Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeted Transposition of Minicircle DNA Using Single-Chain Antibody Conjugated Cyclodextrin-Modified Poly (Propylene Imine) Nanocarriers

Simple Summary Gene therapy for the treatment of malignancies is an emerging and promising area of particular interest. Therefore, it is imperative to develop effective delivery systems for the specific transfer of nucleic acids into tumors. In comparison to viral vectors, non-viral delivery systems tend to be simple to manufacture, show lower immunogenicity, and are associated with fewer regulatory issues when translated into clinical settings. The aim of our study was to develop single-chain antibody conjugated cyclodextrin-modified poly(propylene imine) (PPI) nanocarriers, comprising β-cyclodextrin-modified PPI, mono-biotinylated, maltose-modified PPI, neutravidin and mono-biotinylated prostate stem cell antigen (PSCA)-specific single-chain antibodies for the targeted transposition of minicircle DNA into PSCA-positive tumor cells. Remarkably, we achieved long-term expression of a therapeutic p53 gene in PSCA-positive tumor cells by combining our tumor-specific hybrid polyplexes with the Sleeping Beauty transposon system in minicircle format. Abstract Among non-viral vectors, cationic polymers, such as poly(propylene imine) (PPI), play a prominent role in nucleic acid delivery. However, limitations of polycationic polymer-based DNA delivery systems are (i) insufficient target specificity, (ii) unsatisfactory transgene expression, and (iii) undesired transfer of therapeutic DNA into non-target cells. We developed single-chain antibody fragment (scFv)-directed hybrid polyplexes for targeted gene therapy of prostate stem cell antigen (PSCA)-positive tumors. Besides mono-biotinylated PSCA-specific single-chain antibodies (scFv(AM1-P-BAP)) conjugated to neutravidin, the hybrid polyplexes comprise β-cyclodextrin-modified PPI as well as biotin/maltose-modified PPI as carriers for minicircle DNAs encoding for Sleeping Beauty transposase and a transposon encoding the gene of interest. The PSCA-specific hybrid polyplexes efficiently delivered a GFP gene in PSCA-positive tumor cells, whereas control hybrid polyplexes showed low gene transfer efficiency. In an experimental gene therapy approach, targeted transposition of a codon-optimized p53 into p53-deficient HCT116p53−/−/PSCA cells demonstrated decreased clonogenic survival when compared to mock controls. Noteworthily, p53 transposition in PTEN-deficient H4PSCA glioma cells caused nearly complete loss of clonogenic survival. These results demonstrate the feasibility of combining tumor-targeting hybrid polyplexes and Sleeping Beauty gene transposition, which, due to the modular design, can be extended to other target genes and tumor entities.
Human Capital, Urbanization and Dynamics of Economic Growth and Development

The process of economic growth and development has been shifted towards new strategies of entrepreneurship, institutional development, and market development. The shifting of the development process towards new strategies needs human capital, developed infrastructure, and effective policy reforms. This study investigates how urbanization impacts economic growth and development through the channels of external economies, institutional development, and human capital accumulation. The study focuses first on finding the relationship between human capital and urbanization and their convergence towards economic growth through capacity development. Secondly, it examines the role of urbanization in the formation of human capital and finds the channels through which it facilitates markets. By using econometric time series techniques, we found that urbanization plays a key role in the accumulation of human capital through structural changes and has a long-term relationship with economic growth and development. Our analysis shows that the demographic change of the population from rural to urban stimulates infrastructural development, investment in human capital, and institutional arrangements. Results of the study also suggest that the process of demographic transformation not only increases entrepreneurship activities but also drives up the living standards of citizens through the provision of social services.JEL Classification: O18; J24; O4; H77. Doi: 10.28991/HEF-2021-02-04-06 Full Text: PDF
SPACE UTILIZATION IMPROVEMENT IN CNC MACHINING UNIT THROUGH LEAN LAYOUT

Lean is the term used to describe the production system developed by the Toyota company in the post World War II years. "Lean" comes from the ability to achieve more with less resource, by continuous elimination of waste. Ess Enn Auto CNC Private limited is a leading small scale company manufacturing precision machined components for the past 30 years in Bangalore. The enthused customers of Ess Enn Auto CNC have raised the production demand which could not be fulfilled with existing facilities. In order to continue serving increased customer needs, Ess Enn planned to acquire nine new machines additionally. The space constraint provided an opportunity to integrate lean techniques into the facility layout to accommodate all the new machines and to optimise the material movement with minimal investment. The existing layout was modelled using AutoCAD, software. Product, processing, and resource data were collected to analyse current layout deliverable levels (space utilisation, material travel distance, material handling cost, etc). Alternate layouts were generated using lean layout concepts such as ‘group technology’ and ‘systematic layout planning’, which facilitate relocating the equipment according to product processing. A suitable layout with efficient space utilisation and effective material handling was selected. This selected layout was validated and recommended for implementation. The money saved in Unit-2 monthly rent and overall material movement optimization will lead to a savings of INR 6,72,828 per annum. The recommended layout will incurs an estimated investment of INR 9,90,456 and the ROI will be 1.83 years. The new layout will free up half of the underground floor which can be used for future expansion. The flames of lean philosophy in Ess Enn have been fuelled by executing new layout, and this new layout will craft an opportunity to taste the other flavours of lean concepts such as 5S, Kanban, JIT, small lot production, etc.
Research Policy of the Investigational Drugs in the Clinical Trial

Yousef Ahmed Alomi*, BSc. Pharm, MSc. Clin Pharm, BCPS, BCNSP, DiBA, CDE Critical Care Clinical Pharmacists, TPN Clinical Pharmacist, Freelancer Business Planner, Content Editor, and Data Analyst, Riyadh, SAUDI ARABIA. Amal Hassan Al-Najjar, BSc, MSc, Drug and Poison Information Center, Security Forces Hospitals, Riyadh, SAUDI ARABIA. Hamidah Qasim Ali Abushomi, BSc, MSc. Clin Pharm Dammam Medical Complex, Dammam, SAUDI ARABIA. Maha Hussein Almadany, BSc, Pharm, Health Care Quality Management Professional Diploma (HCQM), Pharmacy Quality Department, King Salman bin Abdulaziz Medical City, Al Madina Al Monwarah, SAUDI ARABIA.
Phase-shifted controlled forward mode AC/AC converters with high frequency AC links

A circuit topology family of the forward mode AC/AC converters with high frequency ac link are proposed. The kind of circuit topologies are constituted of input cycloconverter, high frequency transformer, and output cycloconverter. The phase-shifted control strategy and steady principles are deeply investigated. The output characteristics of the converters are given. By using commutation overlap of the output cycloconverter and the polarity selection of the input voltage and the output filtering inductance current, the leakage inductance energy and the output filtering inductance current are naturally commutated, and the surge voltage and the surge current of the cycloconverters are overcome. The converters have the advantages such as simple topology, two-stage power conversions(LFAC/HFAC/LFAC), bi-directional power flow, high frequency electrical isolation, good line current waveform and output voltage waveform, and strong load adapting function. The converters lay key technical foundation on new-type regulated sinusoidal ac power supplies and electronic transformers. The correction and advancement of the converters are well verified by simulation and principle test.
Vitamin D Deficiency in Women with Breast Cancer: A Correlation with Osteoporosis? A Machine Learning Approach with Multiple Factor Analysis

Breast cancer (BC) is the most frequent malignant tumor in women in Europe and North America, and the use of aromatase inhibitors (AIs) is recommended in women affected by estrogen receptor-positive BCs. AIs, by inhibiting the enzyme that converts androgens into estrogen, cause a decrement in bone mineral density (BMD), with a consequent increased risk of fragility fractures. This study aimed to evaluate the role of vitamin D3 deficiency in women with breast cancer and its correlation with osteoporosis and BMD modifications. This observational cross-sectional study collected the following data regarding bone health: osteoporosis and osteopenia diagnosis, lumbar spine (LS) and femoral neck bone mineral density (BMD), serum levels of 25-hydroxyvitamin D3 (25(OH)D3), calcium and parathyroid hormone. The study included 54 women with BC, mean age 67.3 ± 8.16 years. Given a significantly low correlation with the LS BMD value (r2 = 0.30, p = 0.025), we assessed the role of vitamin D3 via multiple factor analysis and found that BMD and vitamin D3 contributed to the arrangement of clusters, reported as vectors, providing similar trajectories of influence to the construction of the machine learning model. Thus, in a cohort of women with BC undergoing Ais, we identified a very low prevalence (5.6%) of patients with adequate bone health and a normal vitamin D3 status. According to our cluster model, we may conclude that the assessment and management of bone health and vitamin D3 status are crucial in BC survivors.
Impact of Nano- and Micro-Sized Chromium(III) Particles on Cytotoxicity and Gene Expression Profiles Related to Genomic Stability in Human Keratinocytes and Alveolar Epithelial Cells

Exposure to Cr(VI) compounds has been consistently associated with genotoxicity and carcinogenicity, whereas Cr(III) is far less toxic, due to its poor cellular uptake. However, contradictory results have been published in relation to particulate Cr2O3. The aim of the present study was to investigate whether Cr(III) particles exerted properties comparable to water soluble Cr(III) or to Cr(VI), including two nano-sized and one micro-sized particles. The morphology and size distribution were determined by TEM, while the oxidation state was analyzed by XPS. Chromium release was quantified via AAS, and colorimetrically differentiated between Cr(VI) and Cr(III). Furthermore, the toxicological fingerprints of the Cr2O3 particles were established using high-throughput RT-qPCR and then compared to water-soluble Cr(VI) and Cr(III) in A549 and HaCaT cells. Regarding the Cr2O3 particles, two out of three exerted only minor or no toxicity, and the gene expression profiles were comparable to Cr(III). However, one particle under investigation released considerable amounts of Cr(VI), and also resembled the toxicity profiles of Cr(VI); this was also evident in the altered gene expression related to DNA damage signaling, oxidative stress response, inflammation, and cell death pathways. Even though the highest toxicity was found in the case of the smallest particle, size did not appear to be the decisive parameter, but rather the purity of the Cr(III) particles with respect to Cr(VI) content.
A Model Intercomparison Analysis for Controls on C Accumulation in North American Peatlands

Peatland biogeochemical processes have not been adequately represented in existing earth system models, which might have biased the quantification of Arctic carbon‐climate feedbacks. We revise the Peatland Terrestrial Ecosystem Model (PTEM) by incorporating additional peatland biogeochemical processes. The revised PTEM is evaluated by comparing with Holocene Peatland Model (HPM) in simulating peat physical and biogeochemical dynamics in three North American peatlands: a permafrost‐free fen site, a permafrost‐free bog site and a permafrost bog site. Peatland carbon dynamics are simulated from peat initiation to 1990 and then to year 2300. Model responses to the changes in temperature and precipitation are analyzed to identify key processes affecting peatland carbon accumulation rates. We find that the net C balance is sensitive to water table depth and nutrient availability. Future simulations to year 2300 are conducted with both models under RCP 2.6, RCP 4.5, and RCP 8.5. PTEM predicts these peatlands to be C sources or weaker C sinks when insufficient precipitation suppresses soil moisture and thereby net N mineralization and net primary production, while HPM predicts the same when drier climate leads to increasing water table depth. Our results highlight the importance of water balance and C‐N feedback on peatland C dynamics. With a warmer climate, these peatlands could become a weaker C sink or a source under drier conditions, otherwise a larger C sink if wetter. Improved understanding to peatland processes can help future quantification of peatland C dynamics in the boreal and Arctic regions.
Characterization inference based on joint-optimization of multi-layer semantics and deep fusion matching network

The whole sentence representation reasoning process simultaneously comprises a sentence representation module and a semantic reasoning module. This paper combines the multi-layer semantic representation network with the deep fusion matching network to solve the limitations of only considering a sentence representation module or a reasoning model. It proposes a joint optimization method based on multi-layer semantics called the Semantic Fusion Deep Matching Network (SCF-DMN) to explore the influence of sentence representation and reasoning models on reasoning performance. Experiments on text entailment recognition tasks show that the joint optimization representation reasoning method performs better than the existing methods. The sentence representation optimization module and the improved optimization reasoning model can promote reasoning performance when used individually. However, the optimization of the reasoning model has a more significant impact on the final reasoning results. Furthermore, after comparing each module’s performance, there is a mutual constraint between the sentence representation module and the reasoning model. This condition restricts overall performance, resulting in no linear superposition of reasoning performance. Overall, by comparing the proposed methods with other existed methods that are tested using the same database, the proposed method solves the lack of in-depth interactive information and interpretability in the model design which would be inspirational for future improving and studying of natural language reasoning.
On becoming a Possibilist: Some infl uences fr om brief therapies

“” The ecologist has just presented a forceful case for renewable energy, solar and wind powered alternatives to using up the earth’s precious fi nite resources. He is talking at an innovative conference in Gothenburg, Sweden, organised to bring together ecologists and systemic psychotherapists to discuss the inter-weave of ideas and practices that may provide some creative common ground. It is an adventurous attempt at trans-disciplinary learning. After the ecologist has presented his case for lobbying governments and pressure groups in the European Parliament, a sceptical voice speaks out. “You say we should continue to pressurise government departments to take notice and implement the policies you advocate. But”, continues the speaker, “human nature as it is will not respond. We only respond after there has been a disaster. You are an optimist. Too optimistic“. The ecologist pauses and says, “Well, I don’t think I am an
Visualization of Topological Pharmacophore Space with Graph Edit Distance

A topological pharmacophore (TP) is a chemical graph-based pharmacophore representation, where nodes are pharmacophoric features (PF) and edges are topological distances between PFs. Previously proposed sparse pharmacophore graphs (SPhGs) for TPs were shown to be effective in identifying structurally different active compounds while maintaining the interpretability of the graphs. However, one limitation of using SPhGs as queries is that many structurally similar SPhGs can be identified from a set of active compounds, requiring the classification and visualization of SPhGs, followed by an understanding of the pharmacophore hypotheses. In this study, we propose a scheme for SPhG analysis based on dimensionality reduction techniques with the graph edit distance (GED) metric. This metric enables measuring similarities among SPhGs in a quantitative manner. The visualization of SPhGs, which themselves are the graphs shared by active compounds, can help us understand the pharmacophore hypotheses as well as the data set. As a proof-of-concept study, we generated two-dimensional SPhG-maps using three dimensionality reduction techniques for six biological targets. A comparison with other pharmacophore representations was also conducted. We demonstrated knowledge extraction (interpretation of the data set) from the generated maps. Our findings include a suitable mapping algorithm as well as a pharmacophore hypothesis analysis procedure using an SPhG-map.
Hydrogen Sulfide Inhibits Bronchial Epithelial Cell Epithelial Mesenchymal Transition Through Regulating Endoplasm Reticulum Stress

Epithelial mesenchymal transition (EMT) is a contributing factor in remodeling events of chronic obstructive pulmonary disease (COPD). Hydrogen sulfide (H2S) has been implicated in the pathogenesis of COPD, but the effect of H2S in regulating EMT and the underlying mechanisms is not clear. In this study, we assessed endoplasmic reticulum (ER) stress markers, EMT markers and associated signal molecules in rat lungs, bronchial epithelial cells, and human peripheral lung tissues to investigate the effect of H2S in regulating EMT and the underlying mechanisms. We found that EMT and ER stress occurred in lung epithelial cells, especially in the bronchial epithelial cells of smokers and COPD patients. In cigarette smoke (CS)-exposed rats, intraperitoneal injection of NaHS significantly alleviated CS-induced lung tissue damage, small airway fibrosis, ER stress, and EMT, while intraperitoneal injection of propargylglycine (cystathionine-gamma-lyase inhibitor) aggravated these effects induced by CS. In the nicotine-exposed 16HBE cells, an appropriate concentration of H2S donor not only inhibited nicotine-induced ER stress, but also inhibited nicotine-induced enhancement of cell migration ability and EMT. ER stress nonspecific inhibitors taurine and 4-phenyl butyric acid also inhibited nicotine-induced enhancement of cell migration ability and EMT. Both H2S and inositol-requiring enzyme 1 (IRE1) activation inhibitor 4μ8C inhibited nicotine-induced activation of IRE1, Smad2/3 and EMT. These results suggest that H2S inhibits CS- or nicotine-induced ER stress and EMT in bronchial epithelial cells and alleviates CS-induced lung tissue damage and small airway fibrosis. The IRE1 signal pathway and Smad2/3 may be responsible for the inhibitory effect of H2S.
A Novel Activation Function for Brain Tumor Segmentation using V-NET Approach

This work emphasizes on automatic brain tumor segmentation from three dimensional magnetic resonance imaging (3D-MRI) scan images. We have used fully convolutional neural networks (FCNN) for extracting whole tumor. The proposed architecture is based on V-Net architecture. We have developed a new activation function for training the network. ReLU is used and in experiment 2, proposed activation function is used. We have conducted two experiments for brain tumor segmentation by varying the activation functions. In experiment 1, we have also used dice loss as loss function. The proposed method is trained and tested using BraTs 2021 training dataset which contains 2000 volumes of 3D-MRI scans. The proposed method’s performance is closer to the manually segmented images by experienced neurologists available with BraTs 2021 datasets. We have obtained a mean dice score of whole tumor as 99% while using proposed activation function which is higher when compared to the existing methods. We conclude that our novel activation function proposed activation function produced enhanced accuracy and dice score when compared with ReLU activation function.
Potential of Indonesian Community Food Sources which are Rich in Fiber as an Alternative Staple Food for Type 2 Diabetics: A Scoping Review

BACKGROUND: Staple foods as a source of carbohydrates contribute most of human energy needs. Based on Perkeni’s recommendation, diabetic patients can consume at least 45–60% of carbohydrate sources. In addition, several previous studies have shown that increasing the adequacy of dietary fiber above 20–25 g/day can improve glycemic control. AIM: Our scoping review investigated the potential of Indonesian food sources, namely, sorghum and corn as a source of carbohydrates and also fiber as a substitute rice for diabetic patients. METHODS: We systematically used electronic databases searched such as PubMed, Science Direct, Web of Science, Portal Garuda, Sinta Ristekbrin, and Google Scholar. We choose the relevant documents used experimental animals and humans’ studies then published between 2011 and 2021. RESULTS: In total, 17 relevant articles discuss the relationship between giving corn or sorghum with blood glucose levels of animal studies and human. Some studies showed that the effect of eating sorghum or its derivatives can reduce blood glucose. As well as, the other articles indicated eating corn or its derivatives also decrease glycemic response of healthy people and experimental animals. Corn and sorghum contain dietary fiber in the form of resistant starch and have low glycemic index compare with white rice. Furthermore, corn also contains essential fat, mineral, β -Carotene, and isoflavone, while sorghum also includes phenolic components such as phenolic acids and flavonoids. CONCLUSIONS: Sorghum and corn have the potential as an alternative staple food to achieve a better glycemic response in diabetic patients.