Search results for: signaling pathway

Authors: Hari Bezwada, Michelle Cheon, Ryan Divan, Hannah Escritor, Michelle Kagramian, Isha Korgaonkar, Maya MacAdams, Udgita Pamidigantam, Richard Pilny, Eleanor Race, Angadh Singh, Nathan Zhang, LeeAnn Nguyen, Fina Liotta

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Malaria is a deadly disease caused by the Plasmodium parasite, which continues to develop resistance to current antimalarial drugs. In this research project, the effectiveness of numerous thiazole derivatives was explored in inhibiting the PfPKG, a crucial part of the Plasmodium life cycle. This study involved the synthesis of six thiazole-derived amides to inhibit the PfPKG pathway. Nuclear Magnetic Resonance (NMR) spectroscopy and Infrared (IR) spectroscopy were used to characterize these compounds. Furthermore, AutoDocking software was used to predict binding affinities of these thiazole-derived amides in silico. In silico, compound 6 exhibited the highest predicted binding affinity to PfPKG, while compound 5 had the lowest affinity. Compounds 1-4 displayed varying degrees of predicted binding affinity. In-vitro, it was found that compound 4 had the best percent inhibition, while compound 5 had the worst percent inhibition. Overall, all six compounds had weak inhibition (approximately 30-39% at 10 μM), but these results provide a foundation for future drug discovery experiments.

Keywords: Medicinal Chemistry, Malaria, drug discovery, PfPKG, Thiazole, Plasmodium

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Authors: Carlos A. Acosta, Amar Bhalla, Ruyan Guo

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Scraped surface heat exchangers (SSHE) use a rotor shaft assembly with scraping blades to homogenize viscous fluids during the heat transfer process. Obtaining in-situ measurements is difficult because the rotor and scraping blades spin continuously inside the mixing chamber, obstructing the instrumentation pathway. Computational fluid dynamics simulations provide useful insight into the flow behavior around the scraper blades for a variety of fluids and blade geometries. However, numerical solutions often focus on the fluid dynamics and heat transfer phenomena of rotating flow, ignoring the glass-transition temperature and freezing point depression. This research studies the multi-phase fluid dynamics and freezing point depression inside the SSHE with non-isothermal conditions in a time dependent process using an aqueous solution that contains 13.5 wt.% high fructose corn syrup and CO₂. The computational results were validated with in-situ pressure, temperature, and optical spectroscopy measurements. Results from the numerical model show good quantitatively agreement with experimental values.

Keywords: computational fluid dynamics, freezing point depression, phase-transition temperature, multi-phase flow

Procedia PDF Downloads 125

Authors: Kriti Upadhyay, Ashraf Ali, Puja Sohal, Randeep Guleria

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Background: In Chronic Obstructive Pulmonary diseases (COPD) pathogenesis oxidative stress plays an important role. Hypoxia-Inducible factor (HIF-1α) is a dimeric protein complex which Functions as a master transcriptional regulator of the adaptive response to hypoxiaand is a risk factor that increases when oxidative stress triggers. The role ofHIF-1αin COPD due to smoking is lacking. Aim: This study aims to evaluate the role of HIF-1α in smoker COPD patients comparing its association with diseases severity. Method: In this cross-sectional study, we recruited 87 subjects, 57 were smokers with COPD,15 were smokers without COPD and other 15 were non-smoker healthy controls. The mean age was 54.6± 9.32 (cases 57.08±8.15; controls 50.0± 9.8). There were 62%smokers, 25% non-smokers,7% tobacco chewers and 6% ex-smokers. Enzyme-linked immune sorbent assay (ELISA) method was used for analyzing serum samples wherein HIF-1α was analyzed by Sandwich-ELISA. Results: In smoker COPD patients, a significantly higher HIF-1α level showed positive association with hypoxia, smoking status and severity of disease (p=0.03). The mean value of HIF-1α was not significantly different in smokers without COPD and healthy controls. Conclusion: It is found that HIF-1α level was increased in smoker COPD, but not in smokers without COPD. This suggests that development of COPD drive the HIF-1α pathway and it correlates with the severity of diseases.

Keywords: COPD, chronic obstructive pulmonary diseases, smokers, nonsmokers, hypoxia

Procedia PDF Downloads 120

Authors: Waranya Imprasittichai, Patsarawadee Paojinda, Sudaratana R. Krungkrai, Nirianne Marie Q. Palacpac, Toshihiro Horii, Jerapan Krungkrai

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Fusion of the last two enzymes in the pyrimidine biosynthetic pathway in the inversed order by having COOH-terminal orotate phosphoribosyltransferase (OPRT) and NH2-terminal orotidine 5'-monophosphate decarboxylase (OMPDC), as OMPDC-OPRT, are described in many organisms. In this study, we constructed gene fusions of Plasmodium falciparum OMPDC-OPRT (1,836 bp) in pTrcHisA vector and expressed as an 6xHis-tag bifunctional protein in three Escherichia coli strains (BL21, Rosetta, TOP10) at 18 °C, 25 °C and 37 °C. The recombinant bifunctional protein was partially purified by Ni-Nitrilotriacetic acid-affinity chromatography. Specific activities of OPRT and OMPDC domains in the bifunctional enzyme expressed in E. coli TOP10 cells were approximately 3-4-fold higher than those in BL21 cells. There were no enzymatic activities when the construct vector expressed in Rosetta cells. Maximal expression of the fused gene was observed at 18 °C and the bifunctional enzyme had specific activities of OPRT and OMPDC domains in a ratio of 1:2. These results provide greater yields and better catalytic activities of the bifunctional OMPDC-OPRT enzyme for further purification and kinetic study.

Keywords: bifunctional enzyme, orotate phosphoribosyltransferase, orotidine 5'-monophosphate decarboxylase, plasmodium falciparum

Procedia PDF Downloads 335

Authors: Qinghua Xing, Xinyi Tao, Haisheng Wang, Baisuo Zhao

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The first true anaerobic, halophilic alkali thermophile, Natranaerobius thermophilus DSM 18059T, serves as a valuable model for studying cellular adaptations to saline, alkaline and thermal extremes. To uncover the adaptive strategies employed by N. thermophilus in coping with these challenges, we conducted a comprehensive iTRAQ-based quantitative proteomic analysis under different conditions of salinity (3.5 M vs. 2.5 M Na+), pH (pH 9.6 vs. pH 8.6), and temperature (52°C vs. 42°C). The increased intracellular accumulation of glycine betaine, through both synthesis and transport, plays a critical role in N. thermophilus' adaptation to these combined stresses. Under all three stress conditions, the up-regulation of Trk family proteins responsible for K+ transport is observed. Intracellular K+ concentration rises in response to salt and pH levels. Multiple types of Na+/H+ antiporter (NhaC family, Mrp family and CPA family) and a diverse range of FOF1-ATP synthase are identified as vital components for maintaining ionic balance under different stress conditions. Importantly, proteins involved in amino acid metabolism, carbohydrate metabolism, ABC transporters, signaling and chemotaxis, as well as biological macromolecule repair and protection, exhibited significant up-regulation in response to these extreme conditions. These metabolic pathways emerge as critical factors in N. thermophilus' adaptation mechanisms under extreme environmental stress. To validate the proteomic data, ddPCR analysis confirmed changes in mRNA expression, thereby corroborating the up-regulation and down-regulation patterns of 19 co-up-regulated and 36 key proteins under saline, alkaline and thermal stresses. This research enriches our understanding of the complex regulatory systems that enable polyextremophiles to survive in combined extreme conditions.

Keywords: polyextremophiles, natranaerobius thermophilus, saline- alkaline- thermal stresses, combined extremes

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Authors: Fernanda T. Orsati, Julie Causton

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Discursive practices enacted by educators in kindergarten create a blueprint for how the educational trajectories of students with disabilities are constructed. This two-year ethnographic case study critically examine educators’ relationships with students considered to present challenging behaviors in one kindergarten classroom located in a predominantly White middle-class school district in the Northeast of the United States. Focusing on the language and practices used by one special education teacher and three teaching assistants, this paper analyzes how teacher responses to students’ behaviors constructs and positions students over one year of kindergarten education. Using a critical discourse analysis, it shows that educators understand students’ behaviors as a deficit and needing consequences. This study highlights how educators’ responses reflect students' individual characteristics including family background, socioeconomics and ability status. This paper offers in-depth analysis of two students’ stories, which evidenced that the language used by educators amplifies the social positioning of students within the classroom and creates a foundation for who they are constructed to be. Through exploring routine language and practices, this paper demonstrates that educators outlined a blueprint of kindergartners, which positioned students as learners in ways that became the ground for either a limited or a promising educational pathway for them.

Keywords: behavior, early education, special education, critical discourse analysis

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Authors: Dong Il Shim, Geehong Choi, Donghwi Lee, Namkyu Lee, Hyung Hee Cho

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Effective cooling technology is required to secure thermal stability in extreme heat generated systems such as integrated electronic devices and power generated systems. Pool boiling heat transfer is one of the powerful cooling mechanisms using phase change phenomena. Critical heat flux (CHF) and heat transfer coefficient (HTC) are main factors to evaluate the performance of boiling heat transfer. CHF is the limitation of boiling heat transfer before film boiling which occurs thermal failure. Surface wettability is an important surface characteristic of boiling heat transfer. A hydrophilic surface has higher CHF through effective working fluid supply to local hot spots. A hydrophobic surface promotes the onset of nucleate boiling (ONB) to enhance HTC. In this study, superbiphilic surfaces, which is combined with superhydrophillic and superhydrophobic, are applied on boiling experiments to maximize boiling performance. We conducted pool boiling heat transfer using DI water at a saturated temperature and recorded bubble dynamics using a high-speed camera with 2000 fps. As a result, superbiphilic patterned surfaces promote ONB and enhance both CHF and HTC. This study demonstrates the enhanced boiling performance using superbiphilic surfaces by effective nucleation and separation of liquid/vapor pathway. We expect that further enhancement of heat transfer could be achieved in future work using optimized patterned surfaces.

Keywords: boiling heat transfer, wettability, critical heat flux, heat transfer coefficient

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Authors: Maryam Kiani

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In order to enhance the efficiency and stability of an electrocatalyst for formic acid electro-oxidation reaction (FAOR), we developed a method to create Pt/Ni nanoparticles with carbon black. These nanoparticles were prepared using a simple impregnation reduction technique. During the observation, it was found that the nanoparticles had a spherical shape. Additionally, the average particle size remained consistent, falling within the range of about 4 nm. This approach aimed to obtain a loaded Pt-based electrocatalyst that would exhibit improved performance and stability when used in FAOR applications. By utilizing the impregnation reduction method and incorporating Ni nanoparticles along with Pt, we sought to enhance the catalytic properties of the material. By incorporating Ni atoms into the Pt structure, the electronic properties of Pt are modified, resulting in a delay in the chemisorption of harmful CO intermediate species. This modification also promotes the dehydrogenation pathway of the formic acid oxidation reaction (FAOR). Through electrochemical analysis, it has been observed that the Pt3Ni-C catalyst exhibits enhanced performance in FAOR compared to traditional Pt catalysts. This means that the addition of Ni atoms improves the efficiency and effectiveness of the Pt3Ni-C catalyst in facilitating the FAOR process. Overall, the utilization of these alloy nanoparticles as electrocatalysts represents a significant advancement in fuel cell technology.

Keywords: electrocatalyst, impregnation reduction method, formic acid electro-oxidation reaction, fuel cells

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Authors: Peikun Zhang, Chunhua Cui

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Photoelectrochemical (PEC) water splitting provides a promising pathway to convert solar energy into renewable fuels. However, the main and seemingly insurmountable obstacle is that the sluggish kinetics of oxygen evolution reaction (OER) severely jeopardizes the overall efficiency, thus exploring highly active, stable, and appreciable catalysts is urgently requested. Herein a competitive coordination strategy was demonstrated to form a reversible hybrid homo-heterogeneous catalyst for efficient OER in alkaline media. The dynamic process involves an in-situ anchoring of soluble nickel–bipyridine pre-catalyst to a conductive substrate under OER and a re-dissolution course under open circuit potential, induced by the competitive coordination between nickel–bipyridine and nickel-hydroxyls. This catalyst allows to elaborately self-modulate a charge-transfer layer thickness upon the catalytic on-off operation, which affords substantially increased active sites, yet remains light transparency, and sustains the stability of over 200 hours of continuous operation. The integration of this catalyst with exemplified state-of-the-art Ni-sputtered Si photoanode can facilitate a ~250 mV cathodic shift at a current density of 20 mA cm-2. This finding helps the understanding of catalyst from a “dynamic” perspective, which represents a viable alternative to address remaining hurdles toward solar-driven water oxidation.

Keywords: molecular catalyst, oxygen evolution reaction, solar energy, transition metal complex, water splitting

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Authors: Jyoti Singh, Swati Dubey, Mukta Singh, R. P. Singh

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The freshwater microalgae Chlorella sp. is alluring considerable interest as a source for biofuel production due to its fast growth rate and high lipid content. Under nitrogen limited conditions, they can accumulate significant amounts of lipids. Thus, it is important to gain insight into the molecular mechanism of their lipid metabolism. In this study under nitrogen limited conditions, regular pattern of growth characteristics lipid accumulation and gene expression analysis of key regulatory genes of lipid biosynthetic pathway were carried out in microalgae Chlorella sp 3. Our results indicated that under nitrogen limited conditions there is a significant increase in the lipid content and lipid productivity, achieving 44.21±2.64 % and 39.34±0.66 mg/l/d at the end of the cultivation, respectively. Time-course transcript patterns of lipid biosynthesis genes i.e. acetyl coA carboxylase (accD) and diacylglycerol acyltransferase (dgat) showed that during late log phase of microalgae Chlorella sp.3 both the genes were significantly up regulated as compared to early log phase. Moreover, the transcript level of the dgat gene is two-fold higher than the accD gene. The results suggested that both the genes responded sensitively to the nitrogen limited conditions during the late log stage, which proposed their close relevance to lipid biosynthesis. Further, this transcriptome data will be useful for engineering microalgae species by targeting these genes for genetic modification to improve microalgal biofuel quality and production.

Keywords: biofuel, gene, lipid, microalgae

Procedia PDF Downloads 280

Authors: G. Fitzpatrick, S. O. Chonghaile, D. Harmon

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Objective: Chronic pain patients represent a unique challenge in the Emergency Department. Very little literature has been published regarding this group of patients. Our aim was to determine the attitude of patients with chronic pain to the Emergency Department in order to improve and streamline their future visits. Methods: A two-year survey was carried out on Chronic Pain Patients regarding their Emergency Department Attendances. Patients attending the Pain Clinic in Croom Hospital, Co. Limerick were asked to complete a 20-part questionnaire regarding their experiences of visiting the Emergency Department in the preceding year. 46 questionnaires were completed. Results: Unbearable breakthrough pain was the main reason for visiting the Emergency Department. More than half (54%) of those surveyed were not satisfied with the treatment received. Problems indicated included under-treatment of pain (59%), a sense of being under undue suspicion of drug-seeking behaviour (33%) and a perception that the patient themselves understood their condition better than the treating doctor (76%). Paracetamol, NSAIDs, or time off work comprised 72% of the treatments offered – all of which could have been provided by their General Practitioner. Only 4% were offered a nerve block. 67% felt that the creation of personalised Patient Plans, consisting of an agreed plan between the patient, their pain specialist, and the Emergency Department, would expedite their trip through the Emergency Department. Conclusions: Chronic pain patients generally have a negative experience in the ED. Possible future solutions include increasing our empathy and levels of knowledge, provision of nerve blocks in the ED, and use of personalised “Patient Plans” to streamline the treatment pathway for this group of patients.

Keywords: chronic pain, survey, patients, emergency department

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Authors: K. P. Farsana

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Belief in supernatural causation of mental illnesses and resort to religious and faith healing as the method of intervention still continue in many parts of the world. The proposed study intended to find out the belief and causation on health and illness and utilization of religious and faith healing, its implications, and associated socio-cultural and religious factors among Mappila Muslims of Malabar, Kerala, a southern state of India.Thangals are the endogamous community in Kerala, of Yemeni heritage who claim direct descent from the Prophet Mohammed’s family. Because of their sacrosanct status, many Thangal works as religious healers in Malabar, Northern Kerala. Using the case of one Thangal healer as an illustration of the many religious healers in Kerala who engage in the healing practices, it is intended, in this paper to illustrate the religious and ritual healing practices among Mappila Muslims of Malabar. It was found that the majority of the Mappila Muslims believed in supernatural causation on illness, and majority of them consulted religious and faith healers for various health problems before seeking professional help, and a considerable proportion continued to believe in the healing efficiency of the religious and faith healing. A significant proportion of the population found religious and faith healing practices are supportive and more acceptable within the community. Religion and belief system play an important role in the heath seeking behavior of a person.

Keywords: religious and faith healing, mental illness, Mappila Muslims, Malabar

Procedia PDF Downloads 179

Authors: Ravi Raghav Sonani, Niraj Kumar Singh, Jitendra Kumar, Datta Madamwar

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Phycobiliproteins (PBPs) are light harvesting proteins showing very strong absorbance and fluorescence in the visible range of the solar spectrum. Phycoerythrin (PE) and phycocyanin (PC) are majorly found PBPs in the cyanobacteria and red algae. In the present study, we have investigated the reactive oxygen species (ROS)-averting capacity of purified PE and PC of cyanobacterial origin. Furthermore, the possibility - whether the ROS-averting potential of PBPs can be explored in the therapeutics of oxidative stress associated physiological anomalies including aging and neurodegenerative diseases. The nematode Caenorhabditis elegans has been used as model organism in this study. PE and PC treatment moderated normal aging and associated physiological functionalities like pharyngeal pumping and locomotion of C. elegans. Moreover, PE-treatment enhanced the stress (oxidative and heat) tolerance upon PE and PC treatment. Specifically, PE treatment was also noted to moderate the progression of Alzheimer’s disease in transgenic C. elegans CL4176. However, PC-treatment curtailed the polyQ aggregation mediated proteotoxicity in C. elegans AM141 (Huntington disease model) under stressed (paraquat stress) as well as normal conditions. The effectiveness of PE and PC in expanding the lifespan of mutant C. elegans knockout for some up- (daf 16) and down- (daf-2 and age-1) stream regulators of insulin/IGF-1 signalling (IIS) shows the independency of their effects from DAF-2–AGE-1–DAF-16 signalling pathway. In conclusion, the present report demonstrates the anti-aging and neuro-protective potential of cyanobacterial PE and PC.

Keywords: phycobiliproteins, aging, alzheimer, huntington, C. elegans

Procedia PDF Downloads 371

Authors: Shanaj Parvin Jonaki

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After the first wave of the feminist movement, gender has become one of the most important issues to be researched in social science. Many gender theories have been invented and opened a new window to look at. These works showed how gender is a social construct, how gender has been used to oppress, how to rule. While it's the education system’s duty to guide students to understand the concept of gender, it sometimes shows gender-based discrimination. Transgenders exclusion from educational institutes of Bangladesh justifies this very statement. This study aims to figure out how people perceive transgenders’ identity, their inclusion in secondary schools, as well as the underlying barriers in the pathway of inclusion in the context of Bangladesh. A qualitative approach was taken to explore different perspectives towards transgender inclusion from several stakeholders such as students, parents, and teachers of secondary schools and transgenders as well. Data were collected through focus group discussion and interview by convenient sampling. 15 students, 10 parents, and 5 teachers were selected from Bangla Medium school as well as from Madrasha. Collected data were analyzed thematically and were run by experts of gender, education, and psychology to identify the core barriers of inclusion. The study revealed that most of the students, teachers, and parents lacked the knowledge of non-binary gender identities, and they showed unwillingness towards the inclusion of transgender in schools because of the cultural context of Bangladesh. Moreover, this study suggests future initiatives to be taken to ensure the inclusion of transgenders in a secondary school in our country and analyzes it through the lens of feminist theories.

Keywords: education, gender, inclusion, transgender

Procedia PDF Downloads 163

Authors: Junie B. Billones, Maria Constancia O. Carrillo, Voltaire G. Organo, Stephani Joy Y. Macalino, Inno A. Emnacen, Jamie Bernadette A. Sy

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One of the major interferences in the Philippines’ tuberculosis control program is the widespread prevalence of Mtb strains that are resistant to known drugs, such as the MDR-TB (Multi Drug Resistant Tuberculosis) and XDR-TB (Extensively Drug Resistant Tuberculosis). Therefore, there is a pressing need to search for novel Mtb drug targets in order to be able to combat these drug resistant strains. The enzyme 7,8-diaminopelargonic acid aminotransferase enzyme, or more commonly known as BioA, is one such ideal target, as it is known that humans do not possess this enzyme. BioA primarily plays a key role in Mtb’s lipid biosynthesis pathway; more specifically in the synthesis of the enzyme cofactor biotin. In this study, structure-based pharmacophore screening, docking, and ADMET evaluation of compounds obtained from the DrugBank chemical database were performed against the MtbBioA enzyme. Results of the screening, docking, ADMET, and TOPKAT calculations revealed that out of the 6,516 compounds in the library, only 7 compounds indicated more favorable binding energies as compared to the enzyme’s known inhibitor, amiclenomycin (ACM), as well as good solubility and toxicity properties. Moreover, out of these 7 compounds, Molecule 6 exhibited the best solubility and toxicity properties. In the future, these lead compounds may then be subjected to bioactivity assays in vitro or in vivo for further evaluation of its therapeutic efficacy.

Keywords: 7, 8-diaminopelargonic acid aminotransferase, BioA, pharmacophore, molecular docking, ADMET, TOPKAT

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Authors: Bui Phuong Linh, Yuki Sakakibara, Ryuto Tanaka, Elizabeth H. Pigney, Taishi Hashiguchi

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Non-alcoholic steatohepatitis (NASH) is a chronic liver disease, often associated with type II diabetes, which sometimes progresses to more serious conditions such as liver fibrosis and hepatocellular carcinoma (HCC). NASH has become an important health problem worldwide, buttherapeutic agents for NASH have not yet been approved, and animal models with high clinical correlation are required. TheSTAM™ mouse shows the same pathological progression as human NASH patients and has been widely used for both drug efficacy and basic research, such as lipid profiling and gut microbiota research. In this study, we analyzed the RNA-seq data of STAM™mice at each pathological stage (steatosis, steatohepatitis, liver fibrosis, and HCC) and examined the clinical correlation at the genetic level. NASH was induced in male mice by a single subcutaneous injection of 200 µg streptozotocin solution 2 days after birth and feeding with high fat dietafter 4 weeks of age. The mice were sacrificed and livers collected at 6, 8, 10, 12, 16, and 20 weeks of age. For liver samples, the left lateral lobe was snap frozen in liquid nitrogen and stored at -80˚C for RNA-seq analysis. Total RNA of the cells was isolated using RNeasy mini kit. The gene expression of the canonical pathways in NASH progression from steatosis to hepatocellular carcinoma were analyzed, such as immune system process, oxidation-reduction process, lipid metabolic process. Moreover, since it has been reported that genetic traits are involved in the development of NASH-HCC, we next analyzed the genetic mutations in the STAM™mice. The number of individuals showing mutations in Mtorinvolved in Insulin signaling increases as the disease progresses, especially in the liver cancer phase. These results indicated a clinical correlation of gene profiles in the STAM™mouse.

Keywords: steatosis, non-alcoholic steatohepatitis, fibrosis, hepatocellular carcinoma, RNA-seq

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Authors: Ana C. Ramos Valdivia, Ileana Vera-Reyes, Ariana A. Huerta-Heredia

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The conditions of biotic and abiotic stress in plants can lead to the generation of high amounts of reactive oxygen species (ROS), which leads through a signaling cascade and second messengers to different antioxidant defense responses including the production of secondary metabolites. A limited number of species of plants like Uncaria tomentosa (cat claw) typical of the Amazon region produce monoterpenoid oxindole alkaloids (MOA) such as isopteropodine, mitraphylline, rhynchophylline and its isomers. Moreover, in cultivated roots, the glucoindole alkaloid 3α-dihydrocadambine (DHC) is also accumulated. Several studies have demonstrated that MAO has antioxidant properties and possess important pharmacological activities such as antitumor and immunostimulant while DHC, has hypotensive and hypolipidemic effects. In order the study the regulatory concerns operating in MAO production, the links between oxidative stress and antioxidant alkaloid production in U. tomentosa root cultures were examined. Different amount of hydrogen peroxide between 0.2 -1.0 mM was added to 12 days old roots cultures showing that, this substance had a differential effect on the production of DHC and MOA whereas the viability remained in 80% after six days. Addition of 0.2 mM hydrogen peroxide increased approximately 65% MAO and DHC production (0,540 ± 0.018 and 0.618 ± 0.029 mg per g dry weight, respectively) relative to the control. On contrast, after the addition of 0.6 mM and 1 mM hydrogen peroxide, DHC accumulation into the roots gradually decreased to 53% and 93% respectively, without changes in MAO concentration, which was in relation to a twice increase of the intracellular hydrogen peroxide content. On the other hand, concentrations of DHC (0.1, 0.5 and 1.0 mM in methanol) demonstrated free-radical scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical. The calculated IC50 for all tested concentrations was 0.180 mg per ml (0.33 mM) while the calculated TE50 was 276 minutes. Our results suggest that U. tomentosa root cultures both MAO and DHC have antioxidant capacities and respond to oxidative stress with a stimulation of their production; however, in presence of a higher concentration of ROS into the roots, DHC could be oxidized.

Keywords: monoterpenoid indole alkaloid, oxidative stress, root cultures, uncaria tomentosa

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Authors: B. Karabuluter, O. Karaduman

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Traffic management and traffic planning are important issues, especially in big cities. Due to the increase of personal vehicles and the physical constraints of urban roads, the problem of transportation especially in crowded cities over time is revealed. This situation reduces the living standards, and it can put human life at risk because the vehicles such as ambulance, fire department are prevented from reaching their targets. Even if the city planners take these problems into account, emergency planning and traffic management are needed to avoid cases such as traffic congestion, intersections, traffic jams caused by traffic accidents or roadworks. In this study, in smart traffic management issues, proposed solutions using intelligent vehicles acting in cooperation with urban roads are examined. Traffic management is becoming more difficult due to factors such as fatigue, carelessness, sleeplessness, social behavior patterns, and lack of education. However, autonomous vehicles, which remove the problems caused by human weaknesses by providing driving control, are increasing the success of practicing the algorithms developed in city traffic management. Such intelligent vehicles have become an important solution in urban life by using 'swarm intelligence' algorithms and cooperative driving methods to provide traffic flow, prevent traffic accidents, and increase living standards. In this study, studies conducted in this area have been dealt with in terms of traffic jam, intersections, regulation of traffic flow, signaling, prevention of traffic accidents, cooperation and communication techniques of vehicles, fleet management, transportation of emergency vehicles. From these concepts, some taxonomies were made out of the way. This work helps to develop new solutions and algorithms for cities where intelligent vehicles that can perform cooperative driving can take place, and at the same time emphasize the trend in this area.

Keywords: intelligent traffic management, cooperative driving, smart driving, urban road, swarm intelligence, connected vehicles

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Authors: Yaron Katz

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The investigation of immigrants' electoral choices has remained relatively uncharted territory despite the fact that numerous nations extend political rights to their expatriates. This paper centers its attention on the matter of public trust in democracy, with a focus on the intricacies of Israeli politics as a divided system. It delves into the potential implications of political and social transformations stemming from the involvement of expatriate voters in elections taking place in their country of origin. In doing so, the article endeavors to explore a pathway for resolving a persistent challenge facing the stability of the Israeli political landscape over the past decade: the difficulty in forming a resilient government that genuinely represents the majority of voters. An examination is conducted into the role played by a demographic with the capacity to exert significant influence on election outcomes, namely, individuals residing outside of Israel. The objective of this research is to delve into this subject, dissecting social developments and political prospects that may shape the country's trajectory in the coming decades. This inquiry is especially pertinent given the extensive engagement of migrants in Israeli politics and the link between Israelis living abroad and their home country. Nevertheless, the study's findings reveal that while former citizens exhibit extensive involvement in Israeli politics and are cognizant of the potential consequences of permitting them to participate in elections, they maintain steadfastly unfavorable views regarding the inclusion of Israelis living overseas in their home country's electoral processes.

Keywords: trust, globalization, policy, democracy

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Authors: Chien Y. Lin, Jung Y. Huang, Leu-Wei Lo

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A growing body of data reveals that the membrane cholesterol molecules can alter the signaling pathways of living cells. However, the understanding about how membrane cholesterol modulates receptor proteins is still lacking. Single-molecule tracking can effectively probe into the microscopic environments and thermal fluctuations of receptor proteins in a living cell. In this study we applies single-molecule optical tracking on ligand-induced dimerization process of EGFRs in the plasma membranes of two cancer cell lines (HeLa and A431) and one normal endothelial cell line (MCF12A). We tracked individual EGFR and dual receptors, diffusing in a correlated manner in the plasma membranes of live cells. We developed an energetic model by integrating the generalized Langevin equation with the Cahn-Hilliard equation to help extracting important information from single-molecule trajectories. From the study, we discovered that ligand-bound EGFRs move from non-raft areas into lipid raft domains. This ligand-induced motion is a common behavior in both cancer and normal cells. By manipulating the total amount of membrane cholesterol with methyl-β-cyclodextrin and the local concentration of membrane cholesterol with nystatin, we further found that the amount of cholesterol can affect the stability of EGFR dimers. The EGFR dimers in the plasma membrane of normal cells are more sensitive to the local concentration changes of cholesterol than EGFR dimers in the cancer cells. Our method successfully captures dynamic interactions of receptors at the single-molecule level and provides insight into the functional architecture of both the diffusing EGFR molecules and their local cellular environment.

Keywords: membrane proteins, single-molecule tracking, Cahn-Hilliard equation, EGFR dimers

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Authors: Jia Zhang, Fengmei Yao, Yanjing Tan

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The accurate estimation of crop yield is of great importance for the food security. In this study, a process-based mechanism model was modified to estimate yield of C4 crop by modifying the carbon metabolic pathway in the photosynthesis sub-module of the RS-P-YEC (Remote-Sensing-Photosynthesis-Yield estimation for Crops) model. The yield was calculated by multiplying net primary productivity (NPP) and the harvest index (HI) derived from the ratio of grain to stalk yield. The modified RS-P-YEC model was used to simulate maize yield in the Northeast China Plain during the period 2002-2011. The statistical data of maize yield from study area was used to validate the simulated results at county-level. The results showed that the Pearson correlation coefficient (R) was 0.827 (P < 0.01) between the simulated yield and the statistical data, and the root mean square error (RMSE) was 712 kg/ha with a relative error (RE) of 9.3%. From 2002-2011, the yield of maize planting zone in the Northeast China Plain was increasing with smaller coefficient of variation (CV). The spatial pattern of simulated maize yield was consistent with the actual distribution in the Northeast China Plain, with an increasing trend from the northeast to the southwest. Hence the results demonstrated that the modified process-based model coupled with remote sensing data was suitable for yield prediction of maize in the Northeast China Plain at the spatial scale.

Keywords: process-based model, C4 crop, maize yield, remote sensing, Northeast China Plain

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Authors: Soujanya Pasumarthi

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Inverse docking is a relatively new technique that has been used to identify potential receptor targets of small molecules. Our docking software package MDock is well suited for such an application as it is both computationally efficient, yet simultaneously shows adequate results in binding affinity predictions and enrichment tests. As a validation study, we present the first stage results of an inverse-docking study which seeks to identify potential direct targets of PRIMA-1. PRIMA-1 is well known for its ability to restore mutant p53's tumor suppressor function, leading to apoptosis in several types of cancer cells. For this reason, we believe that potential direct targets of PRIMA-1 identified in silico should be experimentally screened for their ability to inhibitcancer cell growth. The highest-ranked human protein of our PRIMA-1 docking results is oxidosqualene cyclase (OSC), which is part of the cholesterol synthetic pathway. The results of two followup experiments which treat OSC as a possible anti-cancer target are promising. We show that both PRIMA-1 and Ro 48-8071, a known potent OSC inhibitor, significantly reduce theviability of BT-474 breast cancer cells relative to normal mammary cells. In addition, like PRIMA-1, we find that Ro 48-8071 results in increased binding of mutant p53 to DNA in BT- 474cells (which highly express p53). For the first time, Ro 48-8071 is shown as a potent agent in killing human breast cancer cells. The potential of OSC as a new target for developing anticancer therapies is worth further investigation.

Keywords: inverse docking, in silico screening, protein-ligand interactions, molecular docking

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Authors: Itti Bist, Snehasis Bhakta, Di Jiang, Tia E. Keyes, Aaron Martin, Robert J. Forster, James F. Rusling

Abstract:

DNA damage from metabolites of lipophilic drugs and pollutants, generated by enzymes, represents a major toxicity pathway in humans. These metabolites can react with DNA to form either 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxodG), which is the oxidative product of DNA or covalent DNA adducts, both of which are genotoxic and hence considered important biomarkers to detect cancer in humans. Therefore, detecting reactions of metabolites with DNA is an effective approach for the safety assessment of new chemicals and drugs. Here we describe a novel electrochemiluminescent (ECL) sensor array which can detect DNA oxidation and chemical DNA damage in a single array, facilitating a more accurate diagnostic tool for genotoxicity screening. Layer-by-layer assembly of DNA and enzyme are assembled on the pyrolytic graphite array which is housed in a microfluidic device for sequential detection of two type of the DNA damages. Multiple enzyme reactions are run on test compounds using the array, generating toxic metabolites in situ. These metabolites react with DNA in the films to cause DNA oxidation and chemical DNA damage which are detected by ECL generating osmium compound and ruthenium polymer, respectively. The method is further validated by the formation of 8-oxodG and DNA adduct using similar films of DNA/enzyme on magnetic bead biocolloid reactors, hydrolyzing the DNA, and analyzing by liquid chromatography-mass spectrometry (LC-MS). Hence, this combined DNA/enzyme array/LC-MS approach can efficiently explore metabolic genotoxic pathways for drugs and environmental chemicals.

Keywords: biosensor, electrochemiluminescence, DNA damage, microfluidic array

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Authors: Sonia Hamiche, Naima Bouzidi, Mohamed Reda Zahi, Yasmina Daghbouche, Abdelmalek Badis, Mohamed El Hattab

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This study was carried out on the brown alga Zonaria tourfortii harvested on the central coast of Algeria. The chemical study enabled the characterization of phenolic compounds, mainly acyl phloroglucinol and chromone metabolites. The study isolated a significant quantity of all-cis-5,8,11,14,17 eicosapentanoic acid (EPA). Based on a literature review, we have proposed a biosynthetic pathway leading from EPA to phenolic metabolites. Bacterial screening from the algal surface led to isolate 30 bacterial strains, including 26 Gram+ containing the Staphylococcus and Bacillus genus, and 4 Gram- containing the Acinetobacter and Enterobacteracea genus. In terms of activity profiles, strain S13 (identified as Bacillus amyloliquefaciens based on 16S rRNA technique) proved highly interesting inhibitory activities against target germs, as well as its production of diffusible and volatile compounds. Bacterial cells from the B. amyloliquefaciens S13 strain were used to recover a volatile fraction. Analysis was carried out by gas chromatography-mass spectrometry. The main volatile compounds identified were: 13-epi-manoyl oxide (29.39%), manool (17.39%), 15,16-dinorlabd-8(20)-en-13-one (13.17%), labda-8(17),13Z-dien-15-ol (9. 51%) and 3-acetoxy-13 epimanoyl oxide (5.26%) belonging to the labdane class of diterpenes, the latter having never been described in the category of microbial volatile organic compounds. Ecological aspects were discussed.

Keywords: chemical analysis, acylphloroglucinols, phenolic compounds, microbial volatiles, Zonaria tournefortii

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Authors: Mario Jose Paillacho Silva, José Ángel Pérez López

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This article delves into the critical role of circular economy principles in unlocking sustainable growth and addressing environmental inequalities in emerging markets. Circular economy practices, rooted in regenerative systems and resource conservation, offer a transformative pathway for dynamic economies to achieve prosperity while minimizing environmental impact. The article comprehensively explores the understanding of the circular economy in emerging markets, emphasizing its economic benefits, social implications, and environmental advantages. It highlights key challenges and opportunities faced by these markets and emphasizes the crucial role of governments in creating supportive policy frameworks. It emphasizes how circular economy practices empower local communities and promote social inclusion and equality. Furthermore, the article underscores how the adoption of circular economy practices can mitigate waste, pollution, and resource scarcity, thus contributing to climate change mitigation and adaptation. Integrating circular economy principles with the United Nations' sustainable development goals (SDGs), the article showcases the potential of circularity in fostering responsible consumption and production, sustainable economic growth, and environmental protection. Overall, the article advocates for cross-sector collaboration and knowledge sharing to overcome barriers and scale circular economy practices in emerging markets, ultimately leading to a more equitable, prosperous, and environmentally sustainable future.

Keywords: circular economy, sustainability, emerging markets, circularity

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Authors: X. Li, J. Sundquist, C. Sjöstedt, M. Winkleby, K. S. Kendler, K. Sundquist

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Aims: This study examines the association between the incidence of drug abuse (DA) and linking (communal) social capital, a theoretical concept describing the amount of trust between individuals and societal institutions. Methods: We present results from an 8-year population-based cohort study that followed all residents in Sweden, aged 15-44, from 2003 through 2010, for a total of 1,700,896 men and 1,642,798 women. Social capital was conceptualized as the proportion of people in a geographically defined neighborhood who voted in local government elections. Multilevel logistic regression was used to estimate odds ratios (ORs) and between-neighborhood variance. Results: We found robust associations between linking social capital (scored as a three level variable) and DA in men and women. For men, the OR for DA in the crude model was 2.11 [95% confidence interval (CI) 2.02-2.21] for those living in areas with the lowest vs. highest level of social capital. After accounting for neighborhood-level deprivation, the OR fell to 1.59 (1.51-1-68), indicating that neighborhood deprivation lies in the pathway between linking social capital and DA. The ORs remained significant after accounting for age, sex, family income, marital status, country of birth, education level, and region of residence, and after further accounting for comorbidities and family history of comorbidities and family history of DA. For women, the OR decreased from 2.15 (2.03-2.27) in the crude model to 1.31 (1.22-1.40) in the final model, adjusted for multiple neighborhood-level and individual-level variables. Conclusions: Our study suggests that low linking social capital may have important independent effects on DA.

Keywords: drug abuse, social linking capital, environment, family

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Authors: Hui-Hsin Huang, Sheng-Tung Huang, Chi-Ming Lee, Chiao-Han Yen, Chun-Mao Lin

Abstract:

At initiation stage, there are no symptoms at initiation stage; however, at late stage, patients suffer symptoms as soon as ovarian cancer metastasis. Moreover, ovarian cancer cells are resistant to some anti-ovarian cancer drugs in clinical. Thus, it is very important to find an effective treatment for resistant ovarian cancer. Anthraquinone derivatives are able to induce DNA damage and lead to cell apoptosis, so several derivatives have been used for clinical application. Therefore, to explore more effective anti-ovarian cancer drugs, this study investigates the mechanism of three new anthraquinone compounds bearing different functional groups to camptothecin-resistance ovarian cell line A2780R2000. Cell viability was determined by MTT assay after treating A2780R2000 with the three new anthraquinone compounds. The results indicated that IC50 values are 33.44μM (Compound I), 25.77μM (Compound II) and 24.59μM (Compound III). Next, through cell cycle analysis, the results demonstrated that three new anthraquinone compounds not only induced A2780R2000 cell cycle arrest at early stage but also apoptosis at late stage. Besides, through apoptosis assay, the results indicated new anthraquinone compound induced apoptosis at late stage. Furthermore, the results of western blot show that the three new anthraquinone compounds lead to A2780R2000 apoptosis through intrinsic pathway. Theses results suggested that three new anthraquinone compounds may be potential new drugs for clinical cancer treatment in the future.

Keywords: anthraquinone, camptothecin, resistance, ovarian cancer

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Authors: Xinyuan Zou, Qihui Tang, Shujian Wang, Yulin Huang, Jie Gui, Xiangping Liu, Gang Liu, Yanqiang Tao

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Childhood trauma can have a long-lasting influence on individuals and contribute to mental disorders, including depression and anxiety. The current study aimed to explore the symptomatic and developmental patterns of depression, anxiety, and stress among adolescents who have suffered from childhood trauma. A total of 3,598 college students (female = 1,617 (44.94%), Mean Age = 19.68, SD Age = 1.35) in China completed the Childhood Trauma Questionnaire (CTQ) and the Depression, Anxiety, and Stress Scales (DASS-21), and 2,337 participants met the selection standard based on the cut-off scores of the CTQ. The symptomatic network and directed acyclic graph (DAG) network approaches were used. The results revealed that males reported experiencing significantly more physical abuse, physical neglect, emotional neglect, and sexual abuse compared to females. However, females scored significantly higher than males on all items of DASS-21, except for “Worthless”. No significant difference between the two genders was observed in the network structure and global strength. Meanwhile, among all participants, “Down-hearted” and “Agitated” appeared to be the most interconnected symptoms, the bridge symptoms in the symptom network, as well as the most vital symptoms in the DAG network. Apart from that, “No-relax” also served as the most prominent symptom in the DAG network. The results suggested that intervention targeted at assisting adolescents in developing more adaptive coping strategies with stress and regulating emotion could benefit the alleviation of comorbid depression, anxiety, and stress.

Keywords: symptom network, childhood trauma, depression, anxiety, stress

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Authors: Zerrin Orbak, Busra Demir

Abstract:

Osteopetrosis is a rare genetic disease characterized by impaired bone resorption and increased bone sclerosis. Clinical presentation is very different in osteopetrosis. It can be asymptomatic or can be seen with typical symptoms. Here, a case of osteopetrosis was presented when evaluated for nystagmus. She was 10 months old. Parents were second-degree relatives. On physical examination, pigeon chest deformity and horizontal nystagmus were observed. There was a failure of thrive but no fracture. The cardiovascular examination was normal. Cranial, vertebral and long bone roentgenograms revealed characteristic deformities of osteopetrosis and diffuse sclerosis. The diagnosis was confirmed by genetic testing. A Homozygous mutation was detected in the TNFRSF11A gene (c.508A>G p.(Arg170Gly)). RANKL is encoded by the tumor necrosis factor ligand superfamily member 11 (TNFSF11) gene, and the binding to its receptor RANK, encoded by the TNFRSF11A gene, determines the activation of the downstream pathway that drives osteoclast differentiation and activation (51). The complete absence of osteoclasts is the key feature of the osteoclast-poor form of osteopetrosis (46). Patients are characterized by the absence of TRAP-positive osteoclasts in bone biopsies. The osteoclast-poor subtype of osteopetrosis caused by mutations in TNFSF11 gene is ultra-rare in humans. Clinical presentation is usually severe, with onset in early infancy or in fetal life. But here, a case was presented with horizontal nystagmus. A case presented with horizontal nystagmus, which was evaluated by neurology and diagnosed incidentally, was shared.

Keywords: osteopetrosis, nystagmus, bone, osteoclast-poor

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Authors: Cristina Costa-Lobo, Priscila Martins, Silvia Amado Cordeiro, Ana Campina

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Behavior directed toward high levels of sports performance and excellence implies task-focused processes, processes of cognitive and emotional regulation. This research aims to understand if subjective well-being, emotional regulation, and motivational orientation influence the performance of competitive athletes. The sample of this study is a non-probabilistic convenience sample, consisting of 50 male athletes, aged 14 to 15 years, who belong to training teams integrated in the pedagogical department of a sports club in the North of Portugal. In terms of performance, the distinction between team A and team B is due to the championships in which the respective athletes participate. Team A participates in national championships where the levels of demand and challenge are more pronounced and the team B only participates in championships at the district level. Was verified the internal consistency of the subjective happiness scale, the emotional regulation scale, and the motivational orientation questionnaire. SPSS, version 22.0, was used in the data treatment. When comparing the dimensions of emotional regulation with performance, it can be seen that athletes with lower sports scores have higher levels of emotional control and emotional self-awareness. As far as situational responsiveness is concerned, only the emotional self-control dimension and the emotional self-awareness dimension show an influence on the income, although, contrary to what would be expected, they appear to be associated with lower incomes. When comparing the motivational orientation with the athletic performance, it is verified that the athletes with the highest performance present an ego-oriented motivation, evidencing the athletes with a lower performance athletic tendency towards the task orientation. Only the ego-oriented dimension seems to be associated with high sport performance. The motivational orientation for the ego and the dimensions emotional control and emotional self-awareness are presented in this study as having influence on sports performance. Following these studies that have shown concern with the characterization of the best athletes and the promotion of higher sports performances, this work contributes to the signaling of psychological variables associated with high sports income.

Keywords: subjective well-being, emotional regulation, motivational orientation, sports performance

Procedia PDF Downloads 255