Search results for: intrastromal donor limbal segments

Authors: Dianne Lyneth Alavado

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At the turn of the millennium, development paradigms in the international scene revolved around one goal: elimination of global poverty without comprising human rights. One measure which achieved high endorsement and visibility in the world of work is the Decent Work Agenda (DWA) championed by the United Nation’s (UN) specialized agency for work, the International Labour Organization (ILO). The DWA has been thoroughly promoted and recommended as an ingredient of development planning and a poverty reduction strategy, particularly in developing countries such as the Philippines. The global imperative of economic growth is measurable not only in the numbers raked in by countries in terms of expanding economy but also by the development and realization of the full capacities of their people. Decent work (DW), as an outcome and not just a development approach, promises poverty eradication by means of providing both quantity and quality work that is accompanied by rights, representation, and protection. As a party to these international pacts, the Philippines is expected to heed the call towards a world free from poverty through well-endorsed measures such as the DWA with the aid of multilateral and donor organizations such as the ILO. This study aims to assess the capacity and readiness of the Philippines to achieve the goals of the DWA. This is a qualitative research using the sociological and juridical lens in the desk analysis of existing Philippine laws, policies, and programs vis-à-vis decent work indicators set forth by the ILO. Interview with experts on the Philippine labor situation is conducted for further validation. The paper identifies gaps within the Philippine legal system and its collection of laws, acts, presidential decrees, department orders and other policy instruments aimed towards achieving the goals of the DWA. Among the major findings of this paper are: the predisposition of Philippine labor laws towards the formal sector; the need for alternative solutions for the informal sector veering away from the usual dole-outs and livelihood projects; the needs for evaluation of policies and programs that are usually self-evaluated; the minimal reach of the labour inspectorate which ensures decent work; and the lack of substantial penalty for non-compliance with labor laws. The paper concludes with policy implications and recommendations towards addressing the potholes on the road to Decent Work.

Keywords: decent work agenda, labor laws, millennium development goals, poverty eradication, sustainable development goal

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Authors: Vedanki Khandenwal, Pawan Srivastava, Kartick Tarafder, Subhasis Ghosh

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We present here the experimental realization of controlled doping of graphene monolayers through charge transfer by trapping selected organic molecules between the graphene layer and underlying substrates. This charge transfer between graphene and trapped molecule leads to controlled n-type or p-type doping in monolayer graphene (MLG), depending on whether the trapped molecule acts as an electron donor or an electron acceptor. Doping controllability has been validated by a shift in corresponding Raman peak positions and a shift in Dirac points. In the transfer characteristics of field effect transistors, a significant shift of Dirac point towards positive or negative gate voltage region provides the signature of p-type or n-type doping of graphene, respectively, as a result of the charge transfer between graphene and the organic molecules trapped within it. In order to facilitate the charge transfer interaction, it is crucial for the trapped molecules to be situated in close proximity to the graphene surface, as demonstrated by findings in Raman and infrared spectroscopies. However, the mechanism responsible for this charge transfer interaction has remained unclear at the microscopic level. Generally, it is accepted that the dipole moment of adsorbed molecules plays a crucial role in determining the charge-transfer interaction between molecules and graphene. However, our findings clearly illustrate that the doping effect primarily depends on the reactivity of the constituent atoms in the adsorbed molecules rather than just their dipole moment. This has been illustrated by trapping various molecules at the graphene−substrate interface. Dopant molecules such as acetone (containing highly reactive oxygen atoms) promote adsorption across the entire graphene surface. In contrast, molecules with less reactive atoms, such as acetonitrile, tend to adsorb at the edges due to the presence of reactive dangling bonds. In the case of low-dipole moment molecules like toluene, there is a lack of substantial adsorption anywhere on the graphene surface. Observation of (i) the emergence of the Raman D peak exclusively at the edges for trapped molecules without reactive atoms and throughout the entire basal plane for those with reactive atoms, and (ii) variations in the density of attached molecules (with and without reactive atoms) to graphene with their respective dipole moments provides compelling evidence to support our claim. Additionally, these observations were supported by first principle density functional calculations.

Keywords: graphene, doping, charge transfer, liquid phase exfoliation

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Authors: Dalya M. Hassan

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Marketplaces and commercial streets represent some of the most used and lively urban public spaces. Not only do they provide an outlet for commercial exchange, but they also facilitate social and recreational encounters. Such encounters can be influenced by both formal as well as informal vending activities. This paper explores and documents forms of informal vending practices and how they relate to social patterns that occur along the sidewalks of Commercial Streets in Cairo. A qualitative single case study approach of ‘Midan El Gami’ marketplace in Heliopolis, Cairo is adopted. The methodology applied includes direct and walk-by observations for two main commercial streets in the marketplace. Four zoomed-in activity maps are also done for three sidewalk segments that displayed varying vending and social features. Main findings include a documentation and classification of types of informal vending practices as well as a documentation of vendors’ distribution patterns in the urban space. Informal vending activities mainly included informal street vendors and shop spillovers, either as product or seating spillovers. Results indicated that staying and lingering activities were more prevalent in sidewalks that had certain physical features, such as diversity of shops, shaded areas, open frontages, and product or seating spillovers. Moreover, differences in social activity patterns were noted between sidewalks with street vendors and sidewalks with spillovers. While the first displayed more buying, selling, and people watching activities, the latter displayed more social relations and bonds amongst traders’ communities and café patrons. Ultimately, this paper provides a documentation, which suggests that informal vending can have a positive influence on creating a lively commercial street and on resulting patterns of use on the sidewalk space. The results can provide a basis for further investigations and analysis concerning this topic. This could aid in better accommodating informal vending activities within the design of future commercial streets.

Keywords: commercial streets, informal vending practices, sidewalks, social encounters

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Authors: Omoruyi G. Idemudia, Alexander P. Sadimenko

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The need for the development of new sustainable bioactive compounds with unique properties that can become potential replacement for commonly used medicinal drugs has continued to gain tremendous research concerns because of the problems of disease resistant to these medicinal drugs and their toxicity effects. NOS-donor heterocycles are particularly of interest as they have showed good pharmacological activities in the midst of their interesting chelating properties towards metal ions, an important characteristic for transition metal based drugs design. These new compounds have also gained application as dye sensitizers in solar cell panels for the generation of renewable solar energy, as greener water purification polymer for supply and management of clean water and as catalysts which are used to reduce the amount of pollutants from industrial reaction processes amongst others, because of their versatile properties. Di-ketone acylpyrazolones and their azomethine schiff bases have been employed as pharmaceuticals as well as analytical reagents, and their application as transition metal complexes have being well established. In this research work, a new 4-propyl-3-methyl-1-phenyl-2-pyrazolin-5-one-thiosemicarbazone was synthesized from the reaction of 4-propyl-3-methyl-1-phenyl-2-pyrazolin-5-one and thiosemicarbazide in methanol. The pure isolate of the thiosemicarbazone was further reacted with aqueous solutions of palladium and platinum salts to obtain their metal complexes, in an effort towards the discovery of transition metal based synthetic drugs. These compounds were characterized by means of analytical, spectroscopic, thermogravimetric analysis TGA, as well as x-ray crystallography. 4-propyl-3-methyl-1-phenyl-2-pyrazolin-5-one thiosemicarbazone crystallizes in a triclinic crystal system with a P-1 (No. 2) space group according to x-ray crystallography. The tridentate NOS ligand formed a tetrahedral geometry on coordinating with metal ions. Reported compounds showed varying antioxidant free radical scavenging activities against 2, 2-diphenyl-1-picrylhydrazyl DPPH radical at 100, 200, 300, 400 and 500 µg/ml concentrations. The platinum complex have shown a very good antioxidant property against DPPH with an IC50 of 76.03 µg/ml compared with standard ascorbic acid (IC50 of 74.66 µg/ml) and as such have been identified as a potential anticancer candidate.

Keywords: acylpyrazolone, free radical scavenging activities, tridentate ligand, x-ray crystallography

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Authors: Matthew Venunye Fianu, Jerry Fiave, Ebenezer Kye-Mensah, Dacosta Aboagye, Felix Osei-Sarpong

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Introduction: Road traffic accidents involving motorbikes are a priority public health concern in Ghana. While there are local initiatives to address this public health challenge, little is known about motor riders’ knowledge and compliance with road safety regulations (RSR) and their association with RTAs. The aim of this study was, therefore, to assess motorbike riders’ knowledge and compliance with RSRs. Methodology: Motorbike riders in Hohoe Municipality were randomly sampled in a cross-sectional study in June 2022. Data were collected from 237 riders using a questionnaire designed in Kobocollect and administered by ten research assistants. A score of 70% or less is considered low for knowledge and compliance. The data were exported into Excel and imported into STATA 17 for analysis. A chi-square test was performed to generate descriptive and inferential statistics to establish the association between independent and dependent variables. Results: All 237 respondents were male, and each of them completed the questionnaire representing a 100% response rate. Participants who had knowledge about speed limit at different segments of the road were 59(24.9%), the use of helmet were 124 (52.3%), and alcohol use were 152 (64.1%). Participants who complied with regulations on speed limits, helmet use, and alcohol use were 108 (45.6%), 179(75.5%), and 168(70.8%), respectively. Riders who had at least junior high school education were 2.43 times more likely to adhere to RSR [cOR =2.43(95%CI= 1.15-6.33) p= 0.023] than those who had less education. Similarly, riders who had high knowledge about RSR were 2.07 times more likely to comply with RSR than those who had less knowledge [AOR= -2.07 (95% CI= 0.34-0.97), p=0.038]. Conclusion: Motor riders in the Hohoe Municipality had low knowledge as well as low compliance with road safety regulations. This could be a contributor to road traffic accidents. It is therefore recommended that road safety regulatory authorities and relevant stakeholders enhance the enforcement of RSR. There should also be country-specific efforts to increase awareness among all motor riders, especially those with less than junior high school education.

Keywords: compliance, motor riders, road safety regulations, road traffic accident

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Authors: Yatimah Alias, Tilagam Marimuthu, M. R. Mahmoudian, Sharifah Mohamad

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The rapid growth of science and technology in energy and environmental fields has enlightened the substantial importance of the conducting polymer and metal composite materials engineered at nano-scale. In this study, polypyrrole-cobalt composites (PPy-Co Cs) and polypyrrole-nickel oxide composites (PPy-NiO Cs) were prepared by a simple and facile chemical polymerization method with an aqueous solution of pyrrole monomer in the presence of metal salt. These composites then fabricated into non-enzymatic hydrogen peroxide (H2O2) and glucose sensor. The morphology and composition of the composites are characterized by the Field Emission Scanning Electron Microscope, Fourier Transform Infrared Spectrum and X-ray Powder Diffraction. The obtained results were compared with the pure PPy and metal oxide particles. The structural and morphology properties of synthesized composites are different from those of pure PPy and metal oxide particles, which were attributed to the strong interaction between the PPy and the metal particles. Besides, a favorable micro-environment for the electrochemical oxidation of H2O2 and glucose was achieved on the modified glassy carbon electrode (GCE) coated with PPy-Co Cs and PPy-NiO Cs respectively, resulting in an enhanced amperometric response. Both PPy-Co/GCE and PPy-NiO/GCE give high response towards target analyte at optimum condition of 500 μl pyrrole monomer content. Furthermore, the presence of pyrrole monomer greatly increases the sensitivity of the respective modified electrode. The PPy-Co/GCE could detect H2O2 in a linear range of 20 μM to 80 mM with two linear segments (low and high concentration of H2O2) and the detection limit for both ranges is 2.05 μM and 19.64 μM, respectively. Besides, PPy-NiO/GCE exhibited good electrocatalytic behavior towards glucose oxidation in alkaline medium and could detect glucose in linear ranges of 0.01 mM to 0.50 mM and 1 mM to 20 mM with detection limit of 0.33 and 5.77 μM, respectively. The ease of modifying and the long-term stability of this sensor have made it superior to enzymatic sensors, which must kept in a critical environment.

Keywords: metal oxide, composite, non-enzymatic sensor, polypyrrole

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Authors: Elizabeth Malebogo Mosepele

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Road transport has become increasingly common in the world; people rely on road networks for transportation purpose on a daily basis. However, environmental impact of roads on surrounding landscapes extends their potential effects even further. This study investigates the impact of road network on natural vegetation. The study will provide baseline knowledge regarding roadside vegetation and would be helpful in future for conservation of biodiversity along the road verges and improvements of road verges. The general hypothesis of this study is that the amount and condition of road side vegetation could be explained by road network conditions. Remote sensing techniques were used to analyze vegetation conditions. Landsat 8 OLI image was used to assess vegetation cover condition. NDVI image was generated and used as a base from which land cover classes were extracted, comprising four categories viz. healthy vegetation, degraded vegetation, bare surface, and water. The classification of the image was achieved using the supervised classification technique. Road networks were digitized from Google Earth. For observed data, transect based quadrats of 50*50 m were conducted next to road segments for vegetation assessment. Vegetation condition was related to road network, with the multinomial logistic regression confirming a significant relationship between vegetation condition and road network. The null hypothesis formulated was that 'there is no variation in vegetation condition as we move away from the road.' Analysis of vegetation condition revealed degraded vegetation within close proximity of a road segment and healthy vegetation as the distance increase away from the road. The Chi Squared value was compared with critical value of 3.84, at the significance level of 0.05 to determine the significance of relationship. Given that the Chi squared value was 395, 5004, the null hypothesis was therefore rejected; there is significant variation in vegetation the distance increases away from the road. The conclusion is that the road network plays an important role in the condition of vegetation.

Keywords: Chi squared, geographic information system, multinomial logistic regression, remote sensing, road side vegetation

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Authors: Piumi L. Denagamage, Vibusha Madanayake

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At the end of a 30-year civil war in Sri Lanka in 2009, Non-Governmental Organizations (NGOs) played a prominent role in post-war development and peacebuilding. Women were a major “beneficiary” of NGO activities on socio-economic empowerment, capacity building for advocacy, and grassroots participation in activism. Undoubtedly, their contribution to Sri Lanka’s post-war transition is tremendous. As development practitioners and researchers who have worked closely with several international and national NGOs in Sri Lanka’s post-war setting, the authors, while practicing self-reflexivity, intend to theorize the grey literature prepared by NGOs against the theoretical frameworks of Transnational and Third World feminisms. Using examples of the grassroots activities conducted by the NGOs with war-affected women, the paper questions whether Colombo-based feminism represents the lived realities of grassroots women at the transnational level. It argues that Colombo-based feminists use their power and exposure to Western feminist approaches to portray diverse forms of oppression women face at grassroots levels, their needs for advocacy, and different modes of resistance on the ground. Many NGOs depend on international donor funding for their grassroots work, which also contributes to their utilization of Western-led knowledge. Despite their efforts to “save marginalized women from oppression,” these modes of intervention are often rejected by the public, including women at local levels. This has also resulted in the rejection of feminism entirely as a culturally root-less alien Western ideology. The analysis connects with the Transnational and Third World theoretical feminist perspectives to problematize the power relations between Western knowledge systems and the lived experiences of grassroots women in the peacebuilding process through NGO activism in Sri Lanka. It also emphasizes that the infiltration of Western knowledge through NGOs has led to the participation of grassroots women only through adjustments of their lived experiences to match the alien knowledge rather than theorizing based on their own lived realities. While sharing a concern that NGOs’ power to adopt Western knowledge systems is often unchecked and unmitigated, the paper signifies the importance of adopting the methods of alternative theorizing to ensure meaningful participation of Third World women in peacebuilding.

Keywords: alternative theorizing, colombo-based feminism, grassroots women in peacebuilding, NGO activism, transnational and third world feminisms

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Authors: Tadesse Menjetta, Daniel Dana, Serkadis Debalke

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Schistosomiasis/Bilharziasis is one of the neglected tropical parasitic diseases caused by different species of genus Schistosoma. Among the species, S. mansoni (causative agents of intestinal schistosomiasis) is one of the causes of severe intestinal parasitic infections with high public and medical importance in Ethiopia. There is a scarcity of information about the status of S. mansoni infection among the fisherman in our study area and in the country at large. Therefore, this study was designed to determine the prevalence and risk factors of S.mansoni infection among fishermen at Lake Hawassa, southern Ethiopia. A cross-sectional study was conducted among the fishermen from April to June 2013 in Hawassa, Southern Ethiopia. A total of 243 fishermen were included by systematic sampling from the lists of the fishermen members in the registration book of fishermen associations in the Hawassa Town. Data on socio-demographic features and risk factors were collected by using semi-structured questionnaires. Stool samples were collected and processed using Kato-Katz thick smear techniques and examined between 30- 40 minute for hookworm and after 24 hours for S. mansoni and other soil-transmitted helminths (STHs). The overall prevalence of S.mansoni among the fishermen was 29.21% (71/243), and the mean intensity of infection was 158.88 egg per gram (EPG). The prevalence of intestinal helminths including S. mansoni was 69.54% (169/243). Moreover, the prevalence of soil-transmitted helminths (STHs) was 40.74% (99/243), 35.80% (87/243) and 5.76% (14/243) for A. lumbricoides, T. trichiura and hookworm species, respectively. Almost similar prevalence of S.mansoni, 31.82%, 31.75%, 31.94% were recorded in age groups of 15-19, 20-24 and 25-29 years, respectively. Fishermen who are swimming always were 2.92 times [95% CI: 1.554, 5.502] more likely to acquire S. mansoni infection than other water contacting habit of the study participants. The results of the current investigation indicated the moderate endemicity of S. mansoni among the fishermen at Lake Hawassa, southern Ethiopia. Fishermen could be the potential risk group for S. mansoni infection and might be responsible for the transmission of S. mansoni to other segments of the communities. Since the high prevalence of STH was recorded among the fishermen, integrated prevention and control strategies from different sectors might be important to tackle the problem.

Keywords: S. mansoni, soil transmitted helminths, fishermen, Lake Hawassa, Ethiopia

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Authors: Ramin Zargarbashi, Hamid Rabie, Behnam Panjavi, Hooman Kamran, Seyedarad Mosalamiaghili, Zohre Erfani, Seyed Peyman Mirghaderi, Maryam Salimi

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Background: Posterior shoulder dislocation is one of the disabling complications of brachial plexus birth injury (BPBI), and various treatment options, including capsule and surrounding muscles release for open reduction, humeral derotational osteotomy, and tendon transfers, have been recommended to manage it. In the present study, we aimed to determine the clinical outcome of open reduction with soft tissue release, tendon transfer, and glenoid osteotomy inpatients with BPBI and posterior shoulder dislocation or subluxation. Methods: From 2018 to 2020, 33 patients that underwent open reduction, glenoid osteotomy, and tendon transfer were included. The glenohumeral deformity was classified according to the Waters radiographic classification. Functional assessment was performed using the Mallet grading system before and at least two years after the surgery. Results: The patients were monitored for 26.88± 5.47 months. Their average age was 27.5±14 months. Significant improvement was seen in the overall Mallet score (from 13.5 to 18.91 points) and its segments, including hand to mouth, hand to the neck, global abduction, global external rotation, abduction degree, and external rotation degree. Hand-to-back score and the presence of trumpet sign were significantly decreased in the post-operation phase (all p values<0.001). The above-mentioned variables significantly changed for both infantile and non-infantile dislocations. Conclusion: Our study demonstrated that open reduction along with glenoid osteotomy improves retroversion, and muscle strengthening with different muscle transfers is an effective technique for BPBI.

Keywords: birth injuries, nerve injury, brachial plexus birth palsy, Erb palsy, tendon transfer

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Authors: Aimen Saleh

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The Silurian Lower Acacus sandstone is one of the main reservoirs in North West Libya. Our aim in this study is to grasp a robust understanding of the hydrocarbon potential and distribution in the area. To date, the depositional environment of the Lower Acacus reservoir still open to discussion and contradiction. Henceforth, building three dimensional (3D) property modelling is one way to support the analysis and description of the reservoir, its properties and characterizations, so this will be of great value in this project. The 3D model integrates different data set, these incorporates well logs data, petrophysical reservoir properties and seismic data as well. The finalized depositional environment model of the Lower Acacus concludes that the area is located in a deltaic transitional depositional setting, which ranges from a wave dominated delta into tide dominated delta type. This interpretation carried out through a series of steps of model generation, core description and Formation Microresistivity Image tool (FMI) interpretation. After the analysis of the core data, the Lower Acacus layers shows a strong effect of tidal energy. Whereas these traces found imprinted in different types of sedimentary structures, for examples; presence of some crossbedding, such as herringbones structures, wavy and flaser cross beddings. In spite of recognition of some minor marine transgression events in the area, on the contrary, the coarsening upward cycles of sand and shale layers in the Lower Acacus demonstrate presence of a major regressive phase of the sea level. However, consequently, we produced a final package of this model in a complemented set of facies distribution, porosity and oil presence. And also it shows the record of the petroleum system, and the procedure of Hydrocarbon migration and accumulation. Finally, this model suggests that the area can be outlined into three main segments of hydrocarbon potential, which can be a textbook guide for future exploration and production strategies in the area.

Keywords: Acacus, Ghadames , Libya, Silurian

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Authors: A. Yousuf, M. Iqbal, A. Mir, S. Aziz

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This study deals with the women’s right to land for gender equality. Economic Transformation Initiative, Gilgit-Baltistan (ETI-GB), an ambitious program supported by International Fund for Agricultural Development United Nation (IFAD, UN), aims to strengthen land reforms process in disputed area of Gilgit-Baltistan (GB) Pakistan, that is taking place first time in the history. This project is a brick to build the foundation of land reforms and land policies in GB. The ETI-GB provides substantive support to government of GB in developing policy measures and initiatives to promote women’s right to have and to own land is kind of unconventional step in a very traditional society. It would be interesting to have discussion and document the people’s response regarding this project. The study has used mixed method for data collection. For qualitative data, content analysis is used to have a thorough understanding of different types of land reforms across the globe particularly in South Asia. Theoretical understanding of the literature is essential which provides the basis why land reforms are important and how far it plays an important role when it comes to eliminating inequality. Focused group discussion was carried out for verification and triangulation of data. For quantitative, survey was conducted to take responses from the people of the region and analyzed. The program is implemented in Ghizer district of GB. 2340 households were identified as beneficiaries of newly developed land. Among them, 2285 were men households, and 55 were women households. There is a significant difference between men and women households. In spite of great difference, it is a great achievement of the donor that in history of GB, first time women are going to be entitled to land ownership. GB is a patriarchal society, many social factors like cultural, religious play role for gender inequality. In developing countries, such as Pakistan, the awareness of land property rights has not been given proper attention to gender equality development frameworks. It is argued that land property rights of women have not been taken into mainstream policymaking in the development of nation building process. Consequently, this has generated deprivation of women’s property rights, low income level, lack of education and poor health. This paper emphasises that there should have proper land property right of women in Gilgit-Baltistan Pakistan, provided that the gender empowerment could be increased in terms of women’s property rights.

Keywords: gender equality, women right to land ownership, property rights, women empowerment

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Authors: S. Archsana, Vajira Balasuriya

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In Trincomalee of Sri Lanka, a post-conflict area, resettlement projects and policy initiatives are taking place to improve the wealth of the rural communities through promoting economic activities by way of encouraging the rural women to opt to commence and operate Micro and Small Scale (MSS) businesses. This study attempts to identify the manner in which the institutional environment could facilitate these MSS businesses owned and operated by women in the rural environment. The respondents of this study are the beneficiaries of the Divi Neguma Development Training Program (DNDTP); a project designed to aid women owned MSS businesses, in Trincomalee district. 96 women business operators, who had obtained financing facilities from the DNDTP, are taken as the sample based on fixed interval random sampling method. The study reveals that primary challenges encountered by 82% of the women business operators are lack of initial capital followed by 71% initial market finding and 35% access to technology. The low level of education and language barriers are the constraints in accessing support agencies/service providers. Institutional support; specifically management and marketing services, have a significant relationship with wealth augmentation. Institutional support at the setting-up stage of businesses are thin whereas terms and conditions of the finance facilities are perceived as ‘too challenging’. Although diversification enhances wealth of the rural women business operators, assistance from the institutional framework to prepare financial reports that are required for business expansion is skinny. The study further reveals that institutional support is very much weak in terms of providing access to new technology and identifying new market networks. A mechanism that could facilitate the institutional framework to support the rural women business operators to access new technology and untapped market segments, and assistance in preparation of legal and financial documentation is recommended.

Keywords: business facilitation, institutional support, rural women business operators, wealth augmentation

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Authors: Morten Brøgger, Kim Wittchen

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Focus on reducing energy consumption in existing buildings at large scale, e.g. in cities or countries, has been increasing in recent years. In order to reduce energy consumption in existing buildings, political incentive schemes are put in place and large scale investments are made by utility companies. Prioritising these investments requires a comprehensive overview of the energy consumption in the existing building stock, as well as potential energy-savings. However, a building stock comprises thousands of buildings with different characteristics making it difficult to model energy consumption accurately. Moreover, the complexity of the building stock makes it difficult to convey model results to policymakers and other stakeholders. In order to manage the complexity of the building stock, building archetypes are often employed in building stock energy models (BSEMs). Building archetypes are formed by segmenting the building stock according to specific characteristics. Segmenting the building stock according to building type and building age is common, among other things because this information is often easily available. This segmentation makes it easy to convey results to non-experts. However, using a single archetypical building to represent all buildings in a segment of the building stock is associated with loss of detail. Thermal characteristics are aggregated while other characteristics, which could affect the energy efficiency of a building, are disregarded. Thus, using a simplified representation of the building stock could come at the expense of the accuracy of the model. The present study evaluates the accuracy of a conventional archetype-based BSEM that segments the building stock according to building type- and age. The accuracy is evaluated in terms of the archetypes’ ability to accurately emulate the average energy demands of the corresponding buildings they were meant to represent. This is done for the buildings’ energy demands as a whole as well as for relevant sub-demands. Both are evaluated in relation to the type- and the age of the building. This should provide researchers, who use archetypes in BSEMs, with an indication of the expected accuracy of the conventional archetype model, as well as the accuracy lost in specific parts of the calculation, due to use of the archetype method.

Keywords: building stock energy modelling, energy-savings, archetype

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Authors: Mohamed Khali Zidi, Mohsen Henchiri, Walid Ben Ahmed

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In the context of a hypogene hydrothermal travertine system, including low-porosity brittle bedrock and rock-mass permeability in Aptian dolostone of Boulaaba, Kasserine is enhanced through faulting and fracturing. This permeability enhancement related to the deformation modes along faults and fractures is likely to be in competition with permeability reduction when microcracks, fractures, and faults all become infilled with breccias and low-permeability hydrothermal precipitates. So that, fault continual or intermittent reactivation is probably necessary for them to keep their potential as structural high-permeability conduits. Dilational normal faults in strong mechanical stratigraphy associated with fault segments with dip changes are sites for porosity and permeability in groundwater infiltration and flow, hydrocarbon reservoirs, and also may be important sources of mineralization. The brecciation mechanism through dilational faulting and gravitational collapse originates according to hosting lithologies chaotic clast-supported breccia in strong lithologies such as sandstones, limestones, and dolostones, and matrix-supported cataclastic in weaker lithologies such as marls and shales. Breccias contribute to controlling fluid flow when the porosity is sealed either by low-permeability hydrothermal precipitates or by fine matrix materials. All these mechanisms of fault-related rock-mass permeability enhancement and reduction can be observed and analyzed in the region of Sidi Boulaaba, Kasserine, central Tunisia, where dilational normal faulting occurs in mechanical strong dolostone layering alternating with more weak marl and shale lithologies, has originated a variety of fault voids (fluid conduits) breccias (chaotic, crackle and mosaic breccias) and carbonate cement.

Keywords: travertine, Aptian dolostone, Boulaaba, fracturing

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Authors: Vephkhvia Grigalashvili

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This paper provides an overview of criteria for good governance in Georgian defense sector and scientific outcomes of comparative research. A respect for good governance and its realization into Georgian national defense sector represents a fundamental institutional necessity as well as country`s politico-legal obligation within the framework of the existing collaboration mechanisms with NATO (especially Building Integrity (BI) Programme) and the Association Agreement between the EU and Georgia. Furthermore good governance is considered as a democracy measuring criterion in country`s Euro-Atlantic integration process. Accordingly, integration and further development of the contemporary approaches of good governance into Georgian defense management model represents a burning issue of the country. The assessment of an existing model of the country, identification of defects and determination of course of institutional reforms in a mutual comparison format of good governance mechanisms of NATO or/and the EU member Eastern European or Baltic countries positively assessed by the international organizations is considered as a precondition for its effective realization. Scientific aims of this study are: (a) to conduct comparative analysis of Georgian national principles and generalized standards of NATO or/and the EU member Eastern European and Baltic countries in following segments of good governance: open governance; anticorruption policy; conflict of interests; integrity; internal and external control bodies; (b) to formulate theoretical and practical recommendations on reforms to be implemented in the country`s national defence sector. As research reveals, although, institutional / legal pillars of good governance in Georgian defense sector generally are in compliance with international principles, the quality of implementation of good government norms still remains as an area that needs further development by raising awareness of public servants and community.

Keywords: anti-corruption policy within Georgian defense governance, conflict of interests within Georgian defense governance, good governance in Georgian defense sector, principles of integrity in Georgian defense management

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Authors: Gargi Prasad, Ashiho A. Mao, Deepu Vijayan, S. Mandal

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The main objective of the present study was to optimize and develop an efficient protocol for in vitro propagation of a medicinally important orchid Cephalantheropsis obcordata (Lindl.) Ormerod along with genetic stability analysis of regenerated plants. This plant has been traditionally used in Chinese folk medicine and the decoction of whole plant is known to possess anticancer activity. Nodal segments used as explants were inoculated on Murashige and Skoog (MS) medium supplemented with various concentrations of isopentenyl adenine (2iP). The rooted plants were successfully acclimatized in the greenhouse with 100% survival rate. Inter-simple sequence repeats (ISSR) markers were used to assess the genetic fidelity of in vitro raised plants and the mother plant. It was revealed that monomorphic bands showing the absence of polymorphism in all in vitro raised plantlets analyzed, confirming the genetic uniformity among the regenerants. Phytochemical analysis was done to compare the antioxidant activities and HPLC fingerprinting assay of 80% aqueous ethanol extract of the leaves and stem of in vitro and in vivo grown C. obcordata. The extracts of the plants were examined for their antioxidant activities by using free radical 1, 1-diphenyl-2-picryl hydrazyl (DPPH) scavenging method, 2,2’-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging ability, reducing power capacity, estimation of total phenolic content, flavonoid content and flavonol content. A simplified method for the detection of ascorbic acid, phenolic acids and flavonoids content was also developed by using reversed phase high-performance liquid chromatography (HPLC). This is the first report on the micropropagation, genetic integrity study and quantitative phytochemical analysis of in vitro regenerated plants of C. obcordata.

Keywords: Cephalantheropsis obcordata, genetic fidelity, ISSR markers, HPLC

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Authors: Abhisek Dash

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This study had three neural networks, one for number segmentation, one for number detection and one for number recognition all of which are coupled to one another. All networks were trained on the MNIST dataset and were convolutional. It was assumed that the images had lighter background and darker foreground. The segmentation network took 28x28 images as input and had sixteen outputs. Segmentation training starts when a dark pixel is encountered. Taking a window(7x7) over that pixel as focus, the eight neighborhood of the focus was checked for further dark pixels. The segmentation network was then trained to move in those directions which had dark pixels. To this end the segmentation network had 16 outputs. They were arranged as “go east”, ”don’t go east ”, “go south east”, “don’t go south east”, “go south”, “don’t go south” and so on w.r.t focus window. The focus window was resized into a 28x28 image and the network was trained to consider those neighborhoods which had dark pixels. The neighborhoods which had dark pixels were pushed into a queue in a particular order. The neighborhoods were then popped one at a time stitched to the existing partial image of the number one at a time and trained on which neighborhoods to consider when the new partial image was presented. The above process was repeated until the image was fully covered by the 7x7 neighborhoods and there were no more uncovered black pixels. During testing the network scans and looks for the first dark pixel. From here on the network predicts which neighborhoods to consider and segments the image. After this step the group of neighborhoods are passed into the detection network. The detection network took 28x28 images as input and had two outputs denoting whether a number was detected or not. Since the ground truth of the bounds of a number was known during training the detection network outputted in favor of number not found until the bounds were not met and vice versa. The recognition network was a standard CNN that also took 28x28 images and had 10 outputs for recognition of numbers from 0 to 9. This network was activated only when the detection network votes in favor of number detected. The above methodology could segment connected and overlapping numbers. Additionally the recognition unit was only invoked when a number was detected which minimized false positives. It also eliminated the need for rules of thumb as segmentation is learned. The strategy can also be extended to other characters as well.

Keywords: convolutional neural networks, OCR, text detection, text segmentation

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Authors: Qin Yang, Fan Zhang, Juan Du, Chongkui Sun, Krishna Kota, Yun-Ling Zheng

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Telomeres are specialized structures at chromosome ends consisting of tandem repetitive DNA sequences [(TTAGGG)n in humans] and associated proteins, which are necessary for telomere function. Telomere lengths are tightly regulated within a narrow range in normal human somatic cells, the basis of cellular senescence and aging. Previous studies have extensively focused on how short telomeres are extended and have demonstrated that telomerase plays a central role in telomere maintenance through elongating the short telomeres. However, the molecular mechanisms of regulating excessively long telomeres are unknown. Here, we found that telomerase enzymatic component hTERT plays a dual role in the regulation of telomeres length. We analyzed single telomere alterations at each chromosomal end led to the discoveries that hTERT shortens excessively long telomeres and elongates short telomeres simultaneously, thus maintaining the optimal telomere length at each chromosomal end for an efficient protection. The hTERT-mediated telomere shortening removes large segments of telomere DNA rapidly without inducing telomere dysfunction foci or affecting cell proliferation, thus it is mechanistically distinct from rapid telomere deletion. We found that expression of hTERT generates telomeric circular DNA, suggesting that telomere homologous recombination may be involved in this telomere shortening process. Moreover, the hTERT-mediated telomere shortening is required its enzymatic activity, but telomerase RNA component hTR is not involved in it. Furthermore, shelterin protein TPP1 interacts with hTERT and recruits it on telomeres to mediate telomere shortening. In addition, telomere-associated proteins, DKC1 and TCAB1 also play roles in this process. This novel hTERT-mediated telomere shortening mechanism not only exists in cancer cells, but also in primary human cells. Thus, the hTERT-mediated telomere shortening is expected to shift the paradigm on current molecular models of telomere length maintenance, with wide-reaching consequences in cancer and aging fields.

Keywords: aging, hTERT, telomerase, telomeres, human cells

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Authors: Metrek Almetrek, Naser Alqahtani, Eisa Ghazwani, Mona Asiri, Mohammed Alqahtani, Magboolah Balobaid

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Background: Advocacy of potential for community coalitions to positively address social determinants of health and quality of life, little is known about the views of stakeholders involved in such efforts. This study sought to assess the provinces leaders’ perspectives about social determinants related to the Health Neighborhood Initiative (HNI), a new county effort to support community coalitions. Method and Subjects: We used a descriptive, qualitative study using personal interviews in 2022. We conducted it in the community coalition's “main cities committees” set across service planning areas that serve vulnerable groups located in the seven registered healthy cities to WHO (Abha, Tareeb, Muhayel, Balqarn, Alharajah, Alamwah, and Bisha). We conducted key informant interviews with 76 governmental, profit, non-profit, and community leaders to understand their perspectives about the HNI. As part of a larger project, this study focused on leaders’ views about social determinants of health related to the HNI. All interviews were audio-recorded and transcribed. An inductive approach to coding was used, with text segments grouped by social determinant categories. Results: Provinces leaders described multiple social determinants of health and quality of life that were relevant to the HNI community coalitions: housing and safety, community violence, economic stability, city services coordination and employment and education. Leaders discussed how social determinants were interconnected with each other and the need for efforts to address multiple social determinants simultaneously to effectively improve health and quality of life. Conclusions: Community coalitions have an opportunity to address multiple social determinants of health and quality of life to meet the social needs of vulnerable groups. Future research should examine how community coalitions, like those in the HNI, can actively engage with community members to identify needs and then deliver evidence-based care.

Keywords: social determinants, health and quality of life, vulnerable groups, qualitative research

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Authors: Nemat Sokhandan Bashir

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Threats from viruses to agricultural crops could be even larger than the losses caused by the other pathogens because, in many cases, the viral infection is latent but crucial from an epidemic point of view. Wild vegetation can be a source of many viruses that eventually find their destiny in crop plants. Although often asymptomatic in wild plants due to adaptation, they can potentially cause serious losses in crops. Therefore, exploring viruses in wild vegetation is very important. Recently, omics have been quite useful for exploring plant viruses from various plant sources, especially wild vegetation. For instance, we have discovered viruses such as Ambrossia asymptomatic virus I (AAV-1) through the application of metagenomics from Oklahoma Prairie Reserve. Accordingly, extracts from randomly-sampled plants are subjected to high speed and ultracentrifugation to separated virus-like particles (VLP), then nucleic acids in the form of DNA or RNA are extracted from such VLPs by treatment with phenol—chloroform and subsequent precipitation by ethanol. The nucleic acid preparations are separately treated with RNAse or DNAse in order to determine the genome component of VLPs. In the case of RNAs, the complementary cDNAs are synthesized before submitting to DNA sequencing. However, for VLPs with DNA contents, the procedure would be relatively straightforward without making cDNA. Because the length of the nucleic acid content of VPLs can be different, various strategies are employed to achieve sequencing. Techniques similar to so-called "chromosome walking" may be used to achieve sequences of long segments. When the nucleotide sequence data were obtained, they were subjected to BLAST analysis to determine the most related previously reported virus sequences. In one case, we determined that the novel virus was AAV-l because the sequence comparison and analysis revealed that the reads were the closest to the Indian citrus ringspot virus (ICRSV). AAV—l had an RNA genome with 7408 nucleotides in length and contained six open reading frames (ORFs). Based on phylogenies inferred from the replicase and coat protein ORFs of the virus, it was placed in the genus Mandarivirus.

Keywords: wild, plant, novel, metagenomics

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Authors: Jennifer Fane, Mike Gray, Melissa Sager

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Children with diagnosed or suspected learning disabilities frequently experience significant skill gaps in foundational learning areas such as reading, writing, and math. Remedial one-to-one instruction is a highly effective means of supporting children with learning differences in building these foundational skills and closing the learning gap between them and their same-age peers. However, due to the learning challenges children with learning disabilities face, and ensuing challenges with self-confidence, many children with learning differences struggle with motivation and self-regulation within remedial one-to-one learning environments - despite the benefits of these sessions. Socially Assistive Robots (SARs) are an innovative educational technology tool that has been trialled in a range of educational settings to support diverse learning needs. Yet, little is known about the impact of SARs on the learning of children with learning differences in a one-to-one remedial instructional setting. This study sought to explore the impact of SARs on the engagement of children (n=9) with learning differences attending one-to-one remedial instruction sessions at a non-profit remedial education provider. The study used a mixed-methods design to explore learner engagement during learning tasks both with and without the use of a SAR to investigate how the use of SARs impacts student learning. The study took place over five weeks, with each session within the study followed the same procedure with the SAR acting as a teaching assistant when in use. Data from the study included analysis of time-sample video segments of the instructional sessions, instructor recorded information about the student’s progress towards their session learning goal and student self-reported mood and energy levels before and after the session. Analysis of the findings indicates that the use of SARs resulted in fewer instances of off-task behaviour and less need for instructor re-direction during learning tasks, allowing students to work in more sustained ways towards their learning goals. This initial research indicates that the use of SARs does have a material and measurable impact on learner engagement for children with learning differences and that further exploration of the impact of SARs during one-to-one remedial instruction is warranted.

Keywords: engagement, learning differences, learning disabilities, instruction, social robotics.

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Authors: Nahela Nowshin, Rafia Sultana, Farzana Misha, Sabina F. Rashid

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Sexual and reproductive health and rights (SRHR) are currently an area of neglect for males (aged 15-24 years) in Bangladesh. The lack of focus on the male youth population has consequences not only for their own health and wellbeing, but the patriarchal structure of Bangladeshi society and socio-cultural norms mean that the male population’s SRH behavior can severely impact the lives of their female counterparts. A majority of sexual and reproductive health and rights-related research and interventions in the country are female-centric. Although the Government of Bangladesh has taken many initiatives to improve the SRHR of the general population, the male youth segment has not been prioritized in most of these interventions. There is an urgent need for male-youth-focused SRHR interventions in Bangladesh, but due to a lack of evidence-based research on this issue, there exist data gaps on how such interventions could be better designed and implemented. Therefore, to ascertain strategies for better program design and smoother implementation of male-youth-focused sexual and reproductive health and rights interventions, we carried out 25 key informant interviews with experts as well as focal persons involved in more than 20 ongoing and recently-ended SRHR-related interventions of national and international non-government organizations in which male youth were targeted or engaged. The results show that program implementers face several challenges at the field, organizational and policy levels. Some of the most common field challenges include high sensitivity to SRHR topics due to cultural reasons, difficulties in acquiring access to boys and young men due to their high mobility and engagement in labor for commercial purposes, as well as accessing them in hard-to-reach areas due to transportation and communication issues. Common organizational-level challenges include a lack of skilled manpower. Policy-level challenges include the prohibition of SRH service provision to unmarried adolescents and youth and lack of readiness of local governments to implement existing action plans. Some ways in which male-youth-focused SRHR interventions can be made more effective are through sensitization of service providers, awareness-raising at the community level to engage parents, advocacy to increase donor interest, and generating data on SRHR of male youth.

Keywords: Bangladesh, intervention, male, SRHR

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Authors: Malgorzata Rudnicka, Waldemar Karcz

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Introduction: Naphthoquinones are widely occurring organic compounds produced by bacteria, fungi, and plants. They can act as the functional components of biochemical systems (plastoquinone) as well as biologically active substances, which have a negative impact on environmental processes. Naphthoquinones seem to act through two mechanisms: a covalent modification of biological molecules at their nucleophilic sites or by generation of reactive oxygen species (ROS) connected with redox cycling. Investigating the effect of naphthoquinones (1,4-naphthoquinone, lawsone and naphthazarin) on the elongation growth, membrane potential and the level of oxidative stress of maize cells seems to be important due to the possibility of using these substances as herbicides. Methods: All experiments were performed on etiolated maize coleoptile segments. Simultaneous measurements of elongation growth and pH of the incubation medium were carried out using an angular position transducer, allowing a precise record of the growth kinetics. To compare the oxidative stress level induced by all tested naphthoquinones, the changes in malondialdehyde content, as well as superoxide dismutase and catalase activities were measured. In order to measure the membrane potential of parenchymal cells the standard electrophysiology technique was used. Results: Naphthoquinones such as: 1,4-naphthoquinone, lawsone and naphthazarin were studied. It was found that all of the naphthoquinones diminished the growth of the maize coleoptile cells depending on the type of naphthoquinones and their concentration. Interestingly, naphthazarin at the intermediate concentration was less toxic compared to the others. In addition, the effect of naphthoquinones on the oxidative stress was dependent on their concentration as well. Superoxide dismutase and catalase activities were changed in the presence of higher concentrations of naphthoquinones. Similar interrelations were observed for membrane potential changes. Conclusion: It can be concluded that naphthoquinones tested differ in their toxic effect on the growth of maize coleoptile cells. Furthermore, naphthoquinones can be distinguish considering the oxidative stress level and membrane potential changes. The results presented here give new insight into the possible opportunities of practical usage of naphthoquinones for herbicides improvement.

Keywords: growth rate, membrane potential, naphthoquinones, oxidative stress

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Authors: Ebru Cubukcu, Gozde Eksioglu Cetintahra, Burcin Hepguzel Hatip, Mert Cubukcu

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Obesity and overweight cause serious health problems. Public and private organizations aim to encourage walking in various ways in order to cope with the problem of obesity and overweight. This study aims to understand how the spatial characteristics of urban street pattern, connectivity and complexity influence young people’s choice to walk or not. 185 public university students in Izmir, the third largest city in Turkey, participated in the study. Each participant had worn an accelerometer and a global positioning (GPS) device for a week. The accelerometer device records data on the intensity of the participant’s activity at a specified time interval, and the GPS device on the activities’ locations. Combining the two datasets, activity maps are derived. These maps are then used to differentiate the participants’ walk trips and motor vehicle trips. Given that, the frequency of walk and motor vehicle trips are calculated at the street segment level, and the street segments are then categorized into two as ‘preferred by pedestrians’ and ‘preferred by motor vehicles’. Graph Theory-based accessibility indices are calculated to quantify the spatial characteristics of the streets in the sample. Six different indices are used: (I) edge density, (II) edge sinuosity, (III) eta index, (IV) node density, (V) order of a node, and (VI) beta index. T-tests show that the index values for the ‘preferred by pedestrians’ and ‘preferred by motor vehicles’ are significantly different. The findings indicate that the spatial characteristics of the street network have a measurable effect on young people’s choice to walk or not. Policy implications are discussed. This study is funded by the Scientific and Technological Research Council of Turkey, Project No: 116K358.

Keywords: graph theory, walkability, accessibility, street network

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Authors: Lauren C. Porter, Andrew Curtis, Eric Jefferis, Susanne Mitchell

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A wealth of research has been generated examining the variation in crime across neighborhoods. However, there is also a striking degree of crime concentration within neighborhoods. A number of studies show that a small percentage of street segments, intersections, or addresses account for a large portion of crime. Not surprisingly, a focus on these crime hot spots can be an effective strategy for reducing community level crime and related ills, such as health problems. However, research is also limited in an important respect. Studies tend to use official data to identify hot spots, such as 911 calls or calls for service. While the use of call data may be more representative of the actual level and distribution of crime than some other official measures (e.g. arrest data), call data still suffer from the 'dark figure of crime.' That is, there is most certainly a degree of error between crimes that occur versus crimes that are reported to the police. In this study, we present an alternative method of identifying crime hot spots, that does not rely on official data. In doing so, we highlight the potential utility of neighborhood-insiders to identify and understand crime dynamics within geographic spaces. Specifically, we use spatial video and geo-narratives to record the crime insights of 36 police, ex-offenders, and residents of a high crime neighborhood in northeast Ohio. Spatial mentions of crime are mapped to identify participant-identified hot spots, and these are juxtaposed with calls for service (CFS) data. While there are bound to be differences between these two sources of data, we find that one location, in particular, a corner store, emerges as a hot spot for all three groups of participants. Yet it does not emerge when we examine CFS data. A closer examination of the space around this corner store and a qualitative analysis of narrative data reveal important clues as to why this store may indeed be a hot spot, but not generate disproportionate calls to the police. In short, our results suggest that researchers who rely solely on official data to study crime hot spots may risk missing some of the most dangerous places.

Keywords: crime, narrative, video, neighborhood

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Authors: Luciano Tarantino, Emanuele Balzano, Aurelio Nasto

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S.R. 53 years. January 2009: HCV-related cirrhosis, Child-Pugh A5 class, EGDS no aesophageal Varices. No important comorbidities. Treated with PEG-IFN+Ribavirin (march-november 2009) with subsequent sustained virologic response. HCVRNA absent overtime. October 2016 :CT detected small HCC nodule in the VIII segment (diam.=12 mm). Treated with US guided RF-ablation. November 2016 CT: complete necrosis. Unfortunately, the patient dropped out US and CT follow-up controls.September 2018: asthenia and weight loss. CT showed a large tumor infiltrating V-VII-VI segments and complete PVTT of right portal vein and its branches . Surgical Consultation excluded indication to Liver resection and OLT . 23 october 2018: ECT of a large peri-hilar area of the tumor including the PVTT. 1 and 3 months post-treatment CT showed complete necrosis and retraction of the thrombus and residual viable tumor in the peripheral portion of the right lobe . Therefor, the patient was reevaluated for OLT and considered eligible in waiting list . March 2019: CT showed no perihilar or portal vein recurrence and distant progression in the right lobe . March 2019 : Trans-arterial-Radio-therapy (TARE) of the right lobe. Post-treatment CT demonstrated no perihilar or portal vein recurrence and extensive necrosis of the residual tumor . December 2019: CT demonstrated several recurrences of HCC infiltrating the VI and VII segment . Howewer no recurrence was observed at hepatic hilum and in portal vessels . Therefore, on February 2020 the patient received OLT. At 44 months follow-up, no complication or recurrence or liver disfunction have been observed.

Keywords: hepatocellular carcinoma, portal vein tumor thrombosis, interventional ultrasound, liver tumor ablation, liver transplantation

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Authors: Farahnaz Sadat Golestan Hashemi, Mohd Razi Ismail, Mohd Y. Rafii

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Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein (Cas) system can facilitate targeted genome editing in organisms. Dual or single guide RNA (gRNA) can program the Cas9 nuclease to cut target DNA in particular areas; thus, introducing concise mutations either via error-prone non-homologous end-joining repairing or via incorporating foreign DNAs by homologous recombination between donor DNA and target area. In spite of high demand of such promising technology, developing a well-organized procedure in order for reliable mining of potential target sites for gRNAs in large genomic data is still challenging. Hence, we aimed to perform high-throughput detection of target sites by specific PAMs for not only common Streptococcus pyogenes (SpCas9) but also for Neisseria meningitides (NmCas9) CRISPR-Cas systems. Previous research confirmed the successful application of such RNA-guided Cas9 orthologs for effective gene targeting and subsequently genome manipulation. However, Cas9 orthologs need their particular PAM sequence for DNA cleavage activity. Activity levels are based on the sequence of the protospacer and specific combinations of favorable PAM bases. Therefore, based on the specific length and sequence of PAM followed by a constant length of the target site for the two orthogonals of Cas9 protein, we created a reliable procedure to explore possible gRNA sequences. To mine CRISPR target sites, four different searching modes of sgRNA binding to target DNA strand were applied. These searching modes are as follows i) coding strand searching, ii) anti-coding strand searching, iii) both strand searching, and iv) paired-gRNA searching. Finally, a complete list of all potential gRNAs along with their locations, strands, and PAMs sequence orientation can be provided for both SpCas9 as well as another potential Cas9 ortholog (NmCas9). The artificial design of potential gRNAs in a genome of interest can accelerate functional genomic studies. Consequently, the application of such novel genome editing tool (CRISPR/Cas technology) will enhance by presenting increased versatility and efficiency.

Keywords: CRISPR/Cas9 genome editing, gRNA mining, SpCas9, NmCas9

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Authors: Yunus Onur Yildiz, Mesut Kirca

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In this study, mechanical properties of a nanoporous metal coated with a different metallic material are studied through a new atomistic modelling technique and molecular dynamics (MD) simulations. This new atomistic modelling technique is based on the Voronoi tessellation method for the purpose of geometric representation of the ligaments. With the proposed technique, atomistic models of nanoporous metals which have randomly oriented ligaments with non-uniform mass distribution along the ligament axis can be generated by enabling researchers to control both ligament length and diameter. Furthermore, by the utilization of this technique, atomistic models of coated nanoporous materials can be numerically obtained for further mechanical or thermal characterization. In general, this study consists of two stages. At the first stage, we use algorithms developed for generating atomic coordinates of the coated nanoporous material. In this regard, coordinates of randomly distributed points are determined in a controlled way to be employed in the establishment of the Voronoi tessellation, which results in randomly oriented and intersected line segments. Then, line segment representation of the Voronoi tessellation is transformed to atomic structure by a special process. This special process includes generation of non-uniform volumetric core region in which atoms can be generated based on a specific crystal structure. As an extension, this technique can be used for coating of nanoporous structures by creating another volumetric region encapsulating the core region in which atoms for the coating material are generated. The ultimate goal of the study at this stage is to generate atomic coordinates that can be employed in the MD simulations of randomly organized coated nanoporous structures. At the second stage of the study, mechanical behavior of the coated nanoporous models is investigated by examining deformation mechanisms through MD simulations. In this way, the effect of coating on the mechanical behavior of the selected material couple is investigated.

Keywords: atomistic modelling, molecular dynamic, nanoporous metals, voronoi tessellation

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Authors: Mike Wei, Nebu Koshy, Koen van Besien, Giorgio Inghirami, Steven M. Horwitz

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T-cell prolymphocytic leukemia (T-PLL) is a rare hematologic disease characterized by a T-cell phenotype, rapid progression, and poor prognosis with median survival of less than a year. Alemtuzumab-based chemotherapy has increased the rate of complete remissions but these are often short-lived, and allogeneic transplant is considered the only curative therapy. In recent studies, JAK3 activating mutations have been identified in T-cell cancers, with T-PLL having the highest rate of JAK3 mutations (30 – 42%). As such, T-PLL is a model disease for evaluating the utility of JAK3 inhibitors. We present a case of a 64-year-old man with relapsed-refractory T-PLL. He was initially treated with alemtuzumab and obtained complete response and was consolidated with matched unrelated donor stem cell transplant. His disease stayed in remission for approximately 1.5 years before relapse, which was then treated with a clinical trial of romidepsin-lenalidomide (partial responses then progression at 6 months) and later alemtuzumab. Due to complications of myelosuppression and CMV reactivation, his treatment was interrupted leading to disease progression. The doubling time of lymphocyte count was approximately 20 days and over a span of 60 days the lymphocyte count rose from 8 x 109/L to 68 x 109/L. Exon sequencing showed a JAK3 mutation. The patient consented to and was treated with FDA-approved tofacitinib (initially 5 mg BID, increased to 10 mg BID after 15 days of treatment). An initial decrease in lymphocyte count was followed by progression. In vitro treatment of the patient’s cells showed modest effects of tofacitinib and ruxolitinib as single agents, in the range of doxorubicin, but synergy between the agents. After 40 days of treatment with tofacitinib and with a lymphocyte count of 150 x 109/L, ruxolitinib (5mg BID) was added. Over the 60 days since dual inhibition was started, the lymphocyte count has stabilized. The patient has remained completely asymptomatic during treatment with tofacitinib and ruxolitinib. Neutrophil count has remained normal. Platelet count and hemoglobin have however declined from ~50 x109/L to ~30 x109/L and from 11 g/dL to 8.1 g/dL respectively, since the introduction of ruxolitinib. The stabilization in lymphocyte count confirms the clinical activity of JAK inhibitors in T-PLL as suggested by the presence of JAK3 mutations and by in-vitro assays. It also suggests clinical synergy between ruxolitinib and tofacitinib in this setting. Prospective studies of JAK inhibitors in PLL patients with formal dose-finding studies are needed.

Keywords: tofacitinib, ruxolitinib, T-cell prolymphocytic leukemia, JAK3

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