Search results for: Cancer Stem Cells

Authors: A. Banerjee, C. Grazon, B. Nadal, T. Pons, Y. Krishnan, B. Dubertret

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Quantum Dots (QDs) have emerged as novel fluorescent probes for biomedical applications. The photophysical properties of QDs such as broad absorption, narrow emission spectrum, reduced blinking, and enhanced photostability make them advantageous over organic fluorophores. However, for some biological applications, QDs need to be first targeted to specific intracellular locations. It parallel, base pairing properties and biocompatibility of DNA has been extensively used for biosensing, targetting and intracellular delivery of numerous bioactive agents. The combination of the photophysical properties of QDs and targettability of DNA has yielded fluorescent, stable and targetable nanosensors. QD-DNA conjugates have used in drug delivery, siRNA, intracellular pH sensing and several other applications; and continue to be an active area of research. In this project, a novel method to synthesise QD-DNA conjugates and their applications in bioimaging are investigated. QDs are first solubilized in water using a thiol based amphiphilic co-polymer and, then conjugated to amine functionalized DNA using a heterobifunctional linker. The conjugates are purified by size exclusion chromatography and characterized by UV-Vis absorption and fluorescence spectroscopy, electrophoresis and microscopy. Parameters that influence the conjugation yield such as reducing agents, the excess of salt and pH have been investigated in detail. In optimized reaction conditions, up to 12 single-stranded DNA (15 mer length) can be conjugated per QD. After conjugation, the QDs retain their colloidal stability and high quantum yield; and the DNA is available for hybridization. The reaction has also been successfully tested on QDs emitting different colors and on Gold nanoparticles and therefore highly generalizable. After extensive characterization and robust synthesis of QD-DNA conjugates in vitro, the physical properties of these conjugates in cellular milieu are being invistigated. Modification of QD surface with DNA appears to remarkably alter the fate of QD inside cells and can have potential implications in therapeutic applications.

Keywords: bioimaging, cellular targeting, drug delivery, photostability

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Authors: Moiseenko F. V., Volkov N. M., Zhabina A. S., Stepanova E. O., Kirillov A. V., Myslik A. V., Artemieva E. V., Agranov I. R., Oganesyan A. P., Egorenkov V. V., Abduloeva N. H., Aleksakhina S. Yu., Ivantsov A. O., Kuligina E. S., Imyanitov E. N., Moiseyenko V. M.

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Analysis of ctDNA in patients with NSCLC is an emerging biomarker. Multiple research efforts of quantitative or at least qualitative analysis before and during the first periods of treatment with TKI showed the prognostic value of ctDNA clearance. Still, these important results are not incorporated in clinical standards. We evaluated the role of ctDNA in EGFR-mutated NSCLC receiving first-line TKI. Firstly, we analyzed sequential plasma samples from 30 patients that were collected before intake of the first tablet (at baseline) and at 6, 12, 24, 36, and 48 hours after the “starting point.” EGFR-M+ allele was measured by ddPCR. Afterward, we included sequential qualitative analysis of ctDNA with cobas® EGFR Mutation Test v2 from 99 NSCLC patients before the first dose, after 2 and 4 months of treatment, and on progression. Early response analysis showed the decline of EGFR-M+ level in plasma within the first 48 hours of treatment in 11 subjects. All these patients showed objective tumor response. 10 patients showed either elevation of EGFR-M+ plasma concentration (n = 5) or stable content of circulating EGFR-M+ after the start of the therapy (n = 5); only 3 of these patients achieved an objective response (p = 0.026) when compared to the former group). The rapid decline of plasma EGFR-M+ DNA concentration also predicted for longer PFS (13.7 vs. 11.4 months, p = 0.030). Long-term ctDNA monitoring showed clinically significant heterogeneity of EGFR-mutated NSCLC treated with 1st line TKIs in terms of progression-free and overall survival. Patients without detectable ctDNA at baseline (N = 32) possess the best prognosis on the duration of treatment (PFS: 24.07 [16.8-31.3] and OS: 56.2 [21.8-90.7] months). Those who achieve clearance after two months of TKI (N = 42) have indistinguishably good PFS (19.0 [13.7 – 24.2]). Individuals who retain ctDNA after 2 months (N = 25) have the worst prognosis (PFS: 10.3 [7.0 – 13.5], p = 0.000). 9/25 patients did not develop ctDNA clearance at 4 months with no statistical difference in PFS from those without clearance at 2 months. Prognostic heterogeneity of EGFR-mutated NSCLC should be taken into consideration in planning further clinical trials and optimizing the outcomes of patients.

Keywords: NSCLC, EGFR, targeted therapy, ctDNA, prognosis

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Authors: Hwang Ahreum, Kang Taejoon, Kim Bongsoo

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Nanosensors for high sensitive detection of diseases have been widely studied to improve the quality of life. Here, we suggest robust nano-plasmonic diagnostic sensor using cysteine tagged protein G (Cys3-protein G) and ultraflat, ultraclean and single-crystalline Au nanoplates. Protein G formed on an ultraflat Au surface provides ideal background for dense and uniform immobilization of antibodies. The Au is highly stable in diverse biochemical environment and can immobilize antibodies easily through Au-S bonding, having been widely used for various biosensing applications. Especially, atomically smooth single-crystalline Au nanomaterials synthesized using chemical vapor transport (CVT) method are very suitable to fabricate reproducible sensitive sensors. As the C-reactive protein (CRP) is a nonspecific biomarker of inflammation and infection, it can be used as a predictive or prognostic marker for various cardiovascular diseases. Cys3-protein G immobilized uniformly on the Au nanoplate enable CRP antibody (anti-CRP) to be ordered in a correct orientation, making their binding capacity be maximized for CRP detection. Immobilization condition for the Cys3-protein G and anti-CRP on the Au nanoplate is optimized visually by AFM analysis. Au nanoparticle - Au nanoplate (NPs-on-Au nanoplate) assembly fabricated from sandwich immunoassay for CRP can reduce zero-signal extremely caused by nonspecific bindings, providing a distinct surface-enhanced Raman scattering (SERS) enhancement still in 10-18 M of CRP concentration. Moreover, the NP-on-Au nanoplate sensor shows an excellent selectivity against non-target proteins with high concentration. In addition, comparing with control experiments employing a Au film fabricated by e-beam assisted deposition and linker molecule, we validate clearly contribution of the Au nanoplate for the attomolar sensitive detection of CRP. We expect that the devised platform employing the complex of single-crystalline Au nanoplates and Cys3-protein G can be applied for detection of many other cancer biomarkers.

Keywords: Au nanoplate, biomarker, diagnostic sensor, protein G, SERS

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Authors: Levylee Bautista, Dawn Grace Santos, Aishwarya Veluchamy, Jesusa Santos, Ghafoor, Jr. I Haque, Rodolfo Rafael

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The booming interest in using natural compounds as an alternative to conventional medications has paved way to focus the attention on plants that provide rich sources of bioactive phytochemicals. For regulatory purposes, evaluation of the genotoxic effects of such alternatives is therefore empirical as part of the plant’s hazard assessment. Sesbania grandiflora is among the plants used as a traditional remedy in folk medicine and a subject of research for its medicinal benefits. This study aimed to evaluate the genotoxic potential induced by S. grandiflora flower methanol extract (SGFME) in terms of the frequency of micronucleus (MN) in polychromatic erythrocyte (PCE) (MNPCE) and PCE ratio employing the micronucleus assay. The frequency of MN was examined in bone marrow cells (BMCs) obtained from male Swiss albino mice exposed in vivo to four different concentrations (11.25, 22.5, 40, and 90 mg/kg) of SGFME and MMC (70 mg/kg; positive control) and sacrificed 24 hours post-intraperitoneal injection. Results showed a significant (p < 0.01) rate of MNPCEs for 11.25 and 22.5 tested concentrations of SGFME and is comparable with the MMC-treated mice. Although PCE ratio values in all doses of SGFME-treated mice were over 0.20, it is worth noting that 40 and 90 tested concentrations of SGFME-treated mice exhibited the lowest value, i.e., 0.22 and 0.28, respectively. The present study has demonstrated that S. grandiflora possesses genotoxic potential for murine BMCs. Such activity could be ascribed from the bioactive compounds present in S. grandiflora that require further isolation and characterization of the active molecules. Likewise, findings of this study warrant a caution of the use of S. grandiflora insomuch as further investigations do not demonstrate their safety.

Keywords: genotoxicity, micronucleus, phytochemicals, Sesbania grandiflora

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Authors: Vahab Behmanesh

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Metabolic syndrome is defined as having at least three of the five metabolic risk factors, including abdominal obesity, high blood pressure, high triglycerides, low HDL, and insulin resistance. Lifestyle changes towards reducing physical activity, unhealthy eating habits Especially the high-fat and high-carbohydrate diet is directly related to metabolic syndrome, and due to the epidemic of overweight and sedentary life, metabolic syndrome is a serious problem worldwide. On the other hand, vitamin D deficiency is considered as one of the most common problems in the world, which is related to the dysfunction of beta cells and insulin resistance, and therefore, vitamin D deficiency is considered as a factor in the occurrence of metabolic syndrome. 40 subjects (age: 16.12 ± 4.4 years and body mass index 25.61 ± 4.4 kg/m2) were randomly assigned to groups of aerobic exercise and placebo, aerobic exercise and vitamin D and placebo (no exercise) were divided. Vitamin D was taken at a dose of 50,000 units per week in a double-blind format for eight weeks, and the daily aerobic exercise program was performed for 50 to 60 minutes, three doses per week, with an intensity of 50-60% of the maximum heart rate. From one-way analysis of variance, Factorial variance analysis (2x2) repeated measurement and correlated t-test were used for data analysis. Aerobic exercise and vitamin D intake reduced all metabolic risk indicators and blood insulin (P < 0.05). However, the subjective feeling of hunger did not change significantly (P < 0.05). Regarding waist circumference and blood glucose, the effect of exercise combined with vitamin D consumption was greater than the corresponding effect in the vitamin D group (P < 0.05). Aerobic exercises and vitamin D intake are safe and effective for improving cardiometabolic health, Imam adds vitamin D to the exercise program has more benefits for weight and blood sugar control, which suggests prescribing it for patients with metabolic syndrome.

Keywords: vitamin D, aerobic exercise, metabolic control, adolescents

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Authors: Josephine Hai, Jie Jiang, Karen M. Lyons

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Of the musculoskeletal tissues, tendon is least understood in terms of biological development. The current study examines Cysteine-rich angiogenic inducer 61, or CCN1, a member of the CCN family of secreted matricellular proteins that regulate cell behavior via intercellular signaling. Though CCN1 is notable in limiting fibrosis by inducing senescence in fibroblasts, little is known about its role in normal fibrous tissue, where it may be essential to the development of ECM-rich structures like tendons. We found that CCN1 knockout mice (using limb-specific Prx1-Cre) exhibited clubfoot and waddling gaits, a unique phenotype not described in any other mutant to date. Histological analysis showed that the Achilles and patellar tendons, where we previously found high CCN1 expression in adult reporter mice, were thicker and denser in the Prx1-Cre knockouts than in their wildtype littermates. We then hypothesized that CCN1 is required directly in tendon progenitor cells for normal tendon development and generated tendon-specific CCN1 knockout mice using Scx-Cre. We observed similar Achilles/patellar tendon morphology among the Scx-Cre and Prx1-Cre mutants, indicating that the phenotype is a direct result of CCN1’s loss in tendon. To further study phenotype onset and progression, we will histologically characterize these tendons across different developmental time-points. We will also perform RNA-seq and qPCR to analyze tenocyte gene expression and expect fibrotic marker upregulation in the Scx-Cre mutants if CCN1 is required to maintain a normal tendon phenotype. Thus, our study aims to elucidate the molecular mechanisms underlying tendon formation and maintenance. Understanding tendons at the most basic level invites novel approaches to tendon repair.

Keywords: development, matricellular, musculoskeletal, tendon

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Authors: Tanakrit Doltanakarn

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Introduction: These days, cannabis is being accepted in many countries due to the fact that cannabis could be use in medical. The medical cannabis is used to treat and reduce the pain many diseases. For example, neuropathic pain, Parkinson, autism disorders, cancer pain reduce the adverse effect of chemotherapy, diabetes, and migraine. Active ingredients in cannabis that modulate patients' perceptions of their conditions include Δ9‐tetrahydrocannabinol (THC), cannabidiol (CBD), flavonoids, and terpenes. However, there is an adverse effect of cannabis, cardiovascular effects, psychosis, schizophrenia, mood disorder, and cognitive alternation. These effects are from the THC and CBD ingredients in the cannabis. The metabolize processes of delta-9 THC to 11-OH-delta 9 -THC (inactive form), THC were cause of adverse effects. Interestingly, the distributions of CYP2C9 gene (CYP2C9*2 and CYP2C9*3, poor metabolizer) that might affect incidences of adverse effects in patients who treated with medical cannabis. Objective: The aim of this study we want to investigate the association between genetic polymorphism of CYP2C9 frequency and Thai patients who treated with medical cannabis. Materials and Methods:We recruited sixty-five unrelated Thai patients from the College of Pharmacy, Rangsit University. DNA were extracted using Genomic DNA Mini Kit. Genotyping of CYP2C9*2 (430C>T, rs1799853) and CYP2C9*3 (1075A>C, rs1057910) were genotyped by the TaqMan Real-time PCR assay. Results: Among these 31 medicals cannabis-induced ADRs patients, they were diagnosed with 22 (33.85%) tachycardia and 3 (4.62%) arrhythmia. There were 34 (52.31%) medical cannabis-tolerant controls who were included in this study.40 (61.53%) Thai patients were female, and 25 (38.46%) were male, with median age of 57 (range 27 – 87) years. In this study, we found none of the medical cannabis-induced ADRs carried CYP2C9*2 variant along with medical cannabis-tolerant control group. CYP2C9*3 variant (intermediate metabolizer, IM) was found just only one of thirty-one (3.23%) in the medical cannabis-induced ADRs and two of thirty-fourth (5.88%) in the tolerant controls. Conclusions: Thus, the distribution of CYP2C9 alleles offer a comprehensive view of pharmacogenomics marker in Thai population that could be used as a reference for worldwide to investigate the pharmacogenomics application.

Keywords: medical cannabis, adverse effect, CYP2C9, thai patients

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Authors: Simona Moravcova, Jiri Novotny, Zdenka Bendova

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The pineal gland of the vertebrate brain is a circumventricular organ which serves as a major neuroendocrine gland with the primary function of rhythmic secretion of neurohormone melatonin under the control of the hypothalamic suprachiasmatic nucleus (SCN). Soon after the onset of the darkness, the activity of the key rate-limiting enzyme for melatonin synthesis, arylalkylamine N-acetyltransferase (AANAT), raises due to the increased release of norepinephrine from sympathetic neurons terminating on the parenchymal cells where it binds to β-adrenergic receptors. Melatonin codes the length of the night, and it is well recognized for its anti-inflammatory effects. However, to our knowledge, less is known about the effect of the immune system on the melatonin biosynthesis and the precise role of the STAT3 in the signaling pathway leading to the expression of AANAT. Lipopolysaccharide (LPS) is the essential component in the outer surface membrane of gram-negative bacteria and acts as a strong stimulator of natural and innate immunity. STAT3 acts as an important factor in immune response. Here we investigated the effect of LPS on the components of the melatonergic synthetic pathway in the pineal gland. The experiments were performed both in vivo and in vitro. The changes in AANAT activity were determined by radioenzymatic assay. PCR analyses were carried out to detect aa-nat, icer, spi-3 and stat3 gene expression. From our results, it is apparent that the high basal level of phosphorylated forms of STAT3 can be elevated after systemic as well as in vitro administration of LPS. Our experiments have shown that LPS reduces melatonin synthesis, nevertheless, the activity of AANAT was increased. Moreover, the basal level of phosphorylated STAT3 counteracts β-adrenergic receptor-mediated aa-nat gene expression and sustains its own and spi-3 gene expression. In conclusion, LPS can affect immunomodulators such as melatonin in the pineal gland.

Keywords: AANAT, lipopolysaccharide, pineal gland, rat, STAT3

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Authors: Kumudini Apsara Munasinghe, Devin Gregory Lissau, Ryan Thomas Wade

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Fresh fruits and vegetables are rich in vitamins, minerals, and fibers and help maintain a healthy weight over high-calorie food. Eating fruits and vegetables protects us from free radicals produced by metabolic reactions and safeguards us from cardiovascular disease and cancer. However, there has been an increased concern about foodborne diseases tied to contaminated farmers’ market produce. In addition, very little information is available about the contribution of eating raw fruits and vegetables to human exposure to antibiotic-resistant bacteria. This research aims to identify bacteria isolated from farmers’ market fruits and vegetables and understand their antibiotic resistance. Vegetables and fruits were collected from farmers’ markets around Frostburg and Cumberland areas in Maryland and transported to the microbiology lab at Frostburg State University for the isolation of bacteria. Bacteria were extracted from tomatoes, cucumber, strawberry, and lettuce using Tryptic soy broth overnight at 37°C, and Tryptic Soy agar was used for the streak plate technique to isolate bacteria. Pure cultures were used to identify bacteria using biochemical reactions after conducting Gram staining technique. The research used many biochemical reactions, including Mannitol Salt agar, MacConkey agar, and Eosin Methylene blue agar, for identification. Antibiotic sensitivity was tested for many different types of antibiotics, including amoxicillin, penicillin, tetracycline, ampicillin, and erythromycin. Most prevalent bacteria in the isolates were Staphylococcus, Bacillus, Micrococcus, Enterococcus, Enterobacter, Citrobacter, and other bacteria from the family Enterobacteriaceae. The data obtained from this research will be useful to educate and train farmers and individuals involved in post-harvest processes such as transportation and selling in farmers’ markets. Further results for bacterial antibiotic resistance will be obtained, and unculturable bacteria will be identified by next-generation DNA sequencing.

Keywords: antibiotic resistance, farmers markets, fruits, bacteria, vegetables

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Authors: Andrey V. Khromov, Antonida V. Makhotenko, Ekaterina A. Snigir, Svetlana S. Makarova, Natalia O. Kalinina, Valentin V. Makarov, Mikhail E. Taliansky

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Due to its simplicity, CRISPR/Cas9 has become widely used and capable of inducing mutations in the genes of organisms of various kingdoms. The aim of this work was to develop applications for the efficient modification of DNA coding sequences of phytoene desaturase (PDS), coilin and vacuolar invertase (Solanum tuberosum) genes, and to develop a new nanoparticles carrier efficient technology to deliver the CRISPR/Cas9 system for editing the plant genome. For each of the genes - coilin, PDS and vacuolar invertase, five single RNA guide (sgRNAs) were synthesized. To determine the most suitable nanoplatform, two types of NP platforms were used: magnetic NPs (MNPS) and gold NPs (AuNPs). To test the penetration efficiency, they were functionalized with fluorescent agents - BSA * FITS and GFP, as well as labeled Cy3 small-sized RNA. To measure the efficiency, a fluorescence and confocal microscopy were used. It was shown that the best of these options were AuNP - both in the case of proteins and in the case of RNA. The next step was to check the possibility of delivering components of the CRISPR/Cas9 system to plant cells for editing target genes. AuNPs were functionalized with a ribonucleoprotein complex consisting of Cas9 and corresponding to target genes sgRNAs, and they were biolistically bombarded to axillary buds and apical meristems of potato plants. After the treatment by the best NP carrier, potato meristems were grown to adult plants. DNA isolated from this plants was sent to a preliminary fragment of the analysis to screen out the non-transformed samples, and then to the NGS. The present work was carried out with the financial support from the Russian Science Foundation (grant No. 16-16-04019).

Keywords: biobombardment, coilin, CRISPR/Cas9, nanoparticles, NPs, PDS, sgRNA, vacuolar invertase

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Authors: Hongquan Zhang

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Inspired by endogenous protein motors, researchers have constructed various synthetic DNA motors based on the specificity and predictability of Watson-Crick base pairing. However, the application of DNA motors to signal amplification and biosensing is limited because of low mobility and difficulty in real-time monitoring of the walking process. The objective of our work was to construct a new type of DNA motor termed target-triggered DNA motors that can walk for hundreds of steps in response to a single target binding event. To improve the mobility and processivity of DNA motors, we used gold nanoparticles (AuNPs) as scaffolds to build high-density, three-dimensional tracks. Hundreds of track strands are conjugated to a single AuNP. To enable DNA motors to respond to specific protein and nucleic acid targets, we adapted the binding-induced DNA assembly into the design of the target-triggered DNA motors. In response to the binding of specific target molecules, DNA motors are activated to autonomously walk along AuNP, which is powered by a nicking endonuclease or DNAzyme-catalyzed cleavage of track strands. Each moving step restores the fluorescence of a dye molecule, enabling monitoring of the operation of DNA motors in real time. The motors can translate a single binding event into the generation of hundreds of oligonucleotides from a single nanoparticle. The motors have been applied to amplify the detection of proteins and nucleic acids in test tubes and live cells. The motors were able to detect low pM concentrations of specific protein and nucleic acid targets in homogeneous solutions without the need for separation. Target-triggered DNA motors are significant for broadening applications of DNA motors to molecular sensing, cell imagining, molecular interaction monitoring, and controlled delivery and release of therapeutics.

Keywords: biosensing, DNA motors, gold nanoparticles, signal amplification

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Authors: Edward Poluyi, Eghosa Morgan, Charles Poluyi, Chibuikem Ikwuegbuenyi, Grace Imaguezegie

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Background: Current epidemiological studies have examined the associations between moderate and severe traumatic brain injury (TBI) and their risks of developing neurodegenerative diseases. Concussion, also known as mild TBI (mTBI), is however quite distinct from moderate or severe TBIs. Only few studies in this burgeoning area have examined concussion—especially repetitive episodes—and neurodegenerative diseases. Thus, no definite relationship has been established between them. Objectives : This review will discuss the available literature linking concussion and amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (AD). Materials and Methods: Given the complexity of this subject, a realistic review methodology was selected which includes clarifying the scope and developing a theoretical framework, developing a search strategy, selection and appraisal, data extraction, and synthesis. A detailed literature matrix was set out in order to get relevant and recent findings on this topic. Results: Presently, there is no objective clinical test for the diagnosis of concussion because the features are less obvious on physical examination. Absence of an objective test in diagnosing concussion sometimes leads to skepticism when confirming the presence or absence of concussion. Intriguingly, several possible explanations have been proposed in the pathological mechanisms that lead to the development of some neurodegenerative disorders (such as ALS and AD) and concussion but the two major events are deposition of tau proteins (abnormal microtubule proteins) and neuroinflammation, which ranges from glutamate excitotoxicity pathways and inflammatory pathways (which leads to a rise in the metabolic demands of microglia cells and neurons), to mitochondrial function via the oxidative pathways.

Keywords: amyotrophic lateral sclerosis, Alzheimer's disease, mild traumatic brain injury, neurodegeneration

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Authors: Giriprasath Ramanathan, Sivakumar Singaravelu, M. D. Raja, Uma Tirichurapalli Sivagnanam

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Collagen is the abundant protein found in the skin of the animal body that has been designed to provide adequate structural support for the adhesion of cells. The dressing material widely used for tissue engineering and biomedical application has to posses good swelling and biological property for the absorption of exudates and cell proliferation. Acid solubilised collagen from the fish skin of the Arothron stellatus was extracted. The collagen with hydroxypropyl and carboxy methyl cellulose has the better biological property to enhance the healing efficiency. The inter property of collagen with interesting perspectives in the tissue engineering process leads to the development of biomaterial with natural polymer with biologically derived collagen. Keeping this as an objective, the composite biomaterial was fabricated to improve the wound healing and biological properties. In this study the collagen from Arothron stellatus fish skin (ACO) was uniformly blended separately with hydroxypropyl methyl cellulose (HPMC) and carboxyl methyl cellulose (CMC) as biosheets. The casted biosheets were impregnated with mupirocin to get rid of infection from the microbes. Further, the results obtained from differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), tensile studies and biocompatibility of the biosheets were assessed. The swelling, porosity and degradation of the casted biosheets were studied to make the biosheets as a suitable wound dressing material. ACO-HPMC and ACO-CMC biosheets both showed good results, but ACO-HPMC biosheet showed better results than ACO-CMC and hence it can be used as a potential dermal substitute in skin tissue engineering.

Keywords: arothron stellatus, biocompatibility, collagen, tensile strenght

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Authors: Frederick Anlimah, Vinod Gopaldasani, Catherine MacPhail, Brian Davies

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Aim: This study aims to identify the barriers and challenges hindering the implementation of effective controls and the adoption of safe work practices to protect workers from respirable crystalline silica (RCS) exposure. Problem or Situation: Tunnelling is one of many occupations that expose workers to the harmful effects of respirable crystalline silica. Despite various control measures, such as engineering controls and personal protective equipment, exposures remain inadequately controlled, leading to incurable silicosis and other severe illnesses, such as lung cancer. Methods: The research involved surveying tunnel construction workers, conducting interviews, and facilitating focus group discussions. Additionally, site observations and content analysis of work procedures and instructions were performed. Results: Preliminary data analysis reveals notable findings. While there is a commendable level of knowledge and commitment among management and workers concerning RCS exposure in tunnelling, there is a striking lack of prioritization regarding dust control. Moreover, the risks associated with dust exposure are not sufficiently acknowledged. Additionally, the data suggests that engineers and supervisors responsible for implementing dust controls often possess limited knowledge regarding the factors influencing the effectiveness of these measures. These findings emphasise the need for a paradigm shift, including higher prioritisation of dust control, adoption of holistic dust reduction strategies, and enhanced knowledge about effective control measures. Conclusion: This research shed light on tunnel construction workers' barriers and challenges in protecting themselves from RCS exposure. This knowledge will be essential in developing interventions and strategies to enhance dust exposure and prevent the adverse health effects of respirable crystalline silica exposure in tunnelling and similar industries.

Keywords: respirable crystalline silica, dust control, worker practices, exposure prevention, silicosis

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Authors: Hakim Derradji, M’Hammedi Yousra, Sabrou Abdelmalek, Tabet Nacer

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Introduction: This is a retrospective study carried out at the Central Hospital of Army from 2017 to 2022. Its objective is to demonstrate the best surgical method for the management of obstructive hydrocephalus secondary to a posterior fossa tumor in children, in pre, per, and post-operative. Patients and Methods: During this period, 24 children (over 1 year old) were admitted for treatment of the posterior fossa tumor with obstructive secondary hydrocephalus and the majority of whom benefited from VCS followed by surgery and excision, the rest, received after evacuation from other hospital structures, were managed there beforehand with ventriculoperitoneal diversion or external drainage. We found that the way hydrocephalus is managed has implications for subsequent management, hence the need for this study to determine the effectiveness of different surgical procedures used in the treatment of hydrocephalus in these patients. The evaluation is made on the basis of revision rate, complications, survival, and radiological evaluation. Results: 6 patients (25%) received a ventriculoperitoneal shunt (VPD), 15 patients (62%) underwent a ventriculocysternostomy (VCS), and 3 patients (12.5%) received temporary ventricular drainage before or during tumor excision. The post-operative results were almost similar. Nevertheless, a high failure rate (25%) was observed. No deaths are recorded. In total, 75% of children who had a DVP were reoperated. The revision by VCS was performed, in addition to the 4 patients benefiting from a DVP, with one patient having received external drainage, and only one revision of a VCS was recorded. In the two patients who received external drainage, restoration of CSF outflow was observed following tumor resection. Conclusion: VCS is indicated in the first intention in the treatment of hydrocephalus secondary to a posterior fossa tumor, in view of the satisfactory results obtained and the high failure rate in DVP, especially with the presence of metastatic cells in the peritoneum, but can be considered as a second-line treatment.

Keywords: posterior fossa tumor, obstructive hydrocephalus, DVP, VCS

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Authors: Saba Amreen Syeda, Summaiah Asim, Syeda, Hafsa, Essam Quraishi

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Mantle Cell Lymphoma (MCL) is a relatively uncommon type of lymphoma that comprises approximately 7 percent of non hodgkin's lymphomas (NHL), Classic MCL presents mostly in lymph nodes and occasionally in extranodal sites. About 26 % of MCL is present primarily in the Gastrointestinal tract. While both the upper GI tract and the lower GI tract could be involved, it is rare to present with concurrent upper and lower GI involvement with MCL. We present the case of a 51-year-old Asian Indian male that presented to our clinic with complaints of chronic diarrhea for the last one year, progressively worsening over the past three months. The Patient also reported black stool as well as bright red blood per rectum. Patient reported severe fatigue on minimal exertion. On a physical exam, the patient was noted to have matted lymphadenopathy in the neck. Patient was noted to be anemic with a hemoglobin to be 8 g/dl. Esophagogastroduodenoscopy and colonoscopy was performed. EGD showed a large 4 cm ulcer in the gastric antrum with thick heaped up edges. There was bleeding on contact. Colonoscopy showed a large 35 mm multilobulated polyp in the ascending colon, which was biopsied. The patient was also noted to have nodular proctitis in the mid rectum. This was localized and extended to about 5 cm. This area was biopsied as well. Biopsies from the stomach, colon, as well as the rectum, returned with findings of mantle cell lymphoma on pathology. Lymphoid cells in the biopsy were stained strongly positive for CD 20, cyclin D1, and CD 5. There was the absence of stain for CD 3 and CD 10. The IHC stain for CD 23 was negative. Biopsies from neck LAD were obtained and were also positive for MCL. The patient was referred to oncology for staging and treatment.

Keywords: mantle cell lymphoma, GI bleed, diarrhea, gastric ulcer, colon polyp

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Authors: Allioua Meryem

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Similar to much of the developing world, Algeria is currently undergoing an epidemiological transition. While mal- and under-nutrition and infectious diseases used to be the main causes of poor health, today there is a higher proportion of chronic, non-communicable diseases (NCDs), including cardiovascular disease, diabetes mellitus, cancer, etc. According to estimates for Algeria from the World Health Organization (WHO), NCDs accounted for 63% of all deaths in 2010. The objective of this study was the assessment of eating habits and anthropometric characteristics in a group of youth aged 15 to 19 years in Tlemcen. This study was conducted on a total effective of 806 youth enrolled in a descriptive cross-sectional study; the classification of nutritional status has been established by international standards IOTF, youth were defined as obese if they had a BMI ≥ 95th percentile, and youth with 85th ≤ BMI ≤ 95th percentile were defined as overweight. Wc is classified by the criteria HD, Wc with moderate risk ≥ 90th percentile and Wc with high risk ≥ 95th percentile. The dietary assessment was based on a 24-hour dietary recall assisted by food records. USDA’S nutrient database for Nutrinux® program was used to analyze dietary intake. Nutrients adequacy ratio was calculated by dividing daily individual intake to dietary recommended intake DRI for each nutrient. 9% of the population was overweight, 3% was obese, 7.5% had abdominal obesity, foods eaten in moderation are chips, cookies, chocolate 1-3 times/day and increased consumption of fried foods in the week, almost half of youth consume sugary drinks more than 3 times per week, we observe a decreased intake of energy, protein (P < 0.001, P = 0.003), SFA (P = 0.018), the NAR of phosphorus, iron, magnesium, vitamin B6, vitamin E, folate, niacin, and thiamin reflecting less consumption of fruit, vegetables, milk, and milk products. Youth surveyed have eating habits at risk of developing obesity and chronic disease.

Keywords: food intake, health, anthropometric characteristics, Algeria

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Authors: Sujata Gupta Kedar, J. N. Tulika

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Early researchers suggested that imprisonment had negative psychological and physical effects on its inmates, leading to psychological deterioration. The term “prisons” in the Consensus Statement of WHO is intended to denote, as those institutions which hold people who have been sentenced to a period of imprisonment by the courts for offences against the law. Thus “prisons” if local circumstances justify it, may also be taken to include secure institutions holding on a compulsory basis on any of the following categories of people: remand prisoners; civil prisoners; juvenile detainees; immigration detainees; some categories of mentally disordered patients; asylum seekers; refugees; people detained pending expulsion, deportation, exile, exclusion or any other form of compulsory transfer to other countries or areas of the country; people detained in police cells; and any other compulsorily detained group. Prisons are aimed to cure the criminal and their behavior but their records are not encouraging. Instead the imprisonment affects all prisoners in different way. From withstanding the shock of entry to the new culture, which is very different from their own, prisoners must try to determine how to spend the time in prison, since the hours appears to be endless in prisons. There is also the fear of deterioration. This article aims to provide an overview of the psychological well being of female prisoners in the prison environment in five areas- satisfaction, efficiency, sociability, mental health and interpersonal relations. Research was done on two different types of imprisonment- under trial prisoner and convict. Total sample included 22 female prisoners of Nagaon Special Jail of Assam. The instrument used for the study was based on Psychological Well Being Scale. Statistical analysis was done with t-test and one way anova test. The result demonstrated that there is no significant difference in the psychological wellbeing of female prisoners in the prison and that there is no significant difference in the psychological well being of different types of female prisoners involved in different crimes but there is significant difference in the mental health of the female prisoners in prison.

Keywords: psychological effect, female prisoners, prison, well being of prisoners

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Authors: Liyun Chang, Cheng-Hsiang Tsai

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To ensure the radiation precisely delivering to the target of cancer patients, the linear accelerator equipped with the pretreatment on-board imaging system is introduced and through it the patient setup is verified before the daily treatment. New generation radiotherapy using beam-intensity modulation, usually associated the treatment with steep dose gradients, claimed to have achieved both a higher degree of dose conformation in the targets and a further reduction of toxicity in normal tissues. However, this benefit is counterproductive if the beam is delivered imprecisely. To avoid shooting critical organs or normal tissues rather than the target, it is very important to carry out the quality assurance (QA) of this on-board imaging system. The QA of the On-Board Imager® (OBI) system of one Varian Clinac-iX linear accelerator was performed through our procedures modified from a relevant report and AAPM TG142. Two image modalities, 2D radiography and 3D cone-beam computed tomography (CBCT), of the OBI system were examined. The daily and monthly QA was executed for five months in the categories of safety, geometrical accuracy and image quality. A marker phantom and a blade calibration plate were used for the QA of geometrical accuracy, while the Leeds phantom and Catphan 504 phantom were used in the QA of radiographic and CBCT image quality, respectively. The reference images were generated through a GE LightSpeed CT simulator with an ADAC Pinnacle treatment planning system. Finally, the image quality was analyzed via an OsiriX medical imaging system. For the geometrical accuracy test, the average deviations of the OBI isocenter in each direction are less than 0.6 mm with uncertainties less than 0.2 mm, while all the other items have the displacements less than 1 mm. For radiographic image quality, the spatial resolution is 1.6 lp/cm with contrasts less than 2.2%. The spatial resolution, low contrast, and HU homogenous of CBCT are larger than 6 lp/cm, less than 1% and within 20 HU, respectively. All tests are within the criteria, except the HU value of Teflon measured with the full fan mode exceeding the suggested value that could be due to itself high HU value and needed to be rechecked. The OBI system in our facility was then demonstrated to be reliable with stable image quality. The QA of OBI system is really necessary to achieve the best treatment for a patient.

Keywords: CBCT, image quality, quality assurance, OBI

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Authors: Faris Tarlochan, Siva Mahesh Tangutooru

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Lateral Geniculate Nucleus (LGN) is the relay center in the visual pathway as it receives most of the input information from retinal ganglion cells (RGC) and sends to visual cortex. Low threshold calcium currents (IT) at the membrane are the unique indicator to characterize this firing functionality of the LGN neurons gained by the RGC input. According to the LGN functional requirements such as functional mapping of RGC to LGN, the morphologies of the LGN neurons were developed. During the neurological disorders like glaucoma, the mapping between RGC and LGN is disconnected and hence stimulating LGN electrically using deep brain electrodes can restore the functionalities of LGN. A computational model was developed for simulating the LGN neurons with three predominant morphologies, each representing different functional mapping of RGC to LGN. The firings of action potentials at LGN neuron due to IT were characterized by varying the stimulation parameters, morphological parameters and orientation. A wide range of stimulation parameters (stimulus amplitude, duration and frequency) represents the various strengths of the electrical stimulation with different morphological parameters (soma size, dendrites size and structure). The orientation (0-1800) of LGN neuron with respect to the stimulating electrode represents the angle at which the extracellular deep brain stimulation towards LGN neuron is performed. A reduced dendrite structure was used in the model using Bush–Sejnowski algorithm to decrease the computational time while conserving its input resistance and total surface area. The major finding is that an input potential of 0.4 V is required to produce the action potential in the LGN neuron which is placed at 100 µm distance from the electrode. From this study, it can be concluded that the neuroprostheses under design would need to consider the capability of inducing at least 0.4V to produce action potentials in LGN.

Keywords: Lateral Geniculate Nucleus, visual cortex, finite element, glaucoma, neuroprostheses

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Authors: Sarah Elshahat, Tina Moffat

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Suboptimal mental health is a considerable global public health challenge that leads to considerable inequalities worldwide. Newcomers are at elevated risk for developing mental health issues as a result of social exclusion, stigmatization, racism, unequal employment opportunities, and discrimination. The problem can be especially serious amongst Arabic-speaking immigrants and refugees (ASIR) whose mental wellness may have already been affected by exposure to political violence, persecution, hunger or war in their countries of origin. A scoping review was conducted to investigate pre- and post-migration mental health determinants amongst ASIR in North America (the U.S. and Canada), who are a rapidly growing population in both regions. Pertinent peer-reviewed papers and grey literature were located through a systematic search of five electronic databases (Medline, Embase, PsycINFO, Anthropology Plus, and Sociology Database). A stakeholder consultation was implemented to validate the analyzed findings of the included 44 studies. About 80% of the studies were carried out in the US, underscoring a lack of Canadian ASIR-mental health research. A gap in qualitative, mixed-method, and longitudinal research was detected, where approximately two-thirds of the studies adopted a cross-sectional method. Pre-migration determinants of mental health were related to the political unrest, violence and armed conflict in the Arab world, increasing post-traumatic stress disorder and psychological distress levels among ASIR. English language illiteracy and generational variations in acculturation patterns were major post-migration mental health triggering factors. Exposure to domestic violence, stigmatization, poverty, racialization, and harassment were significant post-migration mental health determinants that stem from social inequalities, triggering depression, and distress amongst ASIR. Family conflicts linked to child-rearing and gendered norms were considered as both pre- and post-migration mental health triggering factors. Most post-migration mental health protective factors were socio-culturally related and included the maintenance of positive ethnic identity, faith, family support, and community cohesion. Individual resilience, articulated as self-esteem and hope, was a significant negative predictor of depression and psychological distress among ASIR. Community-engaged, mixed-methods, and longitudinal studies are required to address the current gap in mental health research among ASIR in North America. A more thorough determination of potential mental health triggers and protective factors would help inform the development of mental wellness and resilience-promoting programs that are culturally sensitive to ASIR. On the policy level, the Health in All Policies framework of the World Health Organization can be potentially useful for addressing social and health inequalities among ASIR, reducing mental health challenges.

Keywords: depression, post-traumatic stress disorder, psychological distress, resilience

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Authors: Ranjeet Kumar, Pravin Suryakantrao Deshmukh, Sonal Sharma, Basudev Banerjee

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With the tremendous increase in exposure to radiofrequency microwaves emitted by mobile phones, globally public awareness has grown with regard to the potential health hazards of microwaves on the nervous system in the brain. India alone has more than one billion mobile users out of 4.3 billion globally. Our studies have suggested that radio frequency able to affect neuronal alterations in the brain, and hence, affecting cognitive behaviour. However, adverse effect of low-intensity microwave exposure with endoplasmic reticulum stress and autophagy has not been evaluated yet. In this study, we explore whether low-intensity microwave induces endoplasmic reticulum stress and autophagy with varying frequency and time duration in Wistar rat. Ninety-six male Wistar rat were divided into 12 groups of 8 rats each. We studied at 900 MHz, 1800 MHz, and 2450 MHz frequency with reference to sham-exposed group. At the end of the exposure, the rats were sacrificed to collect brain tissue and expression of CHOP, ATF-4, XBP-1, Bcl-2, Bax, LC3 and Atg-4 gene was analysed by real-time PCR. Significant fold change (p < 0.05) of gene expression was found in all groups of 1800 MHz and 2450 MHz exposure group in comparison to sham exposure group. In conclusion, the microwave exposure able to induce ER stress and modulate autophagy. ER (endoplasmic reticulum) stress and autophagy vary with increasing frequency as well as the duration of exposure. Our results suggested that microwave exposure is harmful to neuronal health as it induces ER stress and hampers autophagy in neuron cells and thereby increasing the neuron degeneration which impairs cognitive behaviour of experimental animals.

Keywords: autophagy, ER stress, microwave, nervous system, rat

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Authors: Jiang Xu, Daoping Wang, Yinghong Pan

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The jointing-booting stage is a critical period of both vegetative growth and reproductive growth in rice. Therefore, the proteomic analysis of the mutant Osbri1, whose corresponding gene OsBRI1 encodes the putative BRs receptor OsBRI1, at jointing-booting stage is very important for understanding the effects of BRs on vegetative and reproductive growth. In this study, the proteomes of leaves from an allelic mutant of the DWARF 61 (D61, OsBRI1) gene, Fn189 (dwarf54, d54) and its wild-type variety T65 (Taichung 65) at jointing-booting stage were analysed by using a Q Exactive plus orbitrap mass spectrometer, and more than 3,100 proteins were identified in each sample. Ontology analysis showed that these proteins distribute in various space of the cells, such as the chloroplast, mitochondrion, and nucleus, they functioned as structural components and/or catalytic enzymes and involved in many physiological processes. Moreover, quantitative analysis displayed that 266 proteins were differentially expressed in two samples, among them, 77 proteins decreased and 189 increased more than two times in Fn189 compared with T65, the proteins whose content decreased in Fn189 including b5-like Heme/Steroid binding domain containing protein, putative retrotransposon protein, putative glutaminyl-tRNA synthetase, and higher content proteins such as mTERF, putative Oligopeptidase homologue, zinc knuckle protein, and so on. A former study founded that the transcription level of a mTERF was up-regulated in the leaves of maize seedling after EBR treatment. In our experiments, it was interesting that one mTERF protein increased, but another mTERF decreased in leaves of Fn189 at jointing-booting stage, which suggested that BRs may have differential regulation mechanisms on the expression of various mTERF proteins. The relationship between other differential proteins with BRs is still unclear, and the effects of BRs on rice protein contents and its regulation mechanisms still need further research.

Keywords: bri1 mutant, jointing-booting stage, proteomic analysis, rice

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Authors: Alhaji Modu Bukar, Faez Firdaus Abdullah Jesse, Che Azurahanim Che Abdullah, Mustapha M. Noordin, Mohd-Lila Mohd Azmia

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Orf virus (ORFV) is the causative agent of a proliferative skin lesion known as contagious ecthyma in sheep and goats. Currently used live attenuated vaccines against ORFV infection have been reported to cause severe outbreaks in vaccinated animals. In this study, we investigated the immunogenicity of the B2L and F1L proteins of the virus, which are thought to elicit a protective immune response The 6-week-old 50 female mice were divided into 8 groups: seven experimental groups and one control group. Each animal in the experimental group received an initial immunisation with the nanoparticles or proteins coated with the nanoparticles, followed by two booster immunizations with the same products 14 days apart. Ten days after the last booster inoculation, the mice were either humanely killed or lethally challenged with UPM /HSN-2-ORFV at a dose of 106 TCID50/mL in a volume of 50 μl. The spleen was examined for histopathological changes and quantification of T cells by flow cytometry. On the other hand, the degree of protection of mice from the lethal virus was evaluated by lesion size, weight loss, and histopathological examination of skin and liver. The results showed that mice immunised with rB2L alone, rB2L-Al₂O₃-NPs, rB2L/rF1L, and rB2L/rF1L-Al₂O₃-NPs elicited statistically higher levels of anti-rB2L and/or rF1L-specific IgA/IgG and CD4/CD8 cell immune responses than mice in the control groups (p < 0.01). The vaccine candidate did not exhibit severe skin damage after monitoring histopathology, morbidity, and mortality. Overall, the results suggest that recombinant rB2L and rF1L antigens may be useful universal vaccine candidates against ORFV infections.

Keywords: orf virus, antigen nanoparticles, virus, nanoparticles

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Authors: Manisha Bal, Remya Chinnamma Jose, B.C. Meikap

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Dust particles suspended in air are a major source of air pollution. A self-priming submerged venturi scrubber proven very effective in cases of handling nuclear power plant accidents is an efficient device to remove dust particles from the air and thus aids in pollution control. Venturi scrubbers are compact, have a simple mode of operation, no moving parts, easy to install and maintain when compared to other pollution control devices and can handle high temperatures and corrosive and flammable gases and dust particles. In the present paper, fly ash particles recognized as a high air pollutant substance emitted mostly from thermal power plants is considered as the dust particle. Its exposure through skin contact, inhalation and indigestion can lead to health risks and in severe cases can even root to lung cancer. The main focus of this study is on the removal of fly ash particles from polluted air using a self-priming venturi scrubber in submerged conditions using water as the scrubbing liquid. The venturi scrubber comprising of three sections: converging section, throat and diverging section is submerged inside a water tank. The liquid enters the throat due to the pressure difference composed of the hydrostatic pressure of the liquid and static pressure of the gas. The high velocity dust particles atomize the liquid droplets at the throat and this interaction leads to its absorption into water and thus removal of fly ash from the air. Detailed investigation on the scrubbing of fly ash has been done in this literature. Experiments were conducted at different throat gas velocities, water levels and fly ash inlet concentrations to study the fly ash removal efficiency. From the experimental results, the highest fly ash removal efficiency of 99.78% is achieved at the throat gas velocity of 58 m/s, water level of height 0.77m with fly ash inlet concentration of 0.3 x10⁻³ kg/Nm³ in the submerged condition. The effect of throat gas velocity, water level and fly ash inlet concentration on the removal efficiency has also been evaluated. Furthermore, experimental results of removal efficiency are validated with the developed empirical model.

Keywords: dust particles, fly ash, pollution control, self-priming venturi scrubber

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Authors: K. Bencherif, M. Bellifa

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The expected climatic changes in North Africa are the increase of both intensity and frequencies of the summer droughts and a reduction in water availability during growing season. The exiting coppices and forest formations in the national park of Tlemcen are dominated by holm oak, zen oak and cork oak. These opened-fragmented structures don’t seem enough strong so to hope durable protection against climate change. According to the observed climatic tendency, the objective is to analyze the climatic context and its evolution taking into account the eventual behaving of the oak species during the next 20-30 years on one side and the landscaped context in relation with the most adequate sylvicultural models to choose and especially in relation with human activities on another side. The study methodology is based on Climatic synthesis and Floristic and spatial analysis. Meteorological data of the decade 1989-2009 are used to characterize the current climate. An another approach, based on dendrochronological analysis of a 120 years sample Aleppo pine stem growing in the park, is used so to analyze the climate evolution during one century. Results on the climate evolution during the 50 years obtained through climatic predictive models are exploited so to predict the climate tendency in the park. Spatially, in each forest unit of the Park, stratified sampling is achieved so to reduce the degree of heterogeneity and to easily delineate different stands using the GPS. Results from precedent study are used to analyze the anthropogenic factor considering the forecasts for the period 2025-2100, the number of warm days with a temperature over 25°C would increase from 30 to 70. The monthly mean temperatures of the maxima’s (M) and the minima’s (m) would pass respectively from 30.5°C to 33°C and from 2.3°C to 4.8°C. With an average drop of 25%, precipitations will be reduced to 411.37 mm. These new data highlight the importance of the risk fire and the water stress witch would affect the vegetation and the regeneration process. Spatial analysis highlights the forest and the agricultural dimensions of the park compared to the urban habitat and bare soils. Maps show both fragmentation state and forest surface regression (50% of total surface). At the level of the park, fires affected already all types of covers creating low structures with various densities. On the silvi cultural plan, Zen oak form in some places pure stands and this invasion must be considered as a natural tendency where Zen oak becomes the structuring specie. Climate-related changes have nothing to do with the real impact that South-Mediterranean forests are undergoing because human constraints they support. Nevertheless, hardwoods stand of oak in the national park of Tlemcen will face up to unexpected climate changes such as changing rainfall regime associated with a lengthening of the period of water stress, to heavy rainfall and/or to sudden cold snaps. Faced with these new conditions, management based on mixed uneven aged high forest method promoting the more dynamic specie could be an appropriate measure.

Keywords: global warming, mediterranean forest, oak shrub-lands, Tlemcen

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Authors: Pedro Llanos, Diego García

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This paper is addressed to expanding our understanding of the effects of hypoxia training on our bodies to better model its dynamics and leverage some of its implications and effects on human health. Hypoxia training is a recommended practice for military and civilian pilots that allow them to recognize their early hypoxia signs and symptoms, and Scientist Astronaut Candidates (SACs) who underwent hypobaric hypoxia (HH) exposure as part of a training activity for prospective suborbital flight applications. This observational-analytical study describes physiologic responses and symptoms experienced by a SAC group before, during and after HH exposure and proposes a model for assessing predicted versus observed physiological responses. A group of individuals with diverse Science Technology Engineering Mathematics (STEM) backgrounds conducted a hypobaric training session to an altitude up to 22,000 ft (FL220) or 6,705 meters, where heart rate (HR), breathing rate (BR) and core temperature (Tc) were monitored with the use of a chest strap sensor pre and post HH exposure. A pulse oximeter registered levels of saturation of oxygen (SpO₂), number and duration of desaturations during the HH chamber flight. Hypoxia symptoms as described by the SACs during the HH training session were also registered. This data allowed to generate a preliminary predictive model of the oxygen desaturation and O₂ pressure curve for each subject, which consists of a sixth-order polynomial fit during exposure, and a fifth or fourth-order polynomial fit during recovery. Data analysis showed that HR and BR showed no significant differences between pre and post HH exposure in most of the SACs, while Tc measures showed slight but consistent decrement changes. All subjects registered SpO₂ greater than 94% for the majority of their individual HH exposures, but all of them presented at least one clinically significant desaturation (SpO₂ < 85% for more than 5 seconds) and half of the individuals showed SpO₂ below 87% for at least 30% of their HH exposure time. Finally, real time collection of HH symptoms presented temperature somatosensory perceptions (SP) for 65% of individuals, and task-focus issues for 52.5% of individuals as the most common HH indications. 95% of the subjects experienced HH onset symptoms below FL180; all participants achieved full recovery of HH symptoms within 1 minute of donning their O₂ mask. The current HH study performed on this group of individuals suggests a rapid and fully reversible physiologic response after HH exposure as expected and obtained in previous studies. Our data showed consistent results between predicted versus observed SpO₂ curves during HH suggesting a mathematical function that may be used to model HH performance deficiencies. During the HH study, real-time HH symptoms were registered providing evidenced SP and task focusing as the earliest and most common indicators. Finally, an assessment of HH signs of symptoms in a group of heterogeneous, non-pilot individuals showed similar results to previous studies in homogeneous populations of pilots.

Keywords: slow onset hypoxia, hypobaric chamber training, altitude sickness, symptoms and altitude, pressure cabin

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Authors: Radek Richtr, Petr Pauš

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Social media nowadays connects people more tightly and intensively than ever, but simultaneously, some sort of social distance, incomprehension, lost of social integrity appears. People can be strongly connected to the person on the other side of the world but unaware of neighbours in the same district or street. The Stoa is a type of application from the ”serious games” genre- it is research augmented reality experiment masked as a gaming environment. In the Stoa environment, the player can plant and grow virtual (organic) structure, a Pillar, that represent the whole suburb. Everybody has their own idea of what is an acceptable, admirable or harmful visual intervention in the area they live in; the purpose of this research experiment is to find and/or define residents shared subconscious spirit, genius loci of the Pillars vicinity, where residents live in. The appearance and evolution of Stoa’s Pillars reflect the real world as perceived by not only the creator but also by other residents/players, who, with their actions, refine the environment. Squares, parks, patios and streets get their living avatar depictions; investors and urban planners obtain information on the occurrence and level of motivation for reshaping the public space. As the project is in product conceptual design phase, the function is one of its most important factors. Function-based modelling makes design problem modular and structured and thus decompose it into sub-functions or function-cells. Paper discuss the current conceptual model for Stoa project, the using of different organic structure textures and models, user interface design, UX study and project’s developing to the final state.

Keywords: augmented reality, urban computing, interaction design, mixed reality, social engineering

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Authors: Ruqaiya Khalil, Saman Usmani, Zaheer Ul-Haq

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The accurate characterization of ligand binding affinity is indispensable for designing molecules with optimized binding affinity. Computational tools help in many directions to predict quantitative correlations between protein-ligand structure and their binding affinities. Molecular dynamics (MD) simulation is a modern state-of-the-art technique to evaluate the underlying basis of ligand-protein interactions by characterizing dynamic and energetic properties during the event. Autoimmune diseases arise from an abnormal immune response of the body against own tissues. The current regimen for the described condition is limited to immune-modulators having compromised pharmacodynamics and pharmacokinetics profiles. One of the key player mediating immunity and tolerance, thus invoking autoimmunity is Interleukin-2; a cytokine influencing the growth of T cells. Molecular dynamics simulation techniques are applied to seek insight into the inhibitory mechanisms of newly synthesized compounds that manifested immunosuppressant potentials during in silico pipeline. In addition to estimation of free energies associated with ligand binding, MD simulation yielded us a great deal of information about ligand-macromolecule interactions to evaluate the pattern of interactions and the molecular basis of inhibition. The present study is a continuum of our efforts to identify interleukin-2 inhibitors of both natural and synthetic origin. Herein, we report molecular dynamics simulation studies of Interluekin-2 complexed with different antagonists previously reported by our group. The study of protein-ligand dynamics enabled us to gain a better understanding of the contribution of different active site residues in ligand binding. The results of the study will be used as the guide to rationalize the fragment based synthesis of drug-like interleukin-2 inhibitors as immune-modulators.

Keywords: immuno-modulators, MD simulation, protein-ligand interaction, structure-based drug design

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Authors: Sanjay Singh, Karunanithi Priyanka, Ramoji Kosuru, Raju Prasad Sharma

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Herbal drugs are well known for their mixed pharmacological activities with the benefit of no harmful side effects. The use of herbal drugs is limited because of their higher dose requirement, frequent drug administration, poor bioavailability of phytochemicals and delayed onset of action. Ficus religiosa, a potent anti-oxidant plant useful in the treatment of diabetes and cancer was selected for the study. Solid lipid nanoparticles (SLN) of Ficus religiosa extract was developed for the enhancement in oral bioavailability of stigmasterol and β-sitosterol-d-glucoside, principal components present in the extract. Hot homogenization followed by ultrasonication method was used to develop extract loaded SLN. Developed extract loaded SLN were characterized for particle size, PDI, zeta potential, entrapment efficiency, in vitro drug release and kinetics, fourier transform infra-red spectroscopy, differential scanning calorimetry, powder X-ray diffractrometry and stability studies. Entrapment efficiency of optimized extract loaded SLN was found to be 68.46 % (56.13 % of stigmasterol and 12.33 % of β-sitosteryl-d-glucoside, respectively). RP HPLC method development was done for simultaneous estimation of stigmasterol and β-sitosterol-d-glucoside in Ficus religiosa extract in rat plasma. Bioavailability studies were carried out for extract in suspension form and optimized extract loaded SLN. AUC of stigmasterol and β-sitosterol-d-glucoside were increased by 6.7-folds by 9.2-folds, respectively in rats treated with extract loaded SLN compared to extract suspension. Also, Cmax of stigmasterol and β-sitosterol-d-glucoside were increased by 4.3-folds by 3.9-folds, respectively in rats treated with extract loaded SLN compared to extract suspension. Mean residence times (MRT) for stigmasterol were found to be 12.3 ± 0.67 hours from extract and 7.4 ± 2.1 hours from SLN and for β-sitosterol-d-glucoside, 10.49 ± 2.9 hours from extract and 6.4 ± 0.3 hours from SLN. Hence, it was concluded that SLN enhanced the bioavailability and reduced the MRT of stigmasterol and β-sitosterol-d-glucoside in Ficus religiosa extract which in turn may lead to reduction in dose of Ficus religiosa extract, prolonged duration of action and also enhanced therapeutic efficacy.

Keywords: Ficus religiosa, phytosterolins, bioavailability, solid lipid nanoparticles, stigmasterol and β-sitosteryl-d-glucoside

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