Search results for: dose intensity

Authors: Mohammadreza Hedyehzadeh, Mahdi Yousefi

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Colon cancer is one of the most common cancer, which predicted to increase its prevalence due to the bad eating habits of peoples. Nowadays, due to the busyness of people, the use of fast foods is increasing, and therefore, diagnosis of this disease and its treatment are of particular importance. To determine the best treatment approach for each specific colon cancer patients, the oncologist should be known the stage of the tumor. The most common method to determine the tumor stage is TNM staging system. In this system, M indicates the presence of metastasis, N indicates the extent of spread to the lymph nodes, and T indicates the size of the tumor. It is clear that in order to determine all three of these parameters, an imaging method must be used, and the gold standard imaging protocols for this purpose are CT and PET/CT. In CT imaging, due to the use of X-rays, the risk of cancer and the absorbed dose of the patient is high, while in the PET/CT method, there is a lack of access to the device due to its high cost. Therefore, in this study, we aimed to estimate the tumor size and the extent of its spread to the lymph nodes using MR images. More than 1300 MR images collected from the TCIA portal, and in the first step (pre-processing), histogram equalization to improve image qualities and resizing to get the same image size was done. Two expert radiologists, which work more than 21 years on colon cancer cases, segmented the images and extracted the tumor region from the images. The next step is feature extraction from segmented images and then classify the data into three classes: T0N0، T3N1 و T3N2. In this article, the VGG-16 convolutional neural network has been used to perform both of the above-mentioned tasks, i.e., feature extraction and classification. This network has 13 convolution layers for feature extraction and three fully connected layers with the softmax activation function for classification. In order to validate the proposed method, the 10-fold cross validation method used in such a way that the data was randomly divided into three parts: training (70% of data), validation (10% of data) and the rest for testing. It is repeated 10 times, each time, the accuracy, sensitivity and specificity of the model are calculated and the average of ten repetitions is reported as the result. The accuracy, specificity and sensitivity of the proposed method for testing dataset was 89/09%, 95/8% and 96/4%. Compared to previous studies, using a safe imaging technique (MRI) and non-use of predefined hand-crafted imaging features to determine the stage of colon cancer patients are some of the study advantages.

Keywords: colon cancer, VGG-16, magnetic resonance imaging, tumor size, lymph node metastasis

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Authors: Brian Chi Yan Cheng, Hui Guo, Tao Su, Xiu‐qiong Fu, Ting Li, Zhi‐ling Yu

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Rheumatoid arthritis (RA) affects around 1% of the globe population. Yet, there is still no cure for RA. Toll-like receptor 4 (TLR4) signalling has been found to be involved in the pathogenesis of RA, making it a potential therapeutic target for RA treatment. A herbal formula (RL) consisting of fruits of Rosa Multiflora (Eijitsu rose) and flowers of Lonicera Japonica (Japanese honeysuckle) has been used in treating various inflammatory disorders for more than a thousand year. Both of them are rich sources of nutrients and bioactive phytochemicals, which can be used in producing different food products and supplements. In this study, we would evaluate the anti-arthritic effect of RL on collagen-induced arthritis (CIA) in rats and investigate the involvement of TLR4 signaling in the mode of action of RL. Anti-arthritic efficacy was evaluated using CIA rats induced by bovine type II collagen. The treatment groups were treated with RL (82.5, 165, and 330 mg/kg bw per day, p.o.) or positive control indomethacin (0.25 mg/kg bw per day, p.o.) for 35 days. Clinical signs (hind paw volume and arthritis severity scores), changes in serum inflammatory mediators, pro-/antioxidant status, histological and radiographic changes of joints were investigated. Spleens and peritoneal macrophages were used to determine the effects of RL on innate and adaptive immune responses in CIA rats. The involvement of TLR4 signalling pathways in the anti-arthritic effect of RL was examined in cartilage tissue of CIA rats, murine RAW264.7 macrophages and human THP-1 monocytic cells. The severity of arthritis in the CIA rats was significantly attenuated by RL. Antioxidant status, histological score and radiographic score were efficiently improved by RL. RL could also dose-dependently inhibit pro-inflammatory cytokines in serum of CIA rats. RL significantly inhibited the production of various pro-inflammatory mediators, the expression and/or activity of the components of TLR4 signalling pathways in animal tissue and cell lines. RL possesses anti-arthritic effect on collagen-induced arthritis in rats. The therapeutic effect of RL may be related to its inhibition on pro-inflammatory cytokines in serum. The inhibition of the TAK1/NF-κB and TAK1/MAPK pathways participate in the anti-arthritic effects of RL. This provides a pharmacological justification for the dietary use of RL in the control of various arthritic diseases. Further investigation should be done to develop RL into a anti-arthritic food products and/or supplements.

Keywords: japanese honeysuckle, rheumatoid arthritis, rosa multiflora, rosehip

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Authors: Hilly Moodrick-Even Khen

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This study analyzes the legal regulation of the use of force in international law in the context of three emerging Palestinian forms of struggle against Israeli occupation: the Knife Intifada, Gaza border disturbances, and the launching of incendiary kites. It discusses what legal paradigms or concepts should regulate the type and level of force used in each situation—a question that is complicated by various dilemmas—and appraises the Israel Defence Forces policies tailored in response. Methodologically, the study is based on analysis of scholarship on the conceptual legal issues as well as dicta of the courts. It evaluates the applicability of two legal paradigms regulating the use of force in military operations—(i) the conduct of hostilities and (ii) law enforcement—as well as the concept of self-defense in international law and the escalation of force procedure. While the “Knife Intifada” clearly falls under the law enforcement paradigm, the disturbances at the border and the launching of incendiary kites raise more difficult questions, as applying law enforcement, especially in the latter case, can have undesirable ramifications for safeguarding humanitarian interests. The use of force in the cases of the border disturbances and the incendiary kites should thus be regulated, mutatis mutandis, by the concept of self-defense and escalation of force procedures; and in the latter case, the hostilities paradigm can also be applied. The study provides a factual description and analysis of the background and nature of the forms of struggle in Gaza and the West Bank—in each case surveying the geo-political developments since operation Protective Edge, contextualizing how the organized and unorganized violent activities evolved, and analyzing them in terms of level of organization and intensity. It then presents the two paradigms of the use of force—law enforcement and conduct of hostilities—and the concept of self-defense. Lastly, it uses the factual findings as the basis for legally analyzing which paradigm or concept regulating the use of force applies for each form of struggle. The study concludes that in most cases, the concept of self-defense is preferable to the hostilities or the law enforcement paradigms, as it best safeguards humanitarian interests and ensures the least loss of civilian lives.

Keywords: Israeli-Palestinian conflict, self defense, terrorism, use of force

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Authors: Thu Nhi Tran Caliste

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X-ray Bragg diffraction imaging (“topography”)entered into practical use when Lang designed an “easy” technical setup to characterise the defects / distortions in the high perfection crystals produced for the microelectronics industry. The use of this technique extended to all kind of high quality crystals, and deposited layers, and a series of publications explained, starting from the dynamical theory of diffraction, the contrast of the images of the defects. A quantitative version of “monochromatic topography” known as“Rocking Curve Imaging” (RCI) was implemented, by using synchrotron light and taking advantage of the dramatic improvement of the 2D-detectors and computerised image processing. The rough data is constituted by a number (~300) of images recorded along the diffraction (“rocking”) curve. If the quality of the crystal is such that a one-to-onerelation between a pixel of the detector and a voxel within the crystal can be established (this approximation is very well fulfilled if the local mosaic spread of the voxel is < 1 mradian), a software we developped provides, from the each rocking curve recorded on each of the pixels of the detector, not only the “voxel” integrated intensity (the only data provided by the previous techniques) but also its “mosaic spread” (FWHM) and peak position. We will show, based on many examples, that this new data, never recorded before, open the field to a highly enhanced characterization of the crystal and deposited layers. These examples include the characterization of dislocations and twins occurring during silicon growth, various growth features in Al203, GaNand CdTe (where the diffraction displays the Borrmannanomalous absorption, which leads to a new type of images), and the characterisation of the defects within deposited layers, or their effect on the substrate. We could also observe (due to the very high sensitivity of the setup installed on BM05, which allows revealing these faint effects) that, when dealing with very perfect crystals, the Kato’s interference fringes predicted by dynamical theory are also associated with very small modifications of the local FWHM and peak position (of the order of the µradian). This rather unexpected (at least for us) result appears to be in keeping with preliminary dynamical theory calculations.

Keywords: rocking curve imaging, X-ray diffraction, defect, distortion

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Authors: Joao Gouveia

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This is a study about Hegelian political and moral philosophy. Our aim is to understand the relevance that Hegel attributes to ethics in the concrete political configuration of society. But our analysis isn’t limited to Hegel’s most known political work (the Grundlinien der Philosophie des Rechts). Instead, we also analyze the Phänomenologie des Geistes and establish a comparison between them. In the Moralität of the Grundlinien der Philosophie des Rechts, consciousness acquires the disposition that allows it to see any determination as its own (the certainty about itself or Gewissen). This certainty is the essential disposition that makes itself felt throughout all Sittlichkeit –the dispositions of family member and citizen (Bürger) are only configurations of it. Although consciousness is alienated in these dispositions, it doesn’t lose the certainty about itself that it reached in the Moralität. As our major finding, we point out that it is the moral learning that allows consciousness to resist the temptation of focusing so intensely on specific content that it excludes all the others (a temptation that is stimulated by the very intensity with which each content presents itself to consciousness). As the world of Bildung of the Phänomenologie des Geistes isn’t preceded by a sphere of Moralität, consciousness is thrown into a frenzy of destruction of all the powers of objectivity, and it ends up having to withdraw from the concrete contents and to focus in an abstract whole, where it doesn’t find opposite determinacies. The evidence supporting our thesis is the fact that the transition from abstraction into particularity, that we see in the Grundlinien der Philosophie des Rechts, allows the preservation of abstraction (it isn’t lost as we penetrate in particularity). On the other hand, the transition we find in the Phänomenologie des Geistes is a transition from particularity to abstraction, which takes every particularity to be eliminated in the war with others. While in the Phänomenologie des Geistes, the state may only be seen as a moment or facet of the object (it is only Staatsmacht); in the Grundlinien der Philosophie des Rechts, it is seen as a whole that contains various moments in itself (Staat). Therefore, the element of the Phänomenologie des Geistes that is closer to the State of the Grundlinien der Philosophie des Rechts is language (or the language of perversion) –something that can’t be defined as an individuality. This way, we want to show that, between the Phänomenologie des Geistes and the Grundlinien der Philosophie des Rechts, there is truly no remarkable evolution to report in Hegel’s ethical thought. What the difference in the structure of the two works show is a specific thesis respecting the influence of ethics in the configuration of society, and this thesis has implications at various levels, including in the philosophy of history.

Keywords: Grundlinien der Philosophie des Rechts, Hegelian ethics, Hegelian politics, Phänomenologie des Geistes

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Authors: M. R. Vijayakumar, K. Priyanka, Ramoji Kosuru, Lakshmi, Sanjay Singh

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Trans resveratrol (RES) is a non-flavonoid poly-phenolic compound proved for its therapeutic and preventive effect against various types of cancer. However, the practical application of RES in cancer treatment is limited because of its higher dose (up to 7.5 g/day in humans), low biological half life, rapid metabolism and faster elimination in mammals. PEGylated core-shell type lipid polymer hybrid nanoparticles are the novel drug delivery systems for long circulation and improved anti cancer effect of its therapeutic payloads. Therefore, the main objective of this study is to extend the biological half life (long circulation) and improve the therapeutic efficacy of RES through core shell type of nanoparticles. D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS), a novel surfactant is applied for the preparation of PEGylated lipid polymer hybrid nanoparticles. The prepared nanoparticles were evaluated by various state of the art techniques such as dynamic light scattering (DLS) technique for particle size and zeta potential, TEM for shape, differential scanning calorimetry (DSC) for interaction analysis and XRD for crystalline changes of drug. Entrapment efficiency and invitro drug release were determined by ultracentrifugation method and dialysis bag method, respectively. Cancer cell viability studies were performed by MTT assay, respectively. Pharmacokinetic studies after i.v administration were performed in sprague dawley rats. The prepared NPs were found to be spherical in shape with smooth surfaces. Particle size and zeta potential of prepared NPs were found to be in the range of 179.2±7.45 to 266.8±9.61 nm and -0.63 to -48.35 mV, respectively. DSC revealed absence of potential interaction. XRD study revealed presence of amorphous form in nanoparticles. Entrapment efficiency was found to be 83.7 % and drug release was found to be in controlled manner. MTT assay showed low MEC and pharmacokinetic studies showed higher AUC of nanoformulaition than its pristine drug. All these studies revealed that the RES loaded PEG modified core-shell type lipid polymer hybrid nanoparticles can be an alternative tool for chemopreventive and therapeutic application of RES in cancer.

Keywords: trans resveratrol, cancer nanotechnology, long circulating nanoparticles, bioavailability enhancement, core shell nanoparticles, lipid polymer hybrid nanoparticles

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Authors: Annesha Ghosh, S. B. Agrawal

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Agricultural sector is facing a serious threat due to climate change and exacerbation of different atmospheric pollutants. Tropospheric ozone (O₃) is considered as a dynamic air pollutant imposing substantial phytotoxicity to natural vegetations and agriculture worldwide. Naturally, plants are exposed to different environmental factors and their interactions. Amongst such interactions, studies related to O₃ and water stress are still rare. In the present experiment, wheat cultivar HD2967 were grown in open top chambers (OTC) under two O₃ concentration; ambient O₃ level (A) and elevated O₃ (E) (ambient + 20 ppb O₃) along with two different water supply; well-watered (W) and 50% water stress conditions (WS), with an aim to assess the individual and interactive effect of two most prevailing stress factors in Indo-Gangetic Plains of India. Exposure to elevated O₃ dose caused early senescence symptoms and reduction in growth and biomass of the test cultivar. The adversity was more pronounced under the combined effect of EWS. Significant reduction of stomatal conductance (gs) and assimilation rate were observed under combined stress condition compared to the control (AW). However, plants grown under individual stress conditions displayed higher gs, biomass, and antioxidant defense mechanism compared to the plants grown under the presence of combined stresses. Higher induction in most of the enzyme activities of catalase (CAT), ascorbate peroxidase (APX), glutathione reductase (GR), peroxidase (POD) and superoxide dismutase (SOD) was displayed by HD 2967 under EW while, under the presence of combined stresses (EWS), a moderate increment of APX and CAT activity was observed only at its vegetative phase. Furthermore, variations in nutrient uptake and redistribution to different plants parts were also observed in the present study. Reduction in water availability has checked nutrient uptake (N, K, P, Ca, Cu, Mg, Zn) in above-ground parts (leaf) and below-ground parts (root). On the other hand, carbon (C) accumulation with subsequent C-N ratio was observed to be higher in the leaves under EWS. Such major nutrient check and limitation in carbon fixation due to lower gs under combined stress conditions might have weakened the defense mechanisms of the test cultivar. Grain yield was significantly reduced under EWS followed by AWS and EW as compared to their control, exhibiting an additive effect on the grain yield.

Keywords: antioxidants, open-top chambers, ozone, water stress, wheat, yield

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Authors: Umi Pudji Astuti, Dedi Sugandi

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The effectiveness of agricultural extension is determined by the component in the agricultural extension system among others are agricultural extension methods. Effective methods should be selected and defined based on the characteristics of the target, the resources, the materials, and the objectives to be achieved. Citrus agribusiness development in Lebong is certainly supported by the role of stakeholders and citrus farmers, as well as the proper dissemination methods. Adoption in the extension process substantially can be interpreted as the changes of behavior process such as knowledge (cognitive), attitudes (affective), and skill (psycho-motoric) in a person after receiving "innovation" from extension submitted by target communities. Knowledge and perception are needed as a first step in adopting a innovation, especially of citrus agribusiness development in Lebong. The process of Specific technology adoption is influenced by internal factors and farmer perceptions of technological innovation. Internal factors such as formal education, experience trying to farm, owned land, production farm goods. The output of this study: 1) to analyze the effectiveness of field trial methods in improving cognitive and affective farmers; 2) Knowing the relationship of adoption level and knowledge of farmers; 3) to analyze the factors that influence farmers' adoption of citrus technology innovation. The method of this study is through the survey to 40 respondents in Rimbo Pengadang Sub District, Lebong District in 2014. Analyzing data is done by descriptive and statistical parametric (multiple linear functions). The results showed that: 1) Field trip method is effective to improve the farmer knowledge (23,17% ) and positively affect the farmer attitude; 2) the knowledge level of PTKJS innovation farmers "positively and very closely related".; 3) the factors that influence the level of farmers' adoption are internal factors (education, knowledge, and the intensity of training), and external factors respondents (distance from the house to the garden and from the house to production facilities shop).

Keywords: affect, adoption technology, citrus gerga, effectiveness dissemination

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Authors: Fei Ye, Åsa Barrefelt, Manuchehr Abedi-Valugerdi, Khalid M. Abu-Salah, Salman A. Alrokayan, Mamoun Muhammed, Moustapha Hassan

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With appropriate encapsulation in functional nanoparticles drugs are more stable in physiological environment and the kinetics of the drug can be more carefully controlled and monitored. Furthermore, targeted drug delivery can be developed to improve chemotherapy in cancer treatment, not only by enhancing intracellular uptake by target cells but also by reducing the adverse effects in non-target organs. Inorganic imaging agents, delivered together with anti-cancer drugs, enhance the local imaging contrast and provide precise diagnosis as well as evaluation of therapy efficacy. We have developed biodegradable polymeric vesicles as a nanocarrier system for multimodal bio-imaging and anticancer drug delivery. The poly (lactic-co-glycolic acid) PLGA) vesicles were fabricated by encapsulating inorganic imaging agents of superparamagnetic iron oxide nanoparticles (SPION), manganese-doped zinc sulfide (MN:ZnS) quantum dots (QDs) and the anticancer drug busulfan into PLGA nanoparticles via an emulsion-evaporation method. T2-weighted magnetic resonance imaging (MRI) of PLGA-SPION-Mn:ZnS phantoms exhibited enhanced negative contrast with r2 relaxivity of approximately 523 s-1 mM-1 Fe. Murine macrophage (J774A) cellular uptake of PLGA vesicles started fluorescence imaging at 2 h and reached maximum intensity at 24 h incubation. The drug delivery ability PLGA vesicles was demonstrated in vitro by release of busulfan. PLGA vesicles degradation was studied in vitro, showing that approximately 32% was degraded into lactic and glycolic acid over a period of 5 weeks. The biodistribution of PLGA vesicles was investigated in vivo by MRI in a rat model. Change of contrast in the liver could be visualized by MRI after 7 min and maximal signal loss detected after 4 h post-injection of PLGA vesicles. Histological studies showed that the presence of PLGA vesicles in organs was shifted from the lungs to the liver and spleen over time.

Keywords: biodegradable polymers, multifunctional nanoparticles, quantum dots, anticancer drugs

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Authors: A. Elsayed, M. H. Dewaidar, M. Ghali, M. Elkemary

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The high production cost of the conventional solar cells requires the search for economic methods suitable for solar energy conversion. Cadmium Sulfide (CdS) is one of the most important semiconductors used in photovoltaics, especially in large area solar cells; and can be prepared in a thin film form by a wide variety of deposition techniques. The preparation techniques include vacuum evaporation, sputtering and molecular beam epitaxy. Other techniques, based on chemical solutions, are also used for depositing CdS films with dramatically low-cost compared to other vacuum-based methods. Although this technique is widely used during the last decades, due to simplicity and low-deposition temperature (~100°C), there is still a strong need for more information on the growth process and its relation with the quality of the deposited films. Here, we report on deposition of high-quality CdS thin films; with low-surface roughness ( < 3.0 nm) and sharp optical absorption edge; on low-temperature glass substrates (70°C) using a new method based on the room-temperature chemical solution. In this method, a mixture solution of cadmium acetate and thiourea at room temperature was used under special growth conditions for deposition of CdS films. X-ray diffraction (XRD) measurements were used to examine the crystal structure properties of the deposited CdS films. In addition, UV-VIS transmittance and low-temperature (4K) photoluminescence (PL) measurements were performed for quantifying optical properties of the deposited films. The deposited films show high optical quality as confirmed by observation of both, sharp edge in the transmittance spectra and strong PL intensity at room temperature. Furthermore, we found a strong effect of the growth conditions on the optical band gap of the deposited films; where remarkable red-shift in the absorption edge with temperature is clearly seen in both transmission and PL spectra. Such tuning of both optical band gap of the deposited CdS films can be utilized for tuning the electronic bands' alignments between CdS and other light-harvesting materials, like CuInGaSe or CdTe, for potential improvement in the efficiency of solar cells devices based on these heterostructures.

Keywords: chemical deposition, CdS, optical properties, surface, thin film

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Authors: Adkham Paiziev, Fikrat Kerimov

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Near Infrared Spectroscopy (NIRS) is one of the biophotonic techniques which can be used to monitor oxygenation and hemodynamics in a variety of human tissues, including skeletal muscle. In the present work, we are offering tissue oximetry (OxyPrem) to measure hemodynamic parameters of skeletal muscles in rest and exercise. Purpose: - To elaborate the new wireless, portable, noninvasive, wearable NIRS device to measure skeletal muscle oxygenation during exercise. - To test this device on brachioradialis muscle of wrestler volunteers by using combined method of arterial occlusion (AO) and NIRS (AO+NIRS). Methods: Oxyprem NIRS device has been used together with AO test. AO test and Isometric brachioradialis muscle contraction experiments have been performed on one group of wrestler volunteers. ‘Accu- Measure’ caliper (USA) to measure skinfold thickness (SFT) has been used. Results: Elaborated device consists on power supply box, a sensor head and installed ‘Tubis’ software for data acquisition and to compute deoxyhemoglobin ([HHb), oxyhemoglobin ([O2Hb]), tissue oxygenation (StO2) and muscle tissue oxygen consumption (mVO2). Sensor head consists on four light sources with three light emitting diodes with nominal wavelengths of 760 nm, 805 nm, and 870 nm, and two detectors. AO and isometric voluntary forearm muscle contraction (IVFMC) on five healthy male subjects (23,2±0.84 in age, 0.43±0.05cm of SFT ) and four female subjects (22.0±1.0 in age and 0.24±0.04 cm SFT) has been measured. mVO2 for control group has been calculated (-0.65%/sec±0.07) for male and -0.69%/±0.19 for female subjects). Tissue oxygenation index for wrestlers in average about 75% whereas for control group StO2 =63%. Second experiment was connected with quality monitoring muscle activity during IVFMC at 10%,30% and 50% of MVC. It has been shown, that the concentration changes of HbO2 and HHb positively correlated to the contraction intensity. Conclusion: We have presented a portable multi-channel wireless NIRS device for real-time monitoring of muscle activity. The miniaturized NIRS sensor and the usage of wireless communication make the whole device have a compact-size, thus can be used in muscle monitoring.

Keywords: skeletal muscle, oxygenation, instrumentation, near infrared spectroscopy

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Authors: K. Anas, M. Selvakumar, Samson David, R. R. Babu, S. Chattopadhyay

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The dynamic deformation of a visco elastic material can cause heat generation. This heat generation is aspect energy dissipation. The present work investigates the contribution of various factors like; elastomer structure, cross link type and density, filler networking, reinforcement potential and temperature at energy dissipation mechanism. The influences of these elements are investigated using very high frequency analyzer (VHF ) and dynamical mechanical analysis(DMA).VHF follows transmissibility and vibration isolation principle whereas DMA works on dynamical mechanical deformation principle. VHF analysis of different types of elastomers reveals that elastomer can act as a transmitter or damper of energy depending on the applied frequency ratio (ω/ωn). Dynamic modulus (G') of low damping rubbers like natural rubber does not varies rapidly with frequency but vice-versa for high damping rubber like butyl rubber (IIR). VHF analysis also depicts that polysulfidic linkages has high damping ratio (ζ) than mono sulfidic linkages due to its dissipative nature. At comparable cross link density, mono sulfidic linkages shows higher glass transition temperature (Tg) than poly sulfidic linkages. The intensity and location of loss modulus (G'') peak of different types of carbon black filled natural rubber compounds suggests that segmental relaxation at glass transition temperature (Tg) is seldom affected by filler particles, but the filler networks can influence the cross link density by absorbing the curatives. The filler network breaking and reformation during a dynamic strain is a thermally activated process. Thus, stronger aggregates are highly dissipative in nature. Measurements indicate that at lower temperature regimes polymeric chain friction is highly dissipative in nature.

Keywords: damping ratio, natural frequency, crosslinking density, segmental motion, surface activity, dissipative, polymeric chain friction

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Authors: Joe Collins, Matthias Rother

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Background: Oral non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for the relief of joint pain during and post-exercise. However, oral NSAIDs increase the risk of systemic side effects, even in healthy individuals, and retard recovery from muscle soreness. TDT 064 (Flexiseq®), a topical formulation containing ultra-deformable drug-free Sequessome™ vesicles, has demonstrated equivalent efficacy to oral celecoxib in reducing osteoarthritis-associated joint pain and stiffness. TDT 064 does not cause NSAID-related adverse effects. We describe clinical study data and a case report on the effectiveness of TDT 064 in reducing joint pain after exercise. Methods: Participants with a pain score ≥3 (10-point scale) 12–16 hours post-exercise were randomized to receive TDT 064 plus oral placebo, TDT 064 plus oral ketoprofen, or ketoprofen in ultra-deformable phospholipid vesicles plus oral placebo. Results: In the 168 study participants, pain scores were significantly higher with oral ketoprofen plus TDT 064 than with TDT 064 plus placebo in the 7 days post-exercise (P = 0.0240) and recovery from muscle soreness was significantly longer (P = 0.0262). There was a low incidence of adverse events. These data are supported by clinical experience. A 24-year-old male professional rugby player suffered a traumatic lisfranc fracture in March 2014 and underwent operative reconstruction. He had no relevant medical history and was not receiving concomitant medications. He had undergone anterior cruciate ligament reconstruction in 2008. The patient reported restricted training due to pain (score 7/10), stiffness (score 9/10) and poor function, as well as pain when changing direction and running on consecutive days. In July 2014 he started using TDT 064 twice daily at the recommended dose. In November 2014 he noted reduced pain on running (score 2-3/10), decreased morning stiffness (score 4/10) and improved joint mobility and was able to return to competitive rugby without restrictions. No side effects of TDT 064 were reported. Conclusions: TDT 064 shows efficacy against exercise- and injury-induced joint pain, as well as that associated with osteoarthritis. It does not retard muscle soreness recovery after exercise compared with an oral NSAID, making it an alternative approach for the treatment of joint pain during and post-exercise.

Keywords: exercise, joint pain, TDT 064, phospholipid vesicles

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Authors: Esshili Awatef, Manitz Marie-Pierre, Eßlinger Manuela, Gerhardt Alexandra, Plümper Jennifer, Wachholz Simone, Friebe Astrid, Juckel Georg

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Maternal immune activation (MIA) resulting from maternal viral infection during pregnancy is a known risk factor for schizophrenia. The neural mechanisms by which maternal infections increase the risk for schizophrenia remain unknown, although the prevailing hypothesis argues that an activation of the maternal immune system induces changes in the maternal-fetal environment that might interact with fetal brain development. It may lead to an activation of fetal microglia inducing long-lasting functional changes of these cells. Based on post-mortem analysis showing an increased number of activated microglial cells in patients with schizophrenia, it can be hypothesized that these cells contribute to disease pathogenesis and may actively be involved in gray matter loss observed in such patients. In the present study, we hypothesize that prenatal treatment with the inflammatory agent Poly(I:C) during embryogenesis at contributes to microglial activation in the offspring, which may, therefore, represent a contributing factor to the pathogenesis of schizophrenia and underlines the need for new pharmacological treatment options. Pregnant rats were treated with intraperitoneal injections a single dose of Poly(I:C) or saline on gestation day 17. Brains of control and Poly(I:C) offspring, were removed and into 20-μm-thick coronal sections were cut by using a Cryostat. Brain slices were fixed and immunostained with ba1 antibody. Subsequently, Iba1-immunoreactivity was detected using a secondary antibody, goat anti-rabbit. The sections were viewed and photographed under microscope. The immunohistochemical analysis revealed increases in microglia cell number in the prefrontal cortex, in offspring of poly(I:C) treated-rats as compared to the controls injected with NaCl. However, no significant differences were observed in microglia activation in the cerebellum among the groups. Prenatal immune challenge with Poly(I:C) was able to induce long-lasting changes in the offspring brains. This lead to a higher activation of microglia cells in the prefrontal cortex, a brain region critical for many higher brain functions, including working memory and cognitive flexibility. which might be implicated in possible changes in cortical neuropil architecture in schizophrenia. Further studies will be needed to clarify the association between microglial cells activation and schizophrenia-related behavioral alterations.

Keywords: Microglia, neuroinflammation, PolyI:C, schizophrenia

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Authors: Veerle Van Hoeck, Ingrid Somers, Dany Morisset

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Anti-nutritional factors such as non-starch polysaccharides (NSP) are present in viscous cereals used to feed poultry. Therefore, exogenous carbohydrases are commonly added to monogastric feed to degrade these NSP. Our hypothesis is that xylanase not only improves laying hen performance and digestibility but also induces a significant shift in microbial composition within the intestinal tract and, thereby, can cause a prebiotic effect. In this context, a better understanding of whether and how the chicken gut flora can be modulated by xylanase is needed. To do so, in the herein laying hen study, the effects of dietary supplementation of xylanase on performance, digestibility, and cecal microbiome were evaluated. A total of 96 HiSex laying hens was used in this experiment (3 diets and 16 replicates of 2 hens). Xylanase was added to the diets at concentrations of 0, 45,000 (15 g/t XygestTM HT) and 90,000 U/kg (30 g/t Xygest HT). The diets were based on wheat (~55 %), soybean, and sunflower meal. The lowest dosage, 45,000 U/kg, significantly increased average egg weight and improved feed efficiency compared to the control treatment (p < 0.05). Egg quality parameters were significantly improved in the experiment in response to the xylanase addition. For example, during the last 28 days of the trial, the 45,000 U/kg and the 90,000 U/kg treatments exhibited an increase in Haugh units and albumin heights (p < 0.05). Compared with the control, organic matter digestibility and N retention were drastically improved in the 45,000 U/kg treatment group, which implies better nutrient digestibility at this lowest recommended dosage compared to the control (p < 0.05). Furthermore, gross energy and crude fat digestibility were improved significantly for birds fed 90,000 U/kg group compared to the control. Importantly, 16S rRNA gene analysis revealed that xylanase at 45,000 U/kg dosages can exert a prebiotic effect. This conclusion was drawn based on studying the sequence variation in the 16S rRNA gene in order to characterize diverse microbial communities of the cecal content. A significant increase in beneficial bacteria (Lactobacilli spp and Enterococcus casseliflavus) was documented when adding 45,000 U/kg xylanase to the diet of laying hens. In conclusion, dietary supplementation of xylanase, even at the lowest dose of (45,000 U/kg), significantly improved laying hen performance and digestibility. Furthermore, it is generally accepted that a proper bacterial balance between the number of beneficial bacteria and pathogenic bacteria in the intestine is vital for the host. It seems that the xylanase enzyme is able to modulate the laying hen microbiome beneficially and thus exerts a prebiotic effect. This microbiome plasticity in response to the xylanase provides an attractive target for stimulating intestinal health.

Keywords: laying hen, prebiotic, XygestTM HT, xylanase

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Authors: Bobuchi Ken-Opurum

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The impacts of climate change on urban settlements is growing. In the global south, communities are even more vulnerable and suffer there is an increased vulnerability from due to climate change disasters such as flooding and high temperatures. This is primarily due to high intensity rainfall, low-lying coasts, inadequate infrastructure, and limited resources. According to the Emergency Events Database, floods were the leading cause of disaster -based deaths in the global south between 2006 and 2015. This includes deaths from heat stress related health outcomes. Adapting to climate vulnerabilities is paramount in reducing the significant redevelopment costs from climate disasters. Governments and urban planners provide top-down approaches such as evacuation, and disaster and emergency communication. While they address infrastructure and public services, they are not always able to address the immediate and critical day to day needs of poor and vulnerable populations. There is growing evidence that some bottom-up strategies and grassroots initiatives of self-build housing such as in urban informal settlements are successful in coping and adapting to hydroclimatic impacts. However, these research findings are not consolidated and the evaluation of the resilience outcomes of the bottom-up strategies are limited. Using self-build housing as a model for sustainable and resilient urban planning, this research aimed to consolidate the flood and heat stress resilient design solutions, analyze the effectiveness of these solutions, and develop guidelines and methods for adopting these design solutions into mainstream housing in megathermal climates. The methodological approach comprised of analyses of over 40 ethnographic based peer reviewed literature, white papers, and reports between the years 2000 and 2019 to identify coping strategies and grassroots initiatives that have been applied by occupants and communities of the global south. The results of the research provide a consolidated source and prioritized list of the best bottom-up strategies for communities in megathermal climates to improve the lives of people in some of the most vulnerable places in the world.

Keywords: resilient, design, megathermal, climate change

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Authors: Uliana N. Tumanova, Viacheslav M. Lyapin, Vladimir G. Bychenko, Alexandr I. Shchegolev, Gennady T. Sukhikh

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All cases of stillbirth undoubtedly subject to postmortem examination, since it is necessary to find out the cause of the stillbirths, as well as a forecast of future pregnancies and their outcomes. Determination of the time of death is an important issue which is addressed during the examination of the body of a stillborn. It is mean the period from the time of death until the birth of the fetus. The time for fetal deaths determination is based on the assessment of the severity of the processes of maceration. To study the possibilities of postmortem magnetic resonance imaging (MRI) for determining the time of intrauterine fetal death based on the evaluation of maceration in the kidney. We have conducted MRI morphological comparisons of 7 dead fetuses (18-21 gestational weeks) and 26 stillbirths (22-39 gestational weeks), and 15 bodies of died newborns at the age of 2 hours – 36 days. Postmortem MRI 3T was performed before the autopsy. The signal intensity of the kidney tissue (SIK), pleural fluid (SIF), external air (SIA) was determined on T1-WI and T2-WI. Macroscopic and histological signs of maceration severity and time of death were evaluated in the autopsy. Based on the results of the morphological study, the degree of maceration varied from 0 to 4. In 13 cases, the time of intrauterine death was up to 6 hours, in 2 cases - 6-12 hours, in 4 -12-24 hours, in 9 -2-3 days, in 3 -1 week, in 2 -1,5-2 weeks. At 15 dead newborns, signs of maceration were absent, naturally. Based on the data from SIK, SIF, SIA on MR-tomograms, we calculated the coefficient of MR-maceration (M). The calculation of the time of intrauterine death (MP-t) (hours) was performed by our formula: МR-t = 16,87+95,38×М²-75,32×М. A direct positive correlation of MR-t and autopsy data from the dead at the gestational ages 22-40 weeks, with a dead time, not more than 1 week, was received. The maceration at the antenatal fetal death is characterized by changes in T1-WI and T2-WI signals at postmortem MRI. The calculation of MP-t allows defining accurately the time of intrauterine death within one week at the stillbirths who died on 22-40 gestational weeks. Thus, our study convincingly demonstrates that radiological methods can be used for postmortem study of the bodies, in particular, the bodies of stillborn to determine the time of intrauterine death. Postmortem MRI allows for an objective and sufficiently accurate analysis of pathological processes with the possibility of their documentation, storage, and analysis after the burial of the body.

Keywords: intrauterine death, maceration, postmortem MRI, stillborn

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Authors: Paresh Patel, Priya Patel, Vaidehi Sorathiya, Navin Sheth

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The aim of present work was to fabricate Salmeterol Xinafoate (SX) metered dose inhaler (MDI) for asthma and to evaluate the SX loaded solid lipid nanoparticles (SLNs) for pulmonary delivery. Solid lipid nanoparticles can be used to deliver particles to the lungs via MDI. A modified solvent emulsification diffusion technique was used to prepare Salmeterol Xinafoate loaded solid lipid nanoparticles by using compritol 888 ATO as lipid, tween 80 as surfactant, D-mannitol as cryoprotecting agent and L-leucine was used to improve aerosolization behaviour. Box-Behnken design was applied with 17 runs. 3-D surface response plots and contour plots were drawn and optimized formulation was selected based on minimum particle size and maximum % EE. % yield, in vitro diffusion study, scanning electron microscopy, X-ray diffraction, DSC, FTIR also characterized. Particle size, zeta potential analyzed by Zetatrac particle size analyzer and aerodynamic properties was carried out by cascade impactor. Pre convulsion time was examined for control group, treatment group and compare with marketed group. MDI was evaluated for leakage test, flammability test, spray test and content per puff. By experimental design, particle size and % EE found to be in range between 119-337 nm and 62.04-76.77% by solvent emulsification diffusion technique. Morphologically, particles have spherical shape and uniform distribution. DSC & FTIR study showed that no interaction between drug and excipients. Zeta potential shows good stability of SLNs. % respirable fraction found to be 52.78% indicating reach to the deep part of lung such as alveoli. Animal study showed that fabricated MDI protect the lungs against histamine induced bronchospasm in guinea pigs. MDI showed sphericity of particle in spray pattern, 96.34% content per puff and non-flammable. SLNs prepared by Solvent emulsification diffusion technique provide desirable size for deposition into the alveoli. This delivery platform opens up a wide range of treatment application of pulmonary disease like asthma via solid lipid nanoparticles.

Keywords: salmeterol xinafoate, solid lipid nanoparticles, box-behnken design, solvent emulsification diffusion technique, pulmonary delivery

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Authors: Akulov M. A., Zaharov V. O., Jurishhev P. E., Tomskij A. A.

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Introduction: Spasticity is a severe consequence of stroke, leading to profound disability, decreased quality of life and decrease of rehabilitation efficacy [4]. Spasticity is often associated with pain syndrome, arising from joint damage of paretic limbs (postural arthropathy) or painful spasm of paretic limb muscles. It is generally accepted that injection of botulinum toxin into a cramped muscle leads to decrease of muscle tone and improves motion range in paretic limb, which is accompanied by pain alleviation. Study aim: To evaluate the change in pain syndrome intensity after incections of botulinum toxin A (Xeomin) in stroke patients with upper limb spasticity. Patients and methods. 21 patients aged 47-74 years were evaluated. Inclusion criteria were: acute stroke 4-7 months before the inclusion into the study, leading to spasticity of wrist and/or finger flexors, elbow flexor or forearm pronator, associated with severe pain syndrome. Patients received Xeomin as monotherapy 90-300 U, according to spasticity pattern. Efficacy evaluation was performed using Ashworth scale, disability assessment scale (DAS), caregiver burden scale and global treatment benefit assessment on weeks 2, 4, 8 and 12. Efficacy criterion was the decrease of pain syndrome by week 4 on PQLS and VAS. Results: The study revealed a significant improvement of measured indices after 4 weeks of treatment, which persisted until the 12 week of treatment. Xeomin is effective in reducing muscle tone of flexors of wrist, fingers and elbow, forearm pronators. By the 4th week of treatment we observed a significant improvement on DAS (р < 0,05), Ashworth scale (1-2 points) in all patients (р < 0,05), caregiver burden scale (р < 0,05). A significant decrease of pain syndrome by the 4th week of treatment on PQLS (р < 0,05) и VAS (р < 0,05) was observed. No adverse effect were registered. Conclusion: Xeomin is an effective treatment of pain syndrome in postural upper limb spasticity after stroke. Xeomin treatment leads to a significant improvement on PQLS and VAS.

Keywords: botulinum toxin, pain syndrome, spasticity, stroke

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Authors: Ibrahim M Hassan, Lorna Que, Michael Rutland

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Type I SOD is usually diagnosed by anatomical imaging such as ultrasound, CT and MRCP. However, the types II and III SOD yield negative results despite the presence of significant symptoms. In particular, the type III is difficult to diagnose due to the absence of significant biochemical or anatomical abnormalities. Nuclear Medicine can aid in this diagnostic dilemma by demonstrating functional changes in the bile flow. Low dose Morphine (0.04mg/Kg) stimulates the tone of the sphincter of Oddi (SO) and its usefulness has been shown in diagnosing SOD by causing a delay in bile flow when compared to a non morphine provoked - baseline scan. This work expands on that process by using sublingual GTN at 60 minutes post tracer and morphine injection to relax the SO and induce an improvement in bile outflow, and in some cases show immediate relief of morphine induced abdominal pain. The criteria for positive SOD are as follows: if during the first hour of the morphine provocation showed (1) delayed intrahepatic biliary ducts tracer accumulation; plus (2) delayed appearance but persistent retention of activity in the common bile duct, and (3) delayed bile flow into the duodenum. In addition, patients who required GTN within the first hour to relieve abdominal pain were regarded as highly supportive of the diagnosis. Retrospective analysis of 85 patients (pts) (78F and 6M) referred for suspected SOD (type III) who had been intensively investigated because of recurrent right upper quadrant or abdominal pain post cholecystectomy. 99mTc-HIDA scan with morphine-provocation is performed followed by GTN at 60 minutes post tracer injection and a further thirty minutes of dynamic imaging are acquired. 30 pts were negative. 55 pts were regarded as positive for SOD and 38/55 (60%) of these patients with an abnormal result were further evaluated with a baseline 99mTc-HIDA. As expected, all 38 pts showed better bile flow characteristics than during the morphine provocation. 20/55 (36%) patients were treated by ERCP sphincterotomy and the rest were managed conservatively by medical therapy. In all cases regarded as positive for SOD, the sublingual GTN at 60 minutes showed immediate improvement in bile flow. 11/55(20%) who developed severe post-morphine abdominal pain were relieved by GTN almost instantaneously. We propose that GTN is a useful agent in the diagnosis of SOD when performing 99mTc-HIDA scan and that the satisfactory response to the sublingual GTN could offer additional information in patients who have severe pain at the time the procedure or when presenting to the emergency unit because of biliary pain. And also in determining whether a trial of medical therapy may be used before considering surgery.

Keywords: GTN, HIDA, MORPHINE, SOD

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Authors: Adhitya Mangala, Yobel

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Bittuang geothermal prospect area located at Tana Toraja district, South Sulawesi. The geothermal system of the area related to Karua Volcano eruption product. This area has surface manifestation such as fumarole, hot springs, sinter silica and mineral alteration. Those prove that there are hydrothermal activities in the subsurface. However, the project and development of the area have not implemented yet. One of the important elements in geothermal exploration is to determine upflow and outflow zone. This information very useful to identify the target for geothermal wells and development which it is a risky task. The methods used in this research were Mercury (Hg) anomalies in soil, soil and manifestation temperature distribution and fault fracture density from 93 km² research area. Hg anomalies performed to determine the distribution of hydrothermal alteration. Soil and manifestation temperature distribution were conducted to estimate heat distribution. Fault fracture density (FFD) useful to determine fracture intensity and trend from surface observation. Those deliver Hg anomaly map, soil and manifestation temperature map that combined overlayed to fault fracture density map and geological map. Then, the conceptual model made from north – south, and east – west cross section to delineate upflow and outflow zone in this area. The result shows that upflow zone located in northern – northeastern of the research area with the increase of elevation and decrease of Hg anomalies and soil temperature. The outflow zone located in southern - southeastern of the research area which characterized by chloride, chloride - bicarbonate geothermal fluid type, higher soil temperature, and Hg anomalies. The range of soil temperature distribution from 16 – 19 °C in upflow and 19 – 26.5 °C in the outflow. The range of Hg from 0 – 200 ppb in upflow and 200 – 520 ppb in the outflow. Structural control of the area show northwest – southeast trend. The boundary between upflow and outflow zone in 1550 – 1650 m elevation. This research delivers the conceptual model with innovative methods that useful to identify a target for geothermal wells, project, and development in Bittuang geothermal prospect area.

Keywords: Bittuang geothermal prospect area, Hg anomalies, soil temperature, upflow and outflow zone

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Authors: Sujit Kumar

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Historicity of inter-caste relations can be traced in the early stages of evolution of rural community in the Indian society. These have witnessed vicissitudes during long drawn interactions between caste groups. Inter-caste relations evolved in a more organized form in the guise of Jajmani system. This is a system of permanent and hereditary inter-caste relations and gives a kaleidoscopic view of socio-economic relations among various caste groupings. Universality of its prevalence in rural India for centuries is well recognized and documented. But it has been undergoing metamorphic change in some regions and changing at a slower pace in the others during post-independence period. An empirical study was conducted with the objectives to know whether Jajmani system is in vogue in the rural areas and type and intensity of socio-economic ties among different caste categories and to find out the change in inter-caste relations, if any owing to industrialization and modernization. Information was elicited from 225 respondents using interview schedule designed for this purpose. It is discernible that in majority of cases, inter-caste social relations which find better expression on the occasions like marriage, death, birth and festivals etc. among Brahmins and lower castes vis-à-vis other caste categories have grown weak. The data further unearth that economic relations as maintained on the occasions of marriage, sacred thread ceremony, mundan sacrament, birthday, death, yajna, katha, routine hair cut, manufacture and repair of various iron, earthen, wooden and leather articles between members of higher castes (general category) and lower castes (scheduled castes) are moderate but weak in case of Other Backward Classes vis-à-vis all other caste categories. Overwhelming majority of informants believe that decline in hereditary occupations, depreciation of old products and services and their availability from the market being made by industry are main reasons in descending order for change in inter caste relations. Modernization, westernization, industrialization, transportation and communications, growing materialism and consumerism together have brought change in relations among caste groups affecting about a billion population inhabiting rural India.

Keywords: inter-caste, Jajmani, sacrament, Yajna

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Authors: J. Naalamle Amissah, Dorcas Osei‐Safo, C. M. Asare, Benjamin Missah‐Assihene, Eric. Y. Danquah, Ivan Addae‐Mensah

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Medicinal plants serve as a reservoir of active ingredients for the treatment of common ailments such as cancer, malaria and diabetes. With the recent wave of health consciousness and reliance on plant based medicines, the demand for medicinal plants has increased considerably. This surge in medicinal plant use has raised great concern amongst key players (herbalist, collectors, conservationist and researchers) along the value chain about the sustainability of the raw material. The over reliance on wild crafting as a means to obtain the raw material spells doom for several of Africa’s native medicinal plant species. In this study domestication protocols for the cultivation of Cryptolepis sanguinolenta (CS), a medicinal plant used in the treatment of malaria were developed. Initial surveys were conducted, using questionnaires comprising of open and close ended questions, to gather information that would inform the domestication and cultivation of the species. A field study was then conducted to determine the plant’s cropping cycle and the effect of staking and plant age on the active ingredient (cryptolepine) concentration in its roots. Results of the survey confirmed the demand for the raw material and threw more light on the harvesting methods and intensity of CS collection from the wild. Cryptolepine concentration was found to be highest (~1.84 mg/100 mg of root material) at 289 days after planting (DAP) which coincided with the peak of root dry weight (52.8 g), signifying the best time for root harvest. Staking was found to be important for seed production. The first 105 DAP were characterized by low yields of root dry weight (13.5 g), followed by a period of rapid growth in which the root dry weight increased almost linearly until 289 DAP. Although dry matter partitioned to the vines increased towards the end of the experimental period (60%), dry matter partitioned to the roots remained fairly constant (30%) throughout the experimental period. Cryptolepine was found to increase as the plant aged and the practice of staking CS promoted pod formation. A suitable cropping cycle for the cultivation of CS was also developed.

Keywords: domestication, staking, conservation, wild harvesting

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Authors: Lali Shanshiashvili, Marika Chikviladze, Nino Mamulashvili, Maia Sepashvili, Nana Narmania, David Mikeladze

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Purpose: During demyelinating inflammatory diseases and after the damage of the myelin sheet, myelin-derived proteins, including myelin basic protein (MBP), are secreted into the extracellular space. MBP shows extensive post-translational modifications, including the deimination of arginine residues. Deiminated MBP is structurally less ordered, susceptible to proteolytic attack, and more immunogenic than the unmodified one. It is hypothesized that MBP could change the inflammatory response in astrocytes. Methods: MBP was isolated and purified from bovine brain white matter. Primary astrocyte cultures were prepared from whole brains of 2-day-old Wistar rats. For evaluation of glutamate uptake/release in astrocytes following treatment of cells with MBP charge isomers, Glutamate Assay Kit was used. The expression of EAAT-2 (excitatory amino acid transporters), peroxisome proliferator-activated receptor gamma (PPAR- γ), inhibitor of nuclear factor kappa B (IkB), and high mobility group protein B1 (HMGB1) in astrocytes were assayed by Western Blot analysis. Results: This study investigated the action of deiminated isomer (C8) on the cultured primary astrocytes and compared its effects with the effects of unmodified C1 isomers. The study found that C8 and C1 MBP differently act on the uptake and release of glutamate in astrocytes: nonmodified C1 MBP increases the uptake of glutamate and does not change the release, whereas C8 decreases the release of glutamate but does not alter the uptake. Nevertheless, both isomers increased the expression of PPAR-γ and EAAT2 in the same intensity. However, immunostaining and Western Blots of cell lysates showed a decrease of IkB and increased expression of HMGB1 after the treatment of astrocytes by C8. Moreover, in the presence of C8, astrocytes release more nitric oxide than unmodified C1 isomers. Conclusion: These data suggest that the deiminated isomer of MBP evokes an inflammatory response and enhances the ability of astrocytes to release proinflammatory mediators through activation of NF-kB after the breakdown of myelin sheets. Acknowledgment: This research was supported by the SRNSF Georgia RF17_534 grant.

Keywords: myelin basic protein, glutamate, deimination, astrocytes, inflammation

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Authors: Serpil Kilic, Ihsan Burak Cam, Murat Kilic, Timur Tongur

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Interest in the lead (Pb) has considerably increased due to knowledge about the potential toxic effects of this element, recently. Exposure to heavy metals above the acceptable limit affects human health. Indeed, Pb is accumulated through food chains up to toxic concentrations; therefore, it can pose an adverse potential threat to human health. A sensitive and reliable method for determination of Pb element in red pepper were improved in the present study. Samples (33 red pepper products having different brands) were purchased from different markets in Turkey. The selected method validation criteria (linearity, Limit of Detection, Limit of Quantification, recovery, and trueness) demonstrated. Recovery values close to 100% showed adequate precision and accuracy for analysis. According to the results of red pepper analysis, all of the tested lead element in the samples was determined at various concentrations. A Perkin- Elmer ELAN DRC-e model ICP-MS system was used for detection of Pb. Organic red pepper was used to obtain a matrix for all method validation studies. The certified reference material, Fapas chili powder, was digested and analyzed, together with the different sample batches. Three replicates from each sample were digested and analyzed. The results of the exposure levels of the elements were discussed considering the scientific opinions of the European Food Safety Authority (EFSA), which is the European Union’s (EU) risk assessment source associated with food safety. The Target Hazard Quotient (THQ) was described by the United States Environmental Protection Agency (USEPA) for the calculation of potential health risks associated with long-term exposure to chemical pollutants. THQ value contains intake of elements, exposure frequency and duration, body weight and the oral reference dose (RfD). If the THQ value is lower than one, it means that the exposed population is assumed to be safe and 1 < THQ < 5 means that the exposed population is in a level of concern interval. In this study, the THQ of Pb was obtained as < 1. The results of THQ calculations showed that the values were below one for all the tested, meaning the samples did not pose a health risk to the local population. This work was supported by The Scientific Research Projects Coordination Unit of Akdeniz University. Project Number: FBA-2017-2494.

Keywords: lead analyses, red pepper, risk assessment, daily exposure

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Authors: Nezihe Şengün, Ragip Pala

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To prevent overweight and obesity, individuals need to consume food and beverages according to their nutritional needs, engage in regular exercises, and regularly monitor their body weight. This study aimed to examine the effects of exercise, diet, or combined intervention on changes in blood lipid parameters (total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides) and the level of malondialdehyde (MDA), a marker of oxidative stress, in parallel with the increase in body weight due to poor nutrition and sedentary lifestyle conditions. The study included a total of 48 female students aged 18-28 years with a BMI between 25.0 and 29.9 kg/m². They were divided into four groups: control (C), exercise (Ex), diet (D), and exercise+diet (Ex+D). Those in the exercise groups received aerobic exercises at 60-70% intensity (10 minutes warm-up, 30 minutes running, 10 minutes cool-down), while those in the diet groups were provided with a diet program based on the calculation of energy needs considering basal metabolic rate, physical activity level, age, and BMI. The students’ body weight, body fat mass, Body Mass Index (BMI), and waist-hip ratios were measured at the beginning (day 1) and end (day 60) of the 8-week intervention period. Their total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, and MDA levels were evaluated and analyzed, considering a statistical significance level of p<0.05. As a result, female students in the Ex+D group had the largest difference in body weight, body fat mass, BMI, and waist-hip ratios, and this difference was statistically significant. Except for those in the C group, those in the other groups experienced a decrease in their total cholesterol, LDL cholesterol, and triglyceride levels and an increase in their HDL cholesterol levels. The decrease in total cholesterol, LDL cholesterol, and triglyceride levels was statistically significant for those in the D group, and the increase in HDL cholesterol level was statistically significant for those in the Ex+D group (p<0.05). A decrease in MDA level was found in all groups except those in the C group, and this decrease was significantly higher in the Ex group. In conclusion, our study revealed that the most effective way to achieve weight loss is through a combination of exercise and diet. The application of Ex+D is considered to balance blood lipid levels and suppress oxidative stress.

Keywords: obesity, exercise, diet, body mass index, blood lipids

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Authors: Nicola Menga, Giuseppe Carbone

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Although contact mechanics has been widely focused on the study of contacts between half-space, it has been recently pointed out that in presence of finite thickness elastic layers the results of the contact problem show significant difference in terms of the main contact quantities (e.g. contact area, penetration, mean pressure, etc.). Actually, there exist a wide range of industrial application demanding for this kind of studies, such as seals leakage prediction or pressure-sensitive coatings for electrical applications. In this work, we focus on the contact between a rigid profile and an elastic layer of thickness h confined under two different configurations: rigid constrain and applied uniform pressure. The elastic problem at hand has been formalized following Green’s function method and then numerically solved by means of a matrix inversion. We study different contact conditions, both considering and neglecting adhesive interactions at the interface. This leads to different solution techniques: Adhesive contacts equilibrium solution is found, in term of contact area for given penetration, making stationary the total free energy of the system; whereas, adhesiveless contacts are addressed defining an equilibrium criterion, again on the contact area, relying on the fracture mechanics stress intensity factor KI. In particular, we make the KI vanish at the edges of the contact area, as peculiar for adhesiveless elastic contacts. The results are obtained in terms of contact area, penetration, and mean pressure for both adhesive and adhesiveless contact conditions. As expected, in the case of a uniform applied pressure the slab turns out much more compliant than the rigidly constrained one. Indeed, we have observed that the peak value of the contact pressure, for both the adhesive and adhesiveless condition, is much higher for the rigidly constrained configuration than in the case of applied uniform pressure. Furthermore, we observed that, for little contact area, both systems behave the same and the pull-off occurs at approximately the same contact area and mean contact pressure. This is an expected result since in this condition the ratio between the layers thickness and the contact area is very high and both layer configurations recover the half-space behavior where the pull-off occurrence is mainly controlled by the adhesive interactions, which are kept constant among the cases.

Keywords: contact mechanics, adhesion, friction, thick layer

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Authors: Tais Basaco, Stefanie Pektor, Josue A. Moreno, Matthias Miederer, Andreas Türler

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Radiopharmaceuticals based in monoclonal anti-body (mAb) via chemical linkers have become a potential tool in nuclear medicine because of their specificity and the large variability and availability of therapeutic radiometals. It is important to identify the conjugation sites and number of attached chelator to mAb to obtain radioimmunoconjugates with required immunoreactivity and radiostability. Girentuximab antibody (G250) is a potential candidate for radioimmunotherapy of clear cell carcinomas (RCCs) because it is reactive with CAIX antigen, a transmembrane glycoprotein overexpressed on the cell surface of most ( > 90%) (RCCs). G250 was conjugated with the bifunctional chelating agent DOTA (1,4,7,10-Tetraazacyclododecane-N,N’,N’’,N’’’-tetraacetic acid) via a benzyl-thiocyano group as a linker (p-SCN-Bn-DOTA). DOTA-G250 conjugates were analyzed by size exclusion chromatography (SE-HPLC) and by electrophoresis (SDS-PAGE). The potential site-specific conjugation was identified by liquid chromatography–mass spectrometry (LC/MS-MS) and the number of linkers per molecule of mAb was calculated using the molecular weight (MW) measured by matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The average number obtained in the conjugates in non-reduced conditions was between 8-10 molecules of DOTA per molecule of mAb. The average number obtained in the conjugates in reduced conditions was between 1-2 and 3-4 molecules of DOTA per molecule of mAb in the light chain (LC) and heavy chain (HC) respectively. Potential DOTA modification sites of the chelator were identified in lysine residues. The biological activity of the conjugates was evaluated by flow cytometry (FACS) using CAIX negative (SKRC-18) and CAIX positive (SKRC-52). The DOTA-G250 conjugates were labelled with 177Lu with a radiochemical yield > 95% reaching specific activities of 12 MBq/µg. The stability in vitro of different types of radioconstructs was analyzed in human serum albumin (HSA). The radiostability of 177Lu-DOTA-G250 at high specific activity was increased by addition of sodium ascorbate after the labelling. The immunoreactivity was evaluated in vitro and in vivo. Binding to CAIX positive cells (SK-RC-52) at different specific activities was higher for conjugates with less DOTA content. Protein dose was optimized in mice with subcutaneously growing SK-RC-52 tumors using different amounts of 177Lu- DOTA-G250.

Keywords: mass spectrometry, monoclonal antibody, radiopharmaceuticals, radioimmunotheray, renal cancer

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Authors: Martina Šutovská, Marta Jošková, Ivana Kazimierová, Lenka Pappová, Maroš Adamkov, Soňa Fraňová

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Bronchial asthma is characterized by increased bronchoconstrictor responses to provoking agonists, airway inflammation and remodeling. All these processes involve Ca2+ influx through Ca2+-release-activated Ca2+ channels (CRAC) that are widely expressed in immune, respiratory epithelium and airway smooth muscle (ASM) cells. Our previous study pointed on possible therapeutic potency of CRAC blockers using experimental guinea pigs asthma model. Presented work analyzed complex anti-asthmatic effect of long-term administered CRAC blocker, including impact on allergic inflammation, airways hyperreactivity, and remodeling and mucociliary clearance. Ovalbumin-induced allergic inflammation of the airways according to Franova et al. was followed by 14 days lasted administration of CRAC blocker (3-fluoropyridine-4-carboxylic acid, FPCA) in the dose 1.5 mg/kg bw. For comparative purposes salbutamol, budesonide and saline were applied to control groups. The anti-inflammatory effect of FPCA was estimated by serum and bronchoalveolar lavage fluid (BALF) changes in IL-4, IL-5, IL-13 and TNF-α analyzed by Bio-Plex® assay as well as immunohistochemical staining focused on assessment of tryptase and c-Fos positivity in pulmonary samples. The in vivo airway hyperreactivity was evaluated by Pennock et al. and by organ tissue bath methods in vitro. The immunohistochemical changes in ASM actin and collagen III layer as well as mucin secretion evaluated anti-remodeling effect of FPCA. The measurement of ciliary beat frequency (CBF) in vitro using LabVIEW™ Software determined impact on mucociliary clearance. Long-term administration of FPCA to sensitized animals resulted in: i. Significant decrease in cytokine levels, tryptase and c-Fos positivity similar to budesonide effect; ii.Meaningful decrease in basal and bronchoconstrictors-induced in vivo and in vitro airway hyperreactivity comparable to salbutamol; iii. Significant inhibition of airway remodeling parameters; iv. Insignificant changes in CBF. All these findings confirmed complex anti-asthmatic effect of CRAC channels blocker and evidenced these structures as the rational target in the treatment of allergic bronchial asthma.

Keywords: allergic asthma, CRAC channels, cytokines, respiratory epithelium

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Authors: Mohamed M. Ibrahim, Gaber A. M. Mersal, Salih Al-Juaid, Samir A. El-Shazly

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A series of mixed ligand complexes, viz., [Cu(BPy)(Gly)X]Y {X = Cl (1), Y = 0; X = 0, Y = ClO4- (2); X = H2O, Y = NO3- (3); X = H2O, Y = CH3COO- (4); and [Cu(BPy)(Gly)-(H2O)]2(SO4) (5) have been synthesized. Their structures and properties were characterized by elemental analysis, thermal analaysis, IR, UV–vis, and ESR spectroscopy, as well as electrochemical measurements including cyclic voltammetry, electrical molar conductivity, and magnetic moment measurements. Complexes 1 and 2 formed slightly distorted square-pyramidal coordination geometries of CuN3OCl and CuN3O2, respectively in which the N,O-donor glycine and N,N-donor bipyridyl bind at the basal plane with chloride ion or water as the axial ligand. Complex 3 shows square planar CuN3O coordination geometry, which exhibits chemically significant hydrogen bonding interactions besides showing coordination polymer formation. The superoxide dismutase and catalase-like activities of all complexes were tested and were found to be promising candidates as durable electron-transfer catalyst being close to the efficiency of the mimicking enzymes displaying either catalase or tyrosinase activity to serve for complete reactive oxygen species (ROS) detoxification, both with respect to superoxide radicals and related peroxides. The DNA binding interaction with super coiled pGEM-T plasmid DNA was investigated by using spectral (absorption and emission) titration and electrochemical techniques. The results revealed that DNA intercalate with complexes 1 and 2 through the groove binding mode. The calculated intrinsic binding constant (Kb) of 1 and 2 were 4.71 and 2.429 × 105 M−1, respectively. Gel electrophoresis study reveals the fact that both complexes cleave super coiled pGEM-T plasmid DNA to nicked and linear forms in the absence of any additives. On the other hand, the interaction of both complexes with DNA, the quasi-reversible CuII/CuI redox couple slightly improves its reversibility with considerable decrease in current intensity. All the experimental results indicate that the bipyridyl mixed copper(II) complex (1) intercalate more effectively into the DNA base pairs.

Keywords: enzyme mimics, mixed ligand complexes, X-ray structures, antioxidant, DNA-binding, DNA cleavage

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