Search results for: corrosion mechanisms

Authors: Muhammad Awais Afzal, Lorena Tuchscherr De Hauschopp, Christian Hübner

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Introduction: Autophagy is an evolutionarily conserved lysosome-dependent degradation pathway, which can be induced by extrinsic and intrinsic stressors in living systems to adapt to fluctuating environmental conditions. In the context of inflammatory stress, autophagy contributes to the elimination of invading pathogens, the regulation of innate and adaptive immune mechanisms, and regulation of inflammasome activity as well as tissue damage repair. Lysosomes can be recycled from autolysosomes by the process of autophagic lysosome reformation (ALR), which depends on the presence of several proteins including Spatacsin. Thus ALR contributes to the replenishment of lysosomes that are available for fusion with autophagosomes in situations of increased autophagic turnover, e.g., during bacterial infections, inflammatory stress or sepsis. Objectives: We aimed to assess whether ALR plays a role for cell survival in an in-vitro bacterial infection model. Methods: Mouse embryonic fibroblasts (MEFs) were isolated from wild-type mice and Spatacsin (Spg11-/-) knockout mice. Wild-type MEFs and Spg11-/- MEFs were infected with Staphylococcus aureus (multiplication of infection (MOI) used was 10). After 8 and 16 hours of infection, cell viability was assessed on BD flow cytometer through propidium iodide intake. Bacterial intake by cells was also calculated by plating cell lysates on blood agar plates. Results: in-vitro infection of MEFs with Staphylococcus aureus showed a marked decrease of cell viability in ALR deficient Spatacsin knockout (Spg11-/-) MEFs after 16 hours of infection as compared to wild-type MEFs (n=3 independent experiments; p < 0.0001) although no difference was observed for bacterial intake by both genotypes. Conclusion: Suggesting that ALR is important for the defense of invading pathogens e.g. S. aureus, we observed a marked increase of cell death in an in-vitro infection model in cells with compromised ALR.

Keywords: autophagy, autophagic lysosome reformation, bacterial infections, Staphylococcus aureus

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Authors: Safee Chaudhary, Mahnoor Naseer Gondal, Hira Anees Awan, Abdul Rehman, Ammar Arif, Risham Hussain, Huma Khawar, Zainab Arshad, Muhammad Faizyab Ali Chaudhary, Waleed Ahmed, Muhammad Umer Sultan, Bibi Amina, Salaar Khan, Muhammad Moaz Ahmad, Osama Shiraz Shah, Hadia Hameed, Muhammad Farooq Ahmad Butt, Muhammad Ahmad, Sameer Ahmed, Fayyaz Ahmed, Omer Ishaq, Waqar Nabi, Wim Vanderbauwhede, Bilal Wajid, Huma Shehwana, Muhammad Tariq, Amir Faisal

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Cancer is a manifestation of multifactorial deregulations in biomolecular pathways. These deregulations arise from the complex multi-scale interplay between cellular and extracellular factors. Such multifactorial aberrations at gene, protein, and extracellular scales need to be investigated systematically towards decoding the underlying mechanisms and orchestrating therapeutic interventions for patient treatment. In this work, we propose ‘TISON’, a next-generation web-based multiscale modeling platform for clinical systems oncology. TISON’s unique modeling abstraction allows a seamless coupling of information from biomolecular networks, cell decision circuits, extra-cellular environments, and tissue geometries. The platform can undertake multiscale sensitivity analysis towards in silico biomarker identification and drug evaluation on cellular phenotypes in user-defined tissue geometries. Furthermore, integration of cancer expression databases such as The Cancer Genome Atlas (TCGA) and Human Proteome Atlas (HPA) facilitates in the development of personalized therapeutics. TISON is the next-evolution of multiscale cancer modeling and simulation platforms and provides a ‘zero-code’ model development, simulation, and analysis environment for application in clinical settings.

Keywords: systems oncology, cancer systems biology, cancer therapeutics, personalized therapeutics, cancer modelling

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Authors: Qunying Yuan, Manjula Bomma, Adrian Rhoden, Zhigang Xiao

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Selenium is an essential micronutrient for all mammals and plays an important role in maintaining human physiological functions. The potential applications of selenium as food supplements, cancer-prevention, antimicrobial and anti-inflammatory agents have been investigated in biomedicine and food sciences. Nanoscale of selenium is of particular interest due to its better biocompatibility, higher bioavailability, lower toxicity, more homogeneous distribution, and presumptive controlled release of substances. The objective of this study is to explore whether selenium nanoparticle (SeNP) has the potential to be used as a food preservative to reduce food spoilage. SeNPs were synthesized through ascorbic acid reduction of sodium selenite using the bovine serum albumin (BSA) as capping and stabilizing agent. The chemically synthesized SeNPs had a spherical conformation and a size of 22.8 ± 4.7 nm. FTIR analysis confirmed that the nanoparticles were covered with BSA. We further tested the antimicrobial activity of these SeNPs against common food-borne bacteria. Colony forming unit assay showed that SeNPs exhibited good inhibition on the growth of Listeria Monocytogens (ATCC15313), Staphylococcus epidermidis (ATCC 700583) starting at 0.5µg/mL, but only a moderate inhibitory effect on the growth of Staphylococcus aureus (ATCC12600) and Vibrio alginolyticus (ATCC 33787) at a concentration higher than 10µg/mL and 2.5µg/mL, respectively. There was a mild effect against the growth Salmonella enterica (ATCC19585) when the concentration reached 15µg/mL. No inhibition was observed in the growth of Enterococcus faecalis (ATCC 19433). Surprisingly, SeNPs appeared to promote the growth of Vibrio parahaemolyticus (ATCC43996) and Salmonella enterica (ATCC49284) at 30 µg/mL and above. Our preliminary data suggested that the chemically synthesized SeNPs may be able to inhibit some food-borne bacteria, and SeNP as a food preservative should be used with caution. We will explore the mechanisms of the inhibitory action of chemically synthesized SeNPs on bacterial growth and whether the SeNPs are able to inhibit the development of biofilm and antibiotic resistance.

Keywords: antimicrobial, food-borne bacteria, nanoparticles, selenium

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Authors: Pintusorn Hansakul, Ruchilak Rattarom, Arunporn Itharat

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Background: Benjakul, a Thai traditional herbal formulation, comprises of five plants: Piper chaba, Piper sarmentosum, Piper interruptum, Plumbago indica, and Zingiber officinale. It has been widely used to treat cancer patients in the context of folk medicine in Thailand. This study aimed to investigate the cytotoxic effect of the ethanol extract of Benjakul against three non-small cell lung cancer (NSCLC) cell lines (NCI-H226, A549, COR-L23), small cell lung cancer (SCLC) cell line NCI-H1688 and normal lung fibroblast cell line MRC-5. The study further examined the molecular mechanisms underlying its cytotoxicity via induction of apoptosis in NCI-H226 cells. Methods: The cytotoxic effect of Benjakul was determined by SRB assay. The effect of Benjakul on cell cycle distribution was assessed by flow cytometric analysis. The apoptotic effects of Benjakul were determined by sub-G1 quantitation and Annexin V-FITC/PI flow cytometric analyses as well as by changes in caspase-3 activity. Results: Benjakul exerted potent cytotoxicity on NCI-H226 and A549 cells but lower cytotoxicity on COR-L23 and NCI-H1688 cells without any cytotoxic effect on normal cells. Molecular studies showed that Benjakul extract induced G2/M phase arrest in human NCI-H226 cells in a dose-dependent manner. The highest concentration of Benjakul (150 μg/ml) led to the highest increase in the G2/M population at 12 h, followed by the highest increase in the sub-G1 population (apoptotic cells) at 60 h. Benjakul extract also induced early apoptosis (AnnexinV +/PI−) in NCI-H226 cells in a dose- and time- dependent manner. Moreover, treatment with 150 μg/ml Benjakul extract for 36 h markedly increased caspase-3 activity by 3.5-fold, and pretreatment with the general caspase inhibitor z-VAD-fmk completely abolished such activity. Conclusions: This study reveals for the first time the regulation of apoptosis in human lung cancer NCI-H226 cells through caspase-dependent mechanism by Benjakul extract.

Keywords: apoptosis, Benjakul, caspase activation, cytotoxicity

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Authors: Danielle A. Walker, Kyle L. Johnson, Tara B. Thomas, Sandor Dorgo, Jacen S. Moore

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Approximately 37 million people worldwide are infected with the Human Immunodeficiency Virus (HIV), with the majority located in sub-Saharan Africa. The relationship existing between HIV incidence and socioeconomic inequity confirms the critical need for programs promoting HIV education, prevention and treatment access. This literature review analyzed 36 sources with a specific focus on the Democratic Republic of Congo, whose critically low socioeconomic status and education rate have resulted in a drastically high HIV rates. Relationships between HIV testing and treatment and barriers to care were explored. Cultural and religious considerations were found to be vital when creating and implementing HIV education and testing programs. Partnerships encouraging active support from community-based spiritual leaders to implement HIV educational programs were also key mechanisms to reach communities and individuals. Gender roles were highlighted as a key component for implementation of effective community trust-building and successful HIV education programs. The efficacy of added support by hospitals and clinics in rural areas to facilitate access to HIV testing and care for people living with HIV/AIDS (PLWHA) was discussed. This review highlighted the need for healthcare providers to provide a network of continued education for PLWHA in clinical settings during disclosure and throughout the course of treatment to increase retention in care and promote medication adherence for viral load suppression. Implementation of culturally sensitive models that rely on community familiarity with HIV educators such as ‘train-the-trainer’ were also proposed as efficacious tools for educating rural communities about HIV. Further research is needed to promote community partnerships for HIV education, understand the cultural context of gender roles as barriers to care, and empower local health care providers to be successful within the HIV Continuum of Care.

Keywords: cultural sensitivity, Democratic Republic of the Congo, education, HIV

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Authors: Lai Peng, Cristina Pintucci, Dries Seuntjens, José Carvajal-Arroyo, Siegfried Vlaeminck

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Economic incentives drive the implementation of short-cut nitrogen removal processes such as nitritation/denitritation (Nit/DNit) to manage nitrogen in waste streams devoid of biodegradable organic carbon. However, as any biological nitrogen removal process, the potent greenhouse gas nitrous oxide (N2O) could be emitted from Nit/DNit. Challenges remain in understanding the fundamental mechanisms and development of engineered mitigation strategies for N2O production. To provide answers, this work focuses on manure as a model, the biggest wasted nitrogen mass flow through our economies. A sequencing batch reactor (SBR; 4.5 L) was used treating the centrate (centrifuge supernatant; 2.0 ± 0.11 g N/L of ammonium) from an anaerobic digester processing mainly pig manure, supplemented with a co-substrate. Glycerin was used as external carbon source, a by-product of vegetable oil. Out-selection of nitrite oxidizing bacteria (NOB) was targeted using a combination of low dissolved oxygen (DO) levels (down to 0.5 mg O2/L), high temperature (35ºC) and relatively high free ammonia (FA) (initially 10 mg NH3-N/L). After reaching steady state, the process was able to remove 100% of ammonium with minimum nitrite and nitrate in the effluent, at a reasonably high nitrogen loading rate (0.4 g N/L/d). Substantial N2O emissions (over 15% of the nitrogen loading) were observed at the baseline operational condition, which were even increased under nitrite accumulation and a low organic carbon to nitrogen ratio. Yet, higher DO (~2.2 mg O2/L) lowered aerobic N2O emissions and weakened the dependency of N2O on nitrite concentration, suggesting a shift of N2O production pathway at elevated DO levels. Limiting the greenhouse gas emissions (environmental protection) from such a system could be substantially minimized by increasing the external carbon dosage (a cost factor), but also through the implementation of an intermittent aeration and feeding strategy. Promising steps forward have been presented in this abstract, yet at the conference the insights of ongoing experiments will also be shared.

Keywords: mitigation, nitrous oxide, nitritation/denitritation, pig manure

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Authors: Bouchiha Hanene, Rouabhi Rachid, Bouchama Khaled, Djebar Berrebbah Houraya, Djebar Mohamed Reda

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Recently, some natural products such as essentials oils (EOs) have been used in the fields as alternative to synthetic compounds, to minimize the negative impacts to the environment. This fact has led to questions about the possible impact of EOs on ecosystems. Currently in toxicology, the use of alternative models can help to understand the mechanisms of toxic action, at different levels of organization of ecosystems. Algae, protozoa and bacteria form the base of the food chain and protozoan cells are used as bioindicators often of pollution in environment. Unicellular organisms offer the possibility of direct study of independent cells with specific characteristics of individual cells and whole organisms at the same time. This unicellular facilitates the study of physiological processes, and effects of pollutants at the cellular level, which makes it widely used to assess the toxic effects of various xenobiotics. This study aimed to verify the effects of EOs of one famous plant used tremendously in our folk medicine, namely Artemisia herba alba in causing acute toxicity (24 hours) and chronic (15 days) toxicity for model cellular (Paramecium sp). To this end, cellular’s of paramecium were exposed to various concentrations (Three doses were chosen) of EOs extracted from plant (Artemisia herba alba). In the first experiment, the cellular s cultures were exposed for 48 hours to different concentrations to determine the median lethal concentration (DL50). We followed the evolution of physiological parameters (growth), biochemical (total proteins, respiratory metabolism), as well as the variations of a bio marker the GSH. Our results highlighted a light inhibition of the growth of the protozoa as well as a disturbance of the contents of total proteins and a reduction in the reduced rate of glutathione. The polarographic study revealed a stimulation of the consumption of O2 and this at the treated cells.

Keywords: essential oils, protozoa, bio indicators, toxicity, Growth, bio marker, proteins, polarographic

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Authors: Ana Breda, Catarina Cruz

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Daily, we face unpredictable events, often attributed to chance, as there is no justification for such an occurrence. Chance, understood as a source of uncertainty, is present in several aspects of human life, such as weather forecasts, dice rolling, and lottery. Surprisingly, humans and some animals can quickly adjust their behavior to handle efficiently doubly stochastic processes (random events with two layers of randomness, like unpredictable weather affecting dice rolling). This adjustment ability suggests that the human brain has built-in mechanisms for perceiving, understanding, and responding to simple probabilities. It also explains why current trends in mathematics education include probability concepts in official curriculum programs, starting from the third year of primary education onwards. In the first years of schooling, children learn to use a certain type of (specific) vocabulary such as: never, always, rarely, perhaps, likely, and unlikely, to help them to perceive and understand the probability of some events. These are keywords of crucial importance for their perception and understanding of probabilities. The development of the probabilistic concepts comes from facts and cause-effect sequences resulting from the subject's actions, as well as the notion of chance and intuitive estimates based on everyday experiences. As part of a junior summer school program, which took place at a Portuguese university, a non-formal learning experiment was carried out with 18 children in the 5th and 6th grades. This experience was designed to be implemented in a dynamic of a serious ice-breaking game, to assess their levels of probabilistic, critical, and creative thinking in understanding impossible, certain, equally probable, likely, and unlikely events, and, also, to gain insight into how the non-formal learning context influenced their achievements. The data analysis employs a mixed-methods approach, based on students' written productions, audio recordings, and researchers' field notes. This methodology allowed us to conclude that such an approach is an appropriate and helpful formative assessment tool.

Keywords: critical and creative thinking, non-formal mathematics learning, probabilistic thinking, serious game

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Authors: Katarzyna Palus, Jarosław Całka

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Gastrointestinal disorders, especially acid-related diseases, including peptic and duodenal ulcers, gastroesophageal reflux disease, upper GI bleeding or stress-related mucosal disease, are currently serious health issues encountered very frequently in patients worldwide. However, to date, the response of sympathetic neurons to gastric mucosal injury and local inflammation following hyperacidity is unknown. Thus, the present study was designed to determine possible changes in expression of galanin (GAL) in the CSMG neurons supplying the prepyloric area of the porcine stomach in a physiological state and following experimentally-induced hyperacidity by using combined retrograde tracing and double-labelling immunohistochemistry. The choice of the domestic pig as an experimental model in the present study is not accidental and is justified by the high degree of physiological and anatomical similarity to human digestive system functions. In this experiment ten juvenile female pigs of the Large White Polish breed were used. The animals were divided into two groups: control and animals with hydrochloric acid infusion (HCl). The neuronal retrograde marker Fast Blue (FB) was injected into the anterior prepyloric wall of the stomach of all animals. After 23 days, animals of the HCl-group were reintroduced into a state of general anesthesia and intragastrically given 5 ml/kg of body weight of 0.25 M aqueous solution of hydrochloric acid. On the 28th day, all animals were euthanized. The CSMG complexes were then collected and the CSMG cryostat sections were stained immunocytochemically for GAL and TH (tyrosine hydroxylase). Immunohistochemistry revealed that in the control group 8.40 ± 0.53 % out of 200 FB-positive CSMG neurons contained GAL. In HCl group upregulation of the GAL-IR neurons to 22.52 ± 1.18 % were observed. All GAL-IR neurons in both groups showed the simultaneously TH immunoreactivity. Increase in the expression of GAL in FB-positive neurons of the HCL group may suggest its participation in the protective mechanisms of neurons in different pathological processes, such as gastric hyperacidity.

Keywords: coeliac-superior mesenteric ganglion complex, gastric innervation, hyperacidity, immunohistochemistry

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Authors: Hans Tjio, Wee Meng Seng

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The interaction of contract and property has always been a concern in corporate and commercial law, where there are internal structures created that may not match the externally perceived image generated by the labels attached to those structures. We will focus, in particular, on the priority structures created by affirmative asset partitioning, which have increasingly come under challenge by those attempting to negotiate around them. The most prominent has been the AT1 bonds issued by Credit Suisse which were wiped out before its equity when the troubled bank was acquired by UBS. However, this should not have come as a surprise to those whose “bonds” had similarly been “redeemed” upon the occurrence of certain reference events in countries like Singapore, Hong Kong and Taiwan during their Minibond crisis linked to US sub-prime defaults. These were derivatives classified as debentures and sold as such. At the same time, we are again witnessing “liabilities” seemingly ranking higher up the balance sheet ladder, finding themselves lowered in events of default. We will examine the mechanisms holders of perpetual securities or preference shares have tried to use to protect themselves. This is happening against a backdrop that sees a rise in the strength of private credit and inter-creditor conflicts. The restructuring regime of the hybrid scheme in Singapore now, while adopting the absolute priority rule in Chapter 11 as the quid pro quo for creditor cramdown, does not apply to shareholders and so exempts them from cramdown. Complicating the picture further, shareholders are not exempted from cramdown in the Dutch scheme, but it adopts a relative priority rule. At the same time, the important UK Supreme Court decision in BTI 2014 LLC v Sequana [2022] UKSC 25 has held that directors’ duties to take account of creditor interests are activated only when a company is almost insolvent. All this has been complicated by digital assets created by businesses. Investors are quite happy to have them classified as property (like a thing) when it comes to their transferability, but then when the issuer defaults to have them seen as a claim on the business (as a choice in action), that puts them at the level of a creditor. But these hidden interests will not show themselves on an issuer’s balance sheet until it is too late to be considered and yet if accepted, may also prevent any meaningful restructuring.

Keywords: asset partitioning, creditor priority, restructuring, BTI v Sequana, digital assets

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Authors: Sonia Sassi, Mostapha Tarfaoui, Hamza Ben Yahia

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In this investigation, an experimental technique in which the dynamic response, damage kinetic and heat dissipation are measured simultaneously during high strain rates on adhesively bonded joints materials. The material used in this study is widely used in the design of structures for military applications. It was composed of a 45° Bi-axial fiber-glass mat of 0.286 mm thickness in a Polyester resin matrix. In adhesive bonding, a NORPOL Polyvinylester of 1 mm thickness was used to assemble the composite substrate. The experimental setup consists of a compression Split Hopkinson Pressure Bar (SHPB), a high-speed infrared camera and a high-speed Fastcam rapid camera. For the dynamic compression tests, 13 mm x 13 mm x 9 mm samples for out-of-plane tests were considered from 372 to 1030 s-1. Specimen surface is controlled and monitored in situ and in real time using the high-speed camera which acquires the damage progressive in specimens and with the infrared camera which provides thermal images in time sequence. Preliminary compressive stress-strain vs. strain rates data obtained show that the dynamic material strength increases with increasing strain rates. Damage investigations have revealed that the failure mainly occurred in the adhesive/adherent interface because of the brittle nature of the polymeric adhesive. Results have shown the dependency of the dynamic parameters on strain rates. Significant temperature rise was observed in dynamic compression tests. Experimental results show that the temperature change depending on the strain rate and the damage mode and their maximum exceed 100 °C. The dependence of these results on strain rate indicates that there exists a strong correlation between damage rate sensitivity and heat dissipation, which might be useful when developing damage models under dynamic loading tacking into account the effect of the energy balance of adhesively bonded joints.

Keywords: adhesive bonded joints, Hopkinson bars, out-of-plane tests, dynamic compression properties, damage mechanisms, heat dissipation

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Authors: Rami Faraj, Cezary Graczykowski, Błażej Popławski, Grzegorz Mikułowski, Rafał Wiszowaty

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Progress in the field of sensors, electronics and computing results in more and more often applications of adaptive techniques for dynamic response mitigation. When it comes to systems excited with mechanical impacts, the control system has to take into account the significant limitations of actuators responsible for system adaptation. The paper provides a comprehensive discussion of the problem of appropriate design and implementation of adaptation techniques and mechanisms. Two case studies are presented in order to compare completely different adaptation schemes. The first example concerns a double-chamber pneumatic shock absorber with a fast piezo-electric valve and parameters corresponding to the suspension of a small unmanned aerial vehicle, whereas the second considered system is a safety air cushion applied for evacuation of people from heights during a fire. For both systems, it is possible to ensure adaptive performance, but a realization of the system’s adaptation is completely different. The reason for this is technical limitations corresponding to specific types of shock-absorbing devices and their parameters. Impact mitigation using a pneumatic shock absorber corresponds to much higher pressures and small mass flow rates, which can be achieved with minimal change of valve opening. In turn, mass flow rates in safety air cushions relate to gas release areas counted in thousands of sq. cm. Because of these facts, both shock-absorbing systems are controlled based on completely different approaches. Pneumatic shock-absorber takes advantage of real-time control with valve opening recalculated at least every millisecond. In contrast, safety air cushion is controlled using the semi-passive technique, where adaptation is provided using prediction of the entire impact mitigation process. Similarities of both approaches, including applied models, algorithms and equipment, are discussed. The entire study is supported by numerical simulations and experimental tests, which prove the effectiveness of both adaptive impact mitigation techniques.

Keywords: adaptive control, adaptive system, impact mitigation, pneumatic system, shock-absorber

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Authors: Fuad Abdullah Alatawi

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Microbial infections-based diseases are a significant public health issue around the world, mainly when antibiotic-resistant bacterium types evolve. In this research, we explored the anti-bacterial and anti-cancer potency of iron-oxide (Fe₂O₃) nanoparticles prepared from F. macrocarpa fruit extract. The chemical composition of F. macrocarpa fruit extract was used as a reducing and capping agent for nanoparticles’ synthesis was examined by GC-MS/MS analysis. Then, the prepared nanoparticles were confirmed by various biophysical techniques, including X-ray powder diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), UV-Vis Spectroscopy, and Transmission Electron Microscopy (TEM) and Energy Dispersive Spectroscopy (EDAX), and Dynamic Light Scattering (DLS). Also, the antioxidant capacity of fruit extract was determined through 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), Fluorescence Recovery After Photobleaching (FRAP), Superoxide Dismutase (SOD) assays. Furthermore, the cytotoxicity activities of Fe₂O₃ NPs were determined using the (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) (MTT) test on MCF-7 cells. In the antibacterial assay, lethal doses of the Fe₂O₃NPs effectively inhibited the growth of gram-negative and gram-positive bacteria. The surface damage, ROS production, and protein leakage are the antibacterial mechanisms of Fe₂O₃NPs. Concerning antioxidant activity, the fruit extracts of F. macrocarpa had strong antioxidant properties, which were confirmed by DPPH, ABTS, FRAP, and SOD assays. In addition, the F. microcarpa-derived iron oxide nanomaterials greatly reduced the cell viability of (MCF-7). The GC-MS/MS analysis revealed the presence of 25 main bioactive compounds in the F. microcarpa extract. Overall, the finding of this research revealed that F. microcarpa-derived Fe₂O₃ nanoparticles could be employed as an alternative therapeutic agent to cure microbial infection and breast cancer in humans.

Keywords: ficus microcarpa, iron oxide, antibacterial activity, cytotoxicity

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Authors: Alexandra K. Diem, Giles Richardson, Roxana O. Carare, Neil W. Bressloff

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Alzheimer's disease (AD) is the most common form of dementia and although it has been researched for over 100 years, there is still no cure or preventive medication. Its onset and progression is closely related to the accumulation of the neuronal metabolite Aβ. This raises the question of how metabolites and waste products are eliminated from the brain as the brain does not have a traditional lymphatic system. In recent years the rapid uptake of Aβ into cerebral artery walls and its clearance along those arteries towards the lymph nodes in the neck has been suggested and confirmed in mice studies, which has led to the hypothesis that interstitial fluid (ISF), in the basement membranes in the walls of cerebral arteries, provides the pathways for the lymphatic drainage of Aβ. This mechanism, however, requires a net reverse flow of ISF inside the blood vessel wall compared to the blood flow and the driving forces for such a mechanism remain unknown. While possible driving mechanisms have been studied using mathematical models in the past, a mechanism for net reverse flow has not been discovered yet. Here, we aim to address the question of the driving force of this reverse lymphatic drainage of Aβ (also called perivascular drainage) by using multi-scale numerical and analytical modelling. The numerical simulation software COMSOL Multiphysics 4.4 is used to develop a fluid-structure interaction model of a cerebral artery, which models blood flow and displacements in the artery wall due to blood pressure changes. An analytical model of a layer of basement membrane inside the wall governs the flow of ISF and, therefore, solute drainage based on the pressure changes and wall displacements obtained from the cerebral artery model. The findings suggest that an active role in facilitating a reverse flow is played by the components of the basement membrane and that stiffening of the artery wall during age is a major risk factor for the impairment of brain lymphatics. Additionally, our model supports the hypothesis of a close association between cerebrovascular diseases and the failure of perivascular drainage.

Keywords: Alzheimer's disease, artery wall mechanics, cerebral blood flow, cerebral lymphatics

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Authors: Sadia Munir

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The aim of this study is to investigate changes in placental development and vascular dysfunction which subsequently affect feto-maternal health in pregnancies complicated by gestational diabetes mellitus (GDM). Fetal and postnatal adverse health outcomes of GDM are shown to be associated with disturbances in placental structure and function. Children of women with GDM are more likely to be obese and diabetic in childhood and adulthood. GDM also increases the risk of adverse pregnancy outcomes, including preeclampsia, birth injuries, macrosomia and neonatal hypoglycemia, respiratory distress syndrome, neonatal cardiac dysfunction and stillbirth. Incidences of type 2 diabetes in the MENA region are growing at an alarming rate which is estimated to become more than double by 2030. Five of the top 10 countries for diabetes prevalence in 2010 were in the Gulf region. GDM also increases the risk of development of type 2 diabetes. Interestingly, more than half of the women with GDM develop diabetes later in their life. The human placenta is a temporary organ located at the interface between mother and fetal blood circulation. Placenta has a central role as both a producer as well as a target of several molecules that are involved in placental development and function. We have investigated performed a Pubmed search with key words placenta, GDM, placental villi, vascularization, cytokines, growth factors, inflammation, hypoxia, oxidative stress and pathophysiology. We have investigated differences in the development and vascularization of placenta, their underlying causes and impact on feto-maternal health through literature review. We have also identified gaps in the literature and research questions that need to be answered to completely understand the central role of placenta in the GDM. This study is important in understanding the pathophysiology of placenta due to changes in the vascularization of villi, surface area and diameter of villous capillaries in pregnancies complicated by GDM. It is necessary to understand these mechanisms in order to develop treatments to reverse their effects on placental malfunctioning, which in turn, will result in improved mother and child health.

Keywords: gestational diabetes mellitus, placenta, vasculature, villi

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Authors: Zohreh Bayat, Dariush Minai-Tehrani

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Pseudomonas aeruginosa is a Gram-negative, rode shape and aerobic bacterium that has shown to be resistance to many antibiotics. This resistance makes the bacterium very harmful in some diseases. It can also generate diseases in any part of the gastrointestinal tract from oropharynx to rectum. P. aeruginosa has become an important cause of infection, especially in patients with compromised host defense mechanisms. One of the most important reasons that make P. aeruginosa an emerging opportunistic pathogen in patients is its ability to use various compounds as carbon sources. Lipase is an enzyme that catalyzes the hydrolysis of lipids. Most lipases act at a specific position on the glycerol backbone of lipid substrate. Some lipases are expressed and secreted by pathogenic organisms during the infection. Muscarinic antagonist used as an antispasmodic and in urinary incontinence. The drug has little effect on glandular secretion or the cardiovascular system. It does have some local anesthetic properties and is used in gastrointestinal, biliary, and urinary tract spasms. Aim: In this study the inhibitory effect of a muscarinic antagonist on lipase of P. aeruginosa was investigated. Methods: P. aeruginosa was cultured in minimal salt medium with 1% olive oil as carbon source. The cells were harvested and the supernatant, which contained lipase, was used for enzyme assay. Results: Our results showed that the drug can inhibit P. aeruginosa lipase by competitive manner. In the presence of different concentrations of the drug, the Vmax (2 mmol/min/mg protein) of enzyme did not change, while the Km raised by increasing the drug concentration. The Ki (inhibition constant) and IC50 (the half maximal inhibitory concentration) value of drug was estimated to be about 30 uM and 60 uM which determined that the drug binds to enzyme with high affinity. Maximum activity of the enzyme was observed at pH 8 in the absence and presence of muscarinic antagonist, respectively. The maximum activity of lipase was observed at 600C and the enzyme became inactive at 900C. Conclusion: The muscarinic antagonist drug could inhibit lipase of P. aeruginosa and changed the kinetic parameters of the enzyme. The drug binded to enzyme with high affinity and did not chang the optimum pH of the enzyme. Temperature did not affect the binding of drug to musmuscarinic antagonist.

Keywords: Pseudomonas aeruginosa, drug, enzyme, inhibition

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Authors: Leyla Sattarzadeh, Maghsoud Peeri, Mohammadali Azarbaijani, Hasan Matin Homaee

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Inflammation by various mechanisms may cause atherosclerosis. Systemic circulating inflammatory markers such as C-reactive protein (CRP), pro-inflammatory cytokines such as Interleukin-6 (IL-6) and adhesion molecules like Intracellular Adhesion Molecule-1 (ICAM-1) are the predictors of cardiovascular diseases. Regarding the conflicting results about the effect of resistance exercise training on these inflammatory markers, the present study aimed to examine the effect of eight week different patterns of resistance exercise training on CRP, IL-6 and ICAM-1 levels in healthy untrained women. 40 volunteered and healthy untrained female university students (aged: 21+ 3 yr., Body Mass Index: 21.5+ 3.5 kg/m2) were selected purposefully and divided into three groups. At the end of training protocol and after subjects drop during the protocol in upper body exercise training (n=11), lower body (n=12) completed the eight week of training period although the control group (n=7) did anything. Blood samples gathered pre and post experimental period and CRP, IL-6 and ICAM-1 levels were evaluated using special laboratory kits, then the difference of pre and post values of each indices analyzed using one way Analysis of Variance (α < 0.05). The results of one way ANOVA for difference of pre and post values of CRP and ICAM-1 showed no significant changes due to the exercise training. But there were significant differences between groups about IL-6. Tukey post- hoc test indicated that there is significant difference between the differences of pre and post values of IL-6 between lower body exercise training group and control group, and eight weeks of lower body exercise training lead to significant changes in IL-6 values. There were no changes in anthropometric indices. The findings show that the different patterns of upper and lower body exercise training by involving the different amount of muscles altered the IL-6 values in lower body exercise training group probably because of engaging the bigger amount of muscles, but showed any significant changes about CRP and ICAM-1 probably due to intensity and duration of exercise or the lower levels of these markers at baseline of healthy people.

Keywords: C-reactive protein, interleukin-6, intracellular adhesion molecule-1, resistance training

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Authors: Apichaya Aneksampant, Xuefei Tu, Masami Fukushima, Mitsuo Yamamoto

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The restoration of seaweed beds recovery has been developed using a fertilization technique for supplying dissolved iron to barren coastal areas. The fertilizer is composed of iron oxides as a source of iron and compost as humic substance (HS) source, which can serve as chelator of iron to stabilize the dissolved species under oxic seawater condition. However, elution mechanisms of iron from iron oxide surfaces have not sufficiently elucidated. In particular, roles of microbial activities in the elution of iron from the fertilizer are not sufficiently understood. In the present study, a fertilizer (iron oxide/compost = 1/1, v/v) was incubated in a water tank at Mashike coast, Hokkaido Japan. Microorganisms in the 6-month fertilizer were isolated and identified as Exiguobacterium oxidotolerans sp. (T-2-2). The identified bacteria were inoculated to perform iron elution test in a postgate B medium, prepared in artificial seawater. Hematite was used as a model iron oxide and anthraquinone-2,7-disolfonate (AQDS) as a model for HSs. The elution test performed in presence and absence of bacteria inoculation. ICP-AES was used to analyze total iron and a colorimetric technique using ferrozine employed for the determination of ferrous ion. During the incubation period, sample contained hematite and T-2-2 in both presence and absence of AQDS continuously showed the iron elution and reached at the highest concentration after 9 days of incubation and then slightly decrease to stabilize within 20 days. Comparison to the sample without T-2-2, trace amount of iron was observed, suggesting that iron elution to seawater can be attributed to bacterial activities. The levels of total organic carbon (TOC) in the culture solution with hematite decreased. This may be to the adsorption of organic compound, AQDS, to hematite surfaces. The decrease in UV-vis absorption of AQDS in the culture solution also support the results of TOC that AQDS was adsorbed to hematite surfaces. AQDS can enhance the iron elution, while the adsorption of organic matter suppresses the iron elution from hematite.

Keywords: anthraquinone-2, 7-disolfonate, barren ground, E.oxidotolerans sp., hematite, humic substances, iron elution

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Authors: Nicolas M. Beleski, Gustavo A. G. Lugo

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Robotic agents are taking more and increasingly important roles in society. In order to make these robots and agents more autonomous and efficient, their systems have grown to be considerably complex and convoluted. This growth in complexity has led recent researchers to investigate forms to explain the AI behavior behind these systems in search for more trustworthy interactions. A current problem in explainable AI is the inner workings with the logic inference process and how to conduct a sensibility analysis of the process of valuation and alteration of beliefs. In a social HRI (human-robot interaction) setup, theory of mind is crucial to ease the intentionality gap and to achieve that we should be able to infer over observed human behaviors, such as cases of cognitive dissonance. One specific case inspired in human cognition is the role emotions play on our belief system and the effects caused when observed behavior does not match the expected outcome. In such scenarios emotions can make a person wrongly assume the antecedent P for an observed consequent Q, and as a result, incorrectly assert that P is true. This form of cognitive dissonance where an unproven cause is taken as truth induces changes in the belief base which can directly affect future decisions and actions. If we aim to be inspired by human thoughts in order to apply levels of theory of mind to these artificial agents, we must find the conditions to replicate these observable cognitive mechanisms. To achieve this, a computational architecture is proposed to model the modulation effect emotions have on the belief system and how it affects logic inference process and consequently the decision making of an agent. To validate the model, an experiment based on the prisoner's dilemma is currently under development. The hypothesis to be tested involves two main points: how emotions, modeled as internal argument strength modulators, can alter inference outcomes, and how can explainable outcomes be produced under specific forms of cognitive dissonance.

Keywords: cognitive architecture, cognitive dissonance, explainable ai, sensitivity analysis, theory of mind

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Authors: Ben Main Piotr Ozieranski

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State government spending on pharmaceuticals stands at 1 trillion USD globally, promoting criticism of the pharmaceutical industry's monetization of drug efficacy, product cost overvaluation, and health injustice. This paper elucidates the mechanisms behind a state-institutional response to this problem through the sociological lens of the strategic relational approach to state power. To do so, 30 expert interviews, legal and policy documents are drawn on to explain how state elites in New Zealand have successfully contested a 30-year “pharmaceutical spending containment policy”. Proceeding from Jessop's notion of strategic “selectivity”, encompassing analyses of the enabling features of state actors' ability to harness state structures, a theoretical explanation is advanced. First, a strategic context is described that consists of dynamics around pharmaceutical dealmaking between the state bureaucracy, pharmaceutical pricing strategies (and their effects), and the industry. Centrally, the pricing strategy of "bundling" -deals for packages of drugs that combine older and newer patented products- reflect how state managers have instigated an “incentivization game” that is played by state and industry actors, including HTA professionals, over pharmaceutical products (both current and in development). Second, a protective context is described that is comprised of successive legislative-judicial responses to the strategic context and characterized by the regulation and the societalisation of commercial law. Third, within the policy, the achievement of increased pharmaceutical coverage (pharmaceutical “mix”) alongside contained spending is conceptualized as a state defence of a "social profit". As such, in contrast to scholarly expectations that political and economic cultures of neo-liberalism drive pharmaceutical policy-making processes, New Zealand's state elites' approach is shown to be antipathetic to neo-liberals within an overall capitalist economy. The paper contributes an analysis of state pricing strategies and how they are embedded in state regulatory structures. Additionally, through an analysis of the interconnections of state power and pharmaceutical value Abrahams's neo-liberal corporate bias model for pharmaceutical policy analysis is problematised.

Keywords: pharmaceutical governance, pharmaceutical bureaucracy, pricing strategies, state power, value theory

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Authors: E. Syngelaki, C. C. F. Schinkel, S. Klatt, E. Hörandl

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Environmental influence can alter the conditions for plant development and can trigger changes in epigenetic variation. Thus, the exposure to abiotic environmental stress can lead to different DNA methylation profiles and may have evolutionary consequences for adaptation. Epigenetic control mechanisms may further influence mode of reproduction. The alpine species R. kuepferi has diploid and tetraploid cytotypes, that are mostly sexual and facultative apomicts, respectively. Hence, it is a suitable model system for studying the correlations of mode of reproduction, ploidy, and environmental stress. Diploid and tetraploid individuals were placed in two climate chambers and treated with low (+7°C day/+2°C night, -1°C cold shocks for three nights per week) and warm (control) temperatures (+15°C day/+10°C night). Subsequently, methylation sensitive-Amplified Fragment-Length Polymorphism (AFPL) markers were used to screen genome-wide methylation alterations triggered by stress treatments. The dataset was analyzed for four groups regarding treatment (cold/warm) and ploidy level (diploid/tetraploid), and also separately for full methylated, hemi-methylated and unmethylated sites. Patterns of epigenetic variation suggested that diploids differed significantly in their profiles from tetraploids independent from treatment, while treatments did not differ significantly within cytotypes. Furthermore, diploids are more differentiated than the tetraploids in overall methylation profiles of both treatments. This observation is in accordance with the increased frequency of apomictic seed formation in diploids and maintenance of facultative apomixis in tetraploids during the experiment. Global analysis of molecular variance showed higher epigenetic variation within groups than among them, while locus-by-locus analysis of molecular variance showed a high number (54.7%) of significantly differentiated un-methylated loci. To summarise, epigenetic variation seems to depend on ploidy level, and in diploids may be correlated to changes in mode of reproduction. However, further studies are needed to elucidate the mechanism and possible functional significance of these correlations.

Keywords: apomixis, cold stress, DNA methylation, Ranunculus kuepferi

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Authors: Mpho Mokoatle, Darlington Mapiye, James Mashiyane, Stephanie Muller, Gciniwe Dlamini

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Great advances in high-throughput sequencing technologies have resulted in availability of huge amounts of sequencing data in public and private repositories, enabling a holistic understanding of complex biological phenomena. Sequence data are used for a wide range of applications such as gene annotations, expression studies, personalized treatment and precision medicine. However, this rapid growth in sequence data poses a great challenge which calls for novel data processing and analytic methods, as well as huge computing resources. In this work, a machine and statistical learning approach for DNA sequence classification based on $k$-mer representation of sequence data is proposed. The approach is tested using whole genome sequences of Mycobacterium tuberculosis (MTB) isolates to (i) reduce the size of genomic sequence data, (ii) identify an optimum size of k-mers and utilize it to build classification models, (iii) predict the phenotype from whole genome sequence data of a given bacterial isolate, and (iv) demonstrate computing challenges associated with the analysis of whole genome sequence data in producing interpretable and explainable insights. The classification models were trained on 104 whole genome sequences of MTB isoloates. Cluster analysis showed that k-mers maybe used to discriminate phenotypes and the discrimination becomes more concise as the size of k-mers increase. The best performing classification model had a k-mer size of 10 (longest k-mer) an accuracy, recall, precision, specificity, and Matthews Correlation coeffient of 72.0%, 80.5%, 80.5%, 63.6%, and 0.4 respectively. This study provides a comprehensive approach for resampling whole genome sequencing data, objectively selecting a k-mer size, and performing classification for phenotype prediction. The analysis also highlights the importance of increasing the k-mer size to produce more biological explainable results, which brings to the fore the interplay that exists amongst accuracy, computing resources and explainability of classification results. However, the analysis provides a new way to elucidate genetic information from genomic data, and identify phenotype relationships which are important especially in explaining complex biological mechanisms.

Keywords: AWD-LSTM, bootstrapping, k-mers, next generation sequencing

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Authors: Darlington Mapiye, Mpho Mokoatle, James Mashiyane, Stephanie Muller, Gciniwe Dlamini

Abstract:

Great advances in high-throughput sequencing technologies have resulted in availability of huge amounts of sequencing data in public and private repositories, enabling a holistic understanding of complex biological phenomena. Sequence data are used for a wide range of applications such as gene annotations, expression studies, personalized treatment and precision medicine. However, this rapid growth in sequence data poses a great challenge which calls for novel data processing and analytic methods, as well as huge computing resources. In this work, a machine and statistical learning approach for DNA sequence classification based on k-mer representation of sequence data is proposed. The approach is tested using whole genome sequences of Mycobacterium tuberculosis (MTB) isolates to (i) reduce the size of genomic sequence data, (ii) identify an optimum size of k-mers and utilize it to build classification models, (iii) predict the phenotype from whole genome sequence data of a given bacterial isolate, and (iv) demonstrate computing challenges associated with the analysis of whole genome sequence data in producing interpretable and explainable insights. The classification models were trained on 104 whole genome sequences of MTB isoloates. Cluster analysis showed that k-mers maybe used to discriminate phenotypes and the discrimination becomes more concise as the size of k-mers increase. The best performing classification model had a k-mer size of 10 (longest k-mer) an accuracy, recall, precision, specificity, and Matthews Correlation coeffient of 72.0 %, 80.5 %, 80.5 %, 63.6 %, and 0.4 respectively. This study provides a comprehensive approach for resampling whole genome sequencing data, objectively selecting a k-mer size, and performing classification for phenotype prediction. The analysis also highlights the importance of increasing the k-mer size to produce more biological explainable results, which brings to the fore the interplay that exists amongst accuracy, computing resources and explainability of classification results. However, the analysis provides a new way to elucidate genetic information from genomic data, and identify phenotype relationships which are important especially in explaining complex biological mechanisms

Keywords: AWD-LSTM, bootstrapping, k-mers, next generation sequencing

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Authors: Jung Lee, L. G. Pee

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The 'Like' function in social media platforms represents the immediate responses of social media users to postings and other users. A large number of 'likes' is often attributed to fame, agreement, and support from others that many users are proud of and happy with. However, what 'like' implies exactly in social media context is still in discussion. Some argue that it is an accurate parameter of the preferences of social media users, whereas others refute that it is merely an instant reaction that is volatile and vague. To address this gap, this study investigates how social media users perceive the 'like' function and behave differently based on their perceptions. This study posits the following arguments. First, 'like' is interpreted as a quantified form of social capital that resides in social media platforms. This incarnated social capital rationalizes the attraction of people to social media and belief that social media platforms bring benefits to their relationships with others. This social capital is then conceptualized into cognitive and emotive dimensions, where social capital in the cognitive dimension represents the awareness of the 'likes' quantitatively, whereas social capital in the emotive dimension represents the receptions of the 'likes' qualitatively. Finally, the ambivalent perspective of the social media users on 'like' (i.e., social capital) is applied. This view rationalizes why social media users appreciate the reception of 'likes' from others but are aware that those 'likes' can distort the actual responses of other users by sending erroneous signals. The rationale on this ambivalence is based on whether users perceive social media as private or public spheres. When social media is more publicized, the ambivalence is more strongly observed. By combining the ambivalence and dimensionalities of the social capital, four types of social media users with different mechanisms on liking behaviors are identified. To validate this work, a survey with 300 social media users is conducted. The analysis results support most of the hypotheses and confirm that people have ambivalent perceptions on 'like' as a social capital and that perceptions influence behavioral patterns. The implication of the study is clear. First, this study explains why social media users exhibit different behaviors toward 'likes' in social media. Although most of the people believe that the number of 'likes' is the simplest and most frank measure of supports from other social media users, this study introduces the users who do not trust the 'likes' as a stable and reliable parameter of social media. In addition, this study links the concept of social media openness to explain the different behaviors of social media users. Social media openness has theoretical significance because it defines the psychological boundaries of social media from the perspective of users.

Keywords: ambivalent attitude, like function, social capital, social media

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Authors: Saeed Anwar

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Foreign aid has long been a prominent tool in the pursuit of economic development in recipient countries. This research paper aims to analyze the impact of foreign aid on economic development and explore the effectiveness of aid in promoting sustainable growth, poverty reduction, and improvements in human development indicators. Drawing upon a comprehensive review of existing literature, both theoretical frameworks and empirical evidence are synthesized to provide insights into the complex relationship between foreign aid and economic development. The paper examines various channels through which foreign aid influences economic development, including infrastructure development, education and healthcare investments, technology transfer, and institutional capacity building. It explores the potential positive effects of aid in stimulating economic growth, reducing poverty, and enhancing human capital formation. Additionally, it investigates the potential challenges and limitations associated with aid, such as aid dependency, governance issues, and the potential crowding out of domestic resources. Furthermore, the study assesses the heterogeneity of aid effectiveness across different types of aid modalities, recipient country characteristics, and aid allocation mechanisms. It considers the role of aid conditionality, aid fragmentation, and aid targeting in influencing the effectiveness of aid in promoting economic development. The findings of this research contribute to the ongoing discourse on foreign aid and economic development by providing a comprehensive analysis of the existing literature. The study highlights the importance of context-specific factors, recipient country policies, and aid effectiveness frameworks in determining the impact of foreign aid on economic development outcomes. The insights derived from this research can inform policymakers, donor agencies, and practitioners in designing and implementing effective aid strategies to maximize the positive impact of foreign aid on economic development.

Keywords: foreign aid, economic development, sustainable growth, poverty reduction, human development indicators, infrastructure development, education, healthcare, technology transfer, institutional capacity building, aid effectiveness, aid dependency, governance, crowding out, aid conditionality, aid fragmentation, aid targeting, recipient country policies, aid strategies, donor agencies, policymaking

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Authors: Xi Wang, Yoshio Bando

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Lithium-ion batteries (LIBs) can deliver high levels of energy storage density and offer long operating lifetimes, but their power density is too low for many important applications. Therefore, we developed some new strategies and fabricated novel electrodes for fast Li transport and its facile synthesis including N-doped graphene-SnO2 sandwich papers, bicontinuous nanoporous Cu/Li4Ti5O12 electrode, and binder-free N-doped graphene papers. In addition, by using advanced in-TEM, STEM techniques and the theoretical simulations, we systematically studied and understood their storage mechanisms at the atomic scale, which shed a new light on the reasons of the ultrafast lithium storage property and high capacity for these advanced anodes. For example, by using advanced in-situ TEM, we directly investigated these processes using an individual CuO nanowire anode and constructed a LIB prototype within a TEM. Being promising candidates for anodes in lithium-ion batteries (LIBs), transition metal oxide anodes utilizing the so-called conversion mechanism principle typically suffer from the severe capacity fading during the 1st cycle of lithiation–delithiation. Also we report on the atomistic insights of the GN energy storage as revealed by in situ TEM. The lithiation process on edges and basal planes is directly visualized, the pyrrolic N "hole" defect and the perturbed solid-electrolyte-interface (SEI) configurations are observed, and charge transfer states for three N-existing forms are also investigated. In situ HRTEM experiments together with theoretical calculations provide a solid evidence that enlarged edge {0001} spacings and surface "hole" defects result in improved surface capacitive effects and thus high rate capability and the high capacity is owing to short-distance orderings at the edges during discharging and numerous surface defects; the phenomena cannot be understood previously by standard electron or X-ray diffraction analyses.

Keywords: in-situ TEM, STEM, advanced anode, lithium-ion batteries, storage mechanism

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Authors: P. Annapurna, Cecil Ross, Sudhir Krishna, Sweta Srivastava

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Irradiation plays a pivotal role in cervical cancer treatment, however some tumors exhibit resistance to therapy while some exhibit relapse, due to better repair and enhanced resistance mechanisms operational in their cells. The present study aims to understand the signaling mechanism operational in resistance phenotype and in the present study we report the role of Rho GTPase associated protein kinase (ROCK) signaling in cervical carcinoma radio-resistance. ROCK signaling has been implicated in several tumor progressions and is important for DNA repair. Irradiation of spheroid cultures of SiHa cervical carcinoma derived cell line at 6Gy resulted in generation of resistant cells in vitro which had better clonogenic abilities and formed larger and more colonies, in soft agar colony formation assay, as compared to the non-irradiated cells. These cells also exhibited an enhanced motility phenotype. Cell cycle profiling showed the cells to be blocked in G2M phase with enhanced pCDC2 levels indicating onset of possible DNA repair mechanism. Notably, 3 days post-irradiation, irradiated cells showed increased ROCK2 translocation to the nucleus with enhanced protein expression as compared to the non-irradiated cells. Radio-sensitization of the resistant cells was enhanced using Y27632, an inhibitor to ROCK signaling. The treatment of resistant cells with Y27632 resulted in increased cell death upon further irradiation. This observation has been confirmed using inhibitory antibodies to ROCK1/2. Result show that both ROCK1/2 have a functional contribution in radiation resistance of cervical cancer cells derived from cell lines. Interestingly enrichment of stem like cells (Hoechst negative cells) was also observed upon irradiation and these cells were markedly sensitive to Y27632 treatment. Our results thus suggest the role of ROCK signaling in radio-resistance in cervical carcinoma. Further studies with human biopsies, mice models and mechanistic of ROCK signaling in the context of radio-resistance will clarify the role of this molecule further and allow for therapeutics development.

Keywords: cervical carcinoma, radio-resistance, ROCK signaling, cancer treatment

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Authors: Wendy de Gomez

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Standardization is a critical element in the ability of a society to reduce uncertainty, subjectivity, misrepresentation, and interpretation while simultaneously contributing to innovation. Technological standardization is critical to codify specific operationalization through legal instruments that provide rules of development, expectation, and use. In the current emerging technology landscape Artificial Intelligence (AI) hardware as a general use technology has seen incredible growth as evidenced from AI technology patents between 2012 and 2018 in the United States Patent Trademark Office (USPTO) AI dataset. However, as outlined in the 2023 United States Government National Standards Strategy for Critical and Emerging Technology the codification through standardization of emerging technologies such as AI has not kept pace with its actual technological proliferation. This gap has the potential to cause significant divergent possibilities for the downstream outcomes of AI in both the short and long term. This original empirical research provides an overview of the standardization efforts around AI in different geographies and provides a background to standardization law. It quantifies the longitudinal trend of Artificial Intelligence hardware patents through the USPTO AI dataset. It seeks evidence of existing Standard Essential Patents from these AI hardware patents through a text analysis of the Statement of patent history and the Field of the invention of these patents in Patent Vector and examines their determination as a Standard Essential Patent and their inclusion in existing AI technology standards across the four main AI standards bodies- European Telecommunications Standards Institute (ETSI); International Telecommunication Union (ITU)/ Telecommunication Standardization Sector (-T); Institute of Electrical and Electronics Engineers (IEEE); and the International Organization for Standardization (ISO). Once the analysis is complete the paper will discuss both the theoretical and operational implications of F/Rand Licensing Agreements for the owners of these Standard Essential Patents in the United States Court and Administrative system. It will conclude with an evaluation of how Standard Setting Organizations (SSOs) can work with SEP owners more effectively through various forms of Intellectual Property mechanisms such as patent pools.

Keywords: patents, artifical intelligence, standards, F/Rand agreements

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Authors: Ana Lambelho

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Nowadays is very common that an activity may be performed independently or dependently. In Portugal, the Labour Law exclusively protects the dependent labour relations. The independent work is regulated by civil law, where the autonomy of the will is the main principle. For companies is more advantageous to hire people under a service agreement since, in that case, the relation is not submitted to the limits established in Labour law and collective bargaining. This practice has nothing wrong, if the performance of work is, in fact, made autonomously. The problem is the increased frequency of the celebration of service agreements to hide a legal relation of subordination. Aware of this and regarding the huge difficulty to demonstrate the existence of subordinated work (that often runs against the employee), the Portuguese legislator devoted some legislative rules in order to facilitate the evidence of legal subordination and, on the other hand, to avoid the misuse of the provision of service agreements. This study focuses precisely on the analysis of this solution, namely the so-called presumption of ‘laboralidade’ and on the lawsuit to recognize the existence of a labour contract. The presumption of the existence of a labour contract is present in the Portuguese legal system since 2003, and received, with the 2009 Labour Code, a new redaction that, according to the doctrine and the jurisprudence, finally approached it to a legal presumption, with the consequent reversal of the burden of proof and, in consequence, made easier to proof the legal subordination, because the employee will just have to plead and prove the existence of two of the elements described in the law to use this presumption. Another change in the Portuguese legal framework is related with the competencies of the Authority for Working Conditions (AWC): now, if during an inspection, the Authority finds a situation that seems to be an undeclared employment situation, it may access the company and, if it does not regularize voluntarily the situation, AWC has a duty to communicate to the public prosecutor, who will begin the lawsuit for the recognition of the existence of an employment contract. To defend the public interest, the action to recognize the existence of an employment contract will follow its terms, even against the employee will. Although the existence of these mechanisms does not solve by itself the problem of evasion of labour law and false ‘green receipts’, it is undeniable that it is an important step in combating fraud in this field.

Keywords: independent work, labour contract, Portugal, service agreement

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Authors: Mahdokht Sadeghvishkaei, Azizah Abdul-Hamid, Amin Ismail, Nazamid Saari

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Hypertension is a common and serious chronic health problem and known as the most important risk factor for development of many diseases such as stroke. Since angiotensin I-converting enzyme (ACE) is the key enzyme involved in blood pressure, one of the well accepted mechanisms to control hypertension is through ACE inhibition. The ACE inhibitory effect of Actinopyga lecanora (stone fish) proteolysate in vitro had been reported. Hence, this study aimed to evaluate the ACE inhibitory potential of Actinopyga lecanora proteolysate in vivo in normotensive rats. Therefore the ACE inhibitory capability of the proteolysate to prevent increasing systolic blood pressure, after inducing hypertension by angiotensin I was examined. The pre-fed rats with the proteolysates at various doses (200, 400, 800 mg/kg body weight) revealed the significant (p ≤ 0.05) suppression effect compared with control groups. Furthermore, different doses of the proteolysate (200, 400, 800 mg/kg body weight) were examined to find its optimum effective dose. Results depicted that 800 mg proteolysate/kg body weight significantly reduced systolic blood pressure without negative effect on normal blood pressure (p ≤ 0.05). Furthermore, Sub-acute toxicity study based on OECD guideline demonstrated the safety of the proteolysate in vivo. The present study indicated that the proteolysate at a dose of 1000 mg/kg daily for 14 days did not cause toxicity signs such as death, changes in activity, or piloerection. Since there are no significant differences between treated groups and control groups, hematological and biochemical analysis confirmed safety of the proteolysate (p > 0.05). In addition, there were no significant differences between organs weights of the treated groups and the control groups. Morphologically, neither histopathological changes, nor gross abnormalities were observed. However, the proteolysate caused significant decrease in body weight in relation to the control groups (p ≤ 0.05) probably due to appetite stimulation by the proteolysate, leading to decreased food consumption in sub-acute group. It is concluded that the proteolysate generated from Actinopyga lecanora possess a significant anti-hypertensive effect and would be potentially used as natural alternative of ACE inhibitors.

Keywords: ACE inhibition, Actinopyga lecanora, anti-hypertensive activity, bioactive peptides, normotensive rats

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