Search results for: Gennaro Marino

Authors: Gennaro Marino

Abstract:

This paper concerns a case of a 10.75 inch diameter buried gas transmission line which was exposed to mine subsidence ground movements. The pipeline was buried about 4ft. below the surface with maximum operating pressure of 1440 psi. The mine subsidence movement was the result of long walling ore at a depth of approximately 1600 ft. As ore extraction progressed, the stress in the monitored pipeline worsened and was approaching unacceptable levels. The excessive pipe compression resulted when it was exposed to the compression zone of subsidence basin created by mining. The pipe stress reached a significant compressive level due to the extensive length of the pipe exposed to frictional ground-pipe slip resistance. The backfill ground movement slip resistance depends on normal stress around the pipe, the rate of slip, and the backfill characteristics. Normal stress depends on the burial depth of the backfill density and the lateral subsidence induced stress. The backfill in this site has a soil dry density of approximately 90 PCF. A suite of direct shear tests was conducted a residual friction angle of 36 was determined for the ambient backfill. These tests showed that the residual shearing resistance was reached within a fraction of an inch. The pipe was coated with fusion-bonded epoxy, so friction reduce factory of 0.6 can be considered. To relieve ground movement induced compressive stress, the line was uncovered. As more of the pipeline was exposed, the pipe abruptly bowed in the excavation. An analysis of this pipe formation which was performed is provided in this paper. Also discussed in this paper are ways to mitigate this pipe deformation or upheaval buckling from occurring. Keywords: Pipe Upheaval, Pipe Buckling, Ground subsidence, Buried Pipeline, Pipe Stress Mitigation.

Keywords: pipe upheaval, pipe buckling, ground subsidence, buried pipeline, pipe stress mitigation

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Authors: Aiden Wang, Joseph Marino

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In this study, we investigated the impact of different tempo variations on 1-repetition maximum (1RM) growth, focusing on the eccentric, isometric, and concentric phases of the lift. Through a 6-week longitudinal study involving 20 individuals with 1-5 years of barbell training experience, we compared the effects of various tempo schemes on bench press performance. Our results revealed that subjects who performed a tempo bench press with a 3-second eccentric phase, 3-second isometric phase, and explosive concentric phase on a weekly basis experienced the most significant increases in 1RM. Notably, this tempo also led to improved technique and stability during the exercise. Our findings provide valuable insights for strength trainers and coaches seeking to optimize bench press performance and overcome strength plateaus effectively.

Keywords: exercise science, powerlifting, barbell, interventionist, longitudinal study

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Authors: Isalyne Gennaro

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The lack of access to basic sanitation services and improper water infrastructure pollute the environment and expose people to water-borne diseases. In 2014, to address these concerns, the central government of India launched five-years urban development and sanitation programs. The national vision seemed to encourage the use of technologies which recycle and reuse wastewater for achieving open defecation free cities. As we approach 2019, it is time to reflect on these objectives. This research critically looked at the actual scope and limitations of policies and regulations to promote resource-recovery sanitation systems. This study was based on the case of the fast-growing city of Ahmedabad, Gujarat. The analysis examined the actions and priorities, financial and institutional arrangements and technologies promoted at the national, sub-national and local levels. The research work concluded that a paradigm shift is required, from providing infrastructures in a supply-driven manner to creating inclusive planning framework which focuses on local challenges and generates a demand-responsiveness from the potential users targeted.

Keywords: India, public policy, resource-recovery, urban sanitation

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Authors: Leo Latasch, Mario Di Gennaro

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Introduction: The goal of this project was to increase the resilience of the population as well as rescue organizations to make both quality and time-related improvements in handling crises. A helper network was created for this purpose. Methods: Social questions regarding the structure and purpose of helper networks were considered - specifically with regard to helper motivation, the level of commitment and collaboration between populations and agencies. The exchange of information, the coordinated use of volunteers, and the distribution of available resources will be ensured through defined communication and cooperation routines. Helper smartphones will also be used provide a picture of the situation on the ground. Results: The helper network was established and deployed based on the RESIBES information technology system. It consists of a service platform, a web portal and a smartphone app. The service platform is the central element for collaboration between the various rescue organizations, as well as for persons, associations, and companies from the population offering voluntary aid. The platform was used for: Registering helpers and resources and then requesting and assigning it in case of a disaster. These services allow the population's resources to be organized. The service platform also allows for a secure data exchange between services and external systems. Conclusions: The social and technical work priorities have allowed us to cover a full cycle of advance structural work, gaining an overview, damage management, evaluation, and feedback on experiences. This cycle allows experiences gained while handling the crisis to feed back into the cycle and improve preparations and management strategies.

Keywords: coordination, disaster, resilience, volunteers

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Authors: Atousa Ataieyan, Salvador A. Gomez-Lopera, Gennaro Sepede

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Today, due to the growing urban population and consequently, the increasing water demand in cities, the amount of contaminants entering the water resources is increasing. This can impose harmful effects on the quality of the downstream water. Therefore, predicting the concentration of discharged pollutants at different times and distances of the interested area is of high importance in order to carry out preventative and controlling measures, as well as to avoid consuming the contaminated water. In this paper, the concentration distribution of an injected conservative pollutant in a square reservoir containing four symmetric blocks and three sources using Finite Volume Method (FVM) is simulated. For this purpose, after estimating the flow velocity, classical Advection-Diffusion Equation (ADE) has been discretized over the studying domain by Backward Time- Backward Space (BTBS) scheme. Then, the discretized equations for each node have been derived according to the initial condition, boundary conditions and point contaminant sources. Finally, taking into account the appropriate time step and space step, a computational code was set up in MATLAB. Contaminant concentration was then obtained at different times and distances. Simulation results show how using BTBS differentiating scheme and FVM as a numerical method for solving the partial differential equation of transport is an appropriate approach in the case of two-dimensional contaminant transfer in an advective-diffusive flow.

Keywords: BTBS differentiating scheme, contaminant concentration, finite volume, mass transfer, water pollution

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Authors: Andreas Aceranti, Guido Bighiani, Francesca Crotto, Marco Colorato, Stefania Zaghi, Marino Zanetti, Simonetta Vernocchi

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The management of eye parameters such as convergence, accommodation, and miosis is very complex; in fact, both the neurovegetative system and the complex Oculocephalgiria system come into play. We have found the effectiveness of the "highvelocity low amplitude" technique directed on C7-T1 (where the cilio-spinal nucleus of the budge is located) in improving the convergence parameter through the measurement of the point of maximum convergence. With this research, we set out to investigate whether the improvement obtained through the High Velocity Low Amplitude maneuver lasts over time, carrying out a pre-manipulation measurement, one immediately after manipulation and one month after manipulation. We took a population of 30 subjects with both refractive and non-refractive problems. Of the 30 patients tested, 27 gave a positive result after the High Velocity Low Amplitude maneuver, giving an improvement in the point of maximum convergence. After a month, we retested all 27 subjects: some further improved the result, others kept, and three subjects slightly lost the gain obtained. None of the re-tested patients returned to the point of maximum convergence starting pre-manipulation. This result opens the door to a multidisciplinary approach between ophthalmologists and osteopaths with the aim of addressing oculomotricity and convergence deficits that increasingly afflict our society due to the massive use of devices and for the conduct of life in closed and restricted environments.

Keywords: point of maximum convergence, HVLA, improvement in PPC, convergence

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Authors: Lukasz Grzegorz Broda, Taiwo Oseni, Andrew Stranieri, Rodrigo Marino, Ronelle Welton, Mark Yates

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The oral health of residents in aged care centres in Australia is poor, contributing to infections, hospital admissions, and increased suffering. Although the use of electric toothbrushes has been deployed in many centres, smartbrushes that record and transmit information about brushing patterns and duration are not routinely deployed. Yet, the use of smartbrushes for aged care residents promises better oral care. Thus, a study aimed at investigating the appropriateness and suitability of a smartbrush for aged care residents is currently underway. Due to the peculiarity of the aged care setting, the incorporation of smartbrushes into residents’ care does require careful planning and design considerations. This paper describes an initial design process undertaken through the use of an actor to understand the important elements to be incorporated whilst installing a smartbrush for use in aged care settings. The design covers the configuration settings of the brush and app, including ergonomic factors related to brush and smartphone placement. A design science approach led to an installation re-design and a revised protocol for the planned study, the ultimate aim being to design installations to enhance perceived usefulness, ease of use, and attitudes towards the incorporation of smartbrushes for improving oral health care for aged care residents.

Keywords: smartbrush, applied computing, life and medical sciences, health informatics

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Authors: Ana Corberan-Vallet, Karen C. Florez, Ingrid C. Marino, Jose D. Bermudez

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In 2016, the Region of the Americas was declared free of measles, a viral disease that can cause severe health problems. However, since 2017, measles has reemerged in Venezuela and has subsequently reached neighboring countries. In 2018, twelve American countries reported confirmed cases of measles. Governmental and health authorities in Colombia, a country that shares the longest land boundary with Venezuela, are aware of the need for a strong response to restrict the expanse of the epidemic. In this work, we apply a Bayesian hierarchical Poisson model with an underlying cluster structure to describe disease incidence in Colombia. Concretely, the proposed methodology provides relative risk estimates at the department level and identifies clusters of disease, which facilitates the implementation of targeted public health interventions. Socio-demographic factors, such as the percentage of migrants, gross domestic product, and entry routes, are included in the model to better describe the incidence of disease. Since the model does not impose any spatial correlation at any level of the model hierarchy, it avoids the spatial confounding problem and provides a suitable framework to estimate the fixed-effect coefficients associated with spatially-structured covariates.

Keywords: Bayesian analysis, cluster identification, disease mapping, risk estimation

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Authors: German Marino Rivera

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Linear plantations are a common practice in several countries as living fences (LF) delimiting agroecosystems. They are composed of multipurpose perennial woods that provide assets, protection, and supply services. However, not much is known in some traditional communities like the Andean region, including the species composition and the social and ecological benefits of the species used. In the High Andean Colombian region, LF seems to be very typical and diverse. This study aimed to analyze the traditional knowledge about LF systems, including the species composition and their uses in rural communities of Alto Casanare, Colombia. Field measurements, interviews, guided tours, and species sampling were carried out in order to describe traditional practices and the species used in the LF systems. The use values were estimated through the Coefficient of Importance of the Species (CIS). A total of 26 farms engage in LF practices, covering an area of 9283.3 m. In these systems, 30 species were identified, belonging to 23 families. Alnus acuminata was the specie with the highest CIS. The species presented multipurpose uses for both economic and ecological purposes. The transmission of knowledge (TEK) about the used species is very heterogeneous among the farmers. Many species used were not documented, with reciprocal gaps between the literature and traditional species uses. Exchanging this information would increase the species' versatility, the socioeconomic aspects of these communities, increases the agrobiodiversity and ecological services provided by LF. The description of the TEK on LF provides a better understanding of the relationship of these communities with the natural resources, pointing out creative approaches to achieve local environment conservation in these agroecosystems and promoting socioeconomic development.

Keywords: ethnobotany, living fences, traditional communities, agroecology

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Authors: Alessandra Marino

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This paper thoroughly investigates the design characteristics necessary for intergenerational living and evaluates their applicability within the Italian social panorama in order to identify a model that can serve as a reference for subsequent regulatory adjustments of a new building typology. The applied methodology involves the collaboration of people with various background and architects, all representing the three main ages of life - childhood or youth, adulthood, seniority - through questionnaires aimed at researching the peculiar characteristics that contemporary intergenerational housing should include; the questionnaires are then compared with each other in order to identify any recurring patterns by age group and/or influenced by the specialist knowledge on the subject of the architects compared to the rest of the user sample. The results indicate that among specialist users in the field of architecture, young students identify home automation as the key to the inclusion of the weakest groups within the building, adult architects believe that the identification of intergenerational/community services within the building is the cornerstone, and senior architects focus on widespread spatial accessibility. At the same time, the results among non-specialist users do not identify a significantly diversified model by age group but are generally in agreement in the importance of separation between private environments and collective spaces. The interpretation of the results obtained leads to a compositional study of a new building typology with the future objective of channeling the subsequent outcomes within the regulatory adjustments of the sector.

Keywords: intergenerational living, social sustainability, health, lifestyle, well-being

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Authors: Arlett A. Rosado-Torres, Ismael Marino-Tapia

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Changes in benthic cover of coral dominated systems to macroalgae dominance are widely studied worldwide. Watershed pollutants are potentially as important as overfishing causing phase shift. In certain regions of the world most of the continental inputs are through submarine groundwater discharges (SGD), which can play a significant ecological role because the concentration of its nutrients is usually greater that the one found in surface seawater. These stressors have adversely affected coral reefs, particularly in the Caribbean. Measurements of benthic cover (with video tracing, through a Go Pro camera), reef roughness (acoustic estimates with an Acoustic Doppler Current Velocity profiler and a differential GPS), thermohaline conditions (conductivity-temperature-depth (CTD) instrument) and nutrient measurements were taken in different sites in the reef lagoon of Puerto Morelos, Q. Roo, Mexico including those with influence of SGD and without it. The results suggest a link between SGD, macroalgae cover and structural complexity. Punctual water samples and data series from a CTD Diver confirm the presence of the SGD. On the site where the SGD is, the macroalgae cover is larger than in the other sites. To establish a causal link between this phase shift and SGD, the DELFT 3D hydrodynamic model (FLOW and WAVE modules) was performed under different environmental conditions and discharge magnitudes. The model was validated using measurements of oceanographic instruments anchored in the lagoon and forereef. The SGD is consistently favoring macroalgae populations and affecting structural complexity of the reef.

Keywords: hydrodynamic model, macroalgae, nutrients, phase shift

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Authors: Marianna Ciaccia, Gennaro Agrimi, Isabella Pisano, Maurizio Bettiga, Silvia Rapacioli, Giulia Mensa, Monica Marzagalli

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Objective: Untargeted metabolomic analysis of extracellular metabolites is a powerful approach that focuses on comprehensively profiling in the extracellular space. In this study, we applied extracellular metabolomic analysis to investigate the metabolism of two probiotic microorganisms with health benefits that extend far beyond the digestive tract and the immune system. Methods: Analytical techniques employed in extracellular metabolomic analysis encompass various technologies, including mass spectrometry (MS), which enables the identification of metabolites present in the fermentation media, as well as the comparison of metabolic profiles under different experimental conditions. Multivariate statistical analysis techniques like principal component analysis (PCA) or partial least squares-discriminant analysis (PLS-DA) play a crucial role in uncovering metabolic signatures and understanding the dynamics of metabolic networks. Results: Different types of supernatants from fermentation processes, such as dairy-free, not dairy-free media and media with no cells or pasteurized, were subjected to metabolite profiling, which contained a complex mixture of metabolites, including substrates, intermediates, and end-products. This profiling provided insights into the metabolic activity of the microorganisms. The integration of advanced software tools has facilitated the identification and characterization of metabolites in different fermentation conditions and microorganism strains. Conclusions: In conclusion, untargeted extracellular metabolomic analysis, combined with software tools, allowed the study of the metabolites consumed and produced during the fermentation processes of probiotic microorganisms. Ongoing advancements in data analysis methods will further enhance the application of extracellular metabolomic analysis in fermentation research, leading to improved bioproduction and the advancement of sustainable manufacturing processes.

Keywords: biotechnology, metabolomics, lactic bacteria, probiotics, postbiotics

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Authors: Yuban Sebastian Cuartas-Agudelo, Sandra Marcela López-Hincapié, Vivianna Alexandra Garrido-Altamar, María de los Ángeles Rodríguez-Gázquez, Camilo Ruiz-Mejía, Lina María Martínez-Sánchez, Gloria Inés Martínez-Domínguez, Luis Eduardo Contreras, Felipe Eduardo Marino-Isaza

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Introduction: Doping is a prohibited practice in competitive sports with potential adverse effects; therefore, it is crucial to describe the attitudes of athletes towards this behavior and to determine which o these increase the susceptibility to carry out this practice. Objective: To determine the attitude of high-performance athletes towards doping in a sports institute in the city of Medellin, Colombia. Methods: We performed a cross-sectional study during 2016, with a sample taken to convenience consisting of athletes over 18 years old enrolled in a sports institute of the city of Medellin (Colombia). The athletes filled by themselves the Petroczi and Aidman questionnaire: Performance Enhancement Attitude Scale (PEAS) adapted to the Spanish language by Morente-Sánchez et al. This scale has 17 items with likert answer options, with a score ranging from 1 to 6, with a higher score indicating a stronger tendency towards doping practices. Results: 112 athletes were included with an average age of 21.6 years old, a 60% of them were male and the most frequent sports were karate 17%, judo 12.5% and athletics 9.8%. The average score of the questionnaire was 35.5 points of a 102 possible points. The lowest score was obtained in the following items: Is Doping necessary 1,4 and Doping isn’t cheating, everyone does it 1,5. Conclusion: In our population, there is a low tendency towards doping practices.

Keywords: sports, doping in sports, athletic performance, attitude

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Authors: Averalda van Graan, Joelaine Chetty, Malory Links, Agness Mwangwela, Sitilitha Masangwi, Dalitso Chimwala, Shiban Ghosh, Elizabeth Marino-Costello

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Food composition data is becoming increasingly important as dealing with food insecurity and malnutrition in its persistent form of under-nutrition is now coupled with increasing over-nutrition and its related ailments in the developing world, of which Malawi is not spared. In the absence of a food composition database (FCDB) inherent to our dietary patterns, efforts were made to develop a country-specific FCDB for nutrition practice, research, and programming. The main objective was to develop a multi-user, country-specific food composition database, and table from existing published and unpublished scientific literature. A multi-phased approach guided by the project framework was employed. Phase 1 comprised a scoping mission to assess the nutrition landscape for compilation activities. Phase 2 involved training of a compiler and data collection from various sources, primarily; institutional libraries, online databases, and food industry nutrient data. Phase 3 subsumed evaluation and compilation of data using FAO and IN FOODS standards and guidelines. Phase 4 concluded the process with quality assurance. 316 Malawian food items categorized into eight food groups for 42 components were captured. The majority were from the baby food group (27%), followed by a staple (22%) and animal (22%) food group. Fats and oils consisted the least number of food items (2%), followed by fruits (6%). Proximate values are well represented; however, the percent missing data is huge for some components, including Se 68%, I 75%, Vitamin A 42%, and lipid profile; saturated fat 53%, mono-saturated fat 59%, poly-saturated fat 59% and cholesterol 56%. A multi-phased approach following the project framework led to the development of the first Malawian FCDB and table. The table reflects inherent Malawian dietary patterns and nutritional concerns. The FCDB can be used by various professionals in nutrition and health. Rising over-nutrition, NCD, and changing diets challenge us for nutrient profiles of processed foods and complete lipid profiles.

Keywords: analytical data, dietary pattern, food composition data, multi-phased approach

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Authors: Lucia Billeci, Gennaro Tartarisco, Maurizio Varanini

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Fetal cardiac monitoring by fetal electrocardiogram (fECG) can provide significant clinical information about the healthy condition of the fetus. Despite this potentiality till now the use of fECG in clinical practice has been quite limited due to the difficulties in its measuring. The recovery of fECG from the signals acquired non-invasively by using electrodes placed on the maternal abdomen is a challenging task because abdominal signals are a mixture of several components and the fetal one is very weak. This paper presents an approach for fECG extraction from abdominal maternal recordings, which exploits the characteristics of pseudo-periodicity of fetal ECG. It consists of devising a quality index (fQI) for fECG and of finding the linear combinations of preprocessed abdominal signals, which maximize these fQI (quality index optimization - QIO). It aims at improving the performances of the most commonly adopted methods for fECG extraction, usually based on maternal ECG (mECG) estimating and canceling. The procedure for the fECG extraction and fetal QRS (fQRS) detection is completely unsupervised and based on the following steps: signal pre-processing; maternal ECG (mECG) extraction and maternal QRS detection; mECG component approximation and canceling by weighted principal component analysis; fECG extraction by fQI maximization and fetal QRS detection. The proposed method was compared with our previously developed procedure, which obtained the highest at the Physionet/Computing in Cardiology Challenge 2013. That procedure was based on removing the mECG from abdominal signals estimated by a principal component analysis (PCA) and applying the Independent component Analysis (ICA) on the residual signals. Both methods were developed and tuned using 69, 1 min long, abdominal measurements with fetal QRS annotation of the dataset A provided by PhysioNet/Computing in Cardiology Challenge 2013. The QIO-based and the ICA-based methods were compared in analyzing two databases of abdominal maternal ECG available on the Physionet site. The first is the Abdominal and Direct Fetal Electrocardiogram Database (ADdb) which contains the fetal QRS annotations thus allowing a quantitative performance comparison, the second is the Non-Invasive Fetal Electrocardiogram Database (NIdb), which does not contain the fetal QRS annotations so that the comparison between the two methods can be only qualitative. In particular, the comparison on NIdb was performed defining an index of quality for the fetal RR series. On the annotated database ADdb the QIO method, provided the performance indexes Sens=0.9988, PPA=0.9991, F1=0.9989 overcoming the ICA-based one, which provided Sens=0.9966, PPA=0.9972, F1=0.9969. The comparison on NIdb was performed defining an index of quality for the fetal RR series. The index of quality resulted higher for the QIO-based method compared to the ICA-based one in 35 records out 55 cases of the NIdb. The QIO-based method gave very high performances with both the databases. The results of this study foresees the application of the algorithm in a fully unsupervised way for the implementation in wearable devices for self-monitoring of fetal health.

Keywords: fetal electrocardiography, fetal QRS detection, independent component analysis (ICA), optimization, wearable

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Authors: Tarek Saadawi, Rosario Gennaro, Jonathan Akeley

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There is rapidly growing demand for professionals to fill positions in Cybersecurity. This is recognized as a national priority both by government agencies and the private sector. Cybersecurity is a very wide technical area which encompasses all measures that can be taken in an electronic system to prevent criminal or unauthorized use of data and resources. This requires defending computers, servers, networks, and their users from any kind of malicious attacks. The need to address this challenge has been recognized globally but is particularly acute in the New York metropolitan area, home to some of the largest financial institutions in the world, which are prime targets of cyberattacks. In New York State alone, there are currently around 57,000 jobs in the Cybersecurity industry, with more than 23,000 unfilled positions. The Cybersecurity Program at City College is a collaboration between the Departments of Computer Science and Electrical Engineering. In Fall 2020, The City College of New York matriculated its first students in theCybersecurity Master of Science program. The program was designed to fill gaps in the previous offerings and evolved out ofan established partnership with Facebook on Cybersecurity Education. City College has designed a program where courses, curricula, syllabi, materials, labs, etc., are developed in cooperation and coordination with industry whenever possible, ensuring that students graduating from the program will have the necessary background to seamlessly segue into industry jobs. The Cybersecurity Program has created multiple pathways for prospective students to obtain the necessary prerequisites to apply in order to build a more diverse student population. The program can also be pursued on a part-time basis which makes it available to working professionals. Since City College’s Cybersecurity M.S. program was established to equip students with the advanced technical skills needed to thrive in a high-demand, rapidly-evolving field, it incorporates a range of pedagogical formats. From its outset, the Cybersecurity program has sought to provide both the theoretical foundations necessary for meaningful work in the field along with labs and applied learning projects aligned with skillsets required by industry. The efforts have involved collaboration with outside organizations and with visiting professors designing new courses on topics such as Adversarial AI, Data Privacy, Secure Cloud Computing, and blockchain. Although the program was initially designed with a single asynchronous course in the curriculum with the rest of the classes designed to be offered in-person, the advent of the COVID-19 pandemic necessitated a move to fullyonline learning. The shift to online learning has provided lessons for future development by providing examples of some inherent advantages to the medium in addition to its drawbacks. This talk will address the structure of the newly-implemented Cybersecurity Master’s Program and discuss the innovations, challenges, and possible future directions.

Keywords: cybersecurity, new york, city college, graduate degree, master of science

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Authors: Rijnbout-St.James Willem, Lindner Volkhard, Scholand Mary Beth, Ashton M. Tillett, Di Gennaro Michael Jude, Smith Silvia Enrica

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Introduction: Fibrosing lung diseases are characterized by changes in the lung interstitium and are classified based on etiology: 1) environmental/exposure-related, 2) autoimmune-related, 3) sarcoidosis, 4) interstitial pneumonia, and 4) idiopathic. Among interstitial lung diseases (ILD) idiopathic forms, idiopathic pulmonary fibrosis (IPF) is the most severe. Pathogenesis of IPF is characterized by an increased presence of proinflammatory mediators, resulting in alveolar injury, where injury to alveolar epithelium precipitates an increase in collagen deposition, subsequently thickening the alveolar septum and decreasing gas exchange. Identifying biomarkers implicated in the pathogenesis of lung fibrosis is key to developing new therapies and improving the efficacy of existing therapies. The transforming growth factor-beta (TGF-B1), a mediator of tissue repair associated with WNT5A signaling, is partially responsible for fibroblast proliferation in ILD and is the target of Pirfenidone, one of the antifibrotic therapies used for patients with IPF. Canonical TGF-B signaling is mediated by the proteins SMAD 2/3, which are, in turn, indirectly regulated by Collagen Triple Helix Repeat Containing 1 (CTHRC1). In this study, we tested the following hypotheses: 1) CTHRC1 is more elevated in the ILD cohort compared to unaffected controls, and 2) CTHRC1 is differently expressed among ILD types. Material and Methods: CTHRC1 levels were measured by ELISA in 171 plasma samples from the deidentified University of Utah ILD cohort. Data represent a cohort of 131 ILD-affected participants and 40 unaffected controls. CTHRC1 samples were categorized by a pulmonologist based on affectation status and disease subtypes: IPF (n = 45), sarcoidosis (4), nonspecific interstitial pneumonia (16), hypersensitivity pneumonitis (n = 7), interstitial pneumonia (n=13), autoimmune (n = 15), other ILD - a category that includes undifferentiated ILD diagnoses (n = 31), and unaffected controls (n = 40). We conducted a single-factor ANOVA of plasma CTHRC1 levels to test whether CTHRC1 variance among affected and non-affected participants is statistically significantly different. In-silico analysis was performed with Ingenuity Pathway Analysis® to characterize the role of CTHRC1 in the pathway of lung fibrosis. Results: Statistical analyses of CTHRC1 in plasma samples indicate that the average CTHRC1 level is significantly higher in ILD-affected participants than controls, with the autoimmune ILD being higher than other ILD types, thus supporting our hypotheses. In-silico analyses show that CTHRC1 indirectly activates and phosphorylates SMAD3, which in turn cross-regulates TGF-B1. CTHRC1 also may regulate the expression and transcription of TGFB-1 via WNT5A and its regulatory relationship with CTNNB1. Conclusion: In-silico pathway analyses demonstrate that CTHRC1 may be an important biomarker in ILD. Analysis of plasma samples indicates that CTHRC1 expression is positively associated with ILD affectation, with autoimmune ILD having the highest average CTHRC1 values. While characterizing CTHRC1 levels in plasma can help to differentiate among ILD types and predict response to Pirfenidone, the extent to which plasma CTHRC1 level is a function of ILD severity or chronicity is unknown.

Keywords: interstitial lung disease, CTHRC1, idiopathic pulmonary fibrosis, pathway analyses

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Authors: Raj Chandran, Saul Datwyler, Jaime Marino, Daniel West, Karla Grasso, Adam Buss, Hina Syed, Zina Al Sahouri, Jennifer Yen, Krista Caudle, Beth McQuiston

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The Alinity i TBI test is Therapeutic Goods Administration (TGA) registered and is a panel of in vitro diagnostic chemiluminescent microparticle immunoassays for the measurement of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) in plasma and serum. The Alinity i TBI performance was evaluated in a multi-center pivotal study to demonstrate the capability to assist in determining the need for a CT scan of the head in adult subjects (age 18+) presenting with suspected mild TBI (traumatic brain injury) with a Glasgow Coma Scale score of 13 to 15. TBI has been recognized as an important cause of death and disability and is a growing public health problem. An estimated 69 million people globally experience a TBI annually1. Blood-based biomarkers such as glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) have shown utility to predict acute traumatic intracranial injury on head CT scans after TBI. A pivotal study using prospectively collected archived (frozen) plasma specimens was conducted to establish the clinical performance of the TBI test on the Alinity i system. The specimens were originally collected in a prospective, multi-center clinical study. Testing of the specimens was performed at three clinical sites in the United States. Performance characteristics such as detection limits, imprecision, linearity, measuring interval, expected values, and interferences were established following Clinical and Laboratory Standards Institute (CLSI) guidance. Of the 1899 mild TBI subjects, 120 had positive head CT scan results; 116 of the 120 specimens had a positive TBI interpretation (Sensitivity 96.7%; 95% CI: 91.7%, 98.7%). Of the 1779 subjects with negative CT scan results, 713 had a negative TBI interpretation (Specificity 40.1%; 95% CI: 37.8, 42.4). The negative predictive value (NPV) of the test was 99.4% (713/717, 95% CI: 98.6%, 99.8%). The analytical measuring interval (AMI) extends from the limit of quantitation (LoQ) to the upper LoQ and is determined by the range that demonstrates acceptable performance for linearity, imprecision, and bias. The AMI is 6.1 to 42,000 pg/mL for GFAP and 26.3 to 25,000 pg/mL for UCH-L1. Overall, within-laboratory imprecision (20 day) ranged from 3.7 to 5.9% CV for GFAP and 3.0 to 6.0% CV for UCH-L1, when including lot and instrument variances. The Alinity i TBI clinical performance results demonstrated high sensitivity and high NPV, supporting the utility to assist in determining the need for a head CT scan in subjects presenting to the emergency department with suspected mild TBI. The GFAP and UCH-L1 assays show robust analytical performance across a broad concentration range of GFAP and UCH-L1 and may serve as a valuable tool to help evaluate TBI patients across the spectrum of mild to severe injury.

Keywords: biomarker, diagnostic, neurology, TBI

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Authors: Lizeth Fuentes-Mera, Vanessa Perez-Silos, Nidia K. Moncada-Saucedo, Alejandro Garcia-Ruiz, Alberto Camacho, Jorge Lara-Arias, Ivan Marino-Martinez, Victor Romero-Diaz, Adolfo Soto-Dominguez, Humberto Rodriguez-Rocha, Hang Lin, Victor Pena-Martinez

Abstract:

Biphasic scaffolds in cartilage tissue engineering have been designed to influence not only the recapitulation of the osteochondral architecture but also to take advantage of the healing ability of bone to promote the implant integration with the surrounding tissue and then bone restoration and cartilage regeneration. This study reports the development and characterization of a biphasic scaffold based on the assembly of a cartilage phase constituted by fibroin biofunctionalized with bovine cartilage matrix; cellularized with differentiated pre-chondrocytes from adipose tissue stem cells (autologous) and well attached to a bone phase (bone bovine decellularized) to mimic the structure of the nature of native tissue and to promote the cartilage regeneration in a model of joint damage in pigs. Biphasic scaffolds were assembled by fibroin crystallization with methanol. The histological and ultrastructural architectures were evaluated by optical and scanning electron microscopy respectively. Mechanical tests were conducted to evaluate Young's modulus of the implant. For the biological evaluation, pre-chondrocytes were loaded onto the scaffolds and cellular adhesion, proliferation, and gene expression analysis of cartilage extracellular matrix components was performed. The scaffolds that were cellularized and matured for 10 days were implanted into critical 3 mm in diameter and 9-mm in depth osteochondral defects in a porcine model (n=4). Three treatments were applied per knee: Group 1: monophasic cellular scaffold (MS) (single chondral phase), group 2: biphasic scaffold, cellularized only in the chondral phase (BS1), group 3: BS cellularized in both bone and chondral phases (BS2). Simultaneously, a control without treatment was evaluated. After 4 weeks of surgery, integration and regeneration tissues were analyzed by x-rays, histology and immunohistochemistry evaluation. The mechanical assessment showed that the acellular biphasic composites exhibited Young's modulus of 805.01 kPa similar to native cartilage (400-800 kPa). In vitro biological studies revealed the chondroinductive ability of the biphasic implant, evidenced by an increase in sulfated glycosaminoglycan (GAGs) and type II collagen, both secreted by the chondrocytes cultured on the scaffold during 28 days. No evidence of adverse or inflammatory reactions was observed in the in vivo trial; however, In group 1, the defects were not reconstructed. In group 2 and 3 a good integration of the implant with the surrounding tissue was observed. Defects in group 2 were fulfilled by hyaline cartilage and normal bone. Group 3 defects showed fibrous repair tissue. In conclusion; our findings demonstrated the efficacy of biphasic and bioactive scaffold based on silk fibroin, which entwined chondroinductive features and biomechanical capability with appropriate integration with the surrounding tissue, representing a promising alternative for osteochondral tissue-engineering applications.

Keywords: biphasic scaffold, extracellular cartilage matrix, silk fibroin, osteochondral tissue engineering

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Authors: Leila Noori, Rosario Barone, Francesca Rappa, Antonella Marino Gammazza, Alessandra Maria Vitale, Giuseppe Donato Mangano, Giusy Sentiero, Filippo Macaluso, Kathryn H. Myburgh, Francesco Cappello, Federica Scalia

Abstract:

The neuromuscular system controls, directs, and allows movement of the body through the action of neural circuits, which include motor neurons, sensory neurons, and skeletal muscle fibers. Protein homeostasis of the involved cytotypes appears crucial to maintain the correct and prolonged functions of the neuromuscular system, and both neuronal cells and skeletal muscle fibers express significant quantities of protein chaperones, the molecular machinery responsible to maintain the protein turnover. Genetic mutations or defective post-translational modifications of molecular chaperones (i.e., genetic or acquired chaperonopathies) may lead to neuromuscular disorders called as neurochaperonopathies. The limited knowledge of the effects of the defective chaperones on skeletal muscle fibers and neurons impedes the progression of therapeutic approaches. A distinct genetic variation of CCT5 gene encoding for the subunit 5 of the chaperonin CCT (Chaperonin Containing TCP1; also known as TRiC, TCP1 Ring Complex) was recently described associated with severe distal motor neuropathy by our team. In this study, we investigated the histopathological abnormalities of the skeletal muscle biopsy of the pediatric patient affected by the mutation Leu224Val in the CCT5 subunit. We provide molecular and structural features of the diseased skeletal muscle tissue that we believe may be useful to identify undiagnosed cases of this rare genetic disorder. We investigated the histological abnormalities of the affected tissue via hematoxylin and eosin staining. Then we used immunofluorescence and qPCR techniques to explore the expression and distribution of CCT5 in diseased and healthy skeletal muscle tissue. Immunofluorescence and immunohistochemistry assays were performed to study the sarcomeric and structural proteins of skeletal muscle, including actin, myosin, tubulin, troponin-T, telethonin, and titin. We performed Western blot to examine the protein expression of CCT5 and some heat shock proteins, Hsp90, Hsp60, Hsp27, and α-B crystallin, along with the main client proteins of the CCT5, actin, and tubulin. Our findings revealed muscular atrophy, abnormal morphology, and different sizes of muscle fibers in affected tissue. The swollen nuclei and wide interfiber spaces were seen. Expression of CCT5 had been decreased and showed a different distribution pattern in the affected tissue. Altered expression, distribution, and bandage pattern were detected by confocal microscopy for the interested muscular proteins in tissue from the patient compared to the healthy control. Protein levels of the studied Hsps normally located at the Z-disk were reduced. Western blot results showed increased levels of the actin and tubulin proteins in the diseased skeletal muscle biopsy compared to healthy tissue. Chaperones must be expressed at high levels in skeletal muscle to counteract various stressors such as mechanical, oxidative, and thermal crises; therefore, it seems relevant that defects of molecular chaperones may result in damaged skeletal muscle fibers. So far, several chaperones or cochaperones involved in neuromuscular disorders have been defined. Our study shows that alteration of the CCT5 subunit is associated with the damaged structure of skeletal muscle fibers and alterations of chaperone system components and paves the way to explore possible alternative substrates of chaperonin CCT. However, further studies are underway to investigate the CCT mechanisms of action to design applicable therapeutic strategies.

Keywords: molecular chaperones, neurochaperonopathy, neuromuscular system, protein homeostasis

Procedia PDF Downloads 71