Search results for: drug rewarding behavior
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 8269

Search results for: drug rewarding behavior

7609 The Impact of Perception of Transformational Leadership and Factors of Innovation Culture on Innovative Work Behavior in Junior High School's Teacher

Authors: Galih Mediana

Abstract:

Boarding school can helps students to turn all good qualities into habits. The process of forming one's personality can be done in various ways. In addition to gaining general knowledge at school during learning hours, teachers can instill values in students which can be done while in the dormitory when the learning process has ended. This shows the important role that must be played by boarding school’s teachers. Transformational leadership and a culture of innovation are things that can instill innovative behavior in teachers. This study aims to determine the effect of perceptions of transformational leadership and a culture of innovation on innovative work behavior among Islamic boarding school teachers. Respondents in this study amounted to 70 teachers. To measure transformational leadership, a modified measuring tool is used, namely the Multifactor Leadership Questionnaire (MLQ) by Bass (1985). To measure innovative work behavior, a measurement tool based on dimensions from Janssen (2000) is used. The innovation culture in this study will be measured using the innovation culture factor from Dobni (2008). This study uses multiple regression analysis to test the hypothesis. The results of this study indicate that there is an influence of perceptions of transformational leadership and innovation culture factors on innovative work behavior in Islamic boarding school’s teachers by 57.7%.

Keywords: transformational leadership, innovative work behavior, innovation culture, boarding school, teacher

Procedia PDF Downloads 98
7608 Drug Delivery Cationic Nano-Containers Based on Pseudo-Proteins

Authors: Sophio Kobauri, Temur Kantaria, Nina Kulikova, David Tugushi, Ramaz Katsarava

Abstract:

The elaboration of effective drug delivery vehicles is still topical nowadays since targeted drug delivery is one of the most important challenges of the modern nanomedicine. The last decade has witnessed enormous research focused on synthetic cationic polymers (CPs) due to their flexible properties, in particular as non-viral gene delivery systems, facile synthesis, robustness, not oncogenic and proven gene delivery efficiency. However, the toxicity is still an obstacle to the application in pharmacotherapy. For overcoming the problem, creation of new cationic compounds including the polymeric nano-size particles – nano-containers (NCs) loading with different pharmaceuticals and biologicals is still relevant. In this regard, a variety of NCs-based drug delivery systems have been developed. We have found that amino acid-based biodegradable polymers called as pseudo-proteins (PPs), which can be cleared from the body after the fulfillment of their function are highly suitable for designing pharmaceutical NCs. Among them, one of the most promising are NCs made of biodegradable Cationic PPs (CPPs). For preparing new cationic NCs (CNCs), we used CPPs composed of positively charged amino acid L-arginine (R). The CNCs were fabricated by two approaches using: (1) R-based homo-CPPs; (2) Blends of R-based CPPs with regular (neutral) PPs. According to the first approach NCs we prepared from CPPs 8R3 (composed of R, sebacic acid and 1,3-propanediol) and 8R6 (composed of R, sebacic acid and 1,6-hexanediol). The NCs prepared from these CPPs were 72-101 nm in size with zeta potential within +30 ÷ +35 mV at a concentration 6 mg/mL. According to the second approach, CPPs 8R6 was blended in organic phase with neutral PPs 8L6 (composed of leucine, sebacic acid and 1,6-hexanediol). The NCs prepared from the blends were 130-140 nm in size with zeta potential within +20 ÷ +28 mV depending on 8R6/8L6 ratio. The stability studies of fabricated NCs showed that no substantial change of the particle size and distribution and no big particles’ formation is observed after three months storage. In vitro biocompatibility study of the obtained NPs with four different stable cell lines: A549 (human), U-937 (human), RAW264.7 (murine), Hepa 1-6 (murine) showed both type cathionic NCs are biocompatible. The obtained data allow concluding that the obtained CNCs are promising for the application as biodegradable drug delivery vehicles. This work was supported by the joint grant from the Science and Technology Center in Ukraine and Shota Rustaveli National Science Foundation of Georgia #6298 'New biodegradable cationic polymers composed of arginine and spermine-versatile biomaterials for various biomedical applications'.

Keywords: biodegradable polymers, cationic pseudo-proteins, nano-containers, drug delivery vehicles

Procedia PDF Downloads 150
7607 Effects of Safety Intervention Program towards Behaviors among Rubber Wood Processing Workers Using Theory of Planned Behavior

Authors: Junjira Mahaboon, Anongnard Boonpak, Nattakarn Worrasan, Busma Kama, Mujalin Saikliang, Siripor Dankachatarn

Abstract:

Rubber wood processing is one of the most important industries in southern Thailand. The process has several safety hazards for example unsafe wood cutting machine guarding, wood dust, noise, and heavy lifting. However, workers’ occupational health and safety measures to promote their behaviors are still limited. This quasi-experimental research was to determine factors affecting workers’ safety behaviors using theory of planned behavior after implementing job safety intervention program. The purposes were to (1) determine factors affecting workers’ behaviors and (2) to evaluate effectiveness of the intervention program. The sample of study was 66 workers from a rubber wood processing factory. Factors in the Theory of Planned Behavior model (TPB) were measured before and after the intervention. The factors of TPB included attitude towards behavior, subjective norm, perceived behavioral control, intention, and behavior. Firstly, Job Safety Analysis (JSA) was conducted and Safety Standard Operation Procedures (SSOP) were established. The questionnaire was also used to collect workers’ characteristics and TPB factors. Then, job safety intervention program to promote workers’ behavior according to SSOP were implemented for a four month period. The program included SSOP training, personal protective equipment use, and safety promotional campaign. After that, the TPB factors were again collected. Paired sample t-test and independent t-test were used to analyze the data. The result revealed that attitude towards behavior and intention increased significantly after the intervention at p<0.05. These factors also significantly determined the workers’ safety behavior according to SSOP at p<0.05. However, subjective norm, and perceived behavioral control were not significantly changed nor related to safety behaviors. In conclusion, attitude towards behavior and workers’ intention should be promoted to encourage workers’ safety behaviors. SSOP intervention program e.g. short meeting, safety training, and promotional campaign should be continuously implemented in a routine basis to improve workers’ behavior.

Keywords: job safety analysis, rubber wood processing workers, safety standard operation procedure, theory of planned behavior

Procedia PDF Downloads 188
7606 Authentic Leadership, Task Performance, and Organizational Citizenship Behavior

Authors: C. V. Chen, Y. H. Jeng, S. J. Wang

Abstract:

Leadership is essential to enhancing followers’ psychological empowerment and has an effect on their willingness to take on extra-role behavior and aim for greater performance. Authentic leadership is confirmed to promote employees’ positive affect, psychological empowerment, well-being, and performance. Employees’ spontaneous undertaking of organizationally desired behaviors allows organizations’ gaining the edge in the fiercely competitive business environment. Apart from the contextual factor of leadership, individuals’ goal orientation is found to be highly related to his/her performance. To better understand the psychological process and potential moderation of personal goal orientation, this study investigates the effect of authentic leadership on employees’ task performance and organizational citizenship behavior by including psychological empowerment as the mediating factor and goal orientation as the moderating factor.

Keywords: authentic leadership, task performance, organizational citizenship behavior, goal orientation

Procedia PDF Downloads 789
7605 Influence of Human Resource Management Practices on Agricultural Employees’ Behavior

Authors: B. G. Abiona, O. E. Fapojuwo, T. Akinlawon

Abstract:

This study assessed the influence of human resource management practices on agricultural employees’ behavior. Data were collected from 75 randomly selected respondents using a well-structured questionnaire. The mean age of the employees’ was 43.2 years. Major human resource management practices that influence employees behaviors were: In-service training are given to employees on a regular basis (average value of x=3.44), management reward employees who are committed to their job (average value of x =3.41) and reward are designed to encourage wide participation and activity (average value of x=3.41). Also, major employees’ behavior include: Managers and employees’ wants to create better job performance (average value of x=3.13) and administrator provides praise and recognition for effective performance and show appreciation for special effort (average value of x=3.05). Major factors affecting employees’ behavior were: inadequate training (average value of x=2.93), inadequate local and international training (average value of x=2.87), inadequate grants for training programmes (average value of x= 2.81). A significant relationship was found between gender (χ2 = 37.204, P<0.05), educational qualification (χ2 = 59.093, P<0.05), income (r =0.122, P<0.05) and human resource management practices (r = 0.573, P< 0.05) of the respondents and employees’ behavior. Management should encourage employees who are committed to their job through awards and recognition.

Keywords: human resources management, agricultural employees, behaviour research institutes, Nigeria

Procedia PDF Downloads 247
7604 Using Combination of Sets of Features of Molecules for Aqueous Solubility Prediction: A Random Forest Model

Authors: Muhammet Baldan, Emel Timuçin

Abstract:

Generally, absorption and bioavailability increase if solubility increases; therefore, it is crucial to predict them in drug discovery applications. Molecular descriptors and Molecular properties are traditionally used for the prediction of water solubility. There are various key descriptors that are used for this purpose, namely Drogan Descriptors, Morgan Descriptors, Maccs keys, etc., and each has different prediction capabilities with differentiating successes between different data sets. Another source for the prediction of solubility is structural features; they are commonly used for the prediction of solubility. However, there are little to no studies that combine three or more properties or descriptors for prediction to produce a more powerful prediction model. Unlike available models, we used a combination of those features in a random forest machine learning model for improved solubility prediction to better predict and, therefore, contribute to drug discovery systems.

Keywords: solubility, random forest, molecular descriptors, maccs keys

Procedia PDF Downloads 35
7603 Effect of Ownership Structure and Financial Leverage on Corporate Investment Behavior in Tehran Stock Exchange

Authors: Shamshiri Mitra, Abedi Rahim

Abstract:

This paper investigates corporate investment behavior and its relationship with ownership structure and financial leverage for the listed company of Tehran stock exchange during 2008-2012. The results show that the concentration of ownership has s significant positive effect on corporate investment. The results for the kind of major owners show that institutional ownership had a positive significant effect and state and individual ownership had negative significant effects on the corporate investment but the effect of corporate ownership was not significant. Furthermore the effect of financial leverage was negative and significant.

Keywords: corporate investment behavior, financial leverage, ownership structure corporate investment behavior

Procedia PDF Downloads 521
7602 Towards the Reverse Engineering of UML Sequence Diagrams Using Petri Nets

Authors: C. Baidada, M. H. Abidi, A. Jakimi, E. H. El Kinani

Abstract:

Reverse engineering has become a viable method to measure an existing system and reconstruct the necessary model from tis original. The reverse engineering of behavioral models consists in extracting high-level models that help understand the behavior of existing software systems. In this paper, we propose an approach for the reverse engineering of sequence diagrams from the analysis of execution traces produced dynamically by an object-oriented application using petri nets. Our methods show that this approach can produce state diagrams in reasonable time and suggest that these diagrams are helpful in understanding the behavior of the underlying application. Finally we will discuss approachs and tools that are needed in the process of reverse engineering UML behavior. This work is a substantial step towards providing high-quality methodology for effectiveand efficient reverse engineering of sequence diagram.

Keywords: reverse engineering, UML behavior, sequence diagram, execution traces, petri nets

Procedia PDF Downloads 439
7601 Contractual Complexity and Contract Parties' Opportunistic Behavior in Construction Projects: In a Contractual Function View

Authors: Mengxia Jin, Yongqiang Chen, Wenqian Wang, Yu Wang

Abstract:

The complexity and specificity of construction projects have made common opportunism phenomenon, and contractual governance for opportunism has been a topic of considerable ongoing research. Based on TCE, the research distinguishes control and coordination as different functions of the contract to investigate their complexity separately. And in a nuanced way, the dimensionality of contractual control is examined. Through the analysis of motivation and capability of strong or weak form opportunism, the framework focuses on the relationship between the complexity of above contractual dimensions and different types of opportunistic behavior and attempts to verify the possible explanatory mechanism. The explanatory power of the research model is evaluated in the light of empirical evidence from questionnaires. We collect data from Chinese companies in the construction industry, and the data collection is still in progress. The findings will speak to the debate surrounding the effects of contract complexity on opportunistic behavior. This nuanced research will derive implications for research on the role of contractual mechanisms in dealing with inter-organizational opportunism and offer suggestions for curbing contract parties’ opportunistic behavior in construction projects.

Keywords: contractual complexity, contractual control, contractual coordinatio, opportunistic behavior

Procedia PDF Downloads 379
7600 Cloud Based Supply Chain Traceability

Authors: Kedar J. Mahadeshwar

Abstract:

Concept introduction: This paper talks about how an innovative cloud based analytics enabled solution that could address a major industry challenge that is approaching all of us globally faster than what one would think. The world of supply chain for drugs and devices is changing today at a rapid speed. In the US, the Drug Supply Chain Security Act (DSCSA) is a new law for Tracing, Verification and Serialization phasing in starting Jan 1, 2015 for manufacturers, repackagers, wholesalers and pharmacies / clinics. Similarly we are seeing pressures building up in Europe, China and many countries that would require an absolute traceability of every drug and device end to end. Companies (both manufacturers and distributors) can use this opportunity not only to be compliant but to differentiate themselves over competition. And moreover a country such as UAE can be the leader in coming up with a global solution that brings innovation in this industry. Problem definition and timing: The problem of counterfeit drug market, recognized by FDA, causes billions of dollars loss every year. Even in UAE, the concerns over prevalence of counterfeit drugs, which enter through ports such as Dubai remains a big concern, as per UAE pharma and healthcare report, Q1 2015. Distribution of drugs and devices involves multiple processes and systems that do not talk to each other. Consumer confidence is at risk due to this lack of traceability and any leading provider is at risk of losing its reputation. Globally there is an increasing pressure by government and regulatory bodies to trace serial numbers and lot numbers of every drug and medical devices throughout a supply chain. Though many of large corporations use some form of ERP (enterprise resource planning) software, it is far from having a capability to trace a lot and serial number beyond the enterprise and making this information easily available real time. Solution: The solution here talks about a service provider that allows all subscribers to take advantage of this service. The solution allows a service provider regardless of its physical location, to host this cloud based traceability and analytics solution of millions of distribution transactions that capture lots of each drug and device. The solution platform will capture a movement of every medical device and drug end to end from its manufacturer to a hospital or a doctor through a series of distributor or retail network. The platform also provides advanced analytics solution to do some intelligent reporting online. Why Dubai? Opportunity exists with huge investment done in Dubai healthcare city also with using technology and infrastructure to attract more FDI to provide such a service. UAE and countries similar will be facing this pressure from regulators globally in near future. But more interestingly, Dubai can attract such innovators/companies to run and host such a cloud based solution and become a hub of such traceability globally.

Keywords: cloud, pharmaceutical, supply chain, tracking

Procedia PDF Downloads 523
7599 Combination Therapies Targeting Apoptosis Pathways in Pediatric Acute Myeloid Leukemia (AML)

Authors: Ahlam Ali, Katrina Lappin, Jaine Blayney, Ken Mills

Abstract:

Leukaemia is the most frequently (30%) occurring type of paediatric cancer. Of these, approximately 80% are acute lymphoblastic leukaemia (ALL) with acute myeloid leukaemia (AML) cases making up the remaining 20% alongside other leukaemias. Unfortunately, children with AML do not have promising prognosis with only 60% surviving 5 years or longer. It has been highlighted recently the need for age-specific therapies for AML patients, with paediatric AML cases having a different mutational landscape compared with AML diagnosed in adult patients. Drug Repurposing is a recognized strategy in drug discovery and development where an already approved drug is used for diseases other than originally indicated. We aim to identify novel combination therapies with the promise of providing alternative more effective and less toxic induction therapy options. Our in-silico analysis highlighted ‘cell death and survival’ as an aberrant, potentially targetable pathway in paediatric AML patients. On this basis, 83 apoptotic inducing compounds were screened. A preliminary single agent screen was also performed to eliminate potentially toxic chemicals, then drugs were constructed into a pooled library with 10 drugs per well over 160 wells, with 45 possible pairs and 120 triples in each well. Seven cell lines were used during this study to represent the clonality of AML in paediatric patients (Kasumi-1, CMK, CMS, MV11-14, PL21, THP1, MOLM-13). Cytotoxicity was assessed up to 72 hours using CellTox™ Green reagent. Fluorescence readings were normalized to a DMSO control. Z-Score was assigned to each well based on the mean and standard deviation of all the data. Combinations with a Z-Score <2 were eliminated and the remaining wells were taken forward for further analysis. A well was considered ‘successful’ if each drug individually demonstrated a Z-Score <2, while the combination exhibited a Z-Score >2. Each of the ten compounds in one well (155) had minimal or no effect as single agents on cell viability however, a combination of two or more of the compounds resulted in a substantial increase in cell death, therefore the ten compounds were de-convoluted to identify a possible synergistic pair/triple combinations. The screen identified two possible ‘novel’ drug pairing, with BCL2 inhibitor ABT-737, combined with either a CDK inhibitor Purvalanol A, or AKT/ PI3K inhibitor LY294002. (ABT-737- 100 nM+ Purvalanol A- 1 µM) (ABT-737- 100 nM+ LY294002- 2 µM). Three possible triple combinations were identified (LY2409881+Akti-1/2+Purvalanol A, SU9516+Akti-1/2+Purvalanol A, and ABT-737+LY2409881+Purvalanol A), which will be taken forward for examining their efficacy at varying concentrations and dosing schedules, across multiple paediatric AML cell lines for optimisation of maximum synergy. We believe that our combination screening approach has potential for future use with a larger cohort of drugs including FDA approved compounds and patient material.

Keywords: AML, drug repurposing, ABT-737, apoptosis

Procedia PDF Downloads 198
7598 Flexural Behavior of Heat-Damaged Concrete Beams Reinforced with Fiber Reinforced Polymer (FRP) Bars

Authors: Mohammad R. Irshidat, Rami H. Haddad, Hanadi Al-Mahmoud

Abstract:

Reinforced concrete (RC) is the most common used material for construction in the world. In the past decades, fiber reinforced polymer (FRP) bars had been widely used to substitute the steel bars due to their high resistance to corrosion, high tensile capacity, and low weight in comparison with steel. Experimental studies on the behavior of FRP bar reinforced concrete beams had been carried out worldwide for a few decades. While the research on such structural members under elevated temperatures is still very limited. In this research, the flexural behavior of heat-damaged concrete beams reinforced with FRP bars is studied. Two types of FRP rebar namely, carbon fiber reinforced polymer (CFRP) and glass fiber reinforced polymer (GFRP), are used. The beams are subjected to four levels of temperature before tested to monitor their flexural behavior. The results are compared with other concrete beams reinforced with regular steel bars. The results show that the beams reinforced with CFRP bars and GFRP bars had higher flexural capacity than the beams reinforced with steel bars even if heated up to 400°C and 300°C, respectively. After that the beams reinforced with steel bars had the superiority.

Keywords: concrete beams, FRP rebar, flexural behavior, heat-damaged

Procedia PDF Downloads 438
7597 Analysis of Behavior and Determinants of Cost Stickiness in Manufacturing Companies in Indonesia

Authors: Farizy Yunaz, Catur Sasongko

Abstract:

This research aims to provide the empirical evidence regarding cost stickiness behavior and its determinants on listed manufacturing companies. Hypothesis testing is performed using pooled least square method. The result concludes that there is cost stickiness behavior in selling, general and administrative costs. In term of determinants, firm-specific adjustment costs measured by asset intensity and employee intensity have significant positive impact on the level of cost stickiness. Meanwhile, earnings target and leverage have significant negative impact on the level of cost stickiness. However, the management empire building incentives measured by free cash flow has no significant positive impact.

Keywords: adjustment cost, cost behavior, cost stickiness, earnings target, leverage, management empire building incentive

Procedia PDF Downloads 355
7596 Comparative Study of Mutations Associated with Second Line Drug Resistance and Genetic Background of Mycobacterium tuberculosis Strains

Authors: Syed Beenish Rufai, Sarman Singh

Abstract:

Background: Performance of Genotype MTBDRsl (Hain Life science GmbH Germany) for detection of mutations associated with second-line drug resistance is well known. However, less evidence regarding the association of mutations and genetic background of strains is known which, in the future, is essential for clinical management of anti-tuberculosis drugs in those settings where the probability of particular genotype is predominant. Material and Methods: During this retrospective study, a total of 259 MDR-TB isolates obtained from pulmonary TB patients were tested for second-line drug susceptibility testing (DST) using Genotype MTBDRsl VER 1.0 and compared with BACTEC MGIT-960 as a reference standard. All isolates were further characterized using spoligotyping. The spoligo patterns obtained were compared and analyzed using SITVIT_WEB. Results: Of total 259 MDR-TB isolates which were screened for second-line DST by Genotype MTBDRsl, mutations were found to be associated with gyrA, rrs and emb genes in 82 (31.6%), 2 (0.8%) and 90 (34.7%) isolates respectively. 16 (6.1%) isolates detected mutations associated with both FQ as well as to AG/CP drugs (XDR-TB). No mutations were detected in 159 (61.4%) isolates for corresponding gyrA and rrs genes. Genotype MTBDRsl showed a concordance of 96.4% for detection of sensitive isolates in comparison with second-line DST by BACTEC MGIT-960 and 94.1%, 93.5%, 60.5% and 50% for detection of XDR-TB, FQ, EMB, and AMK/CAP respectively. D94G was the most prevalent mutation found among (38 (46.4%)) OFXR isolates (37 FQ mono-resistant and 1 XDR-TB) followed by A90V (23 (28.1%)) (17 FQ mono-resistant and 6 XDR-TB). Among AG/CP resistant isolates A1401G was the most frequent mutation observed among (11 (61.1%)) isolates (2 AG/CP mono-resistant isolates and 9 XDR-TB isolates) followed by WT+A1401G (6 (33.3%)) and G1484T (1 (5.5%)) respectively. On spoligotyping analysis, Beijing strain (46%) was found to be the most predominant strain among pre-XDR and XDR TB isolates followed by CAS (30%), X (6%), Unique (5%), EAI and T each of 4%, Manu (3%) and Ural (2%) respectively. Beijing strain was found to be strongly associated with D94G (47.3%) and A90V mutations by (47.3%) and 34.8% followed by CAS strain by (31.6%) and 30.4% respectively. However, among AG/CP resistant isolates, only Beijing strain was found to be strongly associated with A1401G and WT+A1401G mutations by 54.5% and 50% respectively. Conclusion: Beijing strain was found to be strongly associated with the most prevalent mutations among pre-XDR and XDR TB isolates. Acknowledgments: Study was supported with Grant by All India Institute of Medical Sciences, New Delhi reference No. P-2012/12452.

Keywords: tuberculosis, line probe assay, XDR TB, drug susceptibility

Procedia PDF Downloads 134
7595 Bioprospecting of Marine Actinobacteria: The Leading Way for Industrially Important Enzymes and Bioactive Natural Products

Authors: Ramesh Subramani, Mathivanan Narayanasamy, William Aalbersberg

Abstract:

It is well accepted by last 35 years of research and on-going programmes that marine environment harbours abundant and unique biodiversity, which is currently playing as an important source in bioprospecting. It has become apparent that marine microorganisms are lead in the biodiscovery. Among marine organisms, actinobacteria are a target phylum for discovering novel antibiotics against increasing the multi-drug resistant human pathogens because of these taxa representing for novel genera and species. Marine actinomycetes are a proven source of new antibiotic leads and novel enzymes with important industrial applications. A total of 183 streptomycete and 25 non-streptomycete strains were isolated from different marine samples collected from north-eastern part of the Indian Ocean. Among them, 111 isolates displayed antibacterial activity against human pathogens and 151 exhibited antifungal activity against phytopathogens. Importantly, most of them produced various extracellular enzymes and 58 of them produced exopolysaccharides. Totally eight small bioactive compounds and a thermostable alkaline protease have been purified from a selected strain, Streptomyces fungicidicus. Besides, our on-going studies on non-streptomycete strains (rare actinomycetes) are most likely promising resource for new and unique compounds against current emerging drug-resistant pathogens. We have just recognised the chemical diversity in marine microorganisms. Therefore it is worthwhile to continue the exploration of marine microorganisms for new drug leads, novel enzymes and other bioprospecting research.

Keywords: bioactive compounds, industrial enzymes, marine actinobacteria, microbial metabolites, marine natural products

Procedia PDF Downloads 270
7594 Docking and Dynamic Molecular Study of Isoniazid Derivatives as Anti-Tuberculosis Drug Candidate

Authors: Richa Mardianingrum, Srie R. N. Endah

Abstract:

In this research, we have designed four isoniazid derivatives i.e., isonicotinohydrazide (1-isonicotinoyl semicarbazide, 1-thiosemi isonicotinoyl carbazide, N '-(1,3-dimethyl-1 h-pyrazole-5-carbonyl) isonicotino hydrazide, and N '-(1,2,3- 4-thiadiazole-carbonyl) isonicotinohydrazide. The docking and molecular dynamic have performed to them in order to study its interaction with Mycobacterium tuberculosis Enoyl-Acyl Carrier Protein Reductase (InhA). Based on this research, all of the compounds were predicted to have a stable interaction with Mycobacterium tuberculosis Enoyl-Acyl Carrier Protein Reductase (INHA) receptor, so they could be used as an anti-tuberculosis drug candidate.

Keywords: anti-tuberculosis, docking, Inhibin alpha subunit, InhA, inhibition, synthesis, isonicotinohydrazide

Procedia PDF Downloads 177
7593 Tripeptide Inhibitor: The Simplest Aminogenic PEGylated Drug against Amyloid Beta Peptide Fibrillation

Authors: Sutapa Som Chaudhury, Chitrangada Das Mukhopadhyay

Abstract:

Alzheimer’s disease is a well-known form of dementia since its discovery in 1906. Current Food and Drug Administration approved medications e.g. cholinesterase inhibitors, memantine offer modest symptomatic relief but do not play any role in disease modification or recovery. In last three decades many small molecules, chaperons, synthetic peptides, partial β-secretase enzyme blocker have been tested for the development of a drug against Alzheimer though did not pass the 3rd clinical phase trials. Here in this study, we designed a PEGylated, aminogenic, tripeptidic polymer with two different molecular weights based on the aggregation prone amino acid sequence 17-20 in amyloid beta (Aβ) 1-42. Being conjugated with poly-ethylene glycol (PEG) which self-assembles into hydrophilic nanoparticles, these PEGylated tripeptides constitute a very good drug delivery system crossing the blood brain barrier while the peptide remains protected from proteolytic degradation and non-specific protein interactions. Moreover, being completely aminogenic they would not raise any side effects. These peptide inhibitors were evaluated for their effectiveness against Aβ42 fibrillation at an early stage of oligomer to fibril formation as well as preformed fibril clearance via Thioflavin T (ThT) assay, dynamic light scattering analyses, atomic force microscopy and scanning electron microscopy. The inhibitors were proved to be safe at a higher concentration of 20µM by the reduction assay of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) dye. Moreover, SHSY5Y neuroblastoma cells have shown a greater survivability when treated with the inhibitors following Aβ42 fibril and oligomer treatment as compared with the control Aβ42 fibril and/or oligomer treated neuroblastoma cells. These make the peptidic inhibitors a promising compound in the aspect of the discovery of alternative medication for Alzheimer’s disease.

Keywords: Alzheimer’s disease, alternative medication, amyloid beta, PEGylated peptide

Procedia PDF Downloads 204
7592 Antibacterial Effects of Zinc Oxide Nanoparticles as Alternative Therapy on Drug-Resistant Group B Streptococcus Strains Isolated from Pregnant Women

Authors: Leila Fozouni, Anahita Mazandarani

Abstract:

Background: Maternal infections are the most common cause of infections in infants, and the level of infection and its severity highly depends on the degree of colonization of the bacteria in the mother; so, the occurrence of aggressive diseases is not unpredictable in mothers with very high colonization. Group B Streptococcus is part of the normal flora of the gastrointestinal and genital tracts in women and is the leading cause of septicemia and meningitis in newborns. Today Zinc oxide nanoparticle is regarded as one of the most commonly used and safest nanoparticles for defeating Gram-positive and Gram-negative bacteria. This study aims to determine the antibacterial effects of Zinc oxide on the growth of drug-resistant group B Streptococcus strains isolated from pregnant women. Materials and Methods: This cross-sectional study was conducted on 150 pregnant women of 28–37 weeks admitted to seven hospitals and maternity wards in Golestan province, northeast of Iran. For bacterial identification, rectovaginal swabs were firstly inoculated to the Todd-Hewitt Broth and cultured in blood agar (containing 5% sheep blood). Then microbiologic and PCR methods were performed to detect group B Streptococci. Disk diffusion and broth microdilution tests were used to determine the bacterial susceptibility to antibiotics according to CLSI M100(2021) criteria. The antibacterial properties of Zinc oxide nanoparticles were evaluated using the agar well-diffusion method. Results: The prevalence of group B Streptococcus was 18% in pregnant women. Out of twenty-seven positive cultures, 62.96% were higher than thirty years old. Ninety percent and 45% of isolates were resistant to clindamycin and erythromycin, respectively, and susceptibility to cefazolin was 71%. In addition, susceptibility to ampicillin and penicillin were 74% and 55%, respectively. The results showed that 82% of erythromycin-resistant, 92% clindamycin-resistant, and 78% of cefazolin-resistant isolates were eliminated by zinc oxide nanoparticles at a concentration of 100 mg/L of the nanoparticle. Furthermore, ZnONPs could inhibit all drug-resistant isolates at a concentration of 200 mg/mL (MIC90 ≥ 200). Conclusion: Since the drug resistance of group B streptococci against various antibiotics is increasing, determining and investigating the drug-resistance pattern of this bacterium to different antibiotics in order to prevent arbitrary consumption of antibiotics by pregnant women and ultimately prevent Infant mortality seems necessary. Generally, ZnONPs showed a high antimicrobial effect, and it was revealed that the bactericide effect increases upon the increase in the concentration of the nanoparticle.

Keywords: group B beta-hemolytic streptococcus, pregnant women, zinc oxide nanoparticles, drug resistance

Procedia PDF Downloads 90
7591 Ab-initio Calculations on the Mechanism of Action of Platinum and Ruthenium Complexes in Phototherapy

Authors: Eslam Dabbish, Fortuna Ponte, Stefano Scoditti, Emilia Sicilia, Gloria Mazzone

Abstract:

The medical techniques based on the use of light for activating the drug are occupying a prominent place in the cancer treatment due to their selectivity that contributes to reduce undesirable side effects of conventional chemotherapy. Among these therapeutic treatments, photodynamic therapy (PDT) and photoactivated chemotherapy (PACT) are emerging as complementary approaches for selective destruction of neoplastic tissue through direct cellular damage. Both techniques rely on the employment of a molecule, photosensitizer (PS), able to absorb within the so-called therapeutic window. Thus, the exposure to light of otherwise inert molecules promotes the population of excited states of the drug, that in PDT are able to produce the cytotoxic species, such as 1O2 and other ROS, in PACT can be responsible of the active species release or formation. Following the success of cisplatin in conventional treatments, many other transition metal complexes were explored as anticancer agents for applications in different medical approaches, including PDT and PACT, in order to improve their chemical, biological and photophysical properties. In this field, several crucial characteristics of candidate PSs can be accurately predicted from first principle calculations, especially in the framework of density functional theory and its time-dependent formulation, contributing to the understanding of the entire photochemical pathways involved which can ultimately help in improving the efficiency of a drug. A brief overview of the outcomes on some platinum and ruthenium-based PSs proposed for the application in the two phototherapies will be provided.

Keywords: TDDFT, metal complexes, PACT, PDT

Procedia PDF Downloads 93
7590 Atypical Retinoid ST1926 Nanoparticle Formulation Development and Therapeutic Potential in Colorectal Cancer

Authors: Sara Assi, Berthe Hayar, Claudio Pisano, Nadine Darwiche, Walid Saad

Abstract:

Nanomedicine, the application of nanotechnology to medicine, is an emerging discipline that has gained significant attention in recent years. Current breakthroughs in nanomedicine have paved the way to develop effective drug delivery systems that can be used to target cancer. The use of nanotechnology provides effective drug delivery, enhanced stability, bioavailability, and permeability, thereby minimizing drug dosage and toxicity. As such, the use of nanoparticle (NP) formulations in drug delivery has been applied in various cancer models and have shown to improve the ability of drugs to reach specific targeted sites in a controlled manner. Cancer is one of the major causes of death worldwide; in particular, colorectal cancer (CRC) is the third most common type of cancer diagnosed amongst men and women and the second leading cause of cancer related deaths, highlighting the need for novel therapies. Retinoids, consisting of natural and synthetic derivatives, are a class of chemical compounds that have shown promise in preclinical and clinical cancer settings. However, retinoids are limited by their toxicity and resistance to treatment. To overcome this resistance, various synthetic retinoids have been developed, including the adamantyl retinoid ST1926, which is a potent anti-cancer agent. However, due to its limited bioavailability, the development of ST1926 has been restricted in phase I clinical trials. We have previously investigated the preclinical efficacy of ST1926 in CRC models. ST1926 displayed potent inhibitory and apoptotic effects in CRC cell lines by inducing early DNA damage and apoptosis. ST1926 significantly reduced the tumor doubling time and tumor burden in a xenograft CRC model. Therefore, we developed ST1926-NPs and assessed their efficacy in CRC models. ST1926-NPs were produced using Flash NanoPrecipitation with the amphiphilic diblock copolymer polystyrene-b-ethylene oxide and cholesterol as a co-stabilizer. ST1926 was formulated into NPs with a drug to polymer mass ratio of 1:2, providing a stable formulation for one week. The contin ST1926-NP diameter was 100 nm, with a polydispersity index of 0.245. Using the MTT cell viability assay, ST1926-NP exhibited potent anti-growth activities as naked ST1926 in HCT116 cells, at pharmacologically achievable concentrations. Future studies will be performed to study the anti-tumor activities and mechanism of action of ST1926-NPs in a xenograft mouse model and to detect the compound and its glucuroconjugated form in the plasma of mice. Ultimately, our studies will support the use of ST1926-NP formulations in enhancing the stability and bioavailability of ST1926 in CRC.

Keywords: nanoparticles, drug delivery, colorectal cancer, retinoids

Procedia PDF Downloads 96
7589 Kidnapping of Migrants by Drug Cartels in Mexico as a New Trend in Contemporary Slavery

Authors: Itze Coronel Salomon

Abstract:

The rise of organized crime and violence related to drug cartels in Mexico has created serious challenges for the authorities to provide security to those who live within its borders. However, to achieve a significant improvement in security is absolute respect for fundamental human rights by the authorities. Irregular migrants in Mexico are at serious risk of abuse. Research by Amnesty International as well as reports of the NHRC (National Human Rights) in Mexico, have indicated the major humanitarian crisis faced by thousands of migrants traveling in the shadows. However, the true extent of the problem remains invisible to the general population. The fact that federal and state governments leave no proper record of abuse and do not publish reliable data contributes to ignorance and misinformation, often spread by the media that portray migrants as the source of crime rather than their victims. Discrimination and intolerance against irregular migrants can generate greater hostility and exclusion. According to the modus operandi that has been recorded criminal organizations and criminal groups linked to drug trafficking structures deprive migrants of their liberty for forced labor and illegal activities related to drug trafficking, even some have been kidnapped for be trained as murderers . If the victim or their family cannot pay the ransom, the kidnapped person may suffer torture, mutilation and amputation of limbs or death. Migrant women are victims of sexual abuse during her abduction as well. In 2011, at least 177 bodies were identified in the largest mass grave found in Mexico, located in the town of San Fernando, in the border state of Tamaulipas, most of the victims were killed by blunt instruments, and most seemed to be immigrants and travelers passing through the country. With dozens of small graves discovered in northern Mexico, this may suggest a change in tactics between organized crime groups to the different means of obtaining revenue and reduce murder profile methods. Competition and conflict over territorial control drug trafficking can provide strong incentives for organized crime groups send signals of violence to the authorities and rival groups. However, as some Mexican organized crime groups are increasingly looking to take advantage of income and vulnerable groups, such as Central American migrants seem less interested in advertising his work to authorities and others, and more interested in evading detection and confrontation. This paper pretends to analyze the introduction of this new trend of kidnapping migrants for forced labors by drug cartels in Mexico into the forms of contemporary slavery and its implications.

Keywords: international law, migration, transnational organized crime

Procedia PDF Downloads 410
7588 Analytical Modelling of the Moment-Rotation Behavior of Top and Seat Angle Connection with Stiffeners

Authors: Merve Sagiroglu

Abstract:

The earthquake-resistant steel structure design is required taking into account the behavior of beam-column connections besides the basic properties of the structure such as material and geometry. Beam-column connections play an important role in the behavior of frame systems. Taking into account the behaviour of connection in analysis and design of steel frames is important due to presenting the actual behavior of frames. So, the behavior of the connections should be well known. The most important force which transmitted by connections in the structural system is the moment. The rotational deformation is customarily expressed as a function of the moment in the connection. So, the moment-rotation curves are the best expression of behaviour of the beam-to-column connections. The designed connections form various moment-rotation curves according to the elements of connection and the shape of placement. The only way to achieve this curve is with real-scale experiments. The experiments of some connections have been carried out partially and are formed in the databank. It has been formed the models using this databank to express the behavior of connection. In this study, theoretical studies have been carried out to model a real behavior of the top and seat angles connections with angles. Two stiffeners in the top and seat angle to increase the stiffness of the connection, and two stiffeners in the beam web to prevent local buckling are used in this beam-to-column connection. Mathematical models have been performed using the database of the beam-to-column connection experiments previously by authors. Using the data of the tests, it has been aimed that analytical expressions have been developed to obtain the moment-rotation curve for the connection details whose test data are not available. The connection has been dimensioned in various shapes and the effect of the dimensions of the connection elements on the behavior has been examined.

Keywords: top and seat angle connection, stiffener, moment-rotation curves, analytical study

Procedia PDF Downloads 171
7587 The Functional Roles of Right Dorsolateral Prefrontal Cortex and Ventromedial Prefrontal Cortex in Risk-Taking Behavior

Authors: Aline M. Dantas, Alexander T. Sack, Elisabeth Bruggen, Peiran Jiao, Teresa Schuhmann

Abstract:

Risk-taking behavior has been associated with the activity of specific prefrontal regions of the brain, namely the right dorsolateral prefrontal cortex (DLPFC) and the ventromedial prefrontal cortex (VMPFC). While the deactivation of the rDLPFC has been shown to lead to increased risk-taking behavior, the functional relationship between VMPFC activity and risk-taking behavior is yet to be clarified. Correlational evidence suggests that the VMPFC is involved in valuation processes that involve risky choices, but evidence on the functional relationship is lacking. Therefore, this study uses brain stimulation to investigate the role of the VMPFC during risk-taking behavior and replicate the current findings regarding the role of the rDLPFC in this same phenomenon. We used continuous theta-burst stimulation (cTBS) to inhibit either the VMPFC or DLPFC during the execution of the computerized Maastricht Gambling Task (MGT) in a within-subject design with 30 participants. We analyzed the effects of such stimulation on risk-taking behavior, participants’ choices of probabilities and average values, and response time. We hypothesized that, compared to sham stimulation, VMPFC inhibition leads to a reduction in risk-taking behavior by reducing the appeal to higher-value options and, consequently, the attractiveness of riskier options. Right DLPFC (rDLPFC) inhibition, on the other hand, should lead to an increase in risk-taking due to a reduction in cognitive control, confirming existent findings. Stimulation of both the rDLPFC and the VMPFC led to an increase in risk-taking behavior and an increase in the average value chosen after both rDLPFC and VMPFC stimulation compared to sham. No significant effect on chosen probabilities was found. A significant increase in response time was observed exclusively after rDLPFC stimulation. Our results indicate that inhibiting DLPFC and VMPFC separately leads to similar effects, increasing both risk-taking behavior and average value choices, which is likely due to the strong anatomical and functional interconnection of the VMPFC and rDLPFC.

Keywords: decision-making, risk-taking behavior, brain stimulation, TMS

Procedia PDF Downloads 104
7586 Predictive Modeling of Student Behavior in Virtual Reality: A Machine Learning Approach

Authors: Gayathri Sadanala, Shibam Pokhrel, Owen Murphy

Abstract:

In the ever-evolving landscape of education, Virtual Reality (VR) environments offer a promising avenue for enhancing student engagement and learning experiences. However, understanding and predicting student behavior within these immersive settings remain challenging tasks. This paper presents a comprehensive study on the predictive modeling of student behavior in VR using machine learning techniques. We introduce a rich data set capturing student interactions, movements, and progress within a VR orientation program. The dataset is divided into training and testing sets, allowing us to develop and evaluate predictive models for various aspects of student behavior, including engagement levels, task completion, and performance. Our machine learning approach leverages a combination of feature engineering and model selection to reveal hidden patterns in the data. We employ regression and classification models to predict student outcomes, and the results showcase promising accuracy in forecasting behavior within VR environments. Furthermore, we demonstrate the practical implications of our predictive models for personalized VR-based learning experiences and early intervention strategies. By uncovering the intricate relationship between student behavior and VR interactions, we provide valuable insights for educators, designers, and developers seeking to optimize virtual learning environments.

Keywords: interaction, machine learning, predictive modeling, virtual reality

Procedia PDF Downloads 124
7585 Hydro-Mechanical Behavior of a Tuff and Calcareous Sand Mixture for Use in Pavement in Arid Region

Authors: I. Goual, M. S. Goual, M. K. Gueddouda, Taïbi Saïd, Abou-Bekr Nabil, A. Ferhat

Abstract:

The aim of the paper is to study the hydro-mechanical behavior of a tuff and calcareous sand mixture. A first experimental phase was carried out in order to find the optimal mixture. This showed that the material composed of 80% tuff and 20% calcareous sand provides the maximum mechanical strength. The second experimental phase concerns the study of the drying-wetting behavior of the optimal mixture was carried out on slurry samples and compacted samples at the MPO. Experimental results let to deduce the parameters necessary for the prediction of the hydro-mechanical behavior of pavement formulated from tuff and calcareous sand mixtures, related to moisture. This optimal mixture satisfies the regulation rules and hence constitutes a good local eco-material, abundantly available, for the conception of pavements.

Keywords: tuff, sandy calcareous, road engineering, hydro mechanical behaviour, suction

Procedia PDF Downloads 435
7584 Policy Evaluation of Republic Act 9502 “Universally Accessible Cheaper and Quality Medicines Act of 2008”

Authors: Trina Isabel D. Santiago, Juan Raphael M. Perez, Maria Angelica O. Soriano, Teresita B. Suing, Jumee F. Tayaban

Abstract:

To achieve universal healthcare for everyone, the World Health Organization has emphasized the importance of National Medicines Policies for increased accessibility and utilization of high-quality and affordable medications. In the Philippines, significant challenges have been identified surrounding the sustainability of essential medicines, resulting in limited access such as high cost and dominance and market dominance and monopoly of multinational companies (MNCs) in the Philippine pharmaceutical industry. These identified challenges have been addressed by several initiatives, such as the Philippine National Drug Policy and Generics Act of 1988 (Republic Act 6675), to attempt to reduce drug prices. Despite these efforts, the concerns with drug accessibility and affordability continue to persist; hence, Republic Act 9502 was enacted. This paper attempts to review RA 9502 in the pursuit of making medicines more affordable for Filipinos, analyze and critique the problems and challenges associated with the law, and provide recommendations to address identified problems and challenges. A literature search and review, as well as an analysis of the law, has been done to evaluate the policy. RA 9502 recognizes the importance of market competition in drug price reduction and quality medicine accessibility. Contentious issues prior to enactment of the law include 1) parallel importation, pointing out that the drug price will depend on the global market price, 2) contrasting approaches in the drafting of the law as the House version focused on medicine price control while the Senate version prioritized market competition, and 3) MNCs opposing the amendments with concerns on discrimination, constitutional violations, and noncompliance with international treaty obligations. There are also criticisms and challenges with the implementation of the law in terms of content or modeling, interpretation and implementation, and other external factors or hindrances. The law has been criticized for its narrow scope as it only covers specific essential medicines with no cooperation with the national health insurance program. Moreover, the law has sections taking advantage of the TRIPS flexibilities, which disallow smaller countries to reap the benefits of flexibilities. The sanctions and penalties have an insignificant role in implementation as they only ask for a small portion of the income of MNCs. Proposed recommendations for policy improvement include aligning existing legislation through strengthened price regulation and expanded law coverage, strengthening penalties to promote law adherence, and promoting research and development to encourage and support local initiatives. Through these comprehensive recommendations, the issues surrounding the policy can be addressed, and the goal of enhancing the affordability and accessibility of medicines in the country can be achieved.

Keywords: drug accessibility, drug affordability, price regulation, Republic Act 9502

Procedia PDF Downloads 38
7583 A Literature Review of Ergonomics Sitting Studies to Characterize Safe and Unsafe Sitting Behaviors

Authors: Yoonjin Lee, Dongwook Hwang, Juhee Park, Woojin Park

Abstract:

As undesirable sitting posture is known to be a major cause of musculoskeletal disorder of office workers, sitting has attracted attention on occupational health. However, there seems to be no consensus on what are safe and unsafe sitting behaviors. The purpose of this study was to characterize safe and unsafe behaviors based on scientific findings of sitting behavior. Three objectives were as follows; to identify different sitting behaviors measure used in ergonomics studies on safe sitting, for each measure identified, to find available findings or recommendations on safe and unsafe sitting behaviors along with relevant empirical grounds, and to synthesize the findings or recommendations to provide characterizations of safe and unsafe behaviors. A systematic review of electronic databases (Google Scholar, PubMed, Web of Science) was conducted for extensive search of sitting behavior. Key terms included awkward sitting position, sedentary sitting, dynamic sitting, sitting posture, sitting posture, and sitting biomechanics, etc. Each article was systemically abstracted to extract a list of studied sitting behaviors, measures used to study the sitting behavior, and presence of empirical evidence of safety of the sitting behaviors. Finally, characterization of safe and unsafe sitting behavior was conducted based on knowledge with empirical evidence. This characterization is expected to provide useful knowledge for evaluation of sitting behavior and about postures to be measured in development of sensing chair.

Keywords: sitting position, sitting biomechanics, sitting behavior, unsafe sitting

Procedia PDF Downloads 295
7582 Can Antipsychotics Use for Schizophrenia on Long Term Lower Serum Cortisol Level?

Authors: Rady A., Elsheshai A., Eltawel M.

Abstract:

Introduction and Aim of work: Literature suggest that antipsychotic medications may decrease cortisol level, an effect that seems to be more present with second generation antipsychotic. Our study aims at assessing effect of long term use of antipsychotics on cortisol level Subjects and Methods: 30 chronic schizophrenic patients on antipsychotics compared to 20 drug naive schizophrenic patients as regards serum cortisol level Results: Cortisol level was significantly lower in chronic schizophrenic patients receiving antipsychotics compared to drug naive patients (P=0.002 <0.05) Conclusion: Antipsychotic medications seem to have the potential to decrease cortisol level in blood. Among hypothesis proposed in literature is the good control of pseudo stress due to psychotic features.

Keywords: schizophrenia, antipsychotic, cortisol, HPA

Procedia PDF Downloads 514
7581 The Influence of the Diameter of the Flow Conducts on the Rheological Behavior of a Non-Newtonian Fluid

Authors: Hacina Abchiche, Mounir Mellal, Imene Bouchelkia

Abstract:

The knowledge of the rheological behavior of the used products in different fields is essential, both in digital simulation and the understanding of phenomenon involved during the flow of these products. The fluids presenting a nonlinear behavior represent an important category of materials used in the process of food-processing, chemical, pharmaceutical and oil industries. The issue is that the rheological characterization by classical rheometer cannot simulate, or take into consideration, the different parameters affecting the characterization of a complex fluid flow during real-time. The main objective of this study is to investigate the influence of the diameter of the flow conducts or pipe on the rheological behavior of a non-Newtonian fluid and Propose a mathematical model linking the rheologic parameters and the diameter of the conduits of flow. For this purpose, we have developed an experimental system based on the principal of a capillary rheometer.

Keywords: rhéologie, non-Newtonian fluids, experimental stady, mathematical model, cylindrical conducts

Procedia PDF Downloads 283
7580 Religious Identity in the Diaspora: Peculiarities of Religious Consciousness and Behavior of Armenians in Tbilisi and Tehran

Authors: Nelli R. Khachaturian

Abstract:

The development of modern societies is largely associated with ethno-religious processes. The study of diasporas through the prism of religious processes is primarily aimed at identifying the impact of religious consciousness and behavior on the processes of reproduction of ethnic identity. Most often, it is religion that is associated with ethnic culture and historical heritage. Due to the peculiarities of the country of residence, different segments of the same ethnic group may demonstrate different religious consciousness and behavior. This paper is devoted to a comparative analysis of the religious behavior and consciousness of the representatives of the Armenian communities of Tbilisi and Tehran, based on the data obtained from the large-scale ethnic-sociological studies realized from 2013 to 2017 in Tehran and Tbilisi in the context of various spheres of public relations. Such research experience is of interest not only for understanding the dynamics of ethno-religious processes in the diasporas but also for understanding the role of religion as one of the most important factors in the formation of the mechanisms of self-preservation of an ethnic group, its current state and development prospects in the context of its own, different ethnic and / or foreign religious (non-confessional) environment.

Keywords: Armenian ethnicity, Armenian diaspora, religious consciousness, religious behavior, Armenian community of Tbilisi, Armenian community of Tehran

Procedia PDF Downloads 19