Search results for: tight binding pproch

Authors: Axel Prettl

Abstract:

This paper provides an overview of the different CFC rule settings in the OECD and 22 additional countries for the years 2004 to 2014 and compares them. In order to do so, it gives a summary of law amendments for every country, provides a comparison and afterwards all CFC rules are rated in their ”power of anti-avoidance” over time. For that rating of CFC rules, the largest common denominator of rule characteristics is used to keep it as abstract as necessary and possible. The paper points out that the CFC rules in the considered countries are very different in their specifications and they reach from very strict to very low binding. All in all these rules get more and more common and important; more countries implement a CFC legislation and the strictness of most of them rises over time.

Keywords: CFC rules, international taxation, corporate taxation, country comparison

Procedia PDF Downloads 307

Authors: E. Kilicay, Z. Karahaliloglu, B. Hazer, E. B. Denkbas

Abstract:

In this study, we have prepared concanavaline A (ConA) functionalized curcumin (CUR) loaded PHBHHx (poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)) nanoparticles as a novel and efficient drug delivery system. CUR is a promising anticancer agent for various cancer types. The aim of this study was to evaluate therapeutic potential of curcumin loaded PHBHHx nanoparticles (CUR-NPs) and concanavaline A conjugated curcumin loaded NPs (ConA-CUR NPs) for ovarian cancer treatment. ConA was covalently connected to the carboxylic group of nanoparticles by EDC/NHS activation method. In the ligand attachment experiment, the binding capacity of ConA on the surface of NPs was found about 90%. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) analysis showed that the prepared nanoparticles were smooth and spherical in shape. The size and zeta potential of prepared NPs were about 228±5 nm and −21.3 mV respectively. ConA-CUR NPs were characterized by FT-IR spectroscopy which confirmed the existence of CUR and ConA in the nanoparticles. The entrapment and loading efficiencies of different polymer/drug weight ratios, 1/0.125 PHBHHx/CUR= 1.25CUR-NPs; 1/0.25 PHBHHx/CUR= 2.5CUR-NPs; 1/0.5 PHBHHx/CUR= 5CUR-NPs, ConA-1.25CUR NPs, ConA-2.5CUR NPs and ConA-5CUR NPs were found to be ≈ 68%-16.8%; 55%-17.7 %; 45%-33.6%; 70%-15.7%; 60%-17%; 51%-30.2% respectively. In vitro drug release showed that the sustained release of curcumin was observed from CUR-NPs and ConA-CUR NPs over a period of 19 days. After binding of ConA, the release rate was slightly increased due to the migration of curcumin to the surface of the nanoparticles and the matrix integrities was decreased because of the conjugation reaction. This functionalized nanoparticles demonstrated high drug loading capacity, sustained drug release profile, and high and long term anticancer efficacy in human cancer cell lines. Anticancer activity of ConA-CUR NPs was proved by MTT assay and reconfirmed by apoptosis and necrosis assay. The anticancer activity of ConA-CUR NPs was measured in ovarian cancer cells (SKOV-3) and the results revealed that the ConA-CUR NPs had better tumor cells decline activity than free curcumin. The nacked nanoparticles have no cytotoxicity against human ovarian carcinoma cells. Thus the developed functionalized nanoformulation could be a promising candidate in cancer therapy.

Keywords: curcumin, curcumin-PHBHHx nanoparticles, concanavalin A, concanavalin A-curcumin PHBHHx nanoparticles, PHBHHx nanoparticles, ovarian cancer cell

Procedia PDF Downloads 395

Authors: Jihane Abdessadak, Hicham Achelhi, Kamal Reklaoui

Abstract:

For any company or organization, change must be natural and binding in order to evolve its business, protect its durability and remain competitive. "Adapt or disappear". But how often managers, leaders or employees develop astonishing ideas that could improve several aspects of the organization and the feedback is less that encouraging and people give unrealistic judgments just to escape change. In this paper, we are going to discuss what we do know about change and resistance to change and what we can do to tame this phenomenon and, above all, the main steps that can follow an idea man in the delicate and decisive implementation of innovations.

Keywords: innovation, change, resistance to change/innovation, barriers to innovation, levers of innovation

Procedia PDF Downloads 292

Authors: Solene Masloh, Anne Chevrel, Maxime Culot, Leonardo Scapozza, Magali Zeisser-Labouebe

Abstract:

The limited stability of clinically proven therapeutic antibodies limits their administration by the parenteral route. However, oral administration remains the best alternative as it is the most convenient and less invasive one. Obtaining a targeted treatment based on biologics, which can be orally administered, would, therefore, be an ideal situation to improve patient adherence and compliance. Nevertheless, the delivery of macromolecules through the intestine remains challenging because of their sensitivity to the harsh conditions of the gastrointestinal tract and their low permeability across the intestinal mucosa. To address this challenge, this project aims to demonstrate that targeting receptor-mediated endocytosis followed by transcytosis could maximize the intestinal uptake and transport of large molecules, such as Nanofitins. These affinity proteins of 7 kDa with binding properties similar to antibodies have already demonstrated retained stability in the digestive tract and local efficiency. However, their size does not allow passive diffusion through the intestinal barrier. Nanofitins having a controlled affinity for membrane receptors involved in the transcytosis mechanism used naturally for the transport of large molecules in humans were generated. Proteins were expressed using ribosome display and selected based on affinity to the targeted receptor and other characteristics. Their uptake and transport ex vivo across viable porcine intestines were investigated using an Ussing chambers system. In this paper, we will report the results achieved while addressing the different challenges linked to this study. To validate the ex vivo model, first, we proved the presence of the receptors targeted in humans on the porcine intestine. Then, after the identification of an optimal way of detection of Nanofitins, transport experiments were performed on porcine intestines with viability followed during the time of the experiment. The results, showing that the physiological process of transcytosis is capable of being triggered by the binding of Nanofitins on their target, will be reported here. In conclusion, the results show that Nanofitins can be transported across the intestinal barrier by triggering the receptor-mediated transcytosis and that the ex vivo model is an interesting technique to assess biologics absorption through the intestine.

Keywords: ex-vivo, Nanofitins, oral administration, transcytosis

Procedia PDF Downloads 174

Authors: Astha Sinha, Anjali Kanagali

Abstract:

The United Kingdom’s withdrawal from the European Union, also termed as “Brexit,” took place on June 23, 2016 and immediately had global repercussions on the stock markets of the world. It is however expected to have a greater impact on the Banking sector in the UK. There is a two-fold effect on the earnings of banks which is being expected. First is of the trading activity and investment banking businesses being hit due to global weakness in financial markets. Second is that the banks having a large presence in the European Union will have to restructure their operations in order to cover other European countries as well increase their operating costs. As per the analysis, banks are expected to face rate cuts, bad loans, and tight liquidity. The directives in the Brexit negotiations on the Markets in Financial Instruments Directive (MiFID) will be a major decision to be taken for the Banking sector. New regulations will be required since most of the regulations governing the financial services industry allowing for the cross-border transactions were at the EU level. This paper aims to analyze the effect of Brexit on the UK Banking sector and changes in regulations that are expected due to the same. It shall also lay down the lessons learnt from the 2008 financial crisis and draw a parallel in terms of potential areas to be focused on for revival of the financial sector of Britain.

Keywords: Brexit, Brexit impact on UK, impact of Brexit on banking, impact of Brexit on financial services

Procedia PDF Downloads 398

Authors: Sweta Pandey, Samridhi Dhyani, Susmita Chaudhuri

Abstract:

Klebsiella pneumoniae causes a wide range of infections, including urinary tract infections, sepsis, bacteremia, pneumonia, and liver abscesses. The emergence of multi-drug resistance in this bacterium led to a major setback for clinical management. WHO also endorsed a need for finding alternative therapy to antibiotics for the treatment of these infections. Development of vaccines and passive antibody therapy has been proven as a potent alternative to antibiotics in the case of MDR, XDR, and PDR Klebsiella infections. Siderophore receptors have been demonstrated to be overexpressed for the internalization of iron siderophore complexes during infections in most Gram-negative bacteria. For the present study, immune response to siderophore receptors to establish this protein as a potential immunogen for the development of therapeutic leads was explored. Clinical strains of Klebsiella pneumoniae were grown in iron-deficient conditions, and the iron-regulated outer membrane proteins were extracted and characterized through mass spectrometry for specific identification. The gene for identified protein was cloned in pET- 28a vector and expressed in E. coli. The native protein and the recombinant protein were isolated and purified and used as antigens for the generation of immune response in BALB/c mice. The native protein of Klebsiella pneumoniae grown in iron-deficient conditions was identified as FepA (Ferrienterobactin receptor) and other siderophore receptors. This 80 kDa protein generated an immune response in BALB/c mice. The antiserum from mice after subsequent booster doses was collected and showed binding with FepA protein in western blot and phagocytic uptake of the K. pneumoniae in the presence antiserum from immunized mice also observed from the animal studies after bacterial challenge post immunisation in mice have shown bacterial clearance. The antiserum from mice showed binding and clearance of the Klebsiella pneumoniae bacteria in vitro and in vivo. These antigens used for generating an active immune response in mice can further be used for therapeutic monoclonal antibody development against Klebsiella pneumoniae infections.

Keywords: antiserum, FepA, Klebsiella pneumoniae, multi drug resistance, siderophore receptor

Procedia PDF Downloads 97

Authors: Basmah Arshad

Abstract:

In the aftermath of the Cambodian genocide, many refugees resettled in America. They carved out a distinctively Cambodian-American space in California with donut shops, establishing a tight-knit community that worked to achieve ‘the American dream’. Urged by traumatic memories of the genocide and American society directly encouraging (if not demanding) cultural assimilation, these refugees and successive generations continuously worked to re-identify themselves as Americans. Artist Phung Huynh grew up in this context of family-owned donut shops and the frantic scramble for stability and security. It is this community that she depicts in her artwork series from the late 2010s, ‘Khmerican: Drawing on Pink Donut Boxes’. Huynh's artwork challenges dominant Western narratives about the Cambodian genocide by pushing forward images of resilience, resistance, and joy, while also allowing for a discussion about issues of assimilation, identity, and nostalgia in the Cambodian-American community. It also provokes deeply relevant questions about how refugees and immigrants deliberately appropriate elements of the Americana (eg, donuts) to assimilate and re-fashion their identity as a tactic for financial stability and social survival.

Keywords: Cambodian diaspora, cultural identity, assimilation, food, artwork

Procedia PDF Downloads 58

Authors: Iman Farasat, Howard M. Salis

Abstract:

The CRISPR/Cas9 system has revolutionized genome engineering by enabling site-directed and high-throughput genome editing, genome insertion, and gene knockdowns in several species, including bacteria, yeast, flies, worms, and human cell lines. This technology has the potential to enable human gene therapy to treat genetic diseases and cancer at the molecular level; however, the current CRISPR/Cas9 system suffers from seemingly sporadic off-target genome mutagenesis that prevents its use in gene therapy. A comprehensive mechanistic model that explains how the CRISPR/Cas9 functions would enable the rational design of the guide-RNAs responsible for target site selection while minimizing unexpected genome mutagenesis. Here, we present the first quantitative model of the CRISPR/Cas9 genome mutagenesis system that predicts how guide-RNA sequences (crRNAs) control target site selection and cleavage activity. We used statistical thermodynamics and law of mass action to develop a five-step biophysical model of cas9 cleavage, and examined it in vivo and in vitro. To predict a crRNA's binding specificities and cleavage rates, we then compiled a nearest neighbor (NN) energy model that accounts for all possible base pairings and mismatches between the crRNA and the possible genomic DNA sites. These calculations correctly predicted crRNA specificity across 5518 sites. Our analysis reveals that cas9 activity and specificity are anti-correlated, and, the trade-off between them is the determining factor in performing an RNA-mediated cleavage with minimal off-targets. To find an optimal solution, we first created a scheme of safe-design criteria for Cas9 target selection by systematic analysis of available high throughput measurements. We then used our biophysical model to determine the optimal Cas9 expression levels and timing that maximizes on-target cleavage and minimizes off-target activity. We successfully applied this approach in bacterial and mammalian cell lines to reduce off-target activity to near background mutagenesis level while maintaining high on-target cleavage rate.

Keywords: biophysical model, CRISPR, Cas9, genome editing

Procedia PDF Downloads 399

Authors: Arkaprabha Bhattacharyya, Makarand Hastak

Abstract:

The COVID-19 pandemic is unprecedented in terms of its global reach and economic impacts. Historically, investment in infrastructure development projects has been touted to boost the economic growth of a nation. The State and Local governments responsible for delivering infrastructure assets work under tight budgets. Therefore, it is important to understand which infrastructure projects have the highest potential of boosting economic growth in the post-pandemic era. This paper presents relationships between infrastructure projects and economic growth. Statistical relationships between investment in different types of infrastructure projects (transit, water and wastewater, highways, power, manufacturing etc.) and indicators of economic growth are presented using historic data between 2002 and 2020 from the U.S. Census Bureau and U.S. Bureau of Economic Analysis (BEA). The outcome of the paper is the comparison of statistical correlations between investment in different types of infrastructure projects and indicators of economic growth. The comparison of the statistical correlations is useful in ranking the types of infrastructure projects based on their ability to influence economic prosperity. Therefore, investment in the infrastructures with the higher rank will have a better chance of boosting the economic growth. Once, the ranks are derived, they can be used by the decision-makers in infrastructure investment related decision-making process.

Keywords: economic growth, infrastructure development, infrastructure projects, strategic investment

Procedia PDF Downloads 167

Authors: Sylwia Wiewiorowska, Zbigniew Muskalski

Abstract:

The article presents part of research on the development of nickel plated welding wire production technology, whose application will enable the elimination of the flaws of currently manufactured welding wires. The nickel plated welding wire will be distinguished by high quality, because the Ni layer which is deposited electrochemically onto it from acid baths is characterized by very good adhesion to the steel wire surface, while the ductile nickel well deforms plastically in the drawing process and the adhesion of the Ni layer increases in the drawing process due to the occurring process of diffusion between the Ni and the steel. The Ni layer obtained in the proposed technology, despite a smaller thickness than when the wire is coated with copper, is continuous and tight, thus ensuring high corrosion resistance, as well as unsusceptible to scaling, which should provide a product that meets requirements imposed by the market. The product will also reduce, to some extent, the amount of copper brought in to steel through recycling, while the wire coating nickel introduced to the weld in the welding process is expected, to a degree, to favorably influence its mechanical properties. The paper describes the tests of the process of nickel plating of f1.96 mm-diameter wires using various nickel plating baths with different process parameters.

Keywords: steel wire, properties, welding process, Ni layer

Procedia PDF Downloads 143

Authors: Iti Roychowdhury

Abstract:

India to the Colonial mind was a crazy quilt of multicoloured patchwork- a land of untold wealth and bejewelled maharajas, of snake charmers and tight rope walkers. India was also the land that offered unparalled game. Indeed Shikar (hunting) was de rigueur for the Raj experience. Tales of shootings and trophies were told and retold in clubs and in company. Foremost among the writers of this genre is Jim Corbett – tracker, hunter, writer, conservationist. Corbett is best known for the killing of man eating tigers and his best known books are Man eaters of Kumaon, The Temple Tiger, Man eating Leopard of Rudraprayag etc. The stories of Jim Corbett are stories of hunting, with no palpable design, no subtext of hegemony, or white man’s burden. The protagonists are the cats. Nevertheless from his writings emerge a vibrant picture of Indian villages, of men, women and children toiling for a livelihood under the constant shadow of the man eaters. Corbett shared a symbiotic relationship with the villagers. They needed him to kill the predators while Corbett needed the support of the locals as drum beaters, coolies and runners to accomplish his tasks. The aim of the present paper is to study the image of Indians in the writings of Jim Corbett and to examine them in the light of colonial perception of Indians.

Keywords: hegemony, orientalism, Shikar literature, White Man's Burden

Procedia PDF Downloads 275

Authors: Wayde Veldman, Ozlem T. Bishop, Igor Polikarpov

Abstract:

In bacteria, mono and disaccharides are phosphorylated during uptake into the cell via the widely used phosphoenolpyruvate (PEP)-dependent phosphotransferase transport system. As an initial step in the phosphorylated disaccharide metabolism pathway, certain glycoside hydrolase family 1 (GH1) enzymes play a crucial role in releasing phosphorylated and non-phosphorylated monosaccharides. However, structural determinants for the specificity of these enzymes still need to be clarified. GH1 enzymes are known to have a wide array of functions. According to the CAZy database, there are twenty-one different enzymatic activities in the GH1 family. Here, the structure and substrate specificity of a GH1 enzyme from Bacillus licheniformis, hereafter known as BlBglH, was investigated. The sequence of the enzyme BlBglH was compared to the sequences of other characterized GH1 enzymes using sequence alignment, sequence identity calculations, phylogenetic analysis, and motif discovery. Through these various analyses, BlBglH was found to have sequence features characteristic of the 6-phospho-β-glucosidase activity enzymes. Additionally, motif and structure comparisons of the three most commonly studied GH1 enzyme-activities revealed a shared loop amongst the different structures that consist of different sequence motifs – this loop is thought to guide specific substrates (depending on activity) towards the active-site. To further affirm BlBglH enzyme activity, molecular docking and molecular dynamics simulations were performed. Docking was carried out using 6-phospho-β-glucosidase enzyme-activity positive (p-Nitrophenyl-beta-D-glucoside-6-phosphate) and negative (p-Nitrophenyl-beta-D-galactoside-6-phosphate) control ligands, followed by 400 ns molecular dynamics simulations. The positive-control ligand maintained favourable interactions within the active site until the end of the simulation. The negative-control ligand was observed exiting the enzyme at 287 ns. Binding free energy calculations showed that the positive-control complex had a substantially more favourable binding energy compared to the negative-control complex. Jointly, the findings of this study suggest that the BlBglH enzyme possesses 6-phospho-β-glucosidase enzymatic activity.

Keywords: 6-P-β-glucosidase, glycoside hydrolase 1, molecular dynamics, sequence analysis, substrate specificity

Procedia PDF Downloads 127

Authors: Jimoh Yusuf Amuda

Abstract:

Human security is a great panacea for sustainable development of world societies. Today the whole globe cum human species is living in nightmares of insecurity. This is due to acts of terrorism by various terrorists’ organization worldwide. The situation is on the increase daily. The number of lives and properties lost to religious insurgency cannot be quantifiably analyzed. It is on this note that this paper examine the book haram menace in northern Nigerian vis-à-vis it’s threat to the existence of human lives. The methodology applied for this research is the multi-disciplinary approach, the use journal articles, news papers, magazines, oral interview. Field trips to areas of terrorist attack and the use of text books. The following recommendations were made base on the findings. First of all the Nigerian government should declare total war on the book haram terrorist, then secondly the source of armament coming to this terrorist should be blocked, thirdly the European world should also place an arms embargo on terrorist source arms demands, also security agencies-police, the military, immigration, customs, state security service should work hand-in-hand, in a security tight measures to reduce the penetration of insurgent into the society.

Keywords: human, insecurity, security, terrorism

Procedia PDF Downloads 335

Authors: K. L. Virupaksha Gupta

Abstract:

Ayurveda offers a holistic outlook regarding skin care. Most Initial step in Ayurveda is to identify the skin type and care accordingly which is highly personalized. Though dermatologically there are various skin type classifications such Baumann skin types (based on 4 parameters i) Oily Vs Dry ii) Sensitive Vs Resistant iii) Pigmented Vs Non-Pigmented iv) Wrinkled Vs Tight (Unwrinkled) etc but Skin typing in Ayurveda is mainly determined by the prakriti (constitution) of the individual as well as the status of Doshas (Humors) which are basically of 3 types – i.e Vata Pitta and Kapha,. Difference between them is mainly attributed to the qualities of each dosha (humor). All the above said skin types can be incorporated under these three types. The skin care modalities in each of the constitution vary greatly. Skin of an individual of Vata constitution would be lustreless, having rough texture and cracks due to dryness and thus should be given warm and unctuous therapies and oil massage for lubrication and natural moisturizers for hydration. Skin of an individual of Pitta constitution would look more vascular (pinkish), delicate and sensitive with a fair complexion, unctuous and tendency for wrinkles and greying of hair at an early age and hence should be given cooling and nurturing therapies and should avoid tanning treatments. Skin of an individual of kapha constitution will have oily skin, they are delicate and look beautiful and radiant and hence these individuals would require therapies to mainly combat oily skin. Hence, the skin typing and skin care in Ayurveda is highly rational and scientific.

Keywords: Ayurveda, dermatology, Dosha, skin types

Procedia PDF Downloads 402

Authors: Alan Luo, Hunter N. B. Moseley

Abstract:

Many macromolecular structure entries in the Protein Data Bank (PDB) have a range of regional (localized) quality issues, be it derived from x-ray crystallography, Nuclear Magnetic Resonance (NMR) spectroscopy, or other experimental approaches. However, most PDB entries are judged by global quality metrics like R-factor, R-free, and resolution for x-ray crystallography or backbone phi-psi distribution statistics and average restraint violations for NMR. Regional quality is often ignored when PDB entries are re-used for a variety of structurally based analyses. The binding of ligands, especially ligands involved in energy metabolism, is of particular interest in many structurally focused protein studies. Using a regional quality metric that provides chemically interpretable information from electron density maps, a significant number of outliers in regional structural quality was detected across x-ray crystallographic PDB entries for proteins bound to biochemically critical ligands. In this study, a series of analyses was performed to evaluate both specific and general potential factors that could promote these outliers. In particular, these potential factors were the minimum distance to a metal ion, the minimum distance to a crystal contact, and the isotropic atomic b-factor. To evaluate these potential factors, Fisher’s exact tests were performed, using regional quality criteria of outlier (top 1%, 2.5%, 5%, or 10%) versus non-outlier compared to a potential factor metric above versus below a certain outlier cutoff. The results revealed a consistent general effect from region-specific normalized b-factors but no specific effect from metal ion contact distances and only a very weak effect from crystal contact distance as compared to the b-factor results. These findings indicate that no single specific potential factor explains a majority of the outlier ligand-bound regions, implying that human error is likely as important as these other factors. Thus, all factors, including human error, should be considered when regions of low structural quality are detected. Also, the downstream re-use of protein structures for studying ligand-bound conformations should screen the regional quality of the binding sites. Doing so prevents misinterpretation due to the presence of structural uncertainty or flaws in regions of interest.

Keywords: biomacromolecular structure, coenzyme, electron density discrepancy analysis, x-ray crystallography

Procedia PDF Downloads 125

Authors: Yannick Willemin

Abstract:

Carbon fibre-reinforced plastic (CFRP) offers outstanding value. However, like all materials, CFRP also has its challenges. Many forming processes are largely manual and hard to automate, making it challenging to control repeatability and reproducibility (R&R); they generate significant scrap and are too slow for high-series production; fibre costs are relatively high and subject to supply and cost fluctuations; the supply chain is fragmented; many forms of CFRP are not recyclable, and many materials have yet to be fully characterized for accurate simulation; shelf life and outlife limitations add cost; continuous-fibre forms have design limitations; many materials are brittle; and small and/or thick parts are costly to produce and difficult to automate. A majority of small structural parts are metal due to high CFRP fabrication costs for the small-size class. The fact that CFRP manufacturing processes that produce the highest performance parts also tend to be the slowest and least automated is another reason CFRP parts are generally higher in cost than comparably performing metal parts, which are easier to produce. Fortunately, business is in the midst of a major manufacturing evolution—Industry 4.0— one technology seeing rapid growth is additive manufacturing/3D printing, thanks to new processes and materials, plus an ability to harness Industry 4.0 tools. No longer limited to just prototype parts, metal-additive technologies are used to produce tooling and mold components for high-volume manufacturing, and polymer-additive technologies can incorporate fibres to produce true composites and be used to produce end-use parts with high aesthetics, unmatched complexity, mass customization opportunities, and high mechanical performance. A new hybrid manufacturing process combines the best capabilities of additive—high complexity, low energy usage and waste, 100% traceability, faster to market—and post-consolidation—tight tolerances, high R&R, established materials, and supply chains—technologies. The platform was developed by Zürich-based 9T Labs AG and is called Additive Fusion Technology (AFT). It consists of a design software offering the possibility to determine optimal fibre layup, then exports files back to check predicted performance—plus two pieces of equipment: a 3d-printer—which lays up (near)-net-shape preforms using neat thermoplastic filaments and slit, roll-formed unidirectional carbon fibre-reinforced thermoplastic tapes—and a post-consolidation module—which consolidates then shapes preforms into final parts using a compact compression press fitted with a heating unit and matched metal molds. Matrices—currently including PEKK, PEEK, PA12, and PPS, although nearly any high-quality commercial thermoplastic tapes and filaments can be used—are matched between filaments and tapes to assure excellent bonding. Since thermoplastics are used exclusively, larger assemblies can be produced by bonding or welding together smaller components, and end-of-life parts can be recycled. By combining compression molding with 3D printing, higher part quality with very-low voids and excellent surface finish on A and B sides can be produced. Tight tolerances (min. section thickness=1.5mm, min. section height=0.6mm, min. fibre radius=1.5mm) with high R&R can be cost-competitively held in production volumes of 100 to 10,000 parts/year on a single set of machines.

Keywords: additive manufacturing, composites, thermoplastic, hybrid manufacturing

Procedia PDF Downloads 92

Authors: Ekta, G. K. Darbha

Abstract:

Nanotechnology offers the potential of simultaneously increasing efficiency as compared to their bulk material as well as reducing harmful environmental impacts of pesticides in field of agriculture. The term nanopesticide covers different pesticides that are cumulative of several surfactants, polymers, metal ions, etc. of nanometer size ranges from 1-1000 nm and exhibit abnormal behavior (high efficacy and high specific surface area) of nanomaterials. Commercial formulations of pesticides used by farmers nowadays cannot be used effectively due to a number of problems associated with them. For example, more than 90% of applied formulations are either lost in the environment or unable to reach the target area required for effective pest control. Around 20−30% of pesticides are lost through emissions. A number of factors (application methods, physicochemical properties of the formulations, and environmental conditions) can influence the extent of loss during application. It is known that among various formulations, polymer-based formulations show the greatest potential due to their greater efficacy, slow release and protection against premature degradation of active ingredient as compared to other commercial formulations. However, the nanoformulations can have a significant effect on the fate of active ingredient as well as may release some new ingredients by reacting with existing soil contaminants. Environmental fate of these newly generated species is still not explored very well which is essential to field scale experiments and hence a lot to be explored in the field of environmental fate, nanotoxicology, transport properties and stability of such formulations. In our preliminary work, we have synthesized polymer based nanoformulation of commercially used weedicide atrazine. Atrazine belongs to triazine class of herbicide, which is used in the effective control of seed germinated dicot weeds and grasses. It functions by binding to the plastoquinone-binding protein in PS-II. Plant death results from starvation and oxidative damage caused by breakdown in electron transport system. The stability of the suspension of nanoformulation containing herbicide has been evaluated by considering different parameters like polydispersity index, particle diameter, zeta-potential under different environmental relevance condition such as pH range 4-10, temperature range from 25°C to 65°C and stability of encapsulation also have been studied for different amount of added polymer. Morphological characterization has been done by using SEM.

Keywords: atrazine, nanoformulation, nanopesticide, nanotoxicology

Procedia PDF Downloads 254

Authors: Jillian M. Hagel, Joseph E. Tucker, Peter J. Facchini

Abstract:

With the aim of establishing a holistic approach for the treatment of central nervous system (CNS) disorders, we are pursuing a drug development program rapidly progressing through discovery and characterization phases. The drug candidates identified in this program are referred to as neuroplastogens owing to their ability to mediate neuroplasticity, which can be beneficial to patients suffering from anxiety, depression, or posttraumatic stress disorder. These and other related neuropsychiatric conditions are associated with the onset of neuronal atrophy, which is defined as a reduction in the number and/or productivity of neurons. The stimulation of neuroplasticity results in an increase in the connectivity between neurons and promotes the restoration of healthy brain function. We have synthesized a substantial catalogue of proprietary indolethylamine derivatives based on the general structures of serotonin (5-hydroxytryptamine) and psychedelic molecules such as N,N-dimethyltryptamine (DMT) and psilocin (4-hydroxy-DMT) that function as neuroplastogens. A primary objective in our screening protocol is the identification of derivatives associated with a significant reduction in hallucination, which will allow administration of the drug at a dose that induces neuroplasticity and triggers other efficacious outcomes in the treatment of targeted CNS disorders but which does not cause a psychedelic response in the patient. Both neuroplasticity and hallucination are associated with engagement of the 5HT2A receptor, requiring drug candidates differentially coupled to these two outcomes at a molecular level. We use novel and proprietary artificial intelligence algorithms to predict the mode of binding to the 5HT2A receptor, which has been shown to correlate with the hallucinogenic response. Hallucination is tested using the mouse head-twitch response model, whereas mouse marble-burying and sucrose preference assays are used to evaluate anxiolytic and anti-depressive potential. Neuroplasticity is assays using dendritic outgrowth assays and cell-based ELISA analysis. Pharmacokinetics and additional receptor-binding analyses also contribute the selection of lead candidates. A summary of the program is presented.

Keywords: neuroplastogen, non-hallucinogenic, drug development, anxiety, depression, PTSD, indolethylamine derivatives, psychedelic-inspired, 5-HT2A receptor, computational chemistry, head-twitch response behavioural model, neurite outgrowth assay

Procedia PDF Downloads 128

Authors: Marina Passero, Tianhua Zhai, Zuyi (Jacky) Huang

Abstract:

Alzheimer’s disease has become a major public health issue, as indicated by the increasing populations of Americans living with Alzheimer’s disease. After decades of extensive research in Alzheimer’s disease, only seven drugs have been approved by Food and Drug Administration (FDA) to treat Alzheimer’s disease. Five of these drugs were designed to treat the dementia symptoms, and only two drugs (i.e., Aducanumab and Lecanemab) target the progression of Alzheimer’s disease, especially the accumulation of amyloid-b plaques. However, controversial comments were raised for the accelerated approvals of either Aducanumab or Lecanemab, especially with concerns on safety and side effects of these two drugs. There is still an urgent need for further drug discovery to target the biological processes involved in the progression of Alzheimer’s disease. Excessive cholesterol has been found to accumulate in the brain of those with Alzheimer’s disease. Cholesterol can be synthesized in both the blood and the brain, but the majority of biosynthesis in the adult brain takes place in astrocytes and is then transported to the neurons via ApoE. The blood brain barrier separates cholesterol metabolism in the brain from the rest of the body. Various proteins contribute to the metabolism of cholesterol in the brain, which offer potential targets for Alzheimer’s treatment. In the astrocytes, SREBP cleavage-activating protein (SCAP) binds to Sterol Regulatory Element-binding Protein 2 (SREBP2) in order to transport the complex from the endoplasmic reticulum to the Golgi apparatus. Cholesterol is secreted out of the astrocytes by ATP-Binding Cassette A1 (ABCA1) transporter. Lipoprotein receptors such as triggering receptor expressed on myeloid cells 2 (TREM2) internalize cholesterol into the microglia, while lipoprotein receptors such as Low-density lipoprotein receptor-related protein 1 (LRP1) internalize cholesterol into the neuron. Cytochrome P450 Family 46 Subfamily A Member 1 (CYP46A1) converts excess cholesterol to 24S-hydroxycholesterol (24S-OHC). Cholesterol has been approved for its direct effect on the production of amyloid-beta and tau proteins. The addition of cholesterol to the brain promotes the activity of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), secretase, and amyloid precursor protein (APP), which all aid in amyloid-beta production. The reduction of cholesterol esters in the brain have been found to reduce phosphorylated tau levels in mice. In this work, a computational pipeline was developed to identify the protein targets involved in cholesterol regulation in brain and further to identify chemical compounds as the inhibitors of a selected protein target. Since extensive evidence shows the strong correlation between brain cholesterol regulation and Alzheimer’s disease, a detailed literature review on genes or pathways related to the brain cholesterol synthesis and regulation was first conducted in this work. An interaction network was then built for those genes so that the top gene targets were identified. The involvement of these genes in Alzheimer’s disease progression was discussed, which was followed by the investigation of existing clinical trials for those targets. A ligand-protein docking program was finally developed to screen 1.5 million chemical compounds for the selected protein target. A machine learning program was developed to evaluate and predict the binding interaction between chemical compounds and the protein target. The results from this work pave the way for further drug discovery to regulate brain cholesterol to combat Alzheimer’s disease.

Keywords: Alzheimer’s disease, drug discovery, ligand-protein docking, gene-network analysis, cholesterol regulation

Procedia PDF Downloads 67

Authors: Oluwayemisi Mary Onyenanakeya, Kevin Onyenankeya

Abstract:

Commercial media entertainment offerings especially mainstream soap operas, in South Africa, are progressively infusing dominant social values and ideas which are alien to South African tribal societies. In most of the commodified television drama series, people who hold tight to traditional beliefs and values are often characterised as traditionalists, while those who have imbibed the western defined dicta and ideology of modernity are seen as progressives. This study, therefore, sought to ascertain how South African tribal language, traditional institutions, values, social norms and ancestral beliefs are portrayed through the television drama, Generations: The Legacy, and what the viewers think about those constructions and the implication for cultural identity. The mixed methods approach was employed involving the administration of questionnaire to 350 participants selected through random sampling and a content analysis of 20 episodes of Generations: The Legacy. The findings further showed that the values and traditions represented in generation do not significantly reflect the South African tribal tradition and values (p-value > 0.05). In most instances where traditional values are represented they tend to be portrayed as old fashioned (p-value > 0.05), and inferior and backward (p-value > 0.05). In addition, the findings indicate that Generations: The legacy is a vehicle for promoting dominant culture.

Keywords: identity, soap opera, South Africa, television

Procedia PDF Downloads 283

Authors: Boukli Hacene Faiza, Soufi Wassila, Ghalem Said

Abstract:

The oral antidiabetics drugs such as alpha glucosidase inhibitors present undesirable effects like acarbose. Flavonoids are class of molecules widely distributed in plants, for this reason we are interested in our work to study the inhibition in silico of alpha glucosidase by natural ligands ( flavonoids analogues) using molecular modeling methods using MOE (Molecular Operating Environment) software to predict their interaction with this enzyme with score energy, ADME /T tests and druglikeness properties experiments. Two flavonoids Beicalein and Apigenin have high binding affinity with alpha glucosidase with lower IC50 supposed potent inhibitors.

Keywords: alpha glucosidase, flavonoides analogues, drug research, molecular modeling

Procedia PDF Downloads 99

Authors: Sharat Chandra, Zilong Wang, Ru-Rong Ji, Andrey Bortsov

Abstract:

Chronic pain (CP) therapeutic approaches have limited efficacy. As a result, doctors are prescribing opioids for chronic pain, leading to opioid overuse, abuse, and addiction epidemic. Therefore, the development of effective and safe CP drugs remains an unmet medical need. Voltage-gated sodium (Nav) channels act as cardiovascular and neurological disorder’s molecular targets. Nav channels selective inhibitors are hard to design because there are nine closely-related isoforms (Nav1.1-1.9) that share the protein sequence segments. We are targeting the Nav1.7 found in the peripheral nervous system and engaged in the perception of pain. The objective of this project was to screen a 1.5 million compound library for identification of inhibitors for Nav1.7 with analgesic effect. In this study, we designed a protocol for identification of isoform-selective inhibitors of Nav1.7, by utilizing the prior information on isoform-selective antagonists. First, a similarity search was performed; then the identified hits were docked into a binding site on the fourth voltage-sensor domain (VSD4) of Nav1.7. We used the FTrees tool for similarity searching and library generation; the generated library was docked in the VSD4 domain binding site using FlexX and compounds were shortlisted using a FlexX score and SeeSAR hyde scoring. Finally, the top 25 compounds were tested with molecular dynamics simulation (MDS). We reduced our list to 9 compounds based on the MDS root mean square deviation plot and obtained them from a vendor for in vitro and in vivo validation. Whole-cell patch-clamp recordings in HEK-293 cells and dorsal root ganglion neurons were conducted. We used patch pipettes to record transient Na⁺ currents. One of the compounds reduced the peak sodium currents in Nav1.7-HEK-293 stable cell line in a dose-dependent manner, with IC50 values at 0.74 µM. In summary, our computer-aided analgesic discovery approach allowed us to develop pre-clinical analgesic candidate with significant reduction of time and cost.

Keywords: chronic pain, voltage-gated sodium channel, isoform-selective antagonist, similarity search, virtual screening, analgesics development

Procedia PDF Downloads 120

Authors: Dimitrios Karanatsis

Abstract:

Non-crimp fabrics (NCFs) allow for high mechanical performance of a manufacture composite component by maintaining the fibre reinforcements parallel to each other. The handling of NCFs is enabled by the stitching of the tows. Although the stitching material has negligible influence to the performance of the manufactured part, it can affect the ability of the structural fabric to shear and drape over the part’s geometry. High resistance to shearing is attributed to the high tensile strain of the stitching yarn and can cause defects in the fabric. In the current study, a correlation based on the stitch tension and shear behaviour is examined. The purpose of the research is to investigate the upper and lower limits of non-crimp fabrics manufacture and how these affect the shear behaviour of the fabrics. Experimental observations show that shear behaviour of the fabrics is significantly affected by the stitch tension, and there is a linear effect to the degree of shear they experience. It was found that the lowest possible stitch tension on the manufacturing line settings produces an NCF that exhibits very low tensile strain on it’s yarns and that has shear properties similar to a woven fabric. Moreover, the highest allowable stitch tension results in reduced formability of the fabric, as the stitch thread rearranges the fibre filaments where these become packed in a tight formation with constricted movement.

Keywords: carbon fibres, composite manufacture, shear testing, textiles

Procedia PDF Downloads 142

Authors: Bhagwant Singh, Sikander Singh Cheema

Abstract:

This paper examines firewall mechanisms routinely implemented for network security in depth. A firewall can't protect you against all the hazards of unauthorized networks. Consequently, many kinds of infrastructure are employed to establish a secure network. Firewall strategies have already been the subject of significant analysis. This study's primary purpose is to avoid unnecessary connections by combining the capability of the firewall with the use of additional firewall mechanisms, which include packet filtering and NAT, VPNs, and backdoor solutions. There are insufficient studies on firewall potential and combined approaches, but there aren't many. The research team's goal is to build a safe network by integrating firewall strength and firewall methods. The study's findings indicate that the recommended concept can form a reliable network. This study examines the characteristics of network security and the primary danger, synthesizes existing domestic and foreign firewall technologies, and discusses the theories, benefits, and disadvantages of different firewalls. Through synthesis and comparison of various techniques, as well as an in-depth examination of the primary factors that affect firewall effectiveness, this study investigated firewall technology's current application in computer network security, then introduced a new technique named "tight coupling firewall." Eventually, the article discusses the current state of firewall technology as well as the direction in which it is developing.

Keywords: firewall strategies, firewall potential, packet filtering, NAT, VPN, proxy services, firewall techniques

Procedia PDF Downloads 94

Authors: Mahboobeh Mohadeszadeh, Majid Saghi

Abstract:

Polyoxometalates (POMs) are important inorganic compounds that have been considered specifically in recent years due to abundant attributes and applications. Those POMs that have one central tetrahedral atom called keggin. The binding Amino-acid groups to keggin structure give the antivirus effect to these compounds. A new organic-inorganic hybrid structure, with formula (Gly)2H4SiW12O40 was synthesized. Investigation on Anti-viral effect of this compound showed the (Gly)2H4SiW12O40 prevents infection of Tobacco Mosaic Virus (TMV) on the Nicotianatabacum plants.

Keywords: Polyoxometalate, Keggin, Organic-inorganic salt, TMV

Procedia PDF Downloads 283

Authors: Mahboobeh Mohadeszadeh, Majid Saghi

Abstract:

Polyoxometalates (POMs) are important inorganic compounds that have been considered specifically in recent years due to abundant attributes and applications. Those POMs that have one central tetrahedral atom called keggin. The binding Amino-acid groups to keggin structure give the antivirus effect to these compounds. A new organic-inorganic hybrid structure, with formula (Gly)2H4SiW12O40 was synthesized. Investigation on Anti-viral effect of this compound showed the (Gly)2H4SiW12O40 prevents infection of Tobacco Mosaic Virus (TMV) on the Nicotianatabacum plants.

Keywords: polyoxometalate, keggin, organic-inorganic salt, TMV

Procedia PDF Downloads 417

Authors: Mahboobeh Mohadeszadeh, Majid Saghi

Abstract:

Polyoxometalates (POMs) are important inorganic compounds that have been considered specifically in recent years due to abundant attributes and applications. Those POMs that have one central tetrahedral atom called keggin. The binding Amino-acid groups to keggin structure give the antivirus effect to these compounds. A new organic-inorganic hybrid structure, with formula (Gly)2H4SiW12O40, was synthesized. Investigation on the anti-viral effect of this compound showed the (Gly)2H4SiW12O40 prevents infection of Tobacco Mosaic Virus (TMV) on the Nicotianatabacum plants.

Keywords: polyoxometalate, keggin, organic-inorganic salt, TMV

Procedia PDF Downloads 284

Authors: Fulwah Alqahtani, Jafar Mahdavi, Lee Weldon, Nick Holliday, Dlawer Ala'Aldeen

Abstract:

There are two isoforms of laminin receptor; monomeric 37 kDa laminin receptor precursor (37 LRP) and mature 67 kDa laminin receptor (67 LR). The relationship between the 67 LR and its precursor 37 LRP is not completely understood, but previous observations have suggested that 37 LRP can undergo homo- and/or hetero- dimerization with Galectin-3 (Gal-3) to form mature 67 LR. Gal-3 is the only member of the chimera-type group of galectins, and has one C-terminal carbohydrate recognition domain (CRD) that is responsible for binding the ß-galactoside moieties of mono- or oligosaccharides on several host and microbial molecules. The aim of this work was to investigate homo- and hetero-dimerization among the 37 LRP and Gal-3 to form mature 67 LR in mammalian cells using bimolecular fluorescence complementation (BiFC).

Keywords: 37 LRP, 67 LR, Gal-3, BiFC

Procedia PDF Downloads 500

Authors: Jana Petru, Marie Kudrnova

Abstract:

The use of technologies working with molten salts is conditioned by finding suitable construction materials that must meet several demanding criteria. In addition to temperature resistance, materials must also show corrosion resistance to salts; they must meet mechanical requirements and other requirements according to the area of use – for example, radiation resistance in Molten Salt Reactors. The present text describes an experimental device for studying the corrosion resistance of candidate materials in molten mixtures of salts and is a partial task of the international project ADAR, dealing with the evaluation of advanced nuclear reactors based on molten salts. The design of the device is based on a test exposure of Inconel 625 in the mixture of salts Hitec in a high temperature tube furnace. The result of the pre-exposure is, in addition to the metallographic evaluation of the behavior of material 625 in the mixture of nitrate salts, mainly a list of operational and construction problems that were essential for the construction of the new experimental equipment. The main output is a scheme of a newly designed gas-tight experimental apparatus capable of operating in an inert argon atmosphere, temperature up to 600 °C, pressure 3 bar, in the presence of a corrosive salt environment, with an exposure time of hundreds of hours. This device will enable the study of promising construction materials for nuclear energy.

Keywords: corrosion, experimental device, molten salt, steel

Procedia PDF Downloads 116

Authors: Dmytro D. Buiadzhy

Abstract:

The modern psychiatric discourse proves the existence of the direct ties between the children's mental health and their success in life as adults. The unresolved mental health problems in childhood are likely to lead individuals to poverty, isolation, and social exclusion as stated by Marcus Richards. Such an approach justifies the involvement of children in the view of supervision and control of power. The discourse, related to the mental health of children, provides a tight impact of family, educational institutions and medical authorities on the child through any manifestations of his psychic, having signs of "abnormality.” Throughout the adult life, the individual continues to feel the pressure of power through legal, political, and economic institutions that also appeal to the mental health regulation. The juvenile law declares the equality of a child and an adult, but in fact simply delegates the powers of parents to impersonal social institutions of the guardianship, education, and social protection. The psychiatric power in this study is considered in accordance with the Michel Foucault’s concept of power as a manifestation of "positive" technologies of power, which include various manifestations of subjectivity, in particular children’s one, in a view of supervision and control of the state power. The main issue disclosed in this paper is how weakening of the parental authority, in the context of legislative ratification of the child rights, strengthens the other forms of power over children, especially the psychiatric power, which justifies and affects the children mancipation.

Keywords: child rights, psychiatric power, discourse, parental authority

Procedia PDF Downloads 341