Search results for: Deformation Induced Mobility

Authors: Min-Chien Su, Tzu-Hsuan Hsu, Guan-Xuan Wu, Shyh-Ming Kuo

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Lung cancer is one of the clinically challenging malignant diseases worldwide. For efficient therapeutics in cancer, combination therapy has developed to acquire a better outcome. PLK-1 was one of the major factors affecting cell mitosis in cancer cells, its inhibitor Bi6727 was proven effective in treating several different cancers namely oral cancer, colon cancer and lung cancer. Despite its low toxicity toward normal cells compared to traditional chemotherapy, it is still yet to be evaluated in detail. Livistona Chinensis (LC) is a Chinese herb that used as a traditional prescription to treat lung cancer. Due to the uncertainty of the efficacy of LC, we utilized a water extraction method to extract the Livistona Chinensis and then lyophilized into powder for further study. In this study we investigated the antiproliferation activities of Bi6727 and LC extracts (LCE) on A549 non-small lung cancer cells. The IC50 of Bi6727 and LCE on A549 are 60 nM and 0.8 mg/mL, respectively. The fluorescent staining images shown nucleolus damage in cells treated with Bi6727 and mitochondrial damage after treated with LCE. A549 cells treated with Bi6727 and LCE showed increased expression of Bax, Caspase-3 and Caspase-9 proteins from Western blot assay. LCE also inhibited A549 cells growth keeping cells at G2-M phase from cell cycle assay. Apoptosis assay results showed that LCE induced late apoptosis of A549 cells. JC-1 assay showed that the mitochondria damaged at the LCE concentration of 0.4 mg/mL. In our preliminary anti-proliferation test of combined LCE and Bi-6727 on A549 cells, we found a dramatically decrease in proliferation after treated with LCE first for 24-h and then Bi-6727 for extra 24-h. This was an important finding regarding synergistic anti-proliferation effect of these drugs, However, the usage, the application sequence of LCE and Bi-6727 on A549 cells and their related mechanisms still need to be evaluated. In summary, the drugs exerted anti-proliferation effect on A549 cells independently. We hopefully combine the usage of these two drugs will bring a different and potential outcome in treating lung cancer.

Keywords: anti-proliferation, A549, Livistona Chinensis fruit extracts, PLK-1 inhibitor

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Authors: Nilesh Bandekar, Sumita Dasgupta, Luis Alberto Allcahuaman Huaya, Souvik Manna

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Cryptobiosis is a dormant state where all measurable metabolic activities are at a halt, allowing an organism to survive in extreme conditions like low temperature (cryobiosis), extreme drought (anhydrobiosis), etc. This phenomenon is observed especially in tardigrades that can retain this state for decades depending on the abiotic environmental conditions. On returning to favorable conditions, tardigrades re-attain a metabolically active state. In this study, cyanobacteria as a model organism are being chosen to induce cryptobiosis for its effective preservation over a long period of time. Preserving cyanobacteria using this strategy will have multiple space applications because of its ability to produce oxygen. In addition, research has shown the survivability of this organism in space for a certain period of time. Few species of cyanobacterial residents of the soil such as Microcoleus, are able to survive in extreme drought as well. This work specifically focuses on Synechococcus elongatus, an endolith cyanobacteria with multiple benefits. It has the capability to produce 25% oxygen in water bodies. It utilizes carbon dioxide to produce oxygen via photosynthesis and also uses carbon dioxide as an energy source to form glucose via the Calvin cycle. There is a fair possibility of initiating cryptobiosis in such an organism by inducing certain proteins extracted from tardigrades such as Heat Shock Proteins (Hsp27 and Hsp30c) and/or hydrophilic Late Embryogenesis Abundant proteins (LEA). Existing methods like cryopreservation are difficult to execute in space keeping in mind their cost and heavy instrumentation. Also, extensive freezing may cause cellular damage. Therefore, cryptobiosis-induced cyanobacteria for its transportation from Earth to Mars as a part of future terraforming missions on Mars will save resources and increase the effectiveness of preservation. Finally, Cyanobacteria species like Synechococcus elongatus can also produce oxygen and glucose on Mars in favorable conditions and holds the key to terraforming Mars.

Keywords: cryptobiosis, cyanobacteria, glucose, mars, Synechococcus elongatus, tardigrades

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Authors: Krishna Dahiya, Esha Charaya

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Induction of labour is a common obstetrical intervention. Around 1 in every 4 patient undergo induction of labour for different indications Purpose: To study the efficacy of the combination of Foley bulb and vaginal misoprostol in comparison to vaginal misoprostol alone for cervical ripening and induction of labour. Methods: A prospective randomised study was conducted on 150 patients with term singleton pregnancy admitted for induction of labour. Seventy-five patients were induced with both Foley bulb, and vaginal misoprostol and another 75 were given vaginal misoprostol alone for induction of labour. Both groups were then compared with respect to change in Bishop score, induction to the active phase of labour interval, induction delivery interval, duration of labour, maternal complications and neonatal outcomes. Data was analysed using statistical software SPSS version 11.5. Tests with P,.05 were considered significant. Results: The two groups were comparable with respect to maternal age, parity, gestational age, indication for induction, and initial Bishop scores. Both groups had a significant change in Bishop score (2.99 ± 1.72 and 2.17 ± 1.48 respectively with statistically significant difference (p=0.001 S, 95% C.I. -0.1978 to 0.8378). Mean induction to delivery interval was significantly lower in the combination group (11.76 ± 5.89 hours) than misoprostol group (14.54 ± 7.32 hours). Difference was of 2.78 hours (p=0.018,S, 95% CI -5.1042 to -0.4558). Induction to delivery interval was significantly lower in nulliparous women of combination group (13.64 ± 5.75 hours) than misoprostol group (18.4±7.09 hours), and the difference was of 4.76 hours (p=0.002, S, 95% CI 1.0465 to 14.7335). There was no difference between the groups in the mode of delivery, infant weight, Apgar score and intrapartum complications. Conclusion: From the present study it was concluded that addition of Foley catheter to vaginal misoprostol have the synergistic effect and results in early cervical ripening and delivery. These results suggest that the combination may be used to achieve timely and safe delivery in the presence of an unfavorable cervix. A combination of the Foley bulb and vaginal misoprostol resulted in a shorter induction-to-delivery time when compared with vaginal misoprostol alone without increasing labor complications.

Keywords: Bishop score, Foley catheter, induction of labor, misoprostol

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Authors: Patrícia Pires, Renata Vaz, Bárbara Teles, Marco Pato, Pedro Beckert

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Introduction: The management of lateral third clavicle fractures can be challenging due to difficulty in distinguishing subtle variations in the fracture pattern, which may be suggestive of potential fracture instability. They occur most often in men between 30 and 50 years of age, and in individuals over 70 years of age, its distribution is equal between both men and women. These fractures account for 10%–30% of all clavicle fractures and roughly 30%–45% of all clavicle nonunion fractures. Lateral third clavicle fractures may be treated conservatively or surgically, and there is no gold standard, although the risk of nonunion or pseudoarthrosis impacts the recommendation of surgical treatment when these fractures are unstable. There are many strategies for surgical treatment, including locking plates, hook plates fixation, coracoclavicular fixation using suture anchors, devices or screws, tension band fixation with suture or wire, transacromial Kirschner wire fixation and arthroscopically assisted techniques. Whenever taking the hardware into consideration, we must not disregard that obtaining adequate lateral fixation of small fragments is a difficult task, and plates are more associated to local irritation. The aim of the appropriate treatment is to ensure fracture healing and a rapid return to preinjury activities of daily living but, as explained, definitive treatment strategies have not been established and the variety of techniques avalilable add up to the discussion of this topic. Methods and Results: We present a clinical case of a 43-year-old man with the diagnosis of a lateral third clavicle fracture (Neer IIC) in the sequence of a fall on his right shoulder after a bicycle fall. He was operated three days after the injury, and through K-wire temporary fixation and indirect reduction using a ZipTight, he underwent osteosynthesis with an interfragmentary figure-of-eight tension band with polydioxanone suture (PDS). Two weeks later, there was a good aligment. He kept the sling until 6 weeks pos-op, avoiding efforts. At 7-weeks pos-op, there was still a good aligment, starting the physiotherapy exercises. After 10 months, he had no limitation in mobility or pain and returned to work with complete recovery in strength. Conclusion: Some distal clavicle fractures may be conservatively treated, but it is widely accepted that unstable fractures require surgical treatment to obtain superior clinical outcomes. In the clinical case presented, the authors chose an osteosuture technique due to the fracture pattern, its location. Since there isn´t a consensus on the prefered fixation method, it is important for surgeons to be skilled in various techniques and decide with their patient which approach is most appropriate for them, weighting the risk-benefit of each method. For instance, with the suture technique used, there is no wire migration or breakage, and it doesn´t require a reoperation for hardware removal; there is also less tissue exposure since it requires a smaller approach in comparison to the plate fixation and avoids cuff tears like the hook plate. The good clinical outcome on this case report serves the purpose of expanding the consideration of this method has a therapeutic option.

Keywords: lateral third, clavicle, suture, fixation

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Authors: Sogand Moshfeghi, Alireza Biglari

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Diabetes is an endocrine disorder that is commonly treated with insulin. However, long-term usage of insulin and hypoglycemic chemical drugs can result in various side effects. Therefore, it is crucial to explore effective compounds with minimal side effects for diabetes treatment. This study aimed to compare the hypoglycemic effects of hydroalcoholic extracts derived from Silybum marianum, Camellia sinensis (green tea), and Urtica dioica plants. Male Wistar rats were allocated to 5 groups. Group 1 received normal Salin. Other groups were diabetic (induced by Streptozotocin 65 mg/kg Ip), group 2 received normal Salin (Ip, qod. 21 days). Group 3 received Silybum Marianum L, hydroalcoholic extract (100 mg/kg, ip.qod, 21 days). Group 4 received Camellia sinesis L, hydroalcoholic extract (100mg/kg,ip,qod,21 days), and group 5 received Urtica dioica L. hydroalcoholic extract (100mg/kg, ip,qod,21 days). Blood samples were collected at 14 and 21 days after the initial injection to evaluate the blood glucose levels. On the fourteenth day, the blood glucose levels for the diabetic groups were as follows: Group 2: 424.7±34.5, Group 3: 390.7±10.5, Group 4: 350.4±16.9, and Group 5: 340±20.5. On the 21st day, the respective blood glucose levels were: Group 2: 432±5.0, Group 3: 410.16±5.0, Group 4: 264.3±17.5, and Group 5: 270.7±24.5. Statistical analysis using the Tukey Anova test indicated that on the fourteenth day, both the green tea and Urtica groups exhibited significant hypoglycemic effects. Furthermore, on the 21st day, Urtica dioica extract demonstrated comparable effects to Camellia Sinensis extract, while Silybum Marianum extract did not significantly lower blood glucose levels compared to the diabetic group. In conclusion, the hydroalcoholic extracts from Camellia sinensis and Urtica dioica plants exhibited promising hypoglycemic effects in diabetic rats. These findings provide valuable insights into the potential use of natural plant extracts as alternative or complementary treatments for diabetes, warranting further investigation to harness their therapeutic benefit effectively.

Keywords: Camellia sinesis, glucose, Silybum marianum, Urtica dioica

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Authors: Supriya Gupta, Paresh Chokshi

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Polymer-particle interactions can be effectively utilized to produce composites that possess physicochemical properties superior to that of neat polymer. The incorporation of fillers with dimensions comparable to polymer chain size produces composites with extra-ordinary properties owing to very high surface to volume ratio. The dispersion of nanoparticles is achieved by inducing steric repulsion realized by grafting particles with polymeric chains. A comprehensive understanding of the interparticle interaction between these functionalized nanoparticles plays an important role in the synthesis of a stable polymer nanocomposite. With the focus on incorporation of clay sheets in a polymer matrix, we theoretically construct the polymer mediated interparticle potential for two nanosheets grafted with polymeric chains. The self-consistent field theory (SCFT) is employed to obtain the inhomogeneous composition field under equilibrium. Unlike the continuum models, SCFT is built from the microscopic description taking in to account the molecular interactions contributed by both intra- and inter-chain potentials. We present the results of SCFT calculations of the interaction potential curve for two grafted nanosheets immersed in the matrix of polymeric chains of dissimilar chemistry to that of the grafted chains. The interaction potential is repulsive at short separation and shows depletion attraction for moderate separations induced by high grafting density. It is found that the strength of attraction well can be tuned by altering the compatibility between the grafted and the mobile chains. Further, we construct the interaction potential between two nanosheets grafted with diblock copolymers with one of the blocks being chemically identical to the free polymeric chains. The interplay between the enthalpic interaction between the dissimilar species and the entropy of the free chains gives rise to a rich behavior in interaction potential curve obtained for two separate cases of free chains being chemically similar to either the grafted block or the free block of the grafted diblock chains.

Keywords: clay nanosheets, polymer brush, polymer nanocomposites, self-consistent field theory

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Authors: Prasamsha Panta, Da Yeon Kim, Ja Yong Jang, Min Jae Kim, Jae Ho Kim, Moon Suk Kim

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Introduction: Among the many anticancer drugs used clinically, doxorubicin (Dox), was one of widely used drugs to treat many types of solid tumors such as liver, colon, breast, or lung. Intratumoral injection of chemotherapeutic agents is a potentially more effective alternative to systemic administration because direct delivery of the anticancer drug to the target may improve both the stability and efficacy of anticancer drugs. Injectable in situ-forming gels have attracted considerable attention because they can achieve site specific drug delivery, long term action periods, and improved patient compliance. Objective: Objective of present study is to confirm clinical benefit of intratumoral chemotherapy using injectable in situ-forming poly(ethylene glycol)-b-polycaprolactone diblock copolymer (MP) and Dox with increase in efficacy and reducing the toxicity in patients with cancer diseases. Methods and methodology: We prepared biodegradable MP hydrogel and measured viscosity for the evaluation of thermo-sensitive property. In vivo antitumor activity was performed with normal saline, MP only, single free Dox, repeat free Dox, and Dox-loaded MP gel. The remaining amount of Dox drug was measured using HPLC after the mouse was sacrified. For cytotoxicity studies WST-1 assay was performed. Histological analysis was done with H&E and TUNEL processes respectively. Results: The works in this experiment showed that Dox-loaded MP have biodegradable drug depot property. Dox-loaded MP gels showed remarkable in vitro cytotoxicity activities against cancer cells. Finally, this work indicates that injection of Dox-loaded MP allowed Dox to act effectively in the tumor and induced long-lasting supression of tumor growth. Conclusion: This work has examined the potential clinical utility of intratumorally injected Dox-loaded MP gel, which shows significant effect of higher local Dox retention compared with systemically administered Dox.

Keywords: injectable in-situ forming hydrogel, anticancer, doxorubicin, intratumoral injection

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Authors: Kitoholi V. Zhimo

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Unlike the cases of cases of homosexuals, haemophilic and or drug users in USA, France, Africa and other countries, in India the first case of HIV/AIDS was detected in heterosexual female sex workers (FSW) in Chennai in 1986. This image played an important role in understanding HIV/AIDS scenario in the country. Similar to popular and dominant metaphors on HIV/AIDS such as ‘gay plague’, ‘new cancer’, ‘lethal disease’, ‘slim disease’, ‘foreign disease’, ‘junkie disease’, etc. around the world, the social construction of the virus was largely attributed to women in India. It was established that women particularly sex workers are ‘carrier’ and ‘transmitter’ of virus and were categorised as High Risk Groups (HRG’s) alongside homosexuals, transgenders and injecting drug users. Recent literature reveals growing rate of HIV infection among housewives since 1997 which revolutionised public health scenario in India. This means shift from high risk group to general public through ‘bridge population’ encompassing long distance truckers and migrant labours who at the expense of their nature of work and mobility comes in contact with HRG’s and transmit the virus to the general public especially women who are confined to the domestic space. As HIV epidemic expands, married women in monogamous relationship/marriage stand highly susceptible to infection with limited control, right and access over their sexual and reproductive health and planning. In context of Nagaland, a small state in North-eastern part of India HIV/AIDS transmission through injecting drug use dominated the early scene of the epidemic. However, paradigm shift occurred with declining trend of HIV prevalence among injecting drug users (IDU’s) over the past years with the introduction of Opioid Substitution Therapy (OST) and easy access/availability of syringes and injecting needles. Reflection on statistical data reveals that out of 36 states and union territories in India, the position of Nagaland in HIV prevalence among IDU’s has significantly dropped down from 6th position in 2003 to 16th position in 2017. The present face of virus in Nagaland is defined by (hetero) sexual mode of transmission which accounts for about 91% of as reported by Nagaland state AIDS control society (NSACS) in 2016 wherein young and married woman were found to be most affected leading to feminization of HIV/AIDS epidemic in the state. Thus, not only is HIV epidemic feminised but emerged victim to domestic violence which is more often accepted as normal part of heterosexual relationship. In the backdrop of these understanding, the present paper based on ethnographic fieldwork explores the plight, lived experiences and images of HIV+ve women with regard to sexual and reproductive rights against the backdrop of patriarchal system in Nagaland.

Keywords: HIV/AIDS, monogamy, Nagaland, sex worker disease, women

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Authors: Saltanat Zhilkibayeva, Muratulla Utenov, Nurzhan Utenov

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The distributed inertia forces of complex nature appear in links of rod mechanisms within the motion process. Such loads raise a number of problems, as the problems of destruction caused by a large force of inertia; elastic deformation of the mechanism can be considerable, that can bring the mechanism out of action. In this work, a new analytical approach for the definition of internal forces in links of robotic systems and mechanisms with statically indeterminate and determinate structures taking into account the distributed inertial and concentrated forces is proposed. The relations between the intensity of distributed inertia forces and link weight with geometrical, physical and kinematic characteristics are determined in this work. The distribution laws of inertia forces and dead weight make it possible at each position of links to deduce the laws of distribution of internal forces along the axis of the link, in which loads are found at any point of the link. The approximation matrixes of forces of an element under the action of distributed inertia loads with the trapezoidal intensity are defined. The obtained approximation matrixes establish the dependence between the force vector in any cross-section of the element and the force vector in calculated cross-sections, as well as allow defining the physical characteristics of the element, i.e., compliance matrix of discrete elements. Hence, the compliance matrixes of an element under the action of distributed inertial loads of trapezoidal shape along the axis of the element are determined. The internal loads of each continual link are unambiguously determined by a set of internal loads in its separate cross-sections and by the approximation matrixes. Therefore, the task is reduced to the calculation of internal forces in a final number of cross-sections of elements. Consequently, it leads to a discrete model of elastic calculation of links of rod mechanisms. The discrete model of the elements of mechanisms and robotic systems and their discrete model as a whole are constructed. The dynamic equilibrium equations for the discrete model of the elements are also received in this work as well as the equilibrium equations of the pin and rigid joints expressed through required parameters of internal forces. Obtained systems of dynamic equilibrium equations are sufficient for the definition of internal forces in links of mechanisms, which structure is statically definable. For determination of internal forces of statically indeterminate mechanisms (in the way of determination of internal forces), it is necessary to build a compliance matrix for the entire discrete model of the rod mechanism, that is reached in this work. As a result by means of developed technique the programs in the MAPLE18 system are made and animations of the motion of the fourth class mechanisms of statically determinate and statically indeterminate structures with construction on links the intensity of cross and axial distributed inertial loads, the bending moments, cross and axial forces, depending on kinematic characteristics of links are obtained.

Keywords: distributed inertial forces, internal forces, statically determinate mechanisms, statically indeterminate mechanisms

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Authors: N. C. Shahi, Anupama Singh, E. Kate

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Drying is practiced to enhance the storage life, to minimize losses during storage, and to reduce transportation costs of agricultural products. Drying processes range from open sun drying to industrial drying. In most of the developing countries, use of fossil fuels for drying of agricultural products has not been practically feasible due to unaffordable costs to majority of the farmers. On the other hand, traditional open sun drying practiced on a large scale in the rural areas of the developing countries suffers from high product losses due to inadequate drying, fungal growth, encroachment of insects, birds and rodents, etc. To overcome these problems a middle technology dryer having low cost need to be developed for farmers. In case of mechanical dryers, the heated air is the main driving force for removal of moisture. The air is heated either electrically or by burning wood, coal, natural gas etc. using heaters. But, all these common sources have finite supplies. The lifetime is estimated to range from 15 years for a natural gas to nearly 250 years for coal. So, mankind must turn towards its safe and reliable utilization and may have undesirable side effects. The mechanical drying involves higher cost of drying and open sun drying deteriorates the quality. The solar tunnel dryer is one of promising option for drying various agricultural and agro-industrial products on large scale. The advantage of Solar tunnel dryer is its relatively cheaper cost of construction and operation. Although many solar dryers have been developed, still there is a scope of modification in them. Therefore, an attempt was made to develop Solar tunnel dryer and test its performance using highly perishable commodity i.e. leafy vegetables (spinach). The effect of air velocity, loading density and shade net on performance parameters namely, collector efficiency, drying efficiency, overall efficiency of dryer and specific heat energy consumption were also studied. Thus, the need for an intermediate level technology was realized and an effort was made to develop a small scale Solar Tunnel Dryer . A dryer consisted of base frame, semi cylindrical drying chamber, solar collector and absorber, air distribution system with chimney and auxiliary heating system, and wheels for its mobility were the main functional components. Drying of fenugreek was carried out to analyze the performance of the dryer. The Solar Tunnel Dryer temperature was maintained using the auxiliary heating system. The ambient temperature was in the range of 12-33oC. The relative humidity was found inside and outside the Solar Tunnel Dryer in the range of 21-75% and 35-79%, respectively. The solar radiation was recorded in the range of 350-780W/m2 during the experimental period. Studies revealed that total drying time was in range of 230 to 420 min. The drying time in Solar Tunnel Dryer was considerably reduced by 67% as compared to sun drying. The collector efficiency, drying efficiency, overall efficiency and specific heat consumption were determined and were found to be in the range of 50.06- 38.71%, 15.53-24.72%, 4.25 to 13.34% and 1897.54-3241.36 kJ/kg, respectively.

Keywords: overall efficiency, solar tunnel dryer, specific heat consumption, sun drying

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Authors: Rania Hanafi Mahmoud Said, Rasha Mohamed Taha

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Background: A recent study has explored the potential of an approach to treating infected root canals using a combination of Mineral Trioxide Aggregate (MTA) and Tetracycline-loaded Nanochitosan. Material and methods: Forty dogs were included in the study, with infected periapical areas induced by leaving access openings in their teeth for four months. Bacteriological samples from the infected root canals were collected and managed anaerobically to identify and count the different microorganisms present. The most common microorganisms detected were Prevotella oris, Fusobacterium nucleatum, Streptococcus viridans, Enterococcus faecalis, Clostridium subterminale, Porphyromonas gingivalis, and Peptostreptococcus anaerobius. The dogs were divided into four groups based on the sealant used to treat the infected periapical areas: Group I: Negative control (no treatment) Group II: Positive control (MTA only) Group III: MTA + tetracycline Group IV: MTA + tetracycline loaded on nanochitosan Results: Periapical areas in Group IV showed significantly more bone healing than those in Groups I, II, and III. The newly formed bone was evaluated radiographically, histologically, and immunohistochemically using Osteopontin (OSP) antibodies. Data collected was statistically analysed using SPSS software at a 0.05 significance level. Conclusion: The study concluded that the combined use of Tetracycline-loaded Nanochitosan and MTA presents a promising approach for the treatment of infected root canals. The potent antimicrobial activity of Tetracycline-loaded Nanochitosan, along with the biocompatibility and desirable properties of MTA, may synergistically contribute to improved clinical outcomes in endodontic therapy. This study has important implications for the clinical management of infected root canals. The combination of Tetracycline-loaded Nanochitosan and MTA could provide a more effective and efficient means of treating these challenging cases. Further research is needed to confirm these findings in humans and to optimize the treatment protocol.

Keywords: mineral trioxide aggregate, tetracycline-loaded nanochitosan, periapical infection, osteopontine

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Authors: Daniel Aberdam

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Haploinsufficiency of PAX6 in humans is the main cause of congenital aniridia, a rare eye disease characterized by reduced visual acuity. Patients have also progressive disorders including cataract, glaucoma and corneal abnormalities making their condition very challenging to manage. Aniridia-related keratopathy (ARK), caused by a combination of factors including limbal stem-cell deficiency, impaired healing response, abnormal differentiation, and infiltration of conjunctival cells onto the corneal surface, affects up to 95% of patients. It usually begins in the first decade of life resulting in recurrent corneal erosions, sub-epithelial fibrosis with corneal decompensation and opacification. Unfortunately, current treatment options for aniridia patients are currently limited. Although animal models partially recapitulate this disease, there is no in vitro cellular model of AKT needed for drug/therapeutic tools screening and validation. We used genome editing (CRISPR/Cas9 technology) to introduce a nonsense mutation found in patients into one allele of the PAX6 gene into limbal stem cells. Resulting mutated clones, expressing half of the amount of PAX6 protein and thus representative of haploinsufficiency were further characterized. Sequencing analysis showed that no off-target mutations were induced. The mutated cells displayed reduced cell proliferation and cell migration but enhanced cell adhesion. Known PAX6 targets expression was also reduced. Remarkably, addition of soluble recombinant PAX6 protein into the culture medium was sufficient to activate endogenous PAX6 gene and, as a consequence, rescue the phenotype. It strongly suggests that our in vitro model recapitulates well the epithelial defect and becomes a powerful tool to identify drugs that could rescue the corneal defect in patients. Furthermore, we demonstrate that the homeotic transcription factor Pax6 is able to be uptake naturally by recipient cells to function into the nucleus.

Keywords: Pax6, crispr/cas9, limbal stem cells, aniridia, gene therapy

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Authors: Aidan Battison, Neliswa Mama

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Environmental pollution by ionic species has been identified as one of the biggest challenges to the sustainable development of communities. The widespread use of organic and inorganic chemical products and the release of toxic chemical species from industrial waste have resulted in a need for advanced monitoring technologies for environment protection, remediation and restoration. Some of the disadvantages of conventional sensing methods include expensive instrumentation, well-controlled experimental conditions, time-consuming procedures and sometimes complicated sample preparation. On the contrary, the development of fluorescent chemosensors for biological and environmental detection of metal ions has attracted a great deal of attention due to their simplicity, high selectivity, eidetic recognition, rapid response and real-life monitoring. Coumarin derivatives S1 and S2 (Scheme 1) containing 1,2,3-triazole moieties at position -3- have been designed and synthesized from azide and alkyne derivatives by CuAAC “click” reactions for the detection of metal ions. These compounds displayed a strong preference for Fe3+ ions with complexation resulting in fluorescent quenching through photo-induced electron transfer (PET) by the “sphere of action” static quenching model. The tested metal ions included Cd2+, Pb2+, Ag+, Na+, Ca2+, Cr3+, Fe3+, Al3+, Cd2+, Ba2+, Cu2+, Co2+, Hg2+, Zn2+ and Ni2+. The detection limits of S1 and S2 were determined to be 4.1 and 5.1 uM, respectively. Compound S1 displayed the greatest selectivity towards Fe3+ in the presence of competing for metal cations. S1 could also be used for the detection of Fe3+ in a mixture of CH3CN/H¬2¬O. Binding stoichiometry between S1 and Fe3+ was determined by using both Jobs-plot and Benesi-Hildebrand analysis. The binding was shown to occur in a 1:1 ratio between the sensor and a metal cation. Reversibility studies between S1 and Fe3+ were conducted by using EDTA. The binding site of Fe3+ to S1 was determined by using 13 C NMR and Molecular Modelling studies. Complexation was suggested to occur between the lone-pair of electrons from the coumarin-carbonyl and the triazole-carbon double bond.

Keywords: chemosensor, "click" chemistry, coumarin, fluorescence, static quenching, triazole

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Authors: Sharmin Sultana, Nicolas Nuns, Pardis Simon, Jean-Marc Giraudon, Jean-Francois Lamonior, Nathalie D. Geyter, Rino Morent

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Environmental issues, especially air pollution, have become a huge concern of environmental legislation as a consequence of growing awareness in our global world. In this regard, control of volatile organic compounds (VOCs) emission has become an important issue due to their potential toxicity, carcinogenicity, and mutagenicity. The research of innovative technologies for VOC abatement is stimulated to accommodate the new stringent standards in terms of VOC emission. One emerging strategy is the coupling of 2 existing complementary technologies, namely here non-thermal plasma (NTP) and heterogeneous catalysis, to get a more efficient process for VOC removal in air. The objective of this current work is to investigate the abatement of trichloroethylene (TCE-highly toxic chlorinated VOC) from moist air (RH=15%) as a function of time by combined use of multi-pin-to-plate negative DC corona/glow discharge with Fe-doped cryptomelanes catalyst downstream i.e. post plasma-catalysis (PPC) process. For catalyst alone case, experiments reveal that, initially, Fe doped cryptomelane (regardless the mode of Fe incorporation by co-precipitation (Fe-K-OMS-2)/ impregnation (Fe/K-OMS-2)) exhibits excellent activity to decompose TCE compared to cryptomelane (K-OMS-2) itself. A maximum obtained value of TCE abatement after 6 min is as follows: Fe-KOMS-2 (73.3%) > Fe/KOMS-2 (48.5) > KOMS-2 (22.6%). However, with prolonged operation time, whatever the catalyst under concern, the abatement of TCE decreases. After 111 min time of exposure, the catalysts can be ranked as follows: Fe/KOMS-2 (11%) < K-OMS-2 (12.3%) < Fe-KOMS-2 (14.5%). Clearly, this phenomenon indicates catalyst deactivation either by chlorination or by blocking the active sites. Remarkably, in PPC configuration (energy density = 60 J/L, catalyst temperature = 150°C), experiments reveal an enhanced performance towards TCE removal regardless the type of catalyst. After 6 min time on stream, the TCE removal efficiency amount as follows: K-OMS-2 (60%) < Fe/K-OMS-2 (79%) < Fe-K-OMS-2 (99.3%). The enhanced performances over Fe-K-OMS-2 catalyst are attributed to its high surface oxygen mobility and structural defects leading to high O₃ decomposition efficiency to give active species able to oxidize the plasma processed hazardous\by-products and the possibly remaining VOC into CO₂. Moreover, both undoped and doped catalysts remain strongly capable to abate TCE with time on stream. The TCE removal efficiencies of the PPC processes with Fe/KOMS-2 and KOMS-2 catalysts are not affected by time on stream indicating an excellent catalyst stability. When using the Fe-K-OMS-2 as catalyst, TCE abatement slightly reduces with time on stream. However, it is noteworthy to stress that still a constant abatement of 83% is observed during at least 30 minutes. These results prove that the combination of NTP with catalysts not only increases the catalytic activity but also allows to avoid, to some extent, the poisoning of catalytic sites resulting in an enhanced catalyst stability. In order to better understand the different surface processes occurring in the course of the total TCE oxidation in PPC experiments, a detailed X-ray Photoelectron Spectroscopy (XPS) and Time of Flight-Secondary Ion Mass Spectrometry (ToF-SIMS) study on the fresh and used catalysts is in progress.

Keywords: Fe doped cryptomelane, non-thermal plasma, plasma-catalysis, stability, trichloroethylene

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Authors: Rob Leslie, Taher Karimian

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The blockage of cross drainage structures is a risk that needs to be understood and managed or lessened through the design. A blockage is a random event, influenced by site-specific factors, which needs to be quantified for design. Under and overestimation of blockage can have major impacts on flood risk and cost associated with drainage structures. The importance of this matter is heightened for those projects located within sensitive lands. It is a particularly complex problem for large linear infrastructure projects (e.g., rail corridors) located within floodplains where blockage factors can influence flooding upstream and downstream of the infrastructure. The selection of the appropriate blockage factors for hydraulic modeling has been subject to extensive research by hydraulic engineers. This paper has been prepared to review the current Australian Rainfall and Runoff 2019 (ARR 2019) methodology for blockage assessment by applying this method to a transport corridor brownfield upgrade case study in New South Wales. The results of applying the method are also validated against asset data and maintenance records. ARR 2019 – Book 6, Chapter 6 includes advice and an approach for estimating the blockage of bridges and culverts. This paper concentrates specifically on the blockage of cross drainage structures. The method has been developed to estimate the blockage level for culverts affected by sediment or debris due to flooding. The objective of the approach is to evaluate a numerical blockage factor that can be utilized in a hydraulic assessment of cross drainage structures. The project included an assessment of over 200 cross drainage structures. In order to estimate a blockage factor for use in the hydraulic model, a process has been advanced that considers the qualitative factors (e.g., Debris type, debris availability) and site-specific hydraulic factors that influence blockage. A site rating associated with the debris potential (i.e., availability, transportability, mobility) at each crossing was completed using the method outlined in ARR 2019 guidelines. The hydraulic results inputs (i.e., flow velocity, flow depth) and qualitative factors at each crossing were developed into an advanced spreadsheet where the design blockage level for cross drainage structures were determined based on the condition relating Inlet Clear Width and L10 (average length of the longest 10% of the debris reaching the site) and the Adjusted Debris Potential. Asset data, including site photos and maintenance records, were then reviewed and compared with the blockage assessment to check the validity of the results. The results of this assessment demonstrate that the estimated blockage factors at each crossing location using ARR 2019 guidelines are well-validated with the asset data. The primary finding of the study is that the ARR 2019 methodology is a suitable approach for culvert blockage assessment that has been validated against a case study spanning a large geographical area and multiple sub-catchments. The study also found that the methodology can be effectively coded within a spreadsheet or similar analytical tool to automate its application.

Keywords: ARR 2019, blockage, culverts, methodology

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Authors: Pouya Taraghi, Yong Li, Nader Yoosef-Ghodsi, Muntaseer Kainat, Samer Adeeb

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Buried pipelines play a crucial role in the transportation of energy products such as oil, gas, and various chemical fluids, ensuring their efficient and safe distribution. However, these pipelines are often susceptible to ground movements caused by geohazards like landslides, fault movements, lateral spreading, and more. Such ground movements can lead to strain-induced failures in pipes, resulting in leaks or explosions, leading to fires, financial losses, environmental contamination, and even loss of human life. Therefore, it is essential to study how buried pipelines respond when traversing geohazard-prone areas to assess the potential impact of ground movement on pipeline design. As such, this study introduces an approach called the Physics-Informed Neural Network (PINN) to predict the strain demand in inelastic pipes subjected to permanent ground displacement (PGD). This method uses a deep learning framework that does not require training data and makes it feasible to consider more realistic assumptions regarding existing nonlinearities. It leverages the underlying physics described by differential equations to approximate the solution. The study analyzes various scenarios involving different geohazard types, PGD values, and crossing angles, comparing the predictions with results obtained from finite element methods. The findings demonstrate a good agreement between the results of the proposed method and the finite element method, highlighting its potential as a simulation-free, data-free, and meshless alternative. This study paves the way for further advancements, such as the simulation-free reliability assessment of pipes subjected to PGD, as part of ongoing research that leverages the proposed method.

Keywords: strain demand, inelastic pipe, permanent ground displacement, machine learning, physics-informed neural network

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Authors: Muhammad Awais Afzal, Lorena Tuchscherr De Hauschopp, Christian Hübner

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Introduction: Autophagy is an evolutionarily conserved lysosome-dependent degradation pathway, which can be induced by extrinsic and intrinsic stressors in living systems to adapt to fluctuating environmental conditions. In the context of inflammatory stress, autophagy contributes to the elimination of invading pathogens, the regulation of innate and adaptive immune mechanisms, and regulation of inflammasome activity as well as tissue damage repair. Lysosomes can be recycled from autolysosomes by the process of autophagic lysosome reformation (ALR), which depends on the presence of several proteins including Spatacsin. Thus ALR contributes to the replenishment of lysosomes that are available for fusion with autophagosomes in situations of increased autophagic turnover, e.g., during bacterial infections, inflammatory stress or sepsis. Objectives: We aimed to assess whether ALR plays a role for cell survival in an in-vitro bacterial infection model. Methods: Mouse embryonic fibroblasts (MEFs) were isolated from wild-type mice and Spatacsin (Spg11-/-) knockout mice. Wild-type MEFs and Spg11-/- MEFs were infected with Staphylococcus aureus (multiplication of infection (MOI) used was 10). After 8 and 16 hours of infection, cell viability was assessed on BD flow cytometer through propidium iodide intake. Bacterial intake by cells was also calculated by plating cell lysates on blood agar plates. Results: in-vitro infection of MEFs with Staphylococcus aureus showed a marked decrease of cell viability in ALR deficient Spatacsin knockout (Spg11-/-) MEFs after 16 hours of infection as compared to wild-type MEFs (n=3 independent experiments; p < 0.0001) although no difference was observed for bacterial intake by both genotypes. Conclusion: Suggesting that ALR is important for the defense of invading pathogens e.g. S. aureus, we observed a marked increase of cell death in an in-vitro infection model in cells with compromised ALR.

Keywords: autophagy, autophagic lysosome reformation, bacterial infections, Staphylococcus aureus

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Authors: Yifat Koren Carmi, Abed Agbarya, Hazem Khamaisi, Raymond Farah, Yelena Shechtman, Roman Korobochka, Jacob Gopas, Jamal Mahajna

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Ovarian cancer (OC), the second most common form of gynecological malignancy, has a poor prognosis and is frequently identified in its late stages. The recommended treatment for OC typically includes a platinum-based chemotherapy, like carboplatin. Nonetheless, OC treatment has proven challenging due to toxicity and development of acquired resistance to therapy. Chemoresistance is a significant obstacle to a long-lasting response in OC patients, believed to arise from alterations within the cancer cells as well as within the tumor microenvironments (TME). Malignant ascites is a presenting feature in more than one-third of OC patients. It serves as a reservoir for a complex mixture of soluble factors, metabolites, and cellular components, providing a pro-inflammatory and tumor-promoting microenvironment for the OC cells. Malignant ascites is also associated with metastasis and chemoresistance. In an attempt to elucidate the role of TME in chemoresistance of OC, we monitored the ability of soluble factors derived from ascites fluids to affect platinum sensitivity of OC cells. This research, compared ascites fluids from non-malignant cirrhotic patients to those from OC patients in terms of their ability to alter the platinum sensitivity of OC cells. Our findings indicated that exposure to OC ascites induces platinum chemoresistance on OC cells in 11 out of 13 cases (85%). In contrast, 75% of cirrhosis ascites (3 out of 4) failed to confer platinum chemoresistance to OC cells. Cytokine array analysis revealed that IL-6, and to a lesser extent HGF were enriched in OC ascites, whereas IL-22 was enriched in cirrhosis ascites. Pharmaceutical inhibitors that target the IL-6/JAK signaling pathway were mildly effective in overcoming the platinum chemoresistance induced by malignant ascites. In contrast, Crizotinib an HGF/c-MET inhibitor, and 2-hydroxyestradiol (2HE2) were effective in restoring platinum chemoresistance to OC. Our findings demonstrate the importance of OC ascites in supporting platinum chemoresistance as well as the potential of a combination therapy with Crizotinib and the estradiol metabolite 2HE2 to regain OC cells chemosensitivity.

Keywords: ovarian cancer, platinum chemoresistance, malignant ascites, tumor microenvironment, IL-6, 2-hydroxyestradiol, HGF, crizotinib

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Authors: Aymen Arfaoui, Abdelkader Soumaya, Noureddine Ben Ayed

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The study region is located in the Tunisian Dorsal Backland (Central Mediterranean), which is the easternmost part of the Saharan Atlas mountain range, trending southwest-northeast. Based on our fieldwork, seismic tomography images, seismicity, and previous studies, we propose an interpretation of the relationship between the surface deformation and fault kinematics in the study area and the internal dynamic processes acting in the Central Mediterranean from the Cenozoic to the present. The subduction and dynamics of internal forces beneath the complicated Maghrebides mobile belt have an impact on the Tertiary and Quaternary tectonic regimes in the Pelagian and Atlassic foreland that is part of our study region. The left lateral reactivation of the major "Tunisian N-S Axis fault" and the development of a compressional relay between the Hammamet Korbous and Messella-Ressas faults are possibly a result of tectonic stresses due to the slab roll-back following the Africa/Eurasia convergence. After the slab segmentation and its eastward migration (5–4 Ma) and the formation of the Strait of Sicily "rift zone" further east, a transtensional tectonic regime has been installed in this area. According to seismic tomography images, the STEP fault of the "North-South Axis" at Hammamet-Korbous coincides with the western edge of the "Slab windows" of the Sicilian Channel and the eastern boundary of the positive anomalies attributed to the residual Slab of Tunisia. On the other hand, significant E-W Plio-Quaternary tectonic activity may be observed along the eastern portion of this STEP fault system in the Grombalia zone as a result of recent vertical lithospheric motion in response to the lateral slab migration eastward to Sicily Channel. According to SKS fast splitting directions, the upper mantle flow pattern beneath Tunisian Dorsal is parallel to the NE-SW to E-W orientation of the Shmin identified in the study area, similar to the Plio-Quaternary extensional orientation in the Central Mediterranean. Additionally, the removal of the lithosphere and the subsequent uplift of the sub-lithospheric mantle beneath the topographic highs of the Dorsal and its surroundings may be the cause of the dominant extensional to transtensional Quaternary regime. The occurrence of strike-slip and extensional seismic events in the Pelagian block reveals that the regional transtensional tectonic regime persists today. Finally, we believe that the geodynamic history of the study area since the Cenozoic is primarily influenced by the preexisting weak zones, the African slab detachment, and the upper mantle flow pattern in the central Mediterranean.

Keywords: Tunisia, lithospheric discontinuity (STEP fault), geodynamic evolution, Tunisian dorsal backland, strike-slip fault, seismic tomography, seismicity, central Mediterranean

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Authors: Muhammad Naeem, Juho Lee, Jin-Wook Yoo

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In this study, we hypothesized that prolonged gastrointestinal transit at the inflamed colon conferred by a pH-triggered mucoadhesive smart nanoparticulate drug delivery system aids in achieving selective and sustained levels of the drug within the inflamed colon for the treatment of ulcerative colitis. We developed budesonide-loaded pH-sensitive charge-reversal solid lipid nanoparticles (SLNs) using a hot homogenization method. Polyetylenimine (PEI) was used to render SLNs cationic (PEI-SLNs). Eudragit S100 (ES) was coated on PEI-SLNs for pH-trigger charge-reversal SLNs (ES-PEI-SLNs). Therapeutic potential of the prepared SNLs formulation was evaluated in ulcerative colitis in mice. The transmission electron microscopy, zeta size and zeta potential data showed the successful formation of SLNs formulations. SLNs and PEI-SLNs showed burst drug release in acidic pH condition mimicking stomach and early small intestine environment which limiting their application as oral delivery systems. However, ES-PEI-SLNs prevented a burst drug release in acidic pH conditions and showed sustained release at a colonic pH. Most importantly, the surface charge of ES-PEI-SLNs switched from negative to positive in colonic conditions by pH-triggered removal of ES coating and accumulated selectively in inflamed colon. Furthermore, a charge reversal ES-PEI-SLNs showed a superior mitigation of dextran sulfate sodium (DSS)-induced acute colitis in mice as compared to SLNs and PEI-SLNs treated groups. Moreover, histopathological analysis of distal colon sections stained with hematoxylin/eosin and E-cadherin immunostaining revealed attenuated inflammation in an ES-PEI-SLNs-treated group. We also found that ES-PEI-SLNs markedly reduced the myeloperoxidase level and expression of TNF-alpha in colon tissue. Our results suggest that the pH-triggered charge reversal SLNs presented in this study would be a promising approach for ulcerative colitis therapy.

Keywords: solid lipid nanoparticles, stimuli-triggered charge-reversal, ulcerative colitis, methacrylate copolymer, budesonide

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Authors: Noam Markovitz

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People with physical disabilities constitute a very large and simultaneously a diverse group of general population, as the term physical disabilities is extensive and covers a wide range of disabilities. Therefore, individuals with physical disabilities are often faced with a new, threatening and stressful reality leading possibly to a multi-crisis in their lives due to the great changes they experience in somatic, socio-economic, occupational and psychological level. The current study seeks to advance understanding of the complex adaptation to physical disabilities by expanding the dynamic-adaptational model of the pursuit of happiness in a hostile world with a new conception of physical self-integrity. Physical self-integrity incorporates an objective dimension, namely physical self-functioning (PSF), and a subjective dimension, namely physical self-concept (PSC). Both of these dimensions constitute an experience of wholeness in the individual’s identification with her or his physical body. The model guiding this work is dialectical in nature and depicts two systems in the individual’s sense of happiness: subjective well-being (SWB) and meaning in life (MIL). Both systems serve as self-adaptive agents that moderate the complementary system of the hostile-world scenario (HWS), which integrates one’s perceived threats to one’s integrity. Thus, in situations of increased HWS, the moderation may take a form of joint activity in which SWB and MIL are amplified or a form of compensation in which one system produces a stronger effect while the other system produces a weaker effect. The current study investigated PSC in relations to SWB and MIL through pleasantness and meanings that are physically or metaphorically grounded in one’s body. In parallel, PSC also relates to HWS by activating representations of inappropriateness, deformation and vulnerability. In view of possibly dialectical positions of opposing and complementary forces within the current model, the current field study that aims to explore PSC as appearing in an independent, cross-sectional, design addressing the model’s variables in a focal group of people with physical disabilities. This study delineated the participation of the PSC in the adaptational functions of SWB and MIL vis-à-vis HWS-related life adversities. The findings showed that PSC could fully complement the main variables of the pursuit of happiness in a hostile world model. The assumed dialectics in the form of a stronger relationship between SWB and MIL in the face of physical disabilities was not supported. However, it was found that when HWS increased, PSC and MIL were strongly linked, whereas PSC and SWB were weakly linked. This highlights the compensatory role of MIL. From a conceptual viewpoint, the current investigation may clarify the role of PSC as an adaptational agent of the individual’s positive health in complementary senses of bodily wholeness. Methodologically, the advantage of the current investigation is the application of an integrative, model-based approach within a specially focused design with a particular relevance to PSC. Moreover, from an applicative viewpoint, the current investigation may suggest how an innovative model may be translated to therapeutic interventions used by clinicians, counselors and practitioners in improving wellness and psychological well-being, particularly among people with physical disabilities.

Keywords: older adults, physical disabilities, physical self-concept, pursuit of happiness in a hostile-world

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Authors: Ana Pinheiro, Fatima Suleman

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Literature has revealed strong awareness of companies in regard of expatriation, but issues associated with repatriation of employees after an international assignment have been overlooked. Repatriation is one of the most challenging human resource practices that affect how companies benefit from acquired skills and high potential employees; and gain competitive advantage through network developed during expatriation. However, empirical evidence achieved so far suggests that expatriates have been disappointed because companies lack an effective repatriation strategy. Repatriates’ professional and emotional needs are often unrecognized, while repatriation is perceived as a non-issue by companies. The underlying assumption is that the return to parent company, and original country, culture and language does not demand for any particular support. Unfortunately, this basic view has non-negligible consequences on repatriates, especially on expatriate retention and turnover rates after expatriation. The goal of our study is to examine the specific policies and practices adopted by companies to support employees after an international assignment. We assume that expatriation is process which ends with repatriation. The latter is such a crucial issue as the expatriation and require due attention through appropriate design of human resource management policies and tools. For this purpose, we use data from a qualitative research based on interviews to a sample of firms operating in Portugal. We attempt to compare how firms accommodate the concerns with repatriation in their policies and practices. Therefore, the interviews collect data on both expatriation and repatriation process, namely the selection and skills of candidates to expatriation, training, mentoring, communication and pay policies. Portuguese labor market seems to be an interesting case study for mainly two reasons. On the one hand, Portuguese Government is encouraging companies to internationalize in the context of an external market-oriented growth model. On the other hand, expatriation is being perceived as a job opportunity in the context of high unemployment rates of both skilled and non-skilled. This is an ongoing research and the data collected until now indicate that companies follow the pattern described in the literature. The interviewed companies recognize the higher relevance of repatriation process than expatriation, but disregard specific human resource policies. They have perceived that unfavorable labor market conditions discourage mobility across companies. It should be stressed that companies underline that employees enhanced the relevance of stable jobs and attach far less importance to career development and other benefits after expatriation. However, there are still cases of turnover and difficulties of retention. Managers’ report non-negligible cases of turnover associated with lack of effective repatriation programs and non-recognition of good performance. Repatriates seem to having acquired entrepreneurial spirit and skills and often create their own company. These results suggest that even in the context of worsening labor market conditions, there should be greater awareness of the need to retain talents, experienced and highly skills employees. Ultimately, other companies poach invaluable assets, while internationalized companies risk being training providers.

Keywords: expatriates, expatriation, international management, repatriation

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Authors: Hamza I. Isa, Gezina C. H. Ferreira, Jan E. Crafford, Christoffel J. Botha

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Moraea pallida Bak. (yellow tulip) poisoning is the most important plant-induced cardiac glycoside toxicosis in South Africa. Cardiac glycoside poisonings collectively account for about 33 and 10 % mortalities due to plants, in large and small stock respectively, in South Africa. The toxic principle is 1α, 2α-epoxyscillirosidine, a bufadienolide. The aim of the study was to investigate the potential to develop a vaccine against epoxyscillirosidine. Epoxyscillirosidine and the related bufadienolides proscillaridin and bufalin, which are commercially available, were conjugated to the carrier proteins [Hen ovalbumin (OVA), bovine serum albumin (BSA) and keyhole limpet haemocyanin (KLH)], rendering them immunogenic. Adult male New Zealand White rabbits were immunized. In Trials 1 and 2, rabbits (n=6) were, each assigned to two groups. Experimental animals (n=3; n=4) were vaccinated with epoxyscillirosidine-OVA conjugate, while the control (n=3; n=2) were vaccinated with OVA, using Freund’s complete and incomplete and Montanide adjuvants, for Trials 1 and 2, respectively. In Trial 3, rabbits (n=15), randomly allocated to 5 equal groups (I, II, III, IV and V), were vaccinated with proscillaridin-BSA, bufalin-BSA, epoxyscillirosidine-KLH, epoxyscillirosidine-BSA conjugates, and BSA respectively, using Montanide as adjuvant. Vaccination was on Days 0, 21 and 42. Additional vaccinations were done on Day 56 and 63 for Trial 1. Vaccination was by intradermal injection of 0.4 ml of the immunogen (4 mg/ml [Trial 1] and 8 mg/ml for Trials 2 and Trial 3, respectively). Blood was collected pre-vaccination and at 3 week intervals following each vaccination. Antibody response was determined using an indirect ELISA. There was poor immune response associated with the dose (0.4 mg per rabbit) and adjuvant used in Trial 1. Antibodies were synthesized against the conjugate administered in Trial 2. For Trail 3, antibodies against the immunogens were successfully raised in rabbits with epoxyscillirosidine-KLH inducing the highest immune response. The antibodies raised against proscillaridin and bufalin cross-reacted with epoxyscillirosidine when used as antigen in the ELISA. The study successfully demonstrated the synthesis of antibodies against the bufadienolide conjugates administered. The cross-reactivity of proscillaridin and bufalin with epoxyscillirosidine could potentially be utilized as alternative to epoxyscillirosidine in future studies to prevent yellow tulp poisoning by vaccination.

Keywords: antibodies , bufadienolides, cross-reactivity, epoxyscillirosidine, Moraea pallida, poisoning

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Authors: Arturo Galvan, Jatziri Y. Moreno-Martinez, Daniel Arroyo-Montoya, Jose M. Gutierrez-Villalobos

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Bridges are one of the most seismically vulnerable structures on highway transportation systems. The general process for assessing the seismic vulnerability of a bridge involves the evaluation of its overall capacity and demand. One of the most common procedures to obtain this capacity is by means of pushover analysis of the structure. Typically, the bridge capacity is assessed using non-linear static methods or non-linear dynamic analyses. The non-linear dynamic approaches use step by step numerical solutions for assessing the capacity with the consuming computer time inconvenience. In this study, a nonlinear static analysis (‘pushover analysis’) was performed to predict the collapse mechanism of a typical bridge built in the central zone of Mexico (Celaya, Guanajuato). The bridge superstructure consists of three simple supported spans with a total length of 76 m: 22 m of the length of extreme spans and 32 m of length of the central span. The deck width is of 14 m and the concrete slab depth is of 18 cm. The bridge is built by means of frames of five piers with hollow box-shaped sections. The dimensions of these piers are 7.05 m height and 1.20 m diameter. The numerical model was created using a commercial software considering linear and non-linear elements. In all cases, the piers were represented by frame type elements with geometrical properties obtained from the structural project and construction drawings of the bridge. The deck was modeled with a mesh of rectangular thin shell (plate bending and stretching) finite elements. The moment-curvature analysis was performed for the sections of the piers of the bridge considering in each pier the effect of confined concrete and its reinforcing steel. In this way, plastic hinges were defined on the base of the piers to carry out the pushover analysis. In addition, time history analyses were performed using 19 accelerograms of real earthquakes that have been registered in Guanajuato. In this way, the displacements produced by the bridge were determined. Finally, pushover analysis was applied through the control of displacements in the piers to obtain the overall capacity of the bridge before the failure occurs. It was concluded that the lateral deformation of the piers due to a critical earthquake occurred in this zone is almost imperceptible due to the geometry and reinforcement demanded by the current design standards and compared to its displacement capacity, they were excessive. According to the analysis, it was found that the frames built with five piers increase the rigidity in the transverse direction of the bridge. Hence it is proposed to reduce these frames of five piers to three piers, maintaining the same geometrical characteristics and the same reinforcement in each pier. Also, the mechanical properties of materials (concrete and reinforcing steel) were maintained. Once a pushover analysis was performed considering this configuration, it was concluded that the bridge would continue having a “correct” seismic behavior, at least for the 19 accelerograms considered in this study. In this way, costs in material, construction, time and labor would be reduced in this study case.

Keywords: collapse mechanism, moment-curvature analysis, overall capacity, push-over analysis

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Authors: S. Kozlovski, S.W. Feigelson, R. Alon

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The b2 integrin ligands ICAM-1 ICAM-2 and the endothelial VLA-4 integrin ligand VCAM-1 are constitutively expressed on different lung vessels and on high endothelial venules (HEVs), the main portal for lymphocyte entry from the blood into lung draining lymph nodes. ICAMs are also ubiquitously expressed by many antigen-presenting leukocytes and have been traditionally suggested as critical for the various antigen-specific immune synapses generated by these distinct leukocytes and specific naïve and effector T cells. Loss of both ICAM-1 and ICAM-2 on the lung vasculature reduces the ability to patrol monocytes and Tregs to patrol the lung vasculature at a steady state. Our new findings suggest, however, that in terms of innate leukocyte trafficking into the lung lamina propria, both constitutively expressed and virus-induced vascular VCAM-1 can functionally compensate for the loss of these ICAMs. In a mouse model for influenza infection, neutrophil and NK cell recruitment and clearance of influenza remained normal in mice deficient in both ICAMs. Strikingly, mice deficient in both ICAMs also mounted normal influenza-specific CD8 proliferation and differentiation. In addition, these mice normally combated secondary influenza infection, indicating that the presence of ICAMs on conventional dendritic cells (cDCs) that present viral antigens are not required for immune synapse formation between these APCs and naïve CD8 T cells as previously suggested. Furthermore, long-lasting humoral responses critical for protection from a secondary homosubtypic influenza infection were also normal in mice deficient in both ICAM-1 and ICAM-2. Collectively, our results suggest that the expression of ICAM-1 and ICAM-2 on lung endothelial and epithelial cells, as well as on DCs and B cells, is not critical for the generation of innate or adaptive anti-viral immunity in the lungs. Our findings also suggest that endothelial VCAM-1 can substitute for the functions of vascular ICAMs in leukocyte trafficking into various lung compartments.

Keywords: emigration, ICAM-1, lymph nodes, VCAM-1

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Authors: Joy Tweed, Jon Pike

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In Thailand, a 4.0 policy has been initiated that is designed to prepare and train an appropriate workforce to support the move to a value-based economy. One aspect of support for this policy is a project to encourage the creation of double degree programmes, specifically between Thai and UK universities. This research into the project, conducted with its key players, explores the factors that can either enable or hinder the development of such programmes. It is an area that has received little research attention to date. Key findings focus on differences in quality assurance requirements, attitudes to benefits, risks, and committed levels of institutional support, thus providing valuable input into future policy making. The Transnational Education (TNE) Development Project was initiated in 2015 by the British Council, in conjunction with the Office for Higher Education Commission (OHEC), Thailand. The purpose of the project was to facilitate opportunities for Thai Universities to partner with UK Universities so as to develop double degree programme models. In this arrangement, the student gains both a UK and a Thai qualification, spending time studying in both countries. Twenty-two partnerships were initiated via the project. Utilizing a qualitative approach, data sources included participation in TNE project workshops, peer reviews, and over 20 semi-structured interviews conducted with key informants within the participating UK and Thai universities. Interviews were recorded, transcribed, and analysed for key themes. The research has revealed that the strength of the relationship between the two partner institutions is critical. Successful partnerships are often built on previous personal contact, have senior-level involvement and are strengthened by partnership on different levels, such as research, student exchange, and other forms of mobility. The support of the British Council was regarded as a key enabler in developing these types of projects for those universities that had not been involved in TNE previously. The involvement of industry is apparent in programmes that have high scientific content but not well developed in other subject areas. Factors that hinder the development of partnership programmes include the approval processes and quality requirements of each institution. Significant differences in fee levels between Thai and UK universities provide a challenge and attempts to bridge them require goodwill on the part of the latter that may be difficult to realise. This research indicates the key factors to which attention needs to be given when developing a TNE programme. Early attention to these factors can reduce the likelihood that the partnership will fail to develop. Representatives in both partner universities need to understand their respective processes of development and approval. The research has important practical implications for policy-makers and planners involved with TNE, not only in relation to the specific TNE project but also more widely in relation to the development of TNE programmes in other countries and other subject areas. Future research will focus on assessing the success of the double degree programmes generated by the TNE Development Project from the perspective of universities, policy makers, and industry partners.

Keywords: double-degree, internationalization, partnerships, Thai-UK

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Authors: Vidya Yadav

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Migration is the demographic process that links rural to urban areas, generating or spurring the growth of cities. Evidence shows the role of the city as a production processes. It looks the city as a power of centre, and a centre of change. It has been observed that not only the professionals want to settle down in an urban area but rural labourers are also coming to cities for employment. These are the people who are compelled to migrate to metropolises because of lack of employment opportunities in their place of residence. However, the cities also fail to provide adequate employment because of limited job opportunity creation and capital-intensive industrialization. So these masses of incoming migrants are force to take up whatever employment absorption is available to them particularly in urban informal activities. Ultimately with this informal job they are compelled to stay in the slum areas, which is another form of deprived housing colonies. The paper seeks to examine the evidences of poverty induced migration from rural to urban areas (particularly in urban agglomeration). The present paper utilizes an abundant rich source of census migration data (D-Series) of 1991-2001. Result shows that Mumbai remain as the most attractive place to migrate. The migrants are mainly from the major states like Uttar Pradesh, Bihar, West Bengal, Jharkhand, Odisha, and Rajasthan. Male dominated migration is related mostly for employment and females due to marriages. The picture of occupational absorption of migrants who moved for employment, cross classified with educational status. Result shows that illiterate males are primarily engaged in low grade production processing work. Illiterate’s females engaged in service sectors; but these are actually very low grade services in urban informal sectors in India like maid servants, domestic help, hawkers, vendors or vegetables sellers. Among the higher educational level, a small percentage of males and females got absorbed in professional or clerical work but the percentage has been increased in the period 1991-2001.

Keywords: informal, job, migration, urban

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Authors: Anna-Mari Kok, Carel B. Oosthuizen, Namrita Lall

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Tuberculosis (TB) is a disease caused by the bacterial pathogen Mycobacterium tuberculosis. It is associated with high mortality rates in both developing and developed countries. Many higher plants are found that are medicinally associated with tuberculosis infection. Plants belonging to thirteen families were selected, based on their traditional usage for tuberculosis and its associated symptoms. Eight plants showed the best antimycobacterial activities (MIC-value ≤ 500.0 µg/ml) against M. tuberculosis H37Rv. LS was found to have a minimum inhibitory concentration (MIC) of 125 µg/ml whereas, Tulbaghia violacea, Heteromorpha arborescens, Sutherlandia frutescens, Eucalyptus deglupta, and Plectranthus neochilus were found to have a MIC value of 250 µg/ml against M. tuberculosis H37Rv. Cytotoxicity values on U937 and HepG2 cells were obtained and the IC50 values ranged between 40 ±4.30 and > 400 µg/ml for the U937 cell line and 72.4 ±1.50 and > 400 µg/ml for the HepG2 cell line. Heteromorpha arborescens had the lowest IC50 value in both cell lines and therefore showed moderate levels of toxicity. Of the 19 samples that underwent the 2, 2- diphenyl- 1- picrylhydrazyl (DPPH) antioxidant assay, Eucalyptus deglupta and Melianthus major showed significant free radical scavenging activities with concentrations of 1.33 and 1.32 µg/ml respectively for the inhibition of DPPH. Hepatotoxicity induced by acetaminophen identified Searsia lancea with hepatoprotective activity of 59.37% at a ¼ IC50 concentration. Out of the 7 samples that were investigated for their immunomodulatory capabilities, Eucalyptus deglupta produced the most IL-12 with Sutherlandia frutescens also showing positive results for IL-12 production. In the present study, Eucalyptus deglupta showed the most promising results with good activity against M. tuberculosis with an MIC-value of 250 µg/ml. It also has potent antioxidant activity with an IC50 value of 1.33 µg/ml. This sample also stimulated high production of the cytokine, IL-12. Searsia lancea showed moderate antimycobacterial acticvity with an MIC-value of 500 µg/ml. The antioxidant potential also showed promising results with an IC50 value of 4.50 µg/ml. The hepatoprotective capability of Searsia lancea was 59.34% at a ¼ IC50 concentration. Another sample Sutherlandia frutescens showed effective antimycobacterial activity with an MIC-value of 250 µg/ml. It also stimulated production of IL-12 with 13.43 pg/ml produced. These three samples can be considered for further studies for the consideration as adjuvants for current tuberculosis treatment.

Keywords: adjuvant, hepatoprotection, immunomodulation, tuberculosis

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Authors: Rafael Alexandre Dos Reis

Abstract:

Research has shown a substantial increase in the participation of Conventionally Fuelled Vehicles (CFVs) in the urban transport modal split. The reasons for this unsustainable reality are multiple, from economic interventions to individual behaviour. The development and delivery of positive incentives for the adoption of more environmental-friendly modes of transport is an emerging strategy to help in tackling the problem of excessive use of conventionally fuelled vehicles. The efficiency of this approach, like other information-based schemes, can benefit from the knowledge of their potential impacts in theoretical constructs of multiple behaviour change theories. The goal of this research is to critically analyse theories of behaviour that are relevant to transport research and the impacts of positive incentives on the theoretical determinants of behaviour, strengthening the current body of evidence about the benefits of this approach. The main method to investigate this will involve a literature review on two main topics: the current theories of behaviour that have empirical support in transport research and the past or ongoing positive incentives programs that had an impact on car use reduction. The reviewed programs of positive incentives were the following: The TravelSmart®; Spitsmijden®; Incentives for Singapore Commuters® (INSINC); COMMUTEGREENER®; MOVESMARTER®; STREETLIFE®; SUPERHUB®; SUNSET® and the EMPOWER® project. The theories analysed were the heory of Planned Behaviour (TPB); The Norm Activation Theory (NAM); Social Learning Theory (SLT); The Theory of Interpersonal Behaviour (TIB); The Goal-Setting Theory (GST) and The Value-Belief-Norm Theory (VBN). After the revisions of the theoretical constructs of each of the theories and their influence on car use, it can be concluded that positive incentives schemes impact on behaviour change in the following manners: -Changing individual’s attitudes through informational incentives; -Increasing feelings of moral obligations to reduce the use of CFVs; -Increase the perceived social pressure to engage in more sustainable mobility behaviours through the use of comparison mechanisms in social media, for example; -Increase the perceived control of behaviour through informational incentives and training incentives; -Increasing personal norms with reinforcing information; -Providing tools for self-monitoring and self-evaluation; -Providing real experiences in alternative modes to the car; -Making the observation of others’ car use reduction possible; -Informing about consequences of behaviour and emphasizing the individual’s responsibility with society and the environment; -Increasing the perception of the consequences of car use to an individual’s valued objects; -Increasing the perceived ability to reduce threats to environment; -Help establishing goals to reduce car use; - iving personalized feedback on the goal; -Increase feelings of commitment to the goal; -Reducing the perceived complexity of the use of alternatives to the car. It is notable that the emerging technique of delivering positive incentives are systematically connected to causal determinants of travel behaviour. The preliminary results of the reviewed programs evidence how positive incentives might strengthen these determinants and help in the process of behaviour change.

Keywords: positive incentives, private car use reduction, sustainable behaviour, voluntary travel behaviour change

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Authors: Maliha Ahmed Suleman, Sidra Ahmed Suleman

Abstract:

Introduction: The use of pacifiers is common amongst infants and young children as a comforting behavior. These non-nutritive sucking habits can be detrimental to the developing occlusion should they persist while the permanent dentition is established. Orthodontic pacifiers have been recommended as an alternative to conventional pacifiers as they are considered to have less interference with orofacial development. However, there is a lack of consensus on whether this is true. Aim and objectives: To review the prevalence of malocclusion associated with the use of orthodontic pacifiers. Methodology: Literature was identified through a rigorous search of the Embase, Pubmed, CINAHL, and Cochrane Library databases. Articles published from 2000 onwards were included. In total, 5 suitable papers were identified. Results: One study showed that the use of orthodontic pacifiers increased the risk of malocclusion, as seen through a greater prevalence of accentuated overjet, posterior crossbites, and anterior open bites in comparison to individuals who did not use pacifiers. However, this study found that there was a clinically significant reduction in the prevalence of anterior open bites amongst orthodontic pacifier users in comparison to conventional pacifier users. Another study found that both types of pacifiers lead to malocclusion; however, they found no difference in the mean overjet and prevalence of anterior open bites amongst conventional and orthodontic pacifier users. In contrast, one study suggested that orthodontic pacifiers do not seem to be related to the development of malocclusions in the primary dentitions, and using them between the ages of 0-3 months was actually beneficial as it prevents thumb-sucking habits. One of the systemic reviews concluded that orthodontic pacifiers do not seem to reduce the occurrence of posterior crossbites; however, they could reduce the development of open bites by virtue of their thin neck design. Whereas another systematic review concluded that there were no differences as to the effects on the stomatognathic system when comparing conventional and orthodontic pacifiers. Conclusion: There is limited and conflicting evidence to support the notion that orthodontic pacifiers can reduce the prevalence of malocclusion when compared to conventional pacifiers. Well-designed randomized controlled trials are required in the future in order to thoroughly assess the effects of orthodontic pacifiers on the developing occlusion and orofacial structures.

Keywords: orthodontics, pacifier, malocclusion, review

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