnO nanoparticles (NPs) generated by nanosecond pulsed laser (Nd:YAG, 1064 nm) through ablation of metallic Zn target in water and air and their comparative analysis as potential nanomaterials for biomedical applications. The prepared nanomaterials were carefully characterized in terms of their structure, composition, morphology and defects. It was found that in addition to the main wurtzite ZnO phase, which is conventionally prepared and reported by others, the sample laser-generated in air also contained some amount of monoclinic zinc hydroxynitrate. Both nanomaterials were then used to modify model wound dressings based on biodegradable poly-L-lactic acid. The as-prepared model dressings were tested as biomedical materials with bactericidal properties towards S. aureus and E. coli strains. The advantages of the NPs prepared in air over their counterparts generated in water found in this work are discussed.

We use state-of-the-art computer-aided drug design (CADD) techniques to identify prospective inhibitors of the main protease enzyme, 3CLpro of the SARS-CoV-2 virus causing COVID-19. From our screening of over one million compounds including approved drugs, investigational drugs, natural products, and organic compounds, and a rescreening protocol incorporating enzyme dynamics via ensemble docking, we have been able to identify a range of prospective 3CLpro inhibitors. Importantly, some of the identified compounds had previously been reported to exhibit inhibitory activities against the 3CLpro enzyme of the closely related SARS-CoV virus. The top- ranking compounds are characterized by the presence of multiple bi- and monocyclic rings, many of them being heterocycles and aromatic, which are flexibly linked allowing the ligands to adapt to the geometry of the 3CLpro substrate site and involve a high amount of functional groups enabling hydrogen bond formation with surrounding amino acid residues, including the catalytic dyad residues H41 and C145. Among the top binding compounds we identified several tyrosine kinase inhibitors, which include a bioflavonoid, the group of natural products that binds best to 3CLpro. Another class of compounds that decently binds to the SARS-CoV-2 main protease are steroid hormones, which thus may be endogenous inhibitors and might provide an explanation for the age-dependent severity of COVID-19. Many of the compounds identified by our work show a considerably stronger binding than found for reference compounds with in vitro demonstrated 3CLpro inhibition and anticoronavirus activity. The compounds determined in this work thus represent a good starting point for the design of inhibitors of SARS-CoV-2 replication.

In advanced world stroke is one of the disabling cause of death that can be managed with thrombolysis if presents early despite further risk of intracerebral haemorrhage. Secondary prevention is an important objective in ischaemic stroke where recurrence is very high with subsequent stroke. Carotid End Arterectomy impact a definitive and effective role for both symptomatic and asymptomatic carotid stenosis for secondary stroke prevention in selective cases. Thrombolysis is a potential primary management for certain group whereas carotid surgery employs secondary preventative measure in a specified ischaemic stroke group.

This study purposes the use of plug-in electric vehicles for demand side management (DSM) considering uncertainties in demand as well as uncertainties due to mobility of PEV to mitigate peak demand. The solution also seeks to reduce electric cost in addition to reducing the effects of greenhouse gases. In recent years DSM using distributed storage system such as battery energy management system (BESS) and plugged-in electric vehicles (PEV) have become very prevalent with most implementations resorting to deterministic load forecast. These methods do not consider the potential growth in demand making their solutions less robust. In this study we propose a real-time density demand forecast and stochastic optimization for robust operation of PEV for a building. This method accounts for demand uncertainties in addition to uncertainties in mobile energy storage as found in PEV, making the resulting solution robust as compared to the deterministic case. A case study on a real site in South Korea is used for verification and testing. The proposed study is verified and tested against existing algorithms. The result verifies the effectiveness of the proposed approach

This work communicates a review on Balmer series hydrogen beta line measurements and applications for analysis of white dwarf stars. Laser-induced plasma investigations explore electron density and temperature ranges comparable to white dwarf star signatures such as Sirius B, the companion to the brightest star observable from the earth. Spectral line shape characteristics of the hydrogen beta line include width, peak separation, and central dip-shift, thereby providing three indicators for electron density measurements. The hydrogen alpha line shows two primary line-profile parameters for electron density determination, namely, width and shift. Both Boltzmann plot and line-to-continuum ratios yield temperature. The line-shifts recorded with temporally- and spatially- resolved optical emission spectroscopy of hydrogen plasma in laboratory settings can be larger than gravitational redshifts that occur in absorption spectra from radiating white dwarfs. Published astrophysical spectra display significantly diminished Stark or pressure broadening contributions to red-shifted atomic lines. Gravitational redshifts allow one to assess the ratio of mass and radius of these stars, and subsequently, the mass from cooling models.

Following an initial mechanical insult, traumatic spinal cord injury (SCI) induces a secondary wave of injury, resulting in a toxic lesion environment inhibitory to axonal regeneration. This review focuses on the glial cell line-derived neurotrophic factor (GDNF) and its application, also in combination with other factors and cell transplantations, for repairing the injured spinal cord. As recent decades of studies strongly suggest combinational treatment approaches hold the greatest therapeutic potential for the central nervous system (CNS) trauma, future directions of combinational therapies will also be discussed.

We prove: (1) the set of all Diophantine equations which have at most finitely many solutions in non-negative integers is not recursively enumerable, (2) the set of all Diophantine equations which have at most finitely many solutions in positive integers is not recursively enumerable, (3) the set of all Diophantine equations which have at most finitely many integer solutions is not recursively enumerable, (4) analogous theorems hold for Diophantine equations D(x₁, …, x_p) = 0, where p ∈ N\{0} and for every i ∈ {1, …, p} the polynomial D(x₁, …, x_p) involves a monomial M with a non-zero coefficient such that x_i divides M, (5) the set of all Diophantine equations which have at most k variables (where k ≥ 9) and at most finitely many solutions in non-negative integers is not recursively enumerable.

In this review article, the occurrence of nor-lignans and their biological activities are explored and described. Nor-lignans have proven to be present in several different families also belonging to chemosystematically distant orders as well as to have many different beneficial pharmacological activities. This review article represents the first one on this argument and is thought to give a first overview on these compounds with the hope that their study may continue if not raise after this.

In our previous papers [1,3], using only the concepts of the zero-point energy and quantized space–times, all the fields including gravity were explained. However, the previous papers had the following limitations: First, the concept of the quantized space-time must be experimentally confirmed. Second, we should clarify the meaning of the quantized Einstein’s gravity equation, which is derived in [1]. Moreover, in another paper [2], we succeeded in describing the neutrinos’ self-energy and their oscillations. However, this paper assumes the rest energy of 3-leptons in advance, which is why we needed to uncover the reason why leptons have 3-generations. As mentioned, using the concepts of the zero-point energy and quantized space–times, we derived the quantized Einstein’s gravity equation in our previous paper [1]. The paper provides an analytical solution of this equalized Einstein’s equation, which implies the conservation of angular momentum in terms of quantized space–times. Employing this solution and without the standard big bang model, a unique form of acceleration equation for the acceleration-expansion universe is derived. Moreover, the temperature of the cosmic microwave background (CMB) emission is also obtained. Further, this solution results in an analytical (not numerical) derivation of the gravity wave. Moreover, based on the configuration of quantized space–times in terms of both electric and magnetic fields, we analytically attempted to calculate every equation in terms of electromagnetic and gravity fields, using the solution of the quantized Einstein’s gravity equation. As a result of this theory, first the calculated acceleration and temperature of CMB emission agree with the measurements. Furthermore, the analytical solution of the quantized Einstein’s gravity equation resulted in all the laws of electromagnetic and gravity fields in addition to the analytically derived gravity wave, which agrees well with the recent measurements. Moreover, the calculations of the energies in the basic configuration of the quantized space–times resulted in all 3-leptons’ rest energies. Considering this basic configuration is uniformly distributed everywhere in the universe, we can conclude that τ-particles or static magnetic field energy derived from the basic configuration of the quantized space–times is the identity of dark energy, which also distributes uniformly in the universe.

In this present study, 3-pentadecyl-phenol was selected as a modifier to prepare a foamable phenolic resin with excellent performance, which was successfully prepared by in-situ modification. Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance (¹H NMR, ¹³C-NMR) were used to test and characterize the molecular structure of the modified resin. The results showed that 3-pentadecyl-phenol successfully modified the molecular structure of phenolic resin with a reduction in resin gel time. The effect of changing the added amount of 3-pentadecyl-phenol on the mechanical properties, microstructure and flame retardancy of the modified foam was investigated. The results showed that when the amount of added 3-pentadecyl-phenol was 15% of the total amount of phenol, this resulted in the best toughness of the modified foam, which could be increased to 300% compared to the bending deflection of the unmodified phenolic foam. The cell structure showed that the modified phenolic foam formed a more regular and dense network structure and the closed cell ratio was high. Furthermore, the compressive strength, bending strength, and limited oxygen index were improved, while the water absorption rate was lowered. However, the foam density could be kept below 40 mg/cm³, which does not affect the load.

Typhonium flagelliforme is an Indonesian herbal plant used and applied traditionally to treat cancer diseases. Gamma rays have irradiated rodent tuber mutant plant at six doses gray to in-crease the chemical compounds of anticancer activity. The effect of isolated compounds from ro-dent tuber mutant plants has never been studied and published yet. Our study unveiled the poten-tial of stigmasterol as a remarkable cytotoxic agent and the significant contribution of NMR spectroscopy, IR, Mass spectra, QTOF MS towards the isolation and identification of this anti-cancer agent. Stigmasterol was isolated from T. flagelliforme mutant plant. Stigmasterol was more effective against MCF-7 cells with an IC50 value of 0.1623 µM than Cisplatin with IC50 value 13.2 µM. It is the most potential and active fraction in the human breast cancer cell line. The mo-lecular docking study analyzed the chemical profile of stigmasterol to confirm the receptor in agonist binding sites. The prediction of the toxicity of stigmasterol compounds using in silico and analysis of its interaction with the receptor can act as a competitive regulator with a high-affinity binding site on FXR. Stigmasterol has potential as a candidate for an anticancer drug that pro-moting further clinical action.

Ferroelectric materials are crucial for today’s technological society, and nanostructured ferroelectric materials are important for downscaling of devices. Controlled and reproducible synthesis of these materials are therefore of immense importance. Hydrothermal synthesis is a well-established synthesis route, with a large parameter space for optimization, but a better understanding of nucleation and growth mechanisms is needed for full utilization and control. Here we use in situ X-ray diffraction to follow the nucleation and growth of BaTiO₃ formed by hydrothermal synthesis using two different titanium precursors, an amorphous titania precipitate slurry and a Ti-citric acid complex solution. Sequential Rietveld refinement was used to extract the time dependency of lattice parameters, crystallite size, strain and atomic displacement parameters. Phase pure BaTiO₃ nanoparticles 10 - 15 nm in size were successfully synthesized at different temperatures (100, 125, and 150 °C) from both precursors after reaction times ranging from a few seconds, to several hours. The two precursors resulted in phase pure BaTiO₃ with similar final crystallite size. Finally, two different growth mechanisms were revealed, where the effect of surfactants present during hydrothermal synthesis is discussed as one of the key parameters.

In this study, a matched-mode autoregressive source depth estimation method (MMAR) based on autoregressive (AR) wavenumber estimation is proposed for a moving source in shallow water waveguides. The signal original frequency and the environmental parameters, namely, the sound speed profile and bottom properties are known as a prior knowledge. The mode wavenumbers are estimated by the AR modal wavenumber spectrum. On the basis of the mode wavenumber estimation, the mode amplitudes can be estimated by the wavenumber spectrum that is obtained by generalized Hankel transform. The source depth estimation is determined by the peak of source depth function wherein the data mode best matches the replica mode that is calculated using a propagation model. Compared with other methods of moving source depth estimation, the proposed method exhibits a better performance in source depth estimation under low signal-to-noise ratio or the small range span. The selection of horizontal line array depth is illustrated by simulation and normal mode theory in details.

Many spectroscopic diagnostics are routinely used as a technique to infer the plasma parameters from line emission spectra but their accuracy depends on the numerical model or code used for the fitting process. However, the validation of a line shape code requires some steps : comparison of the line shape code with other similar codes for some academic (simple) cases and then more complex ones, comparison of the fitting parameters obtained from the best fit of the experimental spectra with those obtained with other diagnostic techniques and/or comparison of the fitting parameters obtained by different codes to fit the same experimental data. Here we compare the profiles of the hydrogen Balmer β line in a helium plasma computed by six codes for a selected set of plasma parameters and we report on the plasma parameters inferred by each of them from the fitting to a number of experimental spectra measured in a helium corona discharge where the pressure was in the range 1- 5 bar.

The war to technology and economic power have been the driver for industrialization in most developed countries. The first industrial revolution (industry 1.0) earned millions for textile mill owners while the second industrial revolution (industry 2.0) opened the way for tycoons and captains of industry like John D. Rockefeller, J.P. Morgan and Henry Ford. The third industrial revolution (industry 3.0) engendered technology giants like Apple and Microsoft, and made magnates of men like Steve Jobs and Bill Gates. Now, the race for the fourth industrial revolution (industry 4.0) is on and there is no option, every country whether developed or developing must participate. Many countries have positively responded to industry 4.0 by developing strategic initiatives to strengthen industry 4.0 implementation. Unlocking the country’s potential to industry 4.0 has been of interest to researchers in the recent past. However, the extent to which industry 4.0 initiatives being launched globally has never been revealed. Therefore, the present study aimed at exploring industry 4.0 initiatives through comprehensive electronic survey of literature to estimate the extend of its launching in different regions. Inferences were drawn from industry 4.0 initiatives in developed nations to be used as the recommendations for East Africa Community. Results of the survey revealed that 117 industry 4.0 initiatives have been launched in 56 countries worldwide consisting of five regions. The country’s percent of industry 4.0 initiatives as per region were: Latin America and the Caribbean (15%), North America (40%), Europe (53%), Asia and Oceania (25%), Middle East and Africa (11%). While the worldwide percent was estimated as 25%. This revealed that the big gap is existing between countries towards the race for industry 4.0.

In silico prediction of the in vivo efficacy of siRNA ionizable-lipid nanoparticles is desirable yet never achieved before. This study aims to computationally predict siRNA nanoparticles in vivo efficacy, which saves time and resources. A data set containing 120 entries was prepared by combining molecular descriptors of the ionizable lipids together with two nanoparticles formulation characteristics. Input descriptor combinations were selected by an evolutionary algorithm. Artificial neural networks, support vector machines and partial least squares regression were used for QSAR modeling. Depending on how the data set is split, two training sets and two external validation sets were prepared. Training and validation sets contained 90 and 30 entries respectively. The results showed the successful predictions of validation set log(dose) with R2val = 0.86 – 0.89 and 0.75 – 80 for validation sets one and two respectively. Artificial neural networks resulted in the best R2val for both validation sets. For predictions that have high bias, improvement of R2val from 0.47 to 0.96 was achieved by selecting the training set lipids lying within the applicability domain. In conclusion, in vivo performance of siRNA nanoparticles was successfully predicted by combining cheminformatics with machine learning techniques.

Many scientific and technological problems are studied with the help of computer codes that simulate the phenomena of interest rather than via traditional laboratory experiments. Such models play an important role in neuroscience where they are used to mimic brain function from the sub-cellular to the macroscopic level. Exploration with computer models carries with it a number of statistical challenges: where to sample the input space for the simulator, how to make sense of the data that is generated, how to estimate unknown parameters in the model, how to validate a model. The simulator setting also has some unique problems and possibilities. This review paper describes statistical research on these issues and how that work might be applied to neural simulations.

Physics behind collimated highly directional nature of lasers, and factors that keep the seven coloured waves that form white light together during their journey from Sun to Earth, in the face of the natural disruptive forces, is not fully understood. Energy levels were measured, in terms of alterations in induced current and voltage, in beams from a red laser, white LED light and the Sunlight before and during their disruption by diffusers (frosted glass for the lasers) and diffractors (diffraction grating for the white light) using a photovoltaic solar cell panel attached to a digital multimeter. Results show that disruption of the beams results in release of extra energy named as ‘Latent Light Binding’ Energy’. It is hypothesized that the ‘binding’ energy keeps laser waves firmly bound together both end-on and side-on enabling laser beams to travel long distances in collimated manner. Likewise, the 7 coloured waves that constitute white light are kept together, probably side-on, in their journey from the Sun to the Earth. The observation that diffraction of sunbeam is associated with increased power generation provides a new lead to improve harnessing of solar energy, where, currently, the focus is mainly on improving efficiency of photovoltaic cell.

With the progress of immunotherapy in cancer, oncolytic viruses (OVs) are getting more and more attention during the past decade. Due to their cancer-selective and immunogenic property, OVs are considered ideal candidates to be combined with immunotherapy to increase both specificity and efficacy in cancer treatment. OVs preferentially replicate in and lyse cancer cells, generating pathogen-associated molecular patterns (PAMPs) and danger (damage)-associated molecular patterns (DAMPs). These signals trigger innate immune response to modulate the solid tumor microenvironment, resulting in in situ autovaccination leading to adaptive anti-virus and anti-tumor immunity. Here, we summarize the conceptual updates of oncolytic virotherapy, immunotherapy, and the strategies to enhance the virus-mediated anti-tumor immune response, including: 1. Arm OVs with cytokines to modulated innate and adaptive immunity; 2. Combine OVs with immune checkpoint inhibitors to release T cell inhibition; 3. Combine OVs with immune co-stimulators to enhance T cell activation.

Electron Beam Melting (EBM) is an increasingly used Additive Manufacturing (AM) technique employed by many industrial sectors, including the medical device and aerospace industries. In-process EBM monitoring for quality assurance purposes has been a popular research area. Electronic imaging has recently been investigated as one of the in-process EBM data collection methods, alongside thermal/ optical imaging techniques. Despite certain capabilities of an electronic imaging system have been investigated, experiments are yet to be carried out to benchmark one of the most important features of any imaging systems – spatial resolution. This article addresses this knowledge gap by: (1) proposing an indicator for the estimation of spatial resolution which includes the Backscattered Electrons (BSE) information depth, (2) estimating the achievable spatial resolution when electronic imaging is carried out inside an Arcam A1 EBM machine, and (3) presenting an experimental method to conduct edge resolution evaluation with the EBM machine. Analyses of experimental results indicated that the spatial resolution was of the order of 0.3mm-0.4mm when electronic imaging was carried out at room temperature. It is believed that by disseminating an analysis and experimental method to estimate and quantify spatial resolution, this study has contributed to the on-going quality assessment research in the field of in-process monitoring of the EBM process.

Myocardial infarction, more commonly known as heart attack, is a huge health problem around the world. It is a result of inadequate blood supply to certain parts of the heart and death of heart muscle cells in that region. Although it has been around for a long time, newer and newer ways of probing myocardial infarction is being followed. Bioinformatics and Systems Biology are relatively recent fields to try to give new insights into myocardial infarction. Following the footsteps of others, this in silico study has tried to chime in on the investigation into myocardial infarction. The study began with the gene expression omnibus dataset uploaded to the NCBI from a whole-genome gene expression analysis carried out at Mayo Clinic in Rochester, Minnesota. From the dataset, differentially expressed genes following first-time myocardial infarction were identified and classified into up-regulated and down-regulated ones. Gene Set Enrichment Analysis (GSEA) was carried out on the up-regulated genes which were statistically significant and corresponded with the NCBI generated annotations. Protein-Protein Interaction Network for these genes was constructed. GSEA revealed 5 transcription factors, 5 microRNAs and 3 pathways significantly associated with them. From the Protein-Protein Interaction Network, 6 key proteins (hub nodes) have been identified. These 6 proteins may open a new window of opportunity for the discovery/design of new drugs for mitigating the damage caused by myocardial infarction.

The concept of DC power distribution has gained interest within the research community in the past years; especially due to rapid prevalence of solar PVs as a tool for distributed generation in DC microgrids. Various efficiency analyses have been presented for the DC distribution paradigm, in comparison to the AC counterpart, considering a variety of scenarios. However, even after a number of such comparative efficiency studies, there seems to be a disparity in the results of research efforts - wherein a definite verdict is still unavailable: 'Is DC distribution a more efficient choice as compared to the conventional AC system?' A final verdict is absent primarily due to conflicting results. In this regard, system modeling and the assumptions made in different studies play a significant role in affecting the results of the study. The current paper is an attempt to critically observe the modeling and assumptions used in the efficiency studies related to the DC distribution system. Several research efforts will be analyzed for their approach towards the system upon which they have performed efficiency studies. Subsequently, the paper aims to propose a model that may alleviate the shortcomings in earlier research efforts and be able to give a definite verdict regarding the comparative efficiency of DC and AC networks for residential power distribution.

In this paper we present the measurement of charged pion two-particle femtoscopic correlation functions in $\sqrt{S_{NN}}$= 200 GeV Au+Au collisions, in 31 average transverse mass bins, separately for positive and negative pion pairs. Lévy-shaped source distributions yield a statistically acceptable description of the measured correlation functions, with three physical parameters: correlation strength parameter λ , Lévy index α and Lévy scale parameter R. The transverse mass dependence of these Lévy parameters is then investigated. Their physical interpretation is also discussed, and the appearance of a new scaling variable is observed.

Since their discovery in 1993, numerous microRNAs (miRNAs) have been identified in humans and other eukaryotic organisms, and their role as key regulators of gene expression is still being elucidated. It is now known that miRNAs not only play a central role in the processes that ensure normal development and physiology, but they are often dysregulated in various diseases. In this review, we present an overview of the role of miRNAs in normal renal development and physiology, in maladaptive renal repair after injury, and in the pathogenesis of renal parenchymal diseases. In addition, we describe methods used for their detection and their potential as therapeutic targets. Continued research on renal miRNAs will undoubtedly improve our understanding of diseases affecting the kidneys and may also lead to new therapeutic agents.

This paper employs the two-step procedure developed by Cheung and Ng (1996) to analyze the causality-in-mean and causality-in-variance between the housing and stock markets of the UK. The empirical findings make two key contributions. First, although previous studies have indicated a one-way causal relation from the housing market to the stock market in the UK, this paper discovered a two-way causal relation between them. Second, a causality-in-variance as well as a causality-in-mean was detected from the housing market to the stock market.

The interfacial polymerization (IP) of piperazine (PIP) and trimesoyl chloride (TMC) has been extensively utilized to synthesize nanofiltration (NF) membranes. However, it is still a huge challenge to monitor the IP reaction, because of the fast reaction rate and the formed ultra-thin film. Herein, two effective strategies were applied to reduce the IP reaction rate: (1) the introduction of hydrophilic interlayers between the porous substrate and the formed polyamide layer, and (2) the addition of macromolecular additives in the aqueous solution of PIP. As a result, in situ Fourier transform infrared (FT-IR) spectroscopy was firstly used to monitor the IP reaction of PIP/TMC with hydrophilic interlayers or macromolecular additives in the aqueous solution of PIP. Moreover, the formed polyamide layer growth on the substrate was studied in a real-time manner. The in situ FTIR experimental results confirmed that the IP reaction rates were effectively suppressed and that the formed polyamide thickness was reduced from 138 ± 24 nm to 46 ± 2 nm according to TEM observation. Furthermore, an optimized NF membrane with excellent performance was consequently obtained, which included boosted water permeation of about 141–238 (L/m²·h·MPa) and superior salt rejection of Na₂SO₄ > 98.4%.

Background: Cancer has been one of the most critical health problems during the past decades which require serious consideration, especially in developing countries. Methods: 80 parents of the children with different types of cancers were studied via both questionnaire and person-to-person interview after announcing their informed consent. Results: The highest delay in patients' initial referral was due to the following factors: lack of attention or ignoring the first symptoms, delay in referring to the physician, low economic status and even lack of family support for the patient. In addition, visiting several doctors after the initial diagnosis, uncertainty about the first proposed method, and high cost of treatment can be mentioned as the main causes of delays in the start of treatment. Conclusion: Education plays an important role in identifying the signs of cancer. In addition, proper relationship and cooperation between the health system and physicians as well as provision of adequate information to patients could lead to the long-term cooperation of these patients in continuing their treatment.

P-glycoprotein (P-gp), a membrane-bound transporter, can eliminate xenobiotics by transporting them out of the cells or blood-brain barrier (BBB) at the expense of ATP hydrolysis. Thus, P-gp mediated efflux plays a pivotal role in altering the absorption and disposition of a wide range of substrates. Nevertheless, the mechanism of P-gp substrate efflux is rather complex since it can take place through active transport and passive permeability in addition to multiple P-gp substrate binding sites. A nonlinear quantitative structure-activity relationship (QSAR) model was developed in this study using the novel machine learning-based hierarchical support vector regression (HSVR) scheme to explore the perplexing relationships between descriptors and efflux ratio. The predictions by HSVR were found to be in good agreement with the observed values for the molecules in the training set (n = 50, r² = 0.96, q²_CV = 0.94, RMSE = 0.10, s = 0.10) and test set (n = 13, q² = 0.80–0.87, RMSE = 0.21, s = 0.22). When subjected to a variety of statistical validations, the developed HSVR model consistently met the most stringent criteria. A mock test also asserted the predictivity of HSVR. Consequently, this HSVR model can be adopted to facilitate drug discovery and development.

Integrating triple bottom line (TBL) goals into supply chains (SCs) is a challenging task which necessitates the careful coordination of numerous stakeholders’ individual interests. Recent technological advancements can impact TBL sustainability by changing the design, structure and management of modern SCs. Blockchain technology enables immutable data records and facilitates a shared data view along the supply chain. The Physical Internet (PI) is an overarching framework that can be applied to create a layered and comprehensive view of the SC. In this conceptual paper I define and combine these technologies and derive several high-level research areas and research questions to investigate adoption, management as well as structural SC issues. I suggest a theory-based research agenda for the years to come that exploits the strengths of rigorous academic research, while remaining relevant for the industry. Furthermore, I suggest various well-established theories to tackle the respective research questions and provide specific directions for future research.

The past decade has witnessed enormous progress, which has seen the noncoding RNAs (ncRNAs) turn from the so called dark matter RNA to critical functional molecules, influencing most physiological processes in development and disease contexts. Many ncRNAs interact with each other and are part of networks that influence the cell transcriptome and proteome and consequently the outcome of biological processes. The regulatory circuits controlled by ncRNAs have become increasingly more relevant in cancer. Further understanding of these complex network interactions and how ncRNAs are regulated, is paving the way for the identification of better therapeutic strategies in cancer.

To better understand the genes with altered expression caused by infection with the novel coronavirus strain SARS-CoV-2 causing COVID-19 infectious disease, a tensor decomposition (TD)-based unsupervised feature extraction (FE) approach was applied to a gene expression profile dataset of the mouse liver and spleen with experimental infection of mouse hepatitis virus, which is regarded as a suitable model of human coronavirus infection. TD-based unsupervised FE selected 134 altered genes, which were enriched in protein-protein interactions with orf1ab, polyprotein, and 3C-like protease that are well known to play critical roles in coronavirus infection, suggesting that these 134 genes can represent the coronavirus infectious process. We then selected compounds targeting the expression of the 134 selected genes based on a public domain database. The identified drug compounds were mainly related to known antiviral drugs, several of which were also included in those previously screened with an in silico method to identify candidate drugs for treating COVID-19.

The acetylcholinesterase (AChE) inhibitors are the main drugs for symptomatic treatment of neurodegenerative disorders like Alzheimer’s disease. A recently designed, synthesized and tested hybrid compound between the AChE inhibitor galantamine (GAL) and the antioxidant polyphenol curcumin (CU) showed high AChE inhibition in vitro. Here, we describe tests for acute and short-term toxicity in mice as well as antioxidant tests on brain homogenates measured the levels of malondialdehide (MDA) and glutathione (GSH). Haematological and serum biochemical analyses were also performed. In the acute toxicity tests, the novel AChE inhibitor given orally in mice showed LD50 of 49 mg/kg. The short-term administration of 2.5 and 5 mg/kg did not show toxicity. In the ex vivo tests, the GAL-CU hybrid performed better than GAL and CU themselves. In a dose of 5 mg/kg, it demonstrates 25% reduction in AChE activity, 28% and 73% increase in the levels of MDA and GSH, respectively. No significant changes in blood biochemical data were observed. The GAL-CU hybrid is a novel non-toxic AChE inhibitor with high antioxidant activity which makes it a perspective multitarget drug candidate for treatment of Alzheimer’s disease.

Groundwater contamination is an ever-growing environmental issue that has attracted much and undiminished attention for the past half century. Groundwater contamination may originate from both anthropogenic (e.g., hydrocarbons) and natural compounds (e.g., nitrate and arsenic); to tackle the removal of these contaminants, different technologies have been developed and implemented. Recently, bioelectrochemical systems (BES) have emerged as a potential treatment for groundwater contamination, with reported in situ applications that showed promising results. Nitrate and hydrocarbons (toluene, phenanthrene, benzene, BTEX and light PAHs) have been successfully removed, due to the interaction of microbial metabolism with poised electrodes, in addition to physical migration due to the electric field generated in a BES. The selection of proper BESs relies on several factors and problems, such as the complexity of groundwater and subsoil environment, scale-up issues, and energy requirements that need to be accounted for. Modeling efforts could help predict case scenarios and select a proper design and approach, while BES-based biosensing could help monitoring remediation processes. In this review, we critically analyze in situ BES applications for groundwater remediation, focusing in particular on different proposed setups, and we identify and discuss the existing research gaps in the field.

Sentinel-1A/B radar remote sensing data were applied for the first time to determine the sixth nuclear test, its underground explosion h-bomb location and affected zone in North Korea, on September 3, 2017. Location of epicenters nuclear test were found according to line-of-sight displacement images via its maximum value. Line-of-sight displacement images were obtained by processing in the GMTSAR package in the VirtualBox virtual machine of the Linux Ubuntu 16.04 operation system. In this research, three scenes Sentinel-B data with descending orbits were considered, one after and two before the event (the nuclear test date) scene were used.

As described in previous work, the use of synthetic chemical ingredients in modern cosmetics is postulated to be a cause of damage to the skin microbiome. The discovery that biodiversity on the human skin is currently the only reliable indicator of skin health, meant that for the first time, a mechanism to test for healthy skin was possible. Using this mechanism and in collaboration with The Medical University of Graz, who carried out the independent study, this work aimed to help answer whether modern day synthetic cosmetics are a main cause of long term damage to the skin microbiome. Thirty-two human participants tested three different face washes for their effect on the skin’s microbial diversity, along with skin pH, moisture and TEWL (trans-epidermal water loss), washing twice a day for four weeks. The upper volar forearm of the volunteers was swabbed at the beginning, two weeks in and end (four weeks). 16S rRNA sequencing was used. One leading ‘natural’ brand full of synthetic ingredients, a leading synthetic brand and a 100% natural face wash were used. Results give the first indications of a link between synthetic ingredients in a cosmetics product, and its effect on skin microbiome biodiversity. It paves the way for future studies on the topic with a larger sample group, longer test period and standardised methodology to create a universal standard for testing the health of skin using benchmark diversity values. This can be used in the future to test the effectiveness of cosmetics or ingredients on skin health, leading to the banning of products proven to harm the skin’s natural environment.

Along just over a century of research we moved from learning how to cultivate tissues in a dish to grasping the concepts for creating an entire brain in a vat. As we approach the divisive moment in which we can first detect signs of awareness in such artificially developed organoids, we need to lay foundation for what lays ahead. It is crucial that ethical, legal and moral implications of organoid research are clear and that boundaries are set to separate scientific progress from human life preservation. The largest obstacle may be the definition of consciousness itself, which has arguably been historically neglected by philosophy, psychology and neurosciences at large. One reason may be the difficulties posed by the underlying qualities of awareness, such as its subjective and heterogeneous nature. Another reason may lie on the possibly that consciousness is an overarching emergent property of our brain. For the time being, one can see brain organoids as philosophical zombies, physical analogues of the human brain which mimic sentient human reactions but lack experiential properties of sensation (a.k.a. qualia).

Background: Barleria lupulina Lindl. (Hop-headed) is a small shrub, possess potent anti-inflammatory, analgesic, anti-leukemic, antitumor, anti-hyperglycemic, anti-amoebic, virucidal, diuretic, bactericidal and antibiotic properties. Methods: Cytotoxicity, bioactive assay and genetic analysis of B. lupulina were investigated in the present communication. The leaf extract was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), Neutral red uptake (NRU), DNA fragment, reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP) assay, gene expression analysis and cDNA synthesis to evaluate anti-cancerous potency using cancerous THP-1 cell lines in vitro and in vivo. Results: HPTLC analysis reveals four spots and GC-MS analysis displayed the presence of eleven bioactive compounds among which benzofuranon, hexadecanoic acid, ethyl 9,12,15-octadecatrienoate, and 3,7,11,15-tetramethyl-2-hexadecanoic acid were the most prominent compounds. The ethanolic extract showed significant cytotoxicity (P<0.5) against THP-1 cell line at a concentration of 1mg/mL. The cells were also observed for apoptosis through DNA fragmentation in B. lupulina treated cells. Conclusions: It can be concluded that if the dose range was further refined within the range of 100-1000 µg/mL there could be dose at which the entire population of the THP-1 cell line would be apoptosis induced. The extract induced ROS in the cells after 30 minutes of exposure displaying cytotoxic effects and DNA fragmentation assay.

Objective: This study assessed hearing aid benefits for people with a normal audiogram but hearing-in-noise problems in everyday listening situations. Design: Exploratory double-blinded case control study whereby participants completed retrospective questionnaires, ecological momentary assessments, speech-in-noise testing, and mental effort testing with and without hearing aids. Twenty-seven adults reporting speech-in-noise problems but normal air-conduction pure-tone audiometry took part in the study. They were randomly separated into an experimental group who trialled mild-gain hearing aids with advanced directional processing and a control group fitted with hearing aids with no gain or directionality. Results: Self-reports showed mild-gain hearing aids reduce hearing-in-noise difficulties and provide a better hearing experience (i.e., improved understanding, participation, and mood). Despite the self-reported benefits, the laboratory tests did not reveal a benefit from the mild-gain hearing aids, with no group differences on speech-in-noise tests or mental effort measures. Further, participants found the elevated cost of hearing aids to be a barrier for their adoption. Conclusions: Hearing aids benefit the listening experience in some listening situations for people with normal audiogram who report hearing difficulties in noise. Decreasing the price of hearing aids may lead to greater accessibility to those seeking remediation for their communication needs.

Thermal interface material (TIM) that can exist as liquid at the service temperature enables efficient heat transfer across two adjacent surfaces in electronic applications. In this work, the thermal conductivities of different phase regions in the Ga-In system at various compositions and temperatures are measured for the first time. A modified comparative cut bar technique is used for the measurement of the thermal conductivities of In_xGa_1-x (x=0, 0.1, 0.214, 0.3, and 0.9) alloys at 40, 60, 80, and 100^oC that are the temperatures commonly encountered in consumer electronics. The thermal conductivity values for the liquid and semi-liquid (liquid+β) Ga-In alloys are higher than the TIM currently used in consumer electronics. These measured quantities, along with the available experimental data from the literature, served as input for the thermal conductivity parameter optimization using the CALPHAD (CALculation of PHase Diagram) method for the pure elements, solution phase, and two-phase region. A set of self-consistent parameters for the description of the thermal conductivity of the Ga-In system is obtained. There is good agreement between the measured and calculated thermal conductivity values for all the phases. Hence, it can be envisaged that liquid/semi-liquid Ga-In alloys can be considered as a potential TIM in consumer electronics due to its high thermal conductivity.

The World Anti-Doping Agency has prohibited gene doping in the context of progress in gene therapy. There is a risk that the artificial regulation of genes using plasmids could be applied for gene doping. However, no gold standard method to detect this has been established. Here, we aimed to develop a method to detect multiple transgene fragments as proof of gene doping. First, gene delivery model mice as a mimic of gene doping were created by injecting firefly luciferase plasmid with polyethylenimine (PEI) into the abdominal cavity. The results confirmed successful establishment of the model, with sufficient luminescence upon in vivo imaging. Next, multiple transgene fragments in the model were detected in plasma cell-free (cf)DNA, blood-cell-fraction DNA, and stool DNA using the TaqMan-qPCR assay, with the highest levels in plasma cfDNA. Using just a single drop of whole blood from the model, we also attempted long-term detection. The results showed that multiple transgene fragments were detected until 11 days. These findings indicate that the combination of plasma cfDNA or just one drop of whole blood with TaqMan-qPCR assay is feasible to detect plasmid-PEI-based gene doping. Our findings could accelerate the development of methods for detecting gene doping in humans.

The present work encompasses an application-oriented perspective to the possible employment of gold nanoparticles as nanomedicine in cancer therapeutics. The rationale of the work lies in the growing needs for assessment of advanced alternative treatment of cancer employing functionalized nanoparticles as nanomedicine. Gold nanoparticles fabricated via green chemistry methods by leaves of a time-honored medicinal plant, Piper betle were ascertained for their synthesis and properties under the umbrella of characterization of nanoparticles, through various techniques like UV-vis spectroscopy, FTIR spectroscopy, X-ray diffraction, and scanning electron microscopy. The cytotoxicity assay of well-characterized gold nanoparticles was monitored against lung cancer cell line (A549) by metabolic and imaging assays. MTT assay or the metabolic assay was performed for a range of nanoparticles’ concentrations. The results were promising and proved to be a leading-edge venture, envisaging the possibility of gold nanoparticles for cancer therapeutics.

Software is playing the most important role in recent vehicle innovation, and consequently the amount of software has been rapidly growing last decades. Safety-critical nature of ships, one sort of vehicles, makes Software Quality Assurance (SQA) has gotten to be a fundamental prerequisite. Just-In-Time Software Defect Prediction (JIT-SDP) aims to conduct software defect prediction (SDP) on commit-level code changes to achieve effective SQA resource allocation. The first case study of SDP in maritime domain reported feasible prediction performance. However, we still consider that the prediction model has still rooms for improvement since the parameters of the model are not optimized yet. Harmony Search (HS) is a widely used music-inspired meta-heuristic optimization algorithm. In this article, we demonstrated that JIT-SDP can produce the better performance of prediction by applying HS-based parameter optimization with balanced fitness value. Using two real-world datasets from the maritime software project, we obtained an optimized model that meets the performance criterion beyond baseline of previous case study throughout various defect to non-defect class imbalance ratio of datasets. Experiments with open source software also showed better recall for all datasets despite we considered balance as performance index. HS-based parameter optimized JIT-SDP can be applied to the maritime domain software with high class imbalance ratio. Finally, we expect that our research can be extended to improve performance of JIT-SDP not only in maritime domain software but also in open source software.

Smenamides are an intriguing class of peptide/polyketide molecules of marine origin showing antiproliferative activity against lung cancer Calu-1 cells at nanomolar concentrations through a clear pro-apoptotic mechanism. To probe the role of the activity-determining structural features, the 16-epi-analogue of smenamide A and eight simplified analogues in the 16-epi series were prepared using a flexible synthetic route. The synthetic analogues were tested on multiple myeloma (MM) cell lines showing that the configuration at C-16 slightly affects the activity, since the 16-epi-derivative is still active at nanomolar concentrations. Interestingly, it was found that the truncated compound 8, mainly composed of the pyrrolinone terminus, was not active while compound 17, essentially lacking the pyrrolinone moiety, was 1000-fold less active than the intact substance and was the most active among all the synthesized compounds.

A significant part of the literature on innovative practice in medicine relates to seizing opportunities and curbing harms for patients in desperate situations. Unfortunately, the term innovation has multiple meanings and a rich rhetorical flourish that adds confusion and misunderstanding to an already difficult debate. This paper aims to enhance the current definition of innovative practice for medicine. First, we replace the term innovation with the more literal of new non-validated practice. To identify this meaning, we analyse the traditional research ethics’ distinction between research, validated practice, and innovation in the Belmont Report. Second, we propose the following explicit definition of new non-validated practice: the first or recent use of diagnostic, therapeutic or preventive interventions that introduce a significant change, with an insufficient level of evidence of safety or efficacy for regular healthcare, and with the main aim to benefit individual patients. This definition is a promising conceptual tool to inform empirical research, ethicists, and the harmonization of its regulation and legislation (e.g. right-to-try laws).

Breast cancer treatment mostly revolved around radiation therapy and surgical interventions, these treatments doesn’t provide satisfactory relief to the patients and carry unmanageable side-effects. Nanomaterials show promising results in treating cancer cells and have many advantages such as high biocompatibility, bioavailability and effective therapeutic capabilities. Interestingly, fluorescent magnetic nanoparticles have been used in many biological and diagnostic applications, but there is no report of use of fluorescent magnetic submicronic polymer nanoparticles (FMSP-nanoparticles) in the treatment of human breast cancer cells. In the present study, we have tested the effect FMSP-nanoparticles on human breast cancer cells (MCF-7). We have tested different concentrations (1.25µg/1mL, 12.5µg/mL and 50µg/1mL) of FMSP-nanoparticles in MCF-7 cells and evaluated the nanoparticles response morphometrically. Our results revealed that FMSP-nanoparticles produced a concentration dependent effect on the cancer cells, dose of 1.25µg/mL produced no significant effect on the cancer cell morphology and cell death, whereas dosages of 12.5µg/mL and 50µg/mL respectively showed significant nuclear augmentation, disintegration, chromatic condensation followed by dose dependent cell death. Our results demonstrate FMSP-nanoparticles have ability to induce cell death in MCF-7 cells and may be considered as a potential anti-cancer agent for breast cancer treatments.

Background: Breast cancer is the leading cause of cancer mortality and morbidity among Indonesian women. Identification of biological pathways leading into therapeutic resistance through in vitro model is an important step to develop alternative effective therapy in breast cancer. Loss of PTEN expression has been associated with resistance to chemotherapy by involving PI3K/PTEN- dependent apoptosis pathway. We conducted in vitro experiment to investigate the association of hsa-miR-21 and PTEN expression in Doxorubicin-resistant MCF-7 cell line. Methods: Parental MCF-7 cells were periodically incubated with Doxorubicin to obtain specific Dox-resistant variant determined by IC50 using MTT assay. PTEN protein expression was analyzed using immunocytochemistry. Expression of mature has-miR-21 was measured using qRT-PCR. Results: The IC50 of Doxorubicin in parental MCF-7 and Doxorubicin-resistant MCF-7 cells (MCF-7/Dox) was 0.68 and 5.78 µg/ml, respectively. Hsa-miR-21 was significantly overexpressed in MCF-7/Dox cells compared to parental MCF cells (7.94 fold changes). Conclusion: PTEN and hsa-miR-21 expression levels were negatively correlated in Doxorubicin resistant-MCF cells. Further study to confirm the causal relationship of miR-21 overexpression and PTEN downregulation in MCF-7/Dox is required.

We study the resonant dipole-dipole interaction energy between two uniformly accelerated identical atoms, one excited and the other in the ground state, prepared in a correlated Bell-type state, and interacting with the scalar field or the electromagnetic field nearby a perfectly reflecting plate. We suppose the two atoms moving with the same uniform acceleration, parallel to the plane boundary, and that their separation is constant during the motion. We separate the contributions of vacuum fluctuations and radiation reaction field to the resonance energy shift of the two-atom system, and show that Unruh thermal fluctuations do not affect the resonance interaction, which is exclusively related to the radiation reaction field. However, nonthermal effects of acceleration in the radiation-reaction contribution, beyond the Unruh acceleration-temperature equivalence, affect the resonance interaction energy. By considering specific geometric configurations of the two-atom system relative to the plate, we show that the presence of the mirror significantly modifies the resonance interaction energy between the two accelerated atoms. In particular, we find that new and different features appear with respect to the case of atoms in the free space, related to the presence of the boundary and to the peculiar structure of the quantum electromagnetic field vacuum in the locally inertial frame. Our results suggest the possibility to exploit the resonance interaction between accelerated atoms, as a probe for detecting the elusive effects of atomic acceleration on radiative processes.

Alkyl moieties—open chain or cyclic—are common in drug molecules and can be internal or terminal. The open-chain alkyls can be linear or branched; the cyclic alkyls may be substituted. Usually, the branches in open-chain alkyls and substituents in cycloalkyls influence both the pharmacokinetics and pharmacodynamics of a drug molecule. The hydrophobicity of alkyl moieties in drug molecules is modified by metabolic hydroxy functionalization via free-radical intermediates to give primary, secondary, or tertiary alcohols depending on the class of the substrate carbon. The hydroxymethyl groups resulting from the functionalization of methyl groups are mostly oxidized further to carboxyl groups to give carboxy metabolites. As observed from the surveyed cases in this review, hydroxy functionalization leads to loss, attenuation, or retention of pharmacologic activity with respect to the parent drug. On the other hand, carboxy functionalization leads to a loss of activity with the exception of only a few cases in which activity is retained. The exceptions are those groups in which the carboxy functionalization occurs at a position distant from a well-defined primary pharmacophore. Some parent-drug equiactive hydroxy metabolites have been developed into metabolite ester prodrugs, while some of the parent-drug carboxy metabolites have been developed into metabolite drugs. In this review, we present and discuss the above state of affairs for a variety of drug classes, using selected drug members to show the effect on pharmacologic activity as well as dependence of the metabolic change on drug molecular structure. Some subtexts found to manifest from the hydroxy and carboxy functionalization of alkyl moieties in drug molecules are presented and discussed. The review provides basis for informed predictions of (i) structural features required for metabolic hydroxy and carboxy functionalization of alkyl moieties in existing or planned small drug molecules; and (ii) whether the resulting metabolites will possess pharmacologic activity or be devoid of it.

Bamboo plastic composites have become a hot research topic and a key focus of research. However, the many strong, polar, hydrophilic hydroxyl groups in bamboo flour (BF) results in poor interfacial compatibility between BF and hydrophobic polymers. Maleic anhydride-esterified (MAH-e-BF) and lactic acid-esterified bamboo flour (LA-e-BF) were prepared using an in situ solid-phase esterification method with BF as the raw material and maleic anhydride or lactic acid as the esterifying agent. Fourier transform infrared spectroscopy results confirmed that BF esterification with maleic anhydride and lactic acid was successful, with the esterification degrees of MAH-e-BF and LA-e-BF at 21.04 and 14.36%%, respectively. Esterified BF was characterized by scanning electron microscopy, contact angle testing, X-ray diffractometry, and thermogravimetric analysis. The results demonstrated that esterified BF surfaces were covered with graft polymer and the surface roughness and bonding degree of MAH-e-BF clearly larger than those of LA-e-BF. The hydrophobicity of esterified BF was significantly higher than BF and the hydrophobicity of MAH-e-BF better than LA-e-BF. The crystalline structure of esterified BF showed some damage, with MAH-e-BF exhibiting a greater decrease in crystallinity than LA-e-BF. Overall, the esterification reaction improved BF thermoplasticity, with the thermoplasticity of MAH-e-BF appearing better than LA-e-BF.