Search results for: statically determinate mechanisms

Authors: Chaoran Liu

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Bioactive polysaccharides and polysaccharide-protein complex derived from mushrooms and fungi have a wide range of immunomodulatory activity with low side-effects and have therefore the potential to be developed as an adjuvant in cancer therapies. Mushrooms sclerotium is rich in polysaccharides and the polysaccharides isolated from the sclerotium of Polyporus rhinocerus have shown potent in vivo and in vitro immunomodulatory effects. Macrophages are considered to be an important component of the innate immune response against bacterial infection and cancer. To better understanding the immunomodulatory effects and its underlying mechanisms of sclerotial water-soluble polysaccharides extracted from P. rhinocerus on macrophages, the objectives of this study are to purify the water-soluble novel sclerotial polysaccharides and to characterize the structure and properties as well as to study the detailed molecular mechanisms of the in vitro immunomodulating effects in murine macrophages. The hot water-soluble fraction PRW from the sclerotium of P. rhinocerus was obtained using solvent extraction. PRW was further fractionated by membrane ultrafiltration to a give a fraction (PRW1) with molecular mass less than 50 kDa. PRW1 was characterized to be a polysaccharide-protein complex composed of 45.7% polysaccharide and 44.2% protein. The chemical structure of the carbohydrate moiety of PRW1 was elucidated by GC and FTIR to be mainly beta-D-glucan with trace amount of galactose and mannose. The immunomodulatory effects of PRW1 on murine RAW 264.7 macrophages were demonstrated in terms of the increase in nitric oxide production and cytokine production. Mechanistically, PRW1 initiates ERK phosphorylation to activate macrophages within 15 min and significantly improves the expression level of inducible NOS (iNOS) from 6 h after treatment. In summary, this study indicates that PRW1 is a potent immunomodulatory agent for macrophages and suggests that mushroom sclerotia from Polyporus rhinocerus requires for further investigation in cancer research.

Keywords: Polyporus rhinocerus, mushroom sclerotia, Polysaccharide-Protein Complex, macrophage activation

Procedia PDF Downloads 233

Authors: Sadman Durlov, Aditya Ganesh-Ram, Hamidreza Hekmatjou, Md Najmus Salehin, Nora Shayesteh Ameri

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In the field of additive manufacturing, tungsten stands out for its exceptional resistance to high temperatures, making it an ideal candidate for use in extreme conditions. However, its inherent brittleness and vulnerability to thermal cracking pose significant challenges to its manufacturability. This study explores the microstructural evolution of tungsten processed through layer-wise rolling in laser powder bed fusion additive manufacturing, utilizing a comprehensive approach that combines advanced simulation techniques with empirical research. We aim to uncover the complex processes of plastic deformation and microstructural transformations, with a particular focus on the dynamics of grain size, boundary evolution, and phase distribution. Our methodology employs a combination of simulation and experimental data, allowing for a detailed comparison that elucidates the key mechanisms influencing microstructural alterations during the rolling process. This approach facilitates a deeper understanding of the material's behavior under additive manufacturing conditions, specifically in terms of deformation and recrystallization. The insights derived from this research not only deepen our theoretical knowledge but also provide actionable strategies for refining manufacturing parameters to improve the tungsten components' mechanical properties and functional performance. By integrating simulation with practical experimentation, this study significantly enhances the field of materials science, offering a robust framework for the development of durable materials suited for challenging operational environments. Our findings pave the way for optimizing additive manufacturing techniques and expanding the use of tungsten across various demanding sectors.

Keywords: additive manufacturing, layer wise rolling, refractory materials, in-situ microstructure modifications

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Authors: B. Gechbaia, K. Goletiani, G. Gabedava, N. Mikeltadze

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At this stage, Georgia is a country which is actively involved in the European integration process, for which the primary priority is effective integration in the European education system. The modern Georgian higher education system is the process of establishing a new sociocultural reality, whose main priorities are determined by the Quality System as a continuous cycle of planning, implementation, checking and acting. Obviously, in this situation, the issue of management of education institutions comes out in the foreground, since the proper planning and implementation of personnel management processes is one of the main determinants of the company's performance. At the same time, one of the most important factors is the psychological comfort of the personnel, ensuring their protection and efficiency of stress management policy. The purpose of this research is to determine how intensely the relationship is between the psychological comfort of the personnel and the efficiency of the quality system in the institution as the quality assurance mechanisms of educational institutions affect the stability of personnel, prevention and management of the stressful situation. The research was carried out within the framework of the Internal Grant Project «The Role of Organizational Culture in the Process of Settlement of Management of Stress and Conflict, Georgian Reality and European Experience » of the Batumi Navigation Teaching University, based on the analysis of the survey results of target groups. The small-scale research conducted by us has revealed that the introduction of quality assurance system and its active implementation increased the quality of management of Georgian educational institutions, increased the level of universal engagement in internal and external processes and as a result, it has improved the quality of education as well as social and psychological comfort indicators of the society.

Keywords: quality assurance, effective management, stability of personnel, psychological comfort, stress management

Procedia PDF Downloads 155

Authors: L. Gyansah, Yanfang Shen, Jiqiang Wang, Tianying Xiong

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SiCₚ/ pure Al composites with different SiC fractions (20 wt %, 30 wt %, and 40 wt %) were precisely cold sprayed, followed by hot axial-compression tests at deformation temperatures of 473 K to 673 K, leading to failure of specimens through routine crack propagation in their multiphase. The plastic deformation behaviour with respect to the SiCₚ contents and the deformation temperatures were studied at strain rate 1s-1.As-sprayed and post-failure specimens were analyzed by X-ray computed tomography (XCT), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). Quasi-static thermomechanical testing results revealed that compressive strength (UTS = 228 MPa and 30.4 %) was the highest in the composites that was thermomechanically compressed at 473 K compared to those of the as-sprayed, while the as-sprayed exhibited a compressive strength of 182.8 MPa related to the increment in SiC fraction. Strength—plasticity synergy was promoted by dynamic recrystallization (DRX) through strengthening and refinement of the grains. The DRX degree depends relevantly on retainment of the uniformly ultrafine SiCₚ particulates, the pinning effects of the interfaces promoted by the ultrafine grain structures (UFG), and the higher deformation temperature. Reconstructed X-ray computed tomography data revealed different crack propagation mechanisms. A single-plane shear crack with multi-laminates fracture morphology yields relatively through the as-sprayed and as-deformed at 473 K deposits, while a multiphase plane shear cracks preeminently existed in high temperature deformed deposits resulting in multiphase-interface delaminations. Three pertinent strengthening mechanisms, videlicet, SiCp dispersed strengthening, refined grain strengthening, and dislocation strengthening, existed in the gradient microstructure, and their detailed contributions to the thermomechanical properties were discussed.

Keywords: cold spraying, hot deformation, deformation temperature, thermomechancal properties, SiC/Al composite

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Authors: Logan Carmichael

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As the world’s governments seek to increasingly digitize their service provisions, there exists a subsequent and fully valid concern about the security underpinning these digital governance provisions. Estonia, a small and innovative Baltic nation, has been refining both its digital governance structure and cybersecurity mechanisms for over three decades and has been praised as global ‘best practice’ in both fields. However, the security of the Estonian digital governance system has been ever-evolving and significantly shaped by cybersecurity crises. This paper examines said crises – 2007 cyberattacks on Estonian government, banks, and news media; the 2017 e-ID crisis; the ongoing COVID-19 pandemic; and the 2022 Russian invasion of Ukraine – and how governance decision-making following these crises has shaped the cybersecurity of the digital governance structure in Estonia. This paper employs a blended constructivist and historical institutionalist theoretical approach as a useful means to view governance and decision-making in the wake of cybersecurity incidents affecting the Estonian digital governance structure. Together, these theoretical groundings frame the topics of cybersecurity and digital governance in an Estonian context through a lens of ideation and experience, as well as institutional path dependencies over time and cybersecurity crises as critical junctures to study. Furthermore, this paper takes a qualitative approach, employing discourse analysis, policy analysis, and elite interviewing of Estonian officials involved in digital governance and cybersecurity in order to glean nuanced perspectives into the processes that followed these four crises. Ultimately, the results of this paper will offer insight into how governments undertake policy-driven change following cybersecurity crises to ensure sufficient security of their digitized service provisions. This paper’s findings are informative not only in continued decision-making in the Estonian system but also in other states currently implementing a digital governance structure, for which security mechanisms are of the utmost importance.

Keywords: cybersecurity, digital governance, Estonia, crisis management, governance in crisis

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Authors: Karl Kingsley

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Many mechanisms are involved in the control of cellular differentiation and growth, which are often dysregulated in many cancers. Many distinct pathways are involved in these mechanisms of control, including deoxyribonuclease (DNA) methyltransferase and histone deacetylase (HDAC) activation that controls both genetic and epigenetic modifications and micro ribonucleic acid (RNA) expression. Less is known about the expression of DNA methyltransferase (DNMT) and HDAC in oral cancers and the effect on microRNA expression. The primary objective of this study was to evaluate the expression of DNMT and HDAC family members in oral cancer and the concomitant expression of cancer-associated microRNAs. Using commercially available oral cancers, including squamous cell carcinoma (SCC)-4, SCC-9, SCC-15, and SCC-25, RNA was extracted and screened for DNMT, HDAC, and microRNA expression using highly-specific primers and quantitative polymerase chain reaction (qPCR). These data revealed low or absent expression of DNMT-1, which is associated with cellular differentiation but increased expression of DNMT-3a and DNMT-3b in all SCC cell lines compared with normal non-cancerous cell controls. In addition, no expression of HDAC1 and HDAC2 expression was found among the normal, non-cancerous cells but was highly expressed in each of the SCC cell lines examined. Differential expression of oncogenic and cancer-associated microRNAs was also observed among the SCC cell lines, including miR-21, miR-133, miR-149, miR-155, miR-365, and miR-720. These findings also appeared to vary according to observed growth rates among these cells. These data may be the first to demonstrate the expression and association between HDAC and DNMT3 family members among oral cancers. In addition, the differential expression of these epigenetic modifiers may be associated with the expression of specific microRNAs in these cancers, which have not previously been observed to the best of the author's knowledge. In addition, some associations and relationships may exist between the expression of these biomarkers and the rates of growth and proliferation, which may suggest that these expression patterns might represent potentially useful biomarkers to determine tumor aggressiveness and other phenotypic behaviors among oral cancers.

Keywords: oral cancer, DNA methyltransferase, histone deacetylase, microRNA

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Authors: Laura Çami (Vorpsi), Xhon Skënderi

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In today's rapidly evolving technological landscape, the traditional principles of contract law are facing significant challenges. The emergence of new technologies, such as electronic signatures, smart contracts, and online dispute resolution mechanisms, is transforming the way contracts are formed, interpreted, and enforced. This paper examines the implications of these technological advancements on the constitutional principles of contract law. One of the fundamental principles of contract law is freedom of contract, which ensures that parties have the autonomy to negotiate and enter into contracts as they see fit. However, the use of technology in the contracting process has the potential to disrupt this principle. For example, online platforms and marketplaces often offer standard-form contracts, which may not reflect the specific needs or interests of individual parties. This raises questions about the equality of bargaining power between parties and the extent to which parties are truly free to negotiate the terms of their contracts. Another important principle of contract law is the requirement of consideration, which requires that each party receives something of value in exchange for their promise. The use of digital assets, such as cryptocurrencies, has created new challenges in determining what constitutes valuable consideration in a contract. Due to the ambiguity in this area, disagreements about the legality and enforceability of such contracts may arise. Furthermore, the use of technology in dispute resolution mechanisms, such as online arbitration and mediation, may raise concerns about due process and access to justice. The use of algorithms and artificial intelligence to determine the outcome of disputes may also raise questions about the impartiality and fairness of the process. Finally, it should be noted that there are many different and complex effects of technical improvements on the fundamental constitutional foundations of contract law. As technology continues to evolve, it will be important for policymakers and legal practitioners to consider the potential impacts on contract law and to ensure that the principles of fairness, equality, and access to justice are preserved in the contracting process.

Keywords: technological advancements, constitutional principles, contract law, smart contracts, online dispute resolution, freedom of contract

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Authors: Suleyman Karabal, Timothy L. Burnett, Egemen Avcu, Andrew H. Sherry, Philip J. Withers

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SA508 Grade 3 steel is widely used in the construction of nuclear pressure vessels, where its fracture toughness plays a critical role in ensuring operational safety and reliability. Understanding the ductile failure mechanisms in this steel grade is crucial for designing robust pressure vessels that can withstand severe nuclear environment conditions. In the present study, round bar specimens of SA508 Grade 3 steel with four distinct notch geometries were subjected to tensile loading while capturing continuous 2D images at 5-second intervals in order to monitor any alterations in their geometries to construct true stress-strain curves of the specimens. 3D reconstructions of X-ray computed tomography (CT) images at high-resolution (a spatial resolution of 0.82 μm) allowed for a comprehensive assessment of the influences of second-phase particles (i.e., manganese sulfide inclusions and cementite particles) on ductile failure initiation as a function of applied plastic strain. Additionally, based on 2D and 3D images, plasticity modeling was executed, and the results were compared to experimental data. A specific ‘two-parameter criterion’ was established and calibrated based on the correlation between stress triaxiality and equivalent plastic strain at failure initiation. The proposed criterion demonstrated substantial agreement with the experimental results, thus enhancing our knowledge of ductile fracture behavior in this steel grade. The implementation of X-ray CT and fractography analysis provided new insights into the diverse roles played by different populations of second-phase particles in fracture initiation under varying stress triaxiality conditions.

Keywords: ductile fracture, two-parameter criterion, x-ray computed tomography, stress triaxiality

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Authors: Sinarwati Mohamad Suhaili, Naomie Salim, Mohamad Nazim Jambli

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Sequence-to-sequence (seq2seq) models augmented with attention mechanisms are playing an increasingly important role in automated customer service. These models, which are able to recognize complex relationships between input and output sequences, are crucial for optimizing chatbot responses. Central to these mechanisms are neural attention weights that determine the focus of the model during sequence generation. Despite their widespread use, there remains a gap in the comparative analysis of different attention weighting functions within seq2seq models, particularly in the domain of chatbots using the Customer Support Twitter (CST) dataset. This study addresses this gap by evaluating four distinct attention-scoring functions—dot, multiplicative/general, additive, and an extended multiplicative function with a tanh activation parameter — in neural generative seq2seq models. Utilizing the CST dataset, these models were trained and evaluated over 10 epochs with the AdamW optimizer. Evaluation criteria included validation loss and BLEU scores implemented under both greedy and beam search strategies with a beam size of k=3. Results indicate that the model with the tanh-augmented multiplicative function significantly outperforms its counterparts, achieving the lowest validation loss (1.136484) and the highest BLEU scores (0.438926 under greedy search, 0.443000 under beam search, k=3). These results emphasize the crucial influence of selecting an appropriate attention-scoring function in improving the performance of seq2seq models for chatbots. Particularly, the model that integrates tanh activation proves to be a promising approach to improve the quality of chatbots in the customer support context.

Keywords: attention weight, chatbot, encoder-decoder, neural generative attention, score function, sequence-to-sequence

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Authors: Husham Bayazed

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Purpose of Presentation: The eye is one of a few sites in the body with immune privilege (IP). However, this IP is relatively easily bypassed in the face of sufficient strong local or systemic immunological responses. As immune responses are crucial elements of the repair response, the eye has developed distinct mechanisms to deliver immune responses to injury in the avascular regions of the eye. This presentation may cover and provide an overview of the mechanisms that dictate immune cell trafficking to the local ocular microenvironment in response to different autoimmune and inflammatory-mediated diseases. Recent Findings: Literature reviews declare that immune responses and inflammation play a key role in a diverse range of eye diseases. In recent years, our understanding of ocular immune responses has widely spread in ocular surface inflammation, uveitis, age-related macular degeneration (AMD), glaucoma, transplantation rejection, and other ocular diseases. It is becoming increasingly clear that multiple seemingly unrelated diseases involve immune responses with common themes in their ocular pathogenesis. Recent studies are focusing on elucidating the pathogenesis of ocular inflammatory disease to identify new targets for immunotherapy that will not only improve efficacy but also minimize adverse effects from traditional therapy. Summary: While IP was believed to protect the eye from day-to-day inflammatory insults, however, it is relatively easily breached in the face of different strong local or systemic immunological and inflammatory responses. Therefore, the ocular immune response encapsulates the full range of classical and non-classical immune responses and demonstrates many features which are reflected in other tissues, but eye tissues, by modifying these responses, may reveal unexpected and novel findings which are relevant to immune responses generally. This may have therapeutic potential for new targeting immunotherapy, restoring immune tolerance in ocular autoimmune and inflammatory diseases, and preventing rejection such as stem cells, currently being considered for treatment of worldwide blinding diseases such as AMD.

Keywords: ocular diseases, immunology, immune privilege, immunotherapy

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Authors: Nermeen Saad Elbeltagy, Hoda Ghareeb, Hesham Adel Elsheshtawy, Nadim Hamed, Amany Ibrahim Mostafa, Sara Hazem Hassan

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Introduction: Depression is one of the most common mental health problems occurring in women during their child bearing years. Perinatal depression refers to major and minor depressive episodes that occur either during pregnancy or aer delivery. Although perinatal depression is common in developing countries, it is under-recognized in low and middle income countries making a substantial contribution to maternal and infant morbidity and mortality. About 12.5 - 42% of pregnant women and, 12 - 50% of post natal mothers in low and middle income countries such as Ethiopia had depression AIM OF THE WORK: To study prevalence, associated factors and impact of maternal perinatal depression in Alexandria. Patients and method: This study was conducted on 300 mothers at the postnatal ward in ElShatby Maternity Hospital from April 2022 unl October 2022. Females with past history of depression before pregnancy or females who receive medications inducing depression were excluded. The participants were asked to complete the questionnaire that includes the Edinburgh Postnatal Depression Scale (EPDS) as a screening test to obtain information concerning the current frame of mind at antepartum, partum and postpartum periods Results: The prevalence of perinatal depression was 22.3%. It was found that there is a significant negave moderate correlation between socioeconomic status and perinatal depression(r=-0.42). The present study revealed that about two thirds (60.7%) of postpartum women had low socioeconomic level. Also, less than one fourth (20%) of parents had high education and only one fourth (25.3%) of postpartum women were working. There was a statically significance difference between the number of previous abortions and perinatal depression (p=0.04). There was a significant moderate correlation between the amount of blood lost during delivery and an increased risk of developing postpartum depression. The prevalence of perinatal depression was high in cases of female neonates more than male ones. Conclusion: the prevalence of perinatal depression among the studied women was 22.3% of studied group. The significant factors identified in this study can be targeted to reduce the occurrence of perinatal depression among pregnant women in Alexandria through appropriate health interventions which includes perinatal depression screening, counseling, and the provision of support for pregnant women during antenatal care as well as lifestyle modification.

Keywords: mental health, depression in pregnancy, mental disorders, psychology in pregnancy

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Authors: Mohamed Abdel-Hamid, Olfat Gamil Shaker, Doha El-Sayed Ellakwa, Eman Fathy Abdel-Maksoud

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Introduction: Despite advances in the knowledge of the molecular virology of hepatitis C virus (HCV), the mechanisms of hepatocellular injury in HCV infection are not completely understood. Hepatitis C viral infection (HCV) influences the susceptibility to apoptosis. This could lead to insufficient antiviral immune response and persistent viral infection. Aim of this study: was to examine whether BCL-2 gene polymorphism at codon 43 (+127G/A or Ala43Thr) has an impact on development of hepatocellular carcinoma caused by chronic hepatitis C Egyptian patients. Subjects and Methods: The study included three groups; group 1: composing of 30 patients with hepatocellular carcinoma (HCC), group 2 composing of 30 patients with HCV, group 3 composing of 30 healthy subjects matching the same age and socioeconomic status were taken as a control group. Gene polymorphism of BCL2 (Ala43Thr) were evaluated by PCR-RFLP technique and measured for all patients and controls. Results: The summed 43Thr genotype was more frequent and statistically significant in HCC patients as compared to control group. This genotype of BCL2 gene may inhibit the programmed cell death which leads to disturbance in tissue and cells homeostasis and reduction in immune regulation. This result leads to viral replication and HCV persistence. Moreover, virus produces variety of mechanisms to block genes participated in apoptosis. This mechanism proves that HCV patients who have 43Thr genotype are more susceptible to HCC. Conclusion: The data suggest for the first time that the BCL2 polymorphism is associated with the susceptibility to HCC in Egyptian populations and might be used as molecular markers for evaluating HCC risk. This study clearly demonstrated that Chronic HCV exhibit a deregulation of apoptosis with the disease progression. This provides an insight into the pathogenesis of chronic HCV infection, and may contribute to the therapy.

Keywords: BCL2 gene, Hepatitis C Virus, Hepatocellular carcinoma, sensitivity, specificity, apoptosis

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Authors: Jiping Cai, Ningzhi Wangyang, Jun Shao

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Traumatic brain injury (TBI) is one of the major causes of morbidity and mortality that leads to structural and functional damage in several parts of the brain, such as cranial nerves, optic nerve tract or other circuitry involved in vision and occipital lobe, depending on its location and severity. As a result, the function associated with vision processing and perception are significantly affected and cause blurred vision, double vision, decreased peripheral vision and blindness. Here two cases complaining of monocular vision loss (actually temporal hemianopia) due to traumatic chiasmal syndrome after frontal head injury were reported, and were compared the findings with individual case reports published in the literature. Reported cases of traumatic chiasmal syndrome appear to share some common features, such as injury to the frontal bone and fracture of the anterior skull base. The degree of bitemporal hemianopia and visual loss acuity have a variable presentation and was not necessarily related to the severity of the craniocerebral trauma. Chiasmal injury may occur even in the absence bony chip impingement. Isolated bitemporal hemianopia is rare and clinical improvement usually may not occur. Mechanisms of damage to the optic chiasm after trauma include direct tearing, contusion haemorrhage and contusion necrosis, and secondary mechanisms such as cell death, inflammation, edema, neurogenesis impairment and axonal damage associated with TBI. Beside visual field test, MRI evaluation of optic pathways seems to the strong objective evidence to demonstrate the impairment of the integrity of visual systems following TBI. Therefore, traumatic chiasmal syndrome should be considered as a differential diagnosis by both neurosurgeons and ophthalmologists in patients presenting with visual impairment, especially bitemporal hemianopia after head injury causing frontal and anterior skull base fracture.

Keywords: bitemporal hemianopia, brain injury, optic chiasma, traumatic chiasmal syndrome.

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Authors: Ella Tyuryumina, Alexey Neznanov

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Finding algorithms to predict the growth of tumors has piqued the interest of researchers ever since the early days of cancer research. A number of studies were carried out as an attempt to obtain reliable data on the natural history of breast cancer growth. Mathematical modeling can play a very important role in the prognosis of tumor process of breast cancer. However, mathematical models describe primary tumor growth and metastases growth separately. Consequently, we propose a mathematical growth model for primary tumor and primary metastases which may help to improve predicting accuracy of breast cancer progression using an original mathematical model referred to CoM-IV and corresponding software. We are interested in: 1) modelling the whole natural history of primary tumor and primary metastases; 2) developing adequate and precise CoM-IV which reflects relations between PT and MTS; 3) analyzing the CoM-IV scope of application; 4) implementing the model as a software tool. The CoM-IV is based on exponential tumor growth model and consists of a system of determinate nonlinear and linear equations; corresponds to TNM classification. It allows to calculate different growth periods of primary tumor and primary metastases: 1) ‘non-visible period’ for primary tumor; 2) ‘non-visible period’ for primary metastases; 3) ‘visible period’ for primary metastases. The new predictive tool: 1) is a solid foundation to develop future studies of breast cancer models; 2) does not require any expensive diagnostic tests; 3) is the first predictor which makes forecast using only current patient data, the others are based on the additional statistical data. Thus, the CoM-IV model and predictive software: a) detect different growth periods of primary tumor and primary metastases; b) make forecast of the period of primary metastases appearance; c) have higher average prediction accuracy than the other tools; d) can improve forecasts on survival of BC and facilitate optimization of diagnostic tests. The following are calculated by CoM-IV: the number of doublings for ‘nonvisible’ and ‘visible’ growth period of primary metastases; tumor volume doubling time (days) for ‘nonvisible’ and ‘visible’ growth period of primary metastases. The CoM-IV enables, for the first time, to predict the whole natural history of primary tumor and primary metastases growth on each stage (pT1, pT2, pT3, pT4) relying only on primary tumor sizes. Summarizing: a) CoM-IV describes correctly primary tumor and primary distant metastases growth of IV (T1-4N0-3M1) stage with (N1-3) or without regional metastases in lymph nodes (N0); b) facilitates the understanding of the appearance period and manifestation of primary metastases.

Keywords: breast cancer, exponential growth model, mathematical modelling, primary metastases, primary tumor, survival

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Authors: Benjaporn Buranrat, Nootchanat Mairuae

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Cratoxylum formosum (Jack) Dyer (CF) has been used for the traditional medicines in South East Asian and Thailand. Normally, northeast Thai vegetables have proven cytotoxic to many cancer cells. Therefore, the present study aims to explore the molecular mechanisms underlying CF-induced cancer cell death and apoptosis on breast and liver cancer cells. The cytotoxicity and antiproliferative effects of CF on the human breast MCF-7 and liver HepG2 cancer cell lines were evaluated using sulforhodamine B assay and colony formation assay. Cell migration assay was measured using wound healing assay. The apoptosis induction mechanisms were investigated through reactive oxygen species formation, caspase 3 activity, and JC-1 activity. Gene expression by real-time PCR and apoptosis related protein levels by Western blot analysis. CF induced MCF-7 and HepG2 cell death by time- and dose-dependent manner. Furthermore, CF had the greater cytotoxic potency on MCF-7 more than HepG2 cells with IC50 values of 85.70+4.52 μM and 219.03±9.96 μM respectively, at 24 h. Treatment with CF also caused a dose-dependent decrease in colony forming ability and cell migration, especially on MCF-7 cells. CF induced ROS formation, increased caspase 3 activities, and decreased the mitochondrial membrane potential, and causing apoptotic body production and DNA fragmentation. CF significantly decreased expression of the cell cycle regulatory protein RAC1 and downstream proteins, cdk6. Additionally, CF enhanced p21 and reduced cyclin D1 protein levels. CF leaf extract induced cell death, apoptosis, antimigration in both of MCF-7 and HepG2 cells. CF could be useful for developing to anticancer drug candidate for breast and liver cancer therapy.

Keywords: cratoxylum formosum (jack) dyer, breast cancer, liver cancer, cell death

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Authors: Brahmanage S. Rangika, Dinithi C. Peiris

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Boiled Aqueous Flower Extract (AFE) of Nyctanthes arbor-tristis L. (Family: Oleaceae) is used in traditional Sri Lankan medicinal system to treat diabetes. However, this is not scientifically proven and the mechanisms by which the flowers reduce diabetes have not been investigated. The present study was carried out to examine the hypoglycemic potential and toxicity effects of aqueous flower extract of N. arbor-tristis. AFE was prepared and mice were treated orally either with 250, 500, and 750 mg/kg of AFE or distilled water (Control). Fasting and random blood glucose levels were determined. In addition, the toxicity of AFE was determined using chronic oral administration. In normoglycemic mice, mid dose (500mg/kg) of AFE significantly (p < 0.01) reduced fasting blood glucose levels by 49% at 4h post treatment. Further, 500mg/kg of AFE significantly (p < 0.01) lowered random blood glucose level of non-fasted normoglycemic mice. AFE significantly lowered total cholesterol and triglyceride levels while increasing the HDL levels in the serum. Further, AFE significantly inhibited the glucose absorption from the lumen of the intestine and it increases the diaphragm uptake of glucose. Alpha-amylase inhibitory activity was also evident. However, AFE did not induce any overt signs of toxicity or hepatotoxicity. There were no adverse effects on food and water intake and body weight of mice during the experimental period. It can be concluded that AFE of N. arbor-tristis posses safe oral anti diabetic potentials mediated via multiple mechanisms. Results of the present study scientifically proved the claims made about the uses of N. arbor-tristis in the treatment of diabetes mellitus in traditional Sri Lankan medicinal system. Further, flowers can also be used for as a remedy to improve blood lipid profile.

Keywords: aqueous extract, hypoglycemic hypolipidemic, Nyctanthes arbor-tristis flowers, hepatotoxicity

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Authors: Ghalia Shamlan, M. Denise Robertson, Adam Collins

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Appetite control (i.e. control of energy intake) is important for weight maintenance. Exercise contributes to the most variable component of energy expenditure (EE) but its impact is beyond the energy cost of exercise including physiological, behavioural, and appetite effects. Exercise is known to acutely influence effect appetite but evidence as to the independent effect of intensity is lacking. This study investigated the role of exercise intensity on appetite, energy intake (EI), appetite related hormone, fat utilisation and subjective measures of appetite. One hour after a standardised breakfast, 10 sedentary overweight volunteers. Subjects undertook either 8 repeated 60 second bouts of cycling at 95% VO2max (high intensity) or 30 minutes of continuous cycling, at a fixed cadence, equivalent to 50% of the participant’s VO2max (low intensity) in a randomised crossover design. Glucose, NEFA, glucagon-like peptide-1 (GLP-1) were measured fasted, postprandial, and pre and post-exercise. Satiety was assessed subjectively throughout the study using visual analogue scales (VAS). Ad libitum intake of a pasta meal was measured at the end (3-h post-breakfast). Interestingly, there was not significant difference in EE fat oxidation between HI and LI post-exercise. Also, no significant effect of high intensity (HI) was observed on the ad libitum meal, 24h and 48h EI post-exercise. However the mean 24h EI was 3000 KJ lower following HI than low intensity (LI). Despite, no significant differences in hunger score, glucose, NEFA and GLP-1 between both intensities were observed. However, NEFA and GLP-1 plasma level were higher until 30 min post LI. In conclusion, the similarity of EE and oxidation outcomes could give overweight individuals an option to choose between intensities. However, HI could help to reduce EI. There are mechanisms and consequences of exercise in short and long-term appetite control; however, these mechanisms warrant further explanation. These results support the need for future research in to the role of in regulation energy balance, especially for obese people.

Keywords: appetite, exercise, food intake, energy expenditure

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Authors: Launcelot.McGrath

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A comprehensive understanding of physiological data is a vital aid to the anaesthesiologist in monitoring and maintaining the well-being of a patient undergoing surgery. Biosignal analysis is one of the most important topics that researchers have tried to develop over the last century to understand numerous human diseases. Understanding which biological signals are most important during anaesthesia is critically important. It is important that the anaesthesiologist understand both the signals themselves and the limitations introduced by the processes of acquisition. In this article, we provide an overview of different types of biological signals as well as the mechanisms applied to acquire them.

Keywords: general biosignals, anaesthesia, biological, electroencephalogram

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Authors: Mohammed Yagoub

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The new orientation to the market economy sponsored by the Algeria government in the early Nineties of the last century, and its desire to develop investment mechanisms and the promotion of development recently, the access into a partnership with the European Union, and the forthcoming accession to the World Trade Organization, foreign direct investment makes one of the most important means of opening up to foreign markets and bring technology and interact with globalization, this article we will discuss the impact of FDI on economic growth in the Algerian.

Keywords: economic, development, markets, FDI, displacement, globalization

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Authors: H. A. Jawan

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This review describes the models of environmental-related crack propagation of aluminum alloys (7xxx) during the last few decades. Acknowledge on effects of different factors on the susceptibility to SCC permits to propose valuable mechanisms on crack advancement. The reliable mechanism of cracking give a possibility to propose the optimum chemical composition and thermal treatment conditions resulting in microstructure the most suitable for real environmental condition and stress state.

Keywords: microstructure, environmental, propagation, mechanism

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Authors: Vinod Kumar Gupta, Narendrakumar M. Chaudhari, Suchismitha Iskepalli, Chitra Dutta

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Background-The community composition of the human microbiome is known to vary at distinct anatomical niches. But little is known about the nature of variations if any, at the genome/sub-genome levels of a specific microbial community across different niches. The present report aims to explore, as a case study, the variations in gene repertoire of 28 Prevotella reference draft genomes derived from different body-sites of human, as reported earlier by the Human Microbiome Consortium. Results-The analysis reveals the exclusive presence of 11798, 3673, 3348 and 934 gene families and exclusive absence of 17, 221, 115 and 645 gene families in Prevotella genomes derived from the human oral cavity, gastro-intestinal tracts (GIT), urogenital tract (UGT) and skin, respectively. The pan-genome for Prevotella remains “open”. Distribution of various functional COG categories differs appreciably among the habitat-specific genes, within Prevotella pan-genome and between the GIT-derived Bacteroides and Prevotella. The skin and GIT isolates of Prevotella are enriched in singletons involved in Signal transduction mechanisms, while the UGT and oral isolates show higher representation of the Defense mechanisms category. No niche-specific variations could be observed in the distribution of KEGG pathways. Conclusion-Prevotella may have developed distinct genetic strategies for adaptation to different anatomical habitats through selective, niche-specific acquisition and elimination of suitable gene-families. In addition, individual microorganisms tend to develop their own distinctive adaptive stratagems through large repertoires of singletons. Such in situ, habitat-driven refurbishment of the genetic makeup can impart substantial intra-lineage genome diversity within the microbes without perturbing their general taxonomic heritage.

Keywords: body niche adaptation, human microbiome, pangenome, Prevotella

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Authors: M. Borgie, Z. Dagher, F. Ledoux, A. Verdin, F. Cazier, H. Greige, P. Shirali, D. Courcot

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In October 2013, the International Agency for Research on Cancer (IARC) classified outdoor air pollution and fine particulate matter (PM2.5) as carcinogenic to humans. Despite the clearly relationship established by epidemiological studies between PM exposure and the onset of respiratory and cardiovascular diseases, uncertainties remain about the physiopathological mechanisms responsible for these diseases. The aim of this work was to evaluate the toxicological effects of two samples of atmospheric PM2.5 collected at urban and rural sites on human bronchial epithelial cells, BEAS-2B, especially to investigate the metabolic activation of organic compounds, the alteration of epigenetic mechanisms (i.e. microRNAs genes expression), the phosphorylation of H2AX and the telomerase activity. Our results showed a significant increase in CYP1A1, CYP1B1, and AhRR genes expression, miR-21 gene expression, H2AX phosphorylation and telomerase activity in BEAS-2B cells after their exposure to PM2.5, both in a dose and site-dependent manner. These results showed that PM2.5, especially urban PM, are able to induce the expression of metabolizing enzymes which can provide metabolic biotransformation of organic compounds into more toxic and carcinogenic metabolites, and to induce the expression of the oncomiR miR-21 which promotes cell growth and enhances tumor invasion and metastasis in lung cancer. In addition, our results have highlighted the role of PM2.5 in the activation of telomerase, which can maintain the telomeres length and subsequently preventing cell death, and have also demonstrated the ability of PM2.5 to induce DNA breaks and thus to increase the risk of mutations or chromosomal translocations that lead to genomic instability. All these factors may contribute to cell abnormalities, and thus the development of cancer.

Keywords: BEAS-2B cells, carcinogenesis, epigenetic alterations and genotoxicity, PM2.5

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Authors: Mary-Ann N. Jallad, Dalal F. Jaber, Alexander M. Abdelnoor

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Introduction: Current evidence confirms that both innate and adaptive immune systems are capable of recognizing and abolishing malignant cells. The emergence of cancerous tumors in patients is, therefore, an indication that certain cancer cells can resist elimination by the immune system through a process known as “immune evasion”. In fact, cancer cells often exploit regulatory mechanisms to escape immunity. Such mechanisms normally exist to control the immune responses and prohibit exaggerated or autoimmune reactions. Recently, immunotherapies have shown promising yet limited results. Therefore this study investigates several immunotherapeutic combinations and devises a triple immunotherapy which harnesses the innate and acquired immune responses towards the annihilation of malignant cells through overcoming their ability of immune evasion, consequently hampering malignant progression and eliminating established tumors. The aims of the study are to rule out acute/chronic toxic effects of the proposed treatment combinations, to assess the effect of these combinations on tumor growth and survival rates, and to investigate potential mechanisms underlying the phenotypic results through analyzing serum levels of anti-tumor cytokines, angiogenic factors and tumor progression indicator, and the tumor-infiltrating immune-cells populations. Methodology: For toxicity analysis, cancer-free C57BL/6 mice are randomized into 9 groups: Group 1 untreated, group 2 treated with sterile saline (solvent of used treatments), group 3 treated with Monophosphoryl-lipid-A, group 4 with anti-CTLA4-antibodies, group 5 with 1-Methyl-Tryptophan (Indolamine-Dioxygenase-1 inhibitor), group 6 with both MPLA and anti-CTLA4-antibodies, group 7 with both MPLA and 1-MT, group 8 with both anti-CTLA4-antibodies and 1-MT, and group 9 with all three: MPLA, anti-CTLA4-antibodies and 1-MT. Mice are monitored throughout the treatment period and for three following months. At that point, histological sections from their main organs are assessed. For tumor progression and survival analysis, a murine melanoma model is generated by injecting analogous mice with B16F10 melanoma cells. These mice are segregated into the listed nine groups. Their tumor size and survival are monitored. For a depiction of underlying mechanisms, melanoma-bearing mice from each group are sacrificed at several time-points. Sera are tested to assess the levels of Interleukin-12 (IL-12), Vascular-Endothelial-Growth Factor (VEGF), and S100B. Furthermore, tumors are excised for analysis of infiltrated immune cell populations including T-cells, macrophages, natural killer cells and immune-regulatory cells. Results: Toxicity analysis shows that all treated groups present no signs of neither acute nor chronic toxicity. Their appearance and weights were comparable to those of control groups throughout the treatment period and for the following 3 months. Moreover, histological sections from their hearts, kidneys, lungs, and livers were normal. Work is ongoing for completion of the remaining study aims. Conclusion: Toxicity was the major concern for the success of the proposed comprehensive combinational therapy. Data generated so far ruled out any acute or chronic toxic effects. Consequently, ongoing work is quite promising and may significantly contribute to the development of more effective immunotherapeutic strategies for the treatment of cancer patients.

Keywords: cancer immunotherapy, check-point blockade, combination therapy, melanoma

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Authors: H. Jawan

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This review describes the models of environmental-related crack propagation of aluminum alloys (7xxx) during the last few decades. Acknowledge on effects of different factors on the susceptibility to SCC permits to propose valuable mechanisms on crack advancement. The reliable mechanism of cracking give a possibility to propose the optimum chemical composition and thermal treatment conditions resulting in microstructure the most suitable for real environmental condition and stress state.

Keywords: microstructure, environmental, propagation, mechanism

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Authors: Almagul Nurgaliyeva

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The phenomenon of novice teacher attrition is an urgent issue. The effective mechanisms to increase the retention rate of novice teachers relate to the nature and level of support provided at an employing site. This study considered novice teacher retention as a motivation-based process, which is based on a variety of support activities employed to satisfy novice teachers’ needs at an early career stage. The purpose of the study was to examine novice teachers’ perceptions of the effectiveness of the induction program and other support structure(s) at a secondary school in Nur-Sultan. The study was guided by Abraham Maslow’s (1943) theory of motivation. Maslow’s hierarchy of needs was used as a theoretical framework to identify the novice teachers’ primary needs and the extent to which the induction programs and other support mechanisms provided by the school administrators fulfill those needs. One school supervisor and eight novice teachers (four current and four former novice teachers) with a maximum of four years of teaching experience took part in the study. To investigate the perspectives and experiences of the participants, an online semi-structured interview was utilized. The responses were collected and analyzed. The study revealed four major challenges: educational, personal-psychological, sociological, and structural which are seen as the main constraints during the adaptation period. Four induction activities, as emerged from the data, are being carried out by the school to address novice teachers’ challenges: socialization activities, mentoring programs, professional development, and administrative support. These activities meet novice teachers’ needs and confront the challenges they face. Sufficient and adequate support structures provided to novice teachers during their first years of working experience is essential, as they may influence their decision to remain in the teaching profession, thereby reducing the attrition rate. The study provides recommendations for policymakers and school administrators about the structure and the content of induction program activities.

Keywords: beginning teacher induction, induction programme, orientation programmes, adaptation challenges, novice teacher retention

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Authors: Natalia Uribe Corrales, Santiago Henao Villegas

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Introduction: The management of pigs in the holding pens at the slaughterhouses is a key point to minimize levels of stress and fear, improve efficiency, maintain a good quality of meat and avoid economic losses. Holding pens should guarantee drinking water continuously, a minimum space of 1.2 m2/ animal; As well as an adequate management in the conduction of the animals towards stun. Objective: To characterize the management practices in holding pens in slaughterhouses in the Valle de Aburrá. Methods: A descriptive cross - sectional study was carried out in Valle de Aburrá benefit plants, which were authorized by National Institute for Food and Medicine Surveillance (INVIMA). Variables such as management mechanisms to the pens, time of housing, water supply, load density, vocalization, slips and falls of the animals in the pens and mechanism of conduction towards desensitization were analyzed. Results: 225 pigs were analyzed, finding that 35.6% were lowered with slaps from the trucks to the waiting pens; The lairage time was greater than 10 hours in 16% of the animals; 12.9% of pigs had no water permanently; 40.9% was subjected to a high load density, while 19.6% had a low load density. Regarding aspects of animal welfare, 37.3% presented high vocalizations; 29.3% and 14.2% presented slips or falls respectively. Regarding the mechanism of conduction towards desensitization, slapping was used in 56% and electrical prod in 4%. Conclusions: It is necessary to continue promoting the learning of the densities of load, since both high and low densities generate inconveniences in animal welfare, favoring the appearance of lesions and stress in the animals. Also, to promote the rule of permanent water in the pens and a time of housing less than 10 hours. In relation to the driving mechanisms, it is necessary to continue animal husbandry campaigns, encouraging the use of other alternatives such as boards or panels to assist the movement of pigs.

Keywords: animal welfare, quality of meat, swine, waiting pens

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Authors: Sruthi Ramagiri, Rajeev T.

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Free radical damage has been entailed as the major culprit in the ischemic stroke contributing for oxidative damage. Recent investigations on Hydroxy Safflower Yellow A (HSYA) suggested its role in cerebral ischemia and various neurodegenerative disorders with unidentified molecular mechanisms. The current study was designed to investigate putative therapeutic role and possible molecular mechanisms of HSYA administration during the onset of reperfusion in cerebral ischemia-reperfusion (I/R) injury in cerebral stroke. Cerebral stroke was achieved by focal ischemic model. HSYA (10 mg/kg) was injected intravenously via the tail vein 5 minutes before reperfusion. Losses of sensorimotor abilities were evaluated by neurological scoring, spontaneous locomotor activity, and rotarod performance. Extent of oxidative stress was evaluated by biochemical parameters i.e., malondialdehyde (MDA), Glutathione (GSH), Super Oxide Dismutase (SOD) and catalase levels. The infarct volume of brain was assessed by 2,3,5-triphenyl tetrazolium chloride (TTC) staining technique. Increased cerebral injury (I/R) was evidenced by motor impairment, increased infarct volume and elevation of MDA levels along with significant reduction in antioxidant i.e.,MDA levels along with significant reduction in antioxidant i.e., GSH, SOD and catalase levels when compared to sham control. However, post conditioning with HSYA (10 mg/kg, i.v.) at the onset of reperfusion has significantly ameliorated sensorimotor abilities, attenuated MDA levels and reduced the infarct volume as compared with vehicle treated I/R injury group. Moreover, HSYA treatments improved antioxidant enzyme levels as compared with vehicle treated I/R-injury group. In conclusion, it may be suggested that HSYA post conditioning could be novel therapeutic approach against I/R injury in cerebral stroke possibly through its anti-oxidant mechanism.

Keywords: HSYA, Ischemia reperfusion injury, oxidative stress, stroke

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Authors: Behzad Hezarkhani, Greys Sosic

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Collaborative purchasing and replenishment have proven to be beneficial in supply chain management. This talk addresses the situation where buyers, potentially in possession of private procurement channels, carry out cooperative purchasing by submitting their bids to a coordinator. The collaborative organization is faced with two basic decisions: (1) who will be allocated with the products, and (2) how much each party should pay. We discuss mechanisms that could achieve desirable outcomes in this settings with special attention to the strategic behavior of the buyers.

Keywords: supply chain management, group purchasing organizations, game theory, mechanism design

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Authors: Noemia Bessa Vilela, Jose Caramelo Gomes

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All law student are familiarized, in the first years of their bachelor of laws with the concepts of “public goods” and “ private goods”; often, such legal concept does not exactly match such economic concept, and there are consequences are some sort of confusion being created. The list of goods that follow under each category is not exhaustive, nor are students given proper mechanisms to acknowledge that some legal fields can, on its own, be considered as a “public good”; this is the case of Competition. Legal authors consider that “competition law is used to promote public interest” and, as such, it is a “public good”; in economics theory, Competition is the first public good in a market economy, as the enabler of allocation efficiency. Competition law is the legal tool to support the proper functioning of the market economy and democracy itself. It is fact that Competition Law only applies to economic activities, still, competition is object of private litigation as an integral part of Public Law. Still, regardless of the importance of Competition Law in the economic activity and market regulation, most student complete their studies in law, join the Bar Associations and engage in their professional activities never having been given sufficient tools to deal with the increasing demands of a globalized world. The lack of knowledge of economics, market functioning and the mechanisms at their reach in order to ensure proper realization of their duties as lawyers/ attorneys-at-law would be tackled if Competition Law would be included as part of the curricula of Law Schools. Proper teaching of Competition Law would combine the foundations of Competition Law, doctrine, case solving and Case Law study. Students should to understand and apply the analytical model. Special emphasis should be given to EU Competition Law, namely the TFEU Articles 101 to 106. Damages Directive should also be part of the curriculum. Students must in the first place acquire and master the economic rationale as competition and the world of competition law are the cornerstone of sound and efficient market. The teaching of Competition Law in undergraduate programs in Law would contribute to fulfill the potential of the students who will deal with matters related to consumer protection, economic and commercial law issues both in private practice and as in-house lawyers for companies.

Keywords: higher education, competition law, legal education, law, market economy, industrial economics

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Authors: William Ceurvels, Dong-Di Zhang

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The true nature of the mechanism by which the pharmaceuticals of the Shang-Han Lun act has been a topic of debate since Wuji Cheng published the first commentary during the Northern Song. Subsequent commentaries employed a number of methodologies in their analysis of pharmaceutical mechanisms, but no commentator was able to garner universal acceptance. During the Qing Dynasty, the proliferation and development of Neo-Confucian scholarship produced a new generation of scholars possessed of rigorous and inventive research methods, one of whom was the famed materia medica scholar, Run-an Zou. Run-an Zou and his successor Zhou Yan advocated analyzing the mechanism of Treatise pharmaceuticals based upon the understanding of those pharmaceuticals during the time period in which the Treatise was written and thereby focused on the Han Dynasty materia medica tract Shen-nong Ben-cao Jing (The Divine Husbandman’s Herbal Foundation Canon). Zou Run-an’s commentary, Ben-jing Shu-zheng won nearly universal praise among materia medica scholars for its scholastic rigor and innovative research methods. However, because Ben-jing Shu-zheng only focuses on individual herbs, as opposed to formulas, its value in analyzing the Shang-Han Lun has limitations. The purpose of this study is to combine Zou Run-an’s single-pharmaceutical commentaries to generate theoretical full formula analyses to gain a fuller picture of Zou’s understanding of the healing mechanism of Shang-Han Lun formulas. Commentaries were gathered from Ben-jing Shu-zheng and Zhou Yan’s Ben-cao Si-bian Lun and combined to produce theoretical full formula model mechanisms of Treatise formulas. Through this study, a new picture of the mechanistic basis of Shang-han formulas emerges, which is based on qi-xue changes as opposed to organ or meridian theory. The author hopes that this modest research study will be of service to scholars of the Shang-han and clinical doctors alike in their pursuit of the true pharmacomechanisms of this great Han dynasty tome.

Keywords: Materia medica, Shang-han Lun, Shen-nong Ben-cao Jing, neo-Confucian scholarship

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