Search results for: weighted localization
75 Mobile Genetic Elements in Trematode Himasthla Elongata Clonal Polymorphism
Authors: Anna Solovyeva, Ivan Levakin, Nickolai Galaktionov, Olga Podgornaya
Abstract:
Animals that reproduce asexually were thought to have the same genotypes within generations for a long time. However, some refuting examples were found, and mobile genetic elements (MGEs) or transposons are considered to be the most probable source of genetic instability. Dispersed nature and the ability to change their genomic localization enables MGEs to be efficient mutators. Hence the study of MGEs genomic impact requires an appropriate object which comprehends both representative amounts of various MGEs and options to evaluate the genomic influence of MGEs. Animals that reproduce asexually seem to be a decent model to study MGEs impact in genomic variability. We found a small marine trematode Himasthla elongata (Himasthlidae) to be a good model for such investigation as it has a small genome size, diverse MGEs and parthenogenetic stages in the lifecycle. In the current work, clonal diversity of cercaria was traced with an AFLP (Amplified fragment length polymorphism) method, diverse zones from electrophoretic patterns were cloned, and the nature of the fragments explored. Polymorphic patterns of individual cercariae AFLP-based fingerprints are enriched with retrotransposons of different families. The bulk of those sequences are represented by open reading frames of non-Long Terminal Repeats containing elements(non-LTR) yet Long-Terminal Repeats containing elements (LTR), to a lesser extent in variable figments of AFLP array. The CR1 elements expose both in polymorphic and conservative patterns are remarkably more frequent than the other non-LTR retrotransposons. This data was confirmed with shotgun sequencing-based on Illumina HiSeq 2500 platform. Individual cercaria of the same clone (i.e., originated from a single miracidium and inhabiting one host) has a various distribution of MGE families detected in sequenced AFLP patterns. The most numerous are CR1 and RTE-Bov retrotransposons, typical for trematode genomes. Also, we identified LTR-retrotransposons of Pao and Gypsy families among DNA transposons of CMC-EnSpm, Tc1/Mariner, MuLE-MuDR and Merlin families. We detected many of them in H. elongata transcriptome. Such uneven MGEs distribution in AFLP sequences’ sets reflects the different patterns of transposons spreading in cercarial genomes as transposons affect the genome in many ways (ectopic recombination, gene structure interruption, epigenetic silencing). It is considered that they play a key role in the origins of trematode clonal polymorphism. The authors greatly appreciate the help received at the Kartesh White Sea Biological Station of the Russian Academy of Sciences Zoological Institute. This work is funded with RSF 19-74-20102 and RFBR 17-04-02161 grants and the research program of the Zoological Institute of the Russian Academy of Sciences (project number AAAA-A19-119020690109-2).Keywords: AFLP, clonal polymorphism, Himasthla elongata, mobile genetic elements, NGS
Procedia PDF Downloads 11774 Changes in Geospatial Structure of Households in the Czech Republic: Findings from Population and Housing Census
Authors: Jaroslav Kraus
Abstract:
Spatial information about demographic processes are a standard part of outputs in the Czech Republic. That was also the case of Population and Housing Census which was held on 2011. This is a starting point for a follow up study devoted to two basic types of households: single person households and households of one completed family. Single person households and one family households create more than 80 percent of all households, but the share and spatial structure is in long-term changing. The increase of single households is results of long-term fertility decrease and divorce increase, but also possibility of separate living. There are regions in the Czech Republic with traditional demographic behavior, and regions like capital Prague and some others with changing pattern. Population census is based - according to international standards - on the concept of currently living population. Three types of geospatial approaches will be used for analysis: (i) firstly measures of geographic distribution, (ii) secondly mapping clusters to identify the locations of statistically significant hot spots, cold spots, spatial outliers, and similar features and (iii) finally analyzing pattern approach as a starting point for more in-depth analyses (geospatial regression) in the future will be also applied. For analysis of this type of data, number of households by types should be distinct objects. All events in a meaningful delimited study region (e.g. municipalities) will be included in an analysis. Commonly produced measures of central tendency and spread will include: identification of the location of the center of the point set (by NUTS3 level); identification of the median center and standard distance, weighted standard distance and standard deviational ellipses will be also used. Identifying that clustering exists in census households datasets does not provide a detailed picture of the nature and pattern of clustering but will be helpful to apply simple hot-spot (and cold spot) identification techniques to such datasets. Once the spatial structure of households will be determined, any particular measure of autocorrelation can be constructed by defining a way of measuring the difference between location attribute values. The most widely used measure is Moran’s I that will be applied to municipal units where numerical ratio is calculated. Local statistics arise naturally out of any of the methods for measuring spatial autocorrelation and will be applied to development of localized variants of almost any standard summary statistic. Local Moran’s I will give an indication of household data homogeneity and diversity on a municipal level.Keywords: census, geo-demography, households, the Czech Republic
Procedia PDF Downloads 9273 Risk Factors for Determining Anti-HBcore to Hepatitis B Virus Among Blood Donors
Authors: Tatyana Savchuk, Yelena Grinvald, Mohamed Ali, Ramune Sepetiene, Dinara Sadvakassova, Saniya Saussakova, Kuralay Zhangazieva, Dulat Imashpayev
Abstract:
Introduction. The problem of viral hepatitis B (HBV) takes a vital place in the global health system. The existing risk of HBV transmission through blood transfusions is associated with transfusion of blood taken from infected individuals during the “serological window” period or from patients with latent HBV infection, the marker of which is anti-HBcore. In the absence of information about other markers of hepatitis B, the presence of anti-HBcore suggests that a person may be actively infected or has suffered hepatitis B in the past and has immunity. Aim. To study the risk factors influencing the positive anti-HBcore indicators among the donor population. Materials and Methods. The study was conducted in 2021 in the Scientific and Production Center of Transfusiology of the Ministry of Healthcare in Kazakhstan. The samples taken from blood donors were tested for anti-HBcore, by CLIA on the Architect i2000SR (ABBOTT). A special questionnaire was developed for the blood donors’ socio-demographic characteristics. Statistical analysis was conducted by the R software (version 4.1.1, USA, 2021). Results.5709 people aged 18 to 66 years were included in the study, the proportion of men and women was 68.17% and 31.83%, respectively. The average age of the participants was 35.7 years. A weighted multivariable mixed effects logistic regression analysis showed that age (p<0.001), ethnicity (p<0.05), and marital status (p<0.05) were statistically associated with anti-HBcore positivity. In particular, analysis adjusting for gender, nationality, education, marital status, family history of hepatitis, blood transfusion, injections, and surgical interventions, with a one-year increase in age (adjOR=1.06, 95%CI:1.05-1.07), showed an 6% growth in odds of having anti-HBcore positive results. Those who were russian ethnicity (adjOR=0.65, 95%CI:0.46-0.93) and representatives of other nationality groups (adjOR=0.56, 95%CI:0.37-0.85) had lower odds of having anti-HBcore when compared to Kazakhs when controlling for other covariant variables. Among singles, the odds of having a positive anti-HBcore were lower by 29% (adjOR = 0.71, 95%CI:0.57-0.89) compared to married participants when adjusting for other variables. Conclusions.Kazakhstan is one of the countries with medium endemicity of HBV prevalence (2%-7%). Results of the study demonstrated the possibility to form a profile of risk factors (age, nationality, marital status). Taking into account the data, it is recommended to increase attention to donor questionnaires by adding leading questions and to improve preventive measures to prevent HBV. Funding. This research was supported by a grant from Abbott Laboratories.Keywords: anti-HBcore, blood donor, donation, hepatitis B virus, occult hepatitis
Procedia PDF Downloads 9772 Simulation and Thermal Evaluation of Containers Using PCM in Different Weather Conditions of Chile: Energy Savings in Lightweight Constructions
Authors: Paula Marín, Mohammad Saffari, Alvaro de Gracia, Luisa F. Cabeza, Svetlana Ushak
Abstract:
Climate control represents an important issue when referring to energy consumption of buildings and associated expenses, both in installation or operation periods. The climate control of a building relies on several factors. Among them, localization, orientation, architectural elements, sources of energy used, are considered. In order to study the thermal behaviour of a building set up, the present study proposes the use of energy simulation program Energy Plus. In recent years, energy simulation programs have become important tools for evaluation of thermal/energy performance of buildings and facilities. Besides, the need to find new forms of passive conditioning in buildings for energy saving is a critical component. The use of phase change materials (PCMs) for heat storage applications has grown in importance due to its high efficiency. Therefore, the climatic conditions of Northern Chile: high solar radiation and extreme temperature fluctuations ranging from -10°C to 30°C (Calama city), low index of cloudy days during the year are appropriate to take advantage of solar energy and use passive systems in buildings. Also, the extensive mining activities in northern Chile encourage the use of large numbers of containers to harbour workers during shifts. These containers are constructed with lightweight construction systems, requiring heating during night and cooling during day, increasing the HVAC electricity consumption. The use of PCM can improve thermal comfort and reduce the energy consumption. The objective of this study was to evaluate the thermal and energy performance of containers of 2.5×2.5×2.5 m3, located in four cities of Chile: Antofagasta, Calama, Santiago, and Concepción. Lightweight envelopes, typically used in these building prototypes, were evaluated considering a container without PCM inclusion as the reference building and another container with PCM-enhanced envelopes as a test case, both of which have a door and a window in the same wall, orientated in two directions: North and South. To see the thermal response of these containers in different seasons, the simulations were performed considering a period of one year. The results show that higher energy savings for the four cities studied are obtained when the distribution of door and window in the container is in the north direction because of higher solar radiation incidence. The comparison of HVAC consumption and energy savings in % for north direction of door and window are summarised. Simulation results show that in the city of Antofagasta 47% of heating energy could be saved and in the cities of Calama and Concepción the biggest savings in terms of cooling could be achieved since PCM reduces almost all the cooling demand. Currently, based on simulation results, four containers have been constructed and sized with the same structural characteristics carried out in simulations, that are, containers with/without PCM, with door and window in one wall. Two of these containers will be placed in Antofagasta and two containers in a copper mine near to Calama, all of them will be monitored for a period of one year. The simulation results will be validated with experimental measurements and will be reported in the future.Keywords: energy saving, lightweight construction, PCM, simulation
Procedia PDF Downloads 27671 Accuracy of Computed Tomography Dose Monitor Values: A Multicentric Study in India
Authors: Adhimoolam Saravana Kumar, K. N. Govindarajan, B. Devanand, R. Rajakumar
Abstract:
The quality of Computed Tomography (CT) procedures has improved in recent years due to technological developments and increased diagnostic ability of CT scanners. Due to the fact that CT doses are the peak among diagnostic radiology practices, it is of great significance to be aware of patient’s CT radiation dose whenever a CT examination is preferred. CT radiation dose delivered to patients in the form of volume CT dose index (CTDIvol) values, is displayed on scanner monitors at the end of each examination and it is an important fact to assure that this information is accurate. The objective of this study was to estimate the CTDIvol values for great number of patients during the most frequent CT examinations, to study the comparison between CT dose monitor values and measured ones, as well as to highlight the fluctuation of CTDIvol values for the same CT examination at different centres and scanner models. The output CT dose indices measurements were carried out on single and multislice scanners for available kV, 5 mm slice thickness, 100 mA and FOV combination used. The 100 CT scanners were involved in this study. Data with regard to 15,000 examinations in patients, who underwent routine head, chest and abdomen CT were collected using a questionnaire sent to a large number of hospitals. Out of the 15,000 examinations, 5000 were head CT examinations, 5000 were chest CT examinations and 5000 were abdominal CT examinations. Comprehensive quality assurance (QA) was performed for all the machines involved in this work. Followed by QA, CT phantom dose measurements were carried out in South India using actual scanning parameters used clinically by the hospitals. From this study, we have measured the mean divergence between the measured and displayed CTDIvol values were 5.2, 8.4, and -5.7 for selected head, chest and abdomen procedures for protocols as mentioned above, respectively. Thus, this investigation revealed an observable change in CT practices, with a much wider range of studies being performed currently in South India. This reflects the improved capacity of CT scanners to scan longer scan lengths and at finer resolutions as permitted by helical and multislice technology. Also, some of the CT scanners have used smaller slice thickness for routine CT procedures to achieve better resolution and image quality. It leads to an increase in the patient radiation dose as well as the measured CTDIv, so it is suggested that such CT scanners should select appropriate slice thickness and scanning parameters in order to reduce the patient dose. If these routine scan parameters for head, chest and abdomen procedures are optimized than the dose indices would be optimal and lead to the lowering of the CT doses. In South Indian region all the CT machines were routinely tested for QA once in a year as per AERB requirements.Keywords: CT dose index, weighted CTDI, volumetric CTDI, radiation dose
Procedia PDF Downloads 25270 Slope Stability and Landslides Hazard Analysis, Limitations of Existing Approaches, and a New Direction
Authors: Alisawi Alaa T., Collins P. E. F.
Abstract:
The analysis and evaluation of slope stability and landslide hazards are landslide hazards are critically important in civil engineering projects and broader considerations of safety. The level of slope stability risk should be identified due to its significant and direct financial and safety effects. Slope stability hazard analysis is performed considering static and/or dynamic loading circumstances. To reduce and/or prevent the failure hazard caused by landslides, a sophisticated and practical hazard analysis method using advanced constitutive modeling should be developed and linked to an effective solution that corresponds to the specific type of slope stability and landslides failure risk. Previous studies on slope stability analysis methods identify the failure mechanism and its corresponding solution. The commonly used approaches include used approaches include limit equilibrium methods, empirical approaches for rock slopes (e.g., slope mass rating and Q-slope), finite element or finite difference methods, and district element codes. This study presents an overview and evaluation of these analysis techniques. Contemporary source materials are used to examine these various methods on the basis of hypotheses, the factor of safety estimation, soil types, load conditions, and analysis conditions and limitations. Limit equilibrium methods play a key role in assessing the level of slope stability hazard. The slope stability safety level can be defined by identifying the equilibrium of the shear stress and shear strength. The slope is considered stable when the movement resistance forces are greater than those that drive the movement with a factor of safety (ratio of the resistance of the resistance of the driving forces) that is greater than 1.00. However, popular and practical methods, including limit equilibrium approaches, are not effective when the slope experiences complex failure mechanisms, such as progressive failure, liquefaction, internal deformation, or creep. The present study represents the first episode of an ongoing project that involves the identification of the types of landslides hazards, assessment of the level of slope stability hazard, development of a sophisticated and practical hazard analysis method, linkage of the failure type of specific landslides conditions to the appropriate solution and application of an advanced computational method for mapping the slope stability properties in the United Kingdom, and elsewhere through geographical information system (GIS) and inverse distance weighted spatial interpolation(IDW) technique. This study investigates and assesses the different assesses the different analysis and solution techniques to enhance the knowledge on the mechanism of slope stability and landslides hazard analysis and determine the available solutions for each potential landslide failure risk.Keywords: slope stability, finite element analysis, hazard analysis, landslides hazard
Procedia PDF Downloads 9369 Features of Fossil Fuels Generation from Bazhenov Formation Source Rocks by Hydropyrolysis
Authors: Anton G. Kalmykov, Andrew Yu. Bychkov, Georgy A. Kalmykov
Abstract:
Nowadays, most oil reserves in Russia and all over the world are hard to recover. That is the reason oil companies are searching for new sources for hydrocarbon production. One of the sources might be high-carbon formations with unconventional reservoirs. Bazhenov formation is a huge source rock formation located in West Siberia, which contains unconventional reservoirs on some of the areas. These reservoirs are formed by secondary processes with low predicting ratio. Only one of five wells is drilled through unconventional reservoirs, in others kerogen has low thermal maturity, and they are of low petroliferous. Therefore, there was a request for tertiary methods for in-situ cracking of kerogen and production of oil. Laboratory experiments of Bazhenov formation rock hydrous pyrolysis were used to investigate features of the oil generation process. Experiments on Bazhenov rocks with a different mineral composition (silica concentration from 15 to 90 wt.%, clays – 5-50 wt.%, carbonates – 0-30 wt.%, kerogen – 1-25 wt.%) and thermal maturity (from immature to late oil window kerogen) were performed in a retort under reservoir conditions. Rock samples of 50 g weight were placed in retort, covered with water and heated to the different temperature varied from 250 to 400°C with the durability of the experiments from several hours to one week. After the experiments, the retort was cooled to room temperature; generated hydrocarbons were extracted with hexane, then separated from the solvent and weighted. The molecular composition of this synthesized oil was then investigated via GC-MS chromatography Characteristics of rock samples after the heating was measured via the Rock-Eval method. It was found, that the amount of synthesized oil and its composition depending on the experimental conditions and composition of rocks. The highest amount of oil was produced at a temperature of 350°C after 12 hours of heating and was up to 12 wt.% of initial organic matter content in the rocks. At the higher temperatures and within longer heating time secondary cracking of generated hydrocarbons occurs, the mass of produced oil is lowering, and the composition contains more hydrocarbons that need to be recovered by catalytical processes. If the temperature is lower than 300°C, the amount of produced oil is too low for the process to be economically effective. It was also found that silica and clay minerals work as catalysts. Selection of heating conditions allows producing synthesized oil with specified composition. Kerogen investigations after heating have shown that thermal maturity increases, but the yield is only up to 35% of the maximum amount of synthetic oil. This yield is the result of gaseous hydrocarbons formation due to secondary cracking and aromatization and coaling of kerogen. Future investigations will allow the increase in the yield of synthetic oil. The results are in a good agreement with theoretical data on kerogen maturation during oil production. Evaluated trends could be tooled up for in-situ oil generation by shale rocks thermal action.Keywords: Bazhenov formation, fossil fuels, hydropyrolysis, synthetic oil
Procedia PDF Downloads 11168 Visco-Hyperelastic Finite Element Analysis for Diagnosis of Knee Joint Injury Caused by Meniscal Tearing
Authors: Eiji Nakamachi, Tsuyoshi Eguchi, Sayo Yamamoto, Yusuke Morita, H. Sakamoto
Abstract:
In this study, we aim to reveal the relationship between the meniscal tearing and the articular cartilage injury of knee joint by using the dynamic explicit finite element (FE) method. Meniscal injuries reduce its functional ability and consequently increase the load on the articular cartilage of knee joint. In order to prevent the induction of osteoarthritis (OA) caused by meniscal injuries, many medical treatment techniques, such as artificial meniscus replacement and meniscal regeneration, have been developed. However, it is reported that these treatments are not the comprehensive methods. In order to reveal the fundamental mechanism of OA induction, the mechanical characterization of meniscus under the condition of normal and injured states is carried out by using FE analyses. At first, a FE model of the human knee joint in the case of normal state – ‘intact’ - was constructed by using the magnetron resonance (MR) tomography images and the image construction code, Materialize Mimics. Next, two types of meniscal injury models with the radial tears of medial and lateral menisci were constructed. In FE analyses, the linear elastic constitutive law was adopted for the femur and tibia bones, the visco-hyperelastic constitutive law for the articular cartilage, and the visco-anisotropic hyperelastic constitutive law for the meniscus, respectively. Material properties of articular cartilage and meniscus were identified using the stress-strain curves obtained by our compressive and the tensile tests. The numerical results under the normal walking condition revealed how and where the maximum compressive stress occurred on the articular cartilage. The maximum compressive stress and its occurrence point were varied in the intact and two meniscal tear models. These compressive stress values can be used to establish the threshold value to cause the pathological change for the diagnosis. In this study, FE analyses of knee joint were carried out to reveal the influence of meniscal injuries on the cartilage injury. The following conclusions are obtained. 1. 3D FE model, which consists femur, tibia, articular cartilage and meniscus was constructed based on MR images of human knee joint. The image processing code, Materialize Mimics was used by using the tetrahedral FE elements. 2. Visco-anisotropic hyperelastic constitutive equation was formulated by adopting the generalized Kelvin model. The material properties of meniscus and articular cartilage were determined by curve fitting with experimental results. 3. Stresses on the articular cartilage and menisci were obtained in cases of the intact and two radial tears of medial and lateral menisci. Through comparison with the case of intact knee joint, two tear models show almost same stress value and higher value than the intact one. It was shown that both meniscal tears induce the stress localization in both medial and lateral regions. It is confirmed that our newly developed FE analysis code has a potential to be a new diagnostic system to evaluate the meniscal damage on the articular cartilage through the mechanical functional assessment.Keywords: finite element analysis, hyperelastic constitutive law, knee joint injury, meniscal tear, stress concentration
Procedia PDF Downloads 23967 Theoretical and Experimental Investigation of Structural, Electrical and Photocatalytic Properties of K₀.₅Na₀.₅NbO₃ Lead- Free Ceramics Prepared via Different Synthesis Routes
Authors: Manish Saha, Manish Kumar Niranjan, Saket Asthana
Abstract:
The K₀.₅Na₀.₅NbO₃ (KNN) system has emerged as one of the most promising lead-free piezoelectric over the years. In this work, we perform a comprehensive investigation of electronic structure, lattice dynamics and dielectric/ferroelectric properties of the room temperature phase of KNN by combining ab-initio DFT-based theoretical analysis and experimental characterization. We assign the symmetry labels to KNN vibrational modes and obtain ab-initio polarized Raman spectra, Infrared (IR) reflectivity, Born-effective charge tensors, oscillator strengths etc. The computed Raman spectrum is found to agree well with the experimental spectrum. In particular, the results suggest that the mode in the range ~840-870 cm-¹ reported in the experimental studies is longitudinal optical (LO) with A_1 symmetry. The Raman mode intensities are calculated for different light polarization set-ups, which suggests the observation of different symmetry modes in different polarization set-ups. The electronic structure of KNN is investigated, and an optical absorption spectrum is obtained. Further, the performances of DFT semi-local, metal-GGA and hybrid exchange-correlations (XC) functionals, in the estimation of KNN band gaps are investigated. The KNN bandgap computed using GGA-1/2 and HSE06 hybrid functional schemes are found to be in excellant agreement with the experimental value. The COHP, electron localization function and Bader charge analysis is also performed to deduce the nature of chemical bonding in the KNN. The solid-state reaction and hydrothermal methods are used to prepare the KNN ceramics, and the effects of grain size on the physical characteristics these ceramics are examined. A comprehensive study on the impact of different synthesis techniques on the structural, electrical, and photocatalytic properties of ferroelectric ceramics KNN. The KNN-S prepared by solid-state method have significantly larger grain size as compared to that for KNN-H prepared by hydrothermal method. Furthermore, the KNN-S is found to exhibit higher dielectric, piezoelectric and ferroelectric properties as compared to KNN-H. On the other hand, the increased photocatalytic activity is observed in KNN-H as compared to KNN-S. As compared to the hydrothermal synthesis, the solid-state synthesis causes an increase in the relative dielectric permittivity (ε^') from 2394 to 3286, remnant polarization (P_r) from 15.38 to 20.41 μC/cm^², planer electromechanical coupling factor (k_p) from 0.19 to 0.28 and piezoelectric coefficient (d_33) from 88 to 125 pC/N. The KNN-S ceramics are also found to have a lower leakage current density, and higher grain resistance than KNN-H ceramic. The enhanced photocatalytic activity of KNN-H is attributed to relatively smaller particle sizes. The KNN-S and KNN-H samples are found to have degradation efficiencies of RhB solution of 20% and 65%, respectively. The experimental study highlights the importance of synthesis methods and how these can be exploited to tailor the dielectric, piezoelectric and photocatalytic properties of KNN. Overall, our study provides several bench-mark important results on KNN that have not been reported so far.Keywords: lead-free piezoelectric, Raman intensity spectrum, electronic structure, first-principles calculations, solid state synthesis, photocatalysis, hydrothermal synthesis
Procedia PDF Downloads 4166 Identification and Characterization of Small Peptides Encoded by Small Open Reading Frames using Mass Spectrometry and Bioinformatics
Authors: Su Mon Saw, Joe Rothnagel
Abstract:
Short open reading frames (sORFs) located in 5’UTR of mRNAs are known as uORFs. Characterization of uORF-encoded peptides (uPEPs) i.e., a subset of short open reading frame encoded peptides (sPEPs) and their translation regulation lead to understanding of causes of genetic disease, proteome complexity and development of treatments. Existence of uORFs within cellular proteome could be detected by LC-MS/MS. The ability of uORF to be translated into uPEP and achievement of uPEP identification will allow uPEP’s characterization, structures, functions, subcellular localization, evolutionary maintenance (conservation in human and other species) and abundance in cells. It is hypothesized that a subset of sORFs are translatable and that their encoded sPEPs are functional and are endogenously expressed contributing to the eukaryotic cellular proteome complexity. This project aimed to investigate whether sORFs encode functional peptides. Liquid chromatography-mass spectrometry (LC-MS) and bioinformatics were thus employed. Due to probable low abundance of sPEPs and small in sizes, the need for efficient peptide enrichment strategies for enriching small proteins and depleting the sub-proteome of large and abundant proteins is crucial for identifying sPEPs. Low molecular weight proteins were extracted using SDS-PAGE from Human Embryonic Kidney (HEK293) cells and Strong Cation Exchange Chromatography (SCX) from secreted HEK293 cells. Extracted proteins were digested by trypsin to peptides, which were detected by LC-MS/MS. The MS/MS data obtained was searched against Swiss-Prot using MASCOT version 2.4 to filter out known proteins, and all unmatched spectra were re-searched against human RefSeq database. ProteinPilot v5.0.1 was used to identify sPEPs by searching against human RefSeq, Vanderperre and Human Alternative Open Reading Frame (HaltORF) databases. Potential sPEPs were analyzed by bioinformatics. Since SDS PAGE electrophoresis could not separate proteins <20kDa, this could not identify sPEPs. All MASCOT-identified peptide fragments were parts of main open reading frame (mORF) by ORF Finder search and blastp search. No sPEP was detected and existence of sPEPs could not be identified in this study. 13 translated sORFs in HEK293 cells by mass spectrometry in previous studies were characterized by bioinformatics. Identified sPEPs from previous studies were <100 amino acids and <15 kDa. Bioinformatics results showed that sORFs are translated to sPEPs and contribute to proteome complexity. uPEP translated from uORF of SLC35A4 was strongly conserved in human and mouse while uPEP translated from uORF of MKKS was strongly conserved in human and Rhesus monkey. Cross-species conserved uORFs in association with protein translation strongly suggest evolutionary maintenance of coding sequence and indicate probable functional expression of peptides encoded within these uORFs. Translation of sORFs was confirmed by mass spectrometry and sPEPs were characterized with bioinformatics.Keywords: bioinformatics, HEK293 cells, liquid chromatography-mass spectrometry, ProteinPilot, Strong Cation Exchange Chromatography, SDS-PAGE, sPEPs
Procedia PDF Downloads 18465 Presence, Distribution and Form of Calcium Oxalate Crystals in Relation to Age of Actinidia Deliciosa Leaves and Petioles
Authors: Muccifora S., Rinallo C., Bellani L.
Abstract:
Calcium (Ca²+) is an element essential to the plant being involved in plant growth and development. At high concentrations, it is toxic and can influence every stage, process and cellular activity of plant life. Given its toxicity, cells implement mechanisms to compartmentalize calcium in a vacuole, endoplasmic reticulum, mitochondria, plastids and cell wall. One of the most effective mechanisms to reduce the excess of calcium, thus avoiding cellular damage, is its complexation with oxalic acid to form calcium oxalate crystals that are no longer osmotically or physiologically active. However, the sequestered calcium can be mobilized when the plant needs it. Calcium crystals can be accumulated in the vacuole of specialized sink-cells called idioblasts, with different crystalline forms (druse, raphyde and styloid) of diverse physiological meanings. Actinidia deliciosa cv. Hayward presents raphydes and styloid localized in idioblasts in cells of photosynthetic and non-photosynthetic tissues. The purpose of this work was to understand if there is a relationship between the age of Actinidia leaves and the presence, distribution, dimension and shape of oxalate crystals by means of light, fluorescent, polarized and transmission electron microscopy. Three vines from female plants were chosen at the beginning of the season and used throughout the study. The leaves with petioles were collected at various stages of development from the bottom to the shoot of the plants monthly from April to July. The samples were taken in corresponding areas of the central and lateral parts of the leaves and of the basal portion of the petiole. The results showed that in the leaves, the number of raphyde idioblasts decreased with the progress of the growing season, while the styloid idioblasts increased progressively, becoming very numerous in the upper nodes of July. In June and in July samples, in the vacuoles of the highest nodes, a portion regular in shape strongly stained with rubeanic acid was present. Moreover, the chlortetracycline (CTC) staining for localization of free calcium marked the wall of the idioblasts and the wall of the cells near vascular bundles. In April petiole samples, moving towards the youngest nodes, the raphydes idioblast decreased in number and in the length of the single raphydes. Besides, crystals stained with rubeanic acid appeared in the vacuoles of some cells. In June samples, numerous raphyde idioblasts oriented parallel to vascular bundles were evident. Under the electron microscope, numerous idioblasts presented not homogeneous electrondense aggregates of material, in which a few crystals (styloids) in the form of regular holes were scattered. In July samples, an increase in the number of styloid idioblasts in the youngest nodes and little masses stained with CTC near styloids were observed. Peculiar cells stained with rubeanic acid were detected and hypothesized to be involved in the formation of the idioblasts. In conclusion, in Actinidia leaves and petioles, it seems to confirm the hypothesis that the formation of styloid idioblasts can be correlated to increasing calcium levels in growing tissues.Keywords: calcium oxalate crystals, actinidia deliciosa, light and electron microscopy, idioblasts
Procedia PDF Downloads 7764 EQMamba - Method Suggestion for Earthquake Detection and Phase Picking
Authors: Noga Bregman
Abstract:
Accurate and efficient earthquake detection and phase picking are crucial for seismic hazard assessment and emergency response. This study introduces EQMamba, a deep-learning method that combines the strengths of the Earthquake Transformer and the Mamba model for simultaneous earthquake detection and phase picking. EQMamba leverages the computational efficiency of Mamba layers to process longer seismic sequences while maintaining a manageable model size. The proposed architecture integrates convolutional neural networks (CNNs), bidirectional long short-term memory (BiLSTM) networks, and Mamba blocks. The model employs an encoder composed of convolutional layers and max pooling operations, followed by residual CNN blocks for feature extraction. Mamba blocks are applied to the outputs of BiLSTM blocks, efficiently capturing long-range dependencies in seismic data. Separate decoders are used for earthquake detection, P-wave picking, and S-wave picking. We trained and evaluated EQMamba using a subset of the STEAD dataset, a comprehensive collection of labeled seismic waveforms. The model was trained using a weighted combination of binary cross-entropy loss functions for each task, with the Adam optimizer and a scheduled learning rate. Data augmentation techniques were employed to enhance the model's robustness. Performance comparisons were conducted between EQMamba and the EQTransformer over 20 epochs on this modest-sized STEAD subset. Results demonstrate that EQMamba achieves superior performance, with higher F1 scores and faster convergence compared to EQTransformer. EQMamba reached F1 scores of 0.8 by epoch 5 and maintained higher scores throughout training. The model also exhibited more stable validation performance, indicating good generalization capabilities. While both models showed lower accuracy in phase-picking tasks compared to detection, EQMamba's overall performance suggests significant potential for improving seismic data analysis. The rapid convergence and superior F1 scores of EQMamba, even on a modest-sized dataset, indicate promising scalability for larger datasets. This study contributes to the field of earthquake engineering by presenting a computationally efficient and accurate method for simultaneous earthquake detection and phase picking. Future work will focus on incorporating Mamba layers into the P and S pickers and further optimizing the architecture for seismic data specifics. The EQMamba method holds the potential for enhancing real-time earthquake monitoring systems and improving our understanding of seismic events.Keywords: earthquake, detection, phase picking, s waves, p waves, transformer, deep learning, seismic waves
Procedia PDF Downloads 2763 Entrepreneurial Dynamism and Socio-Cultural Context
Authors: Shailaja Thakur
Abstract:
Managerial literature abounds with discussions on business strategies, success stories as well as cases of failure, which provide an indication of the parameters that should be considered in gauging the dynamism of an entrepreneur. Neoclassical economics has reduced entrepreneurship to a mere factor of production, driven solely by the profit motive, thus stripping him of all creativity and restricting his decision making to mechanical calculations. His ‘dynamism’ is gauged simply by the amount of profits he earns, marginalizing any discussion on the means that he employs to attain this objective. With theoretical backing, we have developed an Index of Entrepreneurial Dynamism (IED) giving weights to the different moves that the entrepreneur makes during his business journey. Strategies such as changes in product lines, markets and technology are gauged as very important (weighting of 4); while adaptations in terms of technology, raw materials used, upgradations in skill set are given a slightly lesser weight of 3. Use of formal market analysis, diversification in related products are considered moderately important (weight of 2) and being a first generation entrepreneur, employing managers and having plans to diversify are taken to be only slightly important business strategies (weight of 1). The maximum that an entrepreneur can score on this index is 53. A semi-structured questionnaire is employed to solicit the responses from the entrepreneurs on the various strategies that have been employed by them during the course of their business. Binary as well as graded responses are obtained, weighted and summed up to give the IED. This index was tested on about 150 tribal entrepreneurs in Mizoram, a state of India and was found to be highly effective in gauging their dynamism. This index has universal acceptability but is devoid of the socio-cultural context, which is very central to the success and performance of the entrepreneurs. We hypothesize that a society that respects risk taking takes failures in its stride, glorifies entrepreneurial role models, promotes merit and achievement is one that has a conducive socio- cultural environment for entrepreneurship. For obtaining an idea about the social acceptability, we are putting forth questions related to the social acceptability of business to another set of respondents from different walks of life- bureaucracy, academia, and other professional fields. Similar weighting technique is employed, and index is generated. This index is used for discounting the IED of the respondent entrepreneurs from that region/ society. This methodology is being tested for a sample of entrepreneurs from two very different socio- cultural milieus- a tribal society and a ‘mainstream’ society- with the hypothesis that the entrepreneurs in the tribal milieu might be showing a higher level of dynamism than their counterparts in other regions. An entrepreneur who scores high on IED and belongs to society and culture that holds entrepreneurship in high esteem, might not be in reality as dynamic as a person who shows similar dynamism in a relatively discouraging or even an outright hostile environment.Keywords: index of entrepreneurial dynamism, India, social acceptability, tribal entrepreneurs
Procedia PDF Downloads 24262 Experimental-Numerical Inverse Approaches in the Characterization and Damage Detection of Soft Viscoelastic Layers from Vibration Test Data
Authors: Alaa Fezai, Anuj Sharma, Wolfgang Mueller-Hirsch, André Zimmermann
Abstract:
Viscoelastic materials have been widely used in the automotive industry over the last few decades with different functionalities. Besides their main application as a simple and efficient surface damping treatment, they may ensure optimal operating conditions for on-board electronics as thermal interface or sealing layers. The dynamic behavior of viscoelastic materials is generally dependent on many environmental factors, the most important being temperature and strain rate or frequency. Prior to the reliability analysis of systems including viscoelastic layers, it is, therefore, crucial to accurately predict the dynamic and lifetime behavior of these materials. This includes the identification of the dynamic material parameters under critical temperature and frequency conditions along with a precise damage localization and identification methodology. The goal of this work is twofold. The first part aims at applying an inverse viscoelastic material-characterization approach for a wide frequency range and under different temperature conditions. For this sake, dynamic measurements are carried on a single lap joint specimen using an electrodynamic shaker and an environmental chamber. The specimen consists of aluminum beams assembled to adapter plates through a viscoelastic adhesive layer. The experimental setup is reproduced in finite element (FE) simulations, and frequency response functions (FRF) are calculated. The parameters of both the generalized Maxwell model and the fractional derivatives model are identified through an optimization algorithm minimizing the difference between the simulated and the measured FRFs. The second goal of the current work is to guarantee an on-line detection of the damage, i.e., delamination in the viscoelastic bonding of the described specimen during frequency monitored end-of-life testing. For this purpose, an inverse technique, which determines the damage location and size based on the modal frequency shift and on the change of the mode shapes, is presented. This includes a preliminary FE model-based study correlating the delamination location and size to the change in the modal parameters and a subsequent experimental validation achieved through dynamic measurements of specimen with different, pre-generated crack scenarios and comparing it to the virgin specimen. The main advantage of the inverse characterization approach presented in the first part resides in the ability of adequately identifying the material damping and stiffness behavior of soft viscoelastic materials over a wide frequency range and under critical temperature conditions. Classic forward characterization techniques such as dynamic mechanical analysis are usually linked to limitations under critical temperature and frequency conditions due to the material behavior of soft viscoelastic materials. Furthermore, the inverse damage detection described in the second part guarantees an accurate prediction of not only the damage size but also its location using a simple test setup and outlines; therefore, the significance of inverse numerical-experimental approaches in predicting the dynamic behavior of soft bonding layers applied in automotive electronics.Keywords: damage detection, dynamic characterization, inverse approaches, vibration testing, viscoelastic layers
Procedia PDF Downloads 20061 Ibrutinib and the Potential Risk of Cardiac Failure: A Review of Pharmacovigilance Data
Authors: Abdulaziz Alakeel, Roaa Alamri, Abdulrahman Alomair, Mohammed Fouda
Abstract:
Introduction: Ibrutinib is a selective, potent, and irreversible small-molecule inhibitor of Bruton's tyrosine kinase (BTK). It forms a covalent bond with a cysteine residue (CYS-481) at the active site of Btk, leading to inhibition of Btk enzymatic activity. The drug is indicated to treat certain type of cancers such as mantle cell lymphoma (MCL), chronic lymphocytic leukaemia and Waldenström's macroglobulinaemia (WM). Cardiac failure is a condition referred to inability of heart muscle to pump adequate blood to human body organs. There are multiple types of cardiac failure including left and right-sided heart failure, systolic and diastolic heart failures. The aim of this review is to evaluate the risk of cardiac failure associated with the use of ibrutinib and to suggest regulatory recommendations if required. Methodology: Signal Detection team at the National Pharmacovigilance Center (NPC) of Saudi Food and Drug Authority (SFDA) performed a comprehensive signal review using its national database as well as the World Health Organization (WHO) database (VigiBase), to retrieve related information for assessing the causality between cardiac failure and ibrutinib. We used the WHO- Uppsala Monitoring Centre (UMC) criteria as standard for assessing the causality of the reported cases. Results: Case Review: The number of resulted cases for the combined drug/adverse drug reaction are 212 global ICSRs as of July 2020. The reviewers have selected and assessed the causality for the well-documented ICSRs with completeness scores of 0.9 and above (35 ICSRs); the value 1.0 presents the highest score for best-written ICSRs. Among the reviewed cases, more than half of them provides supportive association (four probable and 15 possible cases). Data Mining: The disproportionality of the observed and the expected reporting rate for drug/adverse drug reaction pair is estimated using information component (IC), a tool developed by WHO-UMC to measure the reporting ratio. Positive IC reflects higher statistical association while negative values indicates less statistical association, considering the null value equal to zero. The results of (IC=1.5) revealed a positive statistical association for the drug/ADR combination, which means “Ibrutinib” with “Cardiac Failure” have been observed more than expected when compared to other medications available in WHO database. Conclusion: Health regulators and health care professionals must be aware for the potential risk of cardiac failure associated with ibrutinib and the monitoring of any signs or symptoms in treated patients is essential. The weighted cumulative evidences identified from causality assessment of the reported cases and data mining are sufficient to support a causal association between ibrutinib and cardiac failure.Keywords: cardiac failure, drug safety, ibrutinib, pharmacovigilance, signal detection
Procedia PDF Downloads 12060 Technology Management for Early Stage Technologies
Authors: Ming Zhou, Taeho Park
Abstract:
Early stage technologies have been particularly challenging to manage due to high degrees of their numerous uncertainties. Most research results directly out of a research lab tend to be at their early, if not the infant stage. A long while uncertain commercialization process awaits these lab results. The majority of such lab technologies go nowhere and never get commercialized due to various reasons. Any efforts or financial resources put into managing these technologies turn fruitless. High stake naturally calls for better results, which make a patenting decision harder to make. A good and well protected patent goes a long way for commercialization of the technology. Our preliminary research showed that there was not a simple yet productive procedure for such valuation. Most of the studies now have been theoretical and overly comprehensive where practical suggestions were non-existent. Hence, we attempted to develop a simple and highly implementable procedure for efficient and scalable valuation. We thoroughly reviewed existing research, interviewed practitioners in the Silicon Valley area, and surveyed university technology offices. Instead of presenting another theoretical and exhaustive research, we aimed at developing a practical guidance that a government agency and/or university office could easily deploy and get things moving to later steps of managing early stage technologies. We provided a procedure to thriftily value and make the patenting decision. A patenting index was developed using survey data and expert opinions. We identified the most important factors to be used in the patenting decision using survey ratings. The rating then assisted us in generating good relative weights for the later scoring and weighted averaging step. More importantly, we validated our procedure by testing it with our practitioner contacts. Their inputs produced a general yet highly practical cut schedule. Such schedule of realistic practices has yet to be witnessed our current research. Although a technology office may choose to deviate from our cuts, what we offered here at least provided a simple and meaningful starting point. This procedure was welcomed by practitioners in our expert panel and university officers in our interview group. This research contributed to our current understanding and practices of managing early stage technologies by instating a heuristically simple yet theoretical solid method for the patenting decision. Our findings generated top decision factors, decision processes and decision thresholds of key parameters. This research offered a more practical perspective which further completed our extant knowledge. Our results could be impacted by our sample size and even biased a bit by our focus on the Silicon Valley area. Future research, blessed with bigger data size and more insights, may want to further train and validate our parameter values in order to obtain more consistent results and analyze our decision factors for different industries.Keywords: technology management, early stage technology, patent, decision
Procedia PDF Downloads 34059 A Comparison of Methods for Estimating Dichotomous Treatment Effects: A Simulation Study
Authors: Jacqueline Y. Thompson, Sam Watson, Lee Middleton, Karla Hemming
Abstract:
Introduction: The odds ratio (estimated via logistic regression) is a well-established and common approach for estimating covariate-adjusted binary treatment effects when comparing a treatment and control group with dichotomous outcomes. Its popularity is primarily because of its stability and robustness to model misspecification. However, the situation is different for the relative risk and risk difference, which are arguably easier to interpret and better suited to specific designs such as non-inferiority studies. So far, there is no equivalent, widely acceptable approach to estimate an adjusted relative risk and risk difference when conducting clinical trials. This is partly due to the lack of a comprehensive evaluation of available candidate methods. Methods/Approach: A simulation study is designed to evaluate the performance of relevant candidate methods to estimate relative risks to represent conditional and marginal estimation approaches. We consider the log-binomial, generalised linear models (GLM) with iteratively weighted least-squares (IWLS) and model-based standard errors (SE); log-binomial GLM with convex optimisation and model-based SEs; log-binomial GLM with convex optimisation and permutation tests; modified-Poisson GLM IWLS and robust SEs; log-binomial generalised estimation equations (GEE) and robust SEs; marginal standardisation and delta method SEs; and marginal standardisation and permutation test SEs. Independent and identically distributed datasets are simulated from a randomised controlled trial to evaluate these candidate methods. Simulations are replicated 10000 times for each scenario across all possible combinations of sample sizes (200, 1000, and 5000), outcomes (10%, 50%, and 80%), and covariates (ranging from -0.05 to 0.7) representing weak, moderate or strong relationships. Treatment effects (ranging from 0, -0.5, 1; on the log-scale) will consider null (H0) and alternative (H1) hypotheses to evaluate coverage and power in realistic scenarios. Performance measures (bias, mean square error (MSE), relative efficiency, and convergence rates) are evaluated across scenarios covering a range of sample sizes, event rates, covariate prognostic strength, and model misspecifications. Potential Results, Relevance & Impact: There are several methods for estimating unadjusted and adjusted relative risks. However, it is unclear which method(s) is the most efficient, preserves type-I error rate, is robust to model misspecification, or is the most powerful when adjusting for non-prognostic and prognostic covariates. GEE estimations may be biased when the outcome distributions are not from marginal binary data. Also, it seems that marginal standardisation and convex optimisation may perform better than GLM IWLS log-binomial.Keywords: binary outcomes, statistical methods, clinical trials, simulation study
Procedia PDF Downloads 10758 Characterizing the Spatially Distributed Differences in the Operational Performance of Solar Power Plants Considering Input Volatility: Evidence from China
Authors: Bai-Chen Xie, Xian-Peng Chen
Abstract:
China has become the world's largest energy producer and consumer, and its development of renewable energy is of great significance to global energy governance and the fight against climate change. The rapid growth of solar power in China could help achieve its ambitious carbon peak and carbon neutrality targets early. However, the non-technical costs of solar power in China are much higher than at international levels, meaning that inefficiencies are rooted in poor management and improper policy design and that efficiency distortions have become a serious challenge to the sustainable development of the renewable energy industry. Unlike fossil energy generation technologies, the output of solar power is closely related to the volatile solar resource, and the spatial unevenness of solar resource distribution leads to potential efficiency spatial distribution differences. It is necessary to develop an efficiency evaluation method that considers the volatility of solar resources and explores the mechanism of the influence of natural geography and social environment on the spatially varying characteristics of efficiency distribution to uncover the root causes of managing inefficiencies. The study sets solar resources as stochastic inputs, introduces a chance-constrained data envelopment analysis model combined with the directional distance function, and measures the solar resource utilization efficiency of 222 solar power plants in representative photovoltaic bases in northwestern China. By the meta-frontier analysis, we measured the characteristics of different power plant clusters and compared the differences among groups, discussed the mechanism of environmental factors influencing inefficiencies, and performed statistical tests through the system generalized method of moments. Rational localization of power plants is a systematic project that requires careful consideration of the full utilization of solar resources, low transmission costs, and power consumption guarantee. Suitable temperature, precipitation, and wind speed can improve the working performance of photovoltaic modules, reasonable terrain inclination can reduce land cost, and the proximity to cities strongly guarantees the consumption of electricity. The density of electricity demand and high-tech industries is more important than resource abundance because they trigger the clustering of power plants to result in a good demonstration and competitive effect. To ensure renewable energy consumption, increased support for rural grids and encouraging direct trading between generators and neighboring users will provide solutions. The study will provide proposals for improving the full life-cycle operational activities of solar power plants in China to reduce high non-technical costs and improve competitiveness against fossil energy sources.Keywords: solar power plants, environmental factors, data envelopment analysis, efficiency evaluation
Procedia PDF Downloads 8157 The Properties of Risk-based Approaches to Asset Allocation Using Combined Metrics of Portfolio Volatility and Kurtosis: Theoretical and Empirical Analysis
Authors: Maria Debora Braga, Luigi Riso, Maria Grazia Zoia
Abstract:
Risk-based approaches to asset allocation are portfolio construction methods that do not rely on the input of expected returns for the asset classes in the investment universe and only use risk information. They include the Minimum Variance Strategy (MV strategy), the traditional (volatility-based) Risk Parity Strategy (SRP strategy), the Most Diversified Portfolio Strategy (MDP strategy) and, for many, the Equally Weighted Strategy (EW strategy). All the mentioned approaches were based on portfolio volatility as a reference risk measure but in 2023, the Kurtosis-based Risk Parity strategy (KRP strategy) and the Minimum Kurtosis strategy (MK strategy) were introduced. Understandably, they used the fourth root of the portfolio-fourth moment as a proxy for portfolio kurtosis to work with a homogeneous function of degree one. This paper contributes mainly theoretically and methodologically to the framework of risk-based asset allocation approaches with two steps forward. First, a new and more flexible objective function considering a linear combination (with positive coefficients that sum to one) of portfolio volatility and portfolio kurtosis is used to alternatively serve a risk minimization goal or a homogeneous risk distribution goal. Hence, the new basic idea consists in extending the achievement of typical risk-based approaches’ goals to a combined risk measure. To give the rationale behind operating with such a risk measure, it is worth remembering that volatility and kurtosis are expressions of uncertainty, to be read as dispersion of returns around the mean and that both preserve adherence to a symmetric framework and consideration for the entire returns distribution as well, but also that they differ from each other in that the former captures the “normal” / “ordinary” dispersion of returns, while the latter is able to catch the huge dispersion. Therefore, the combined risk metric that uses two individual metrics focused on the same phenomena but differently sensitive to its intensity allows the asset manager to express, in the context of an objective function by varying the “relevance coefficient” associated with the individual metrics, alternatively, a wide set of plausible investment goals for the portfolio construction process while serving investors differently concerned with tail risk and traditional risk. Since this is the first study that also implements risk-based approaches using a combined risk measure, it becomes of fundamental importance to investigate the portfolio effects triggered by this innovation. The paper also offers a second contribution. Until the recent advent of the MK strategy and the KRP strategy, efforts to highlight interesting properties of risk-based approaches were inevitably directed towards the traditional MV strategy and SRP strategy. Previous literature established an increasing order in terms of portfolio volatility, starting from the MV strategy, through the SRP strategy, arriving at the EQ strategy and provided the mathematical proof for the “equalization effect” concerning marginal risks when the MV strategy is considered, and concerning risk contributions when the SRP strategy is considered. Regarding the validity of similar conclusions when referring to the MK strategy and KRP strategy, the development of a theoretical demonstration is still pending. This paper fills this gap.Keywords: risk parity, portfolio kurtosis, risk diversification, asset allocation
Procedia PDF Downloads 5656 A Failure to Strike a Balance: The Use of Parental Mediation Strategies by Foster Carers and Social Workers
Authors: Jennifer E Simpson
Abstract:
Background and purpose: The ubiquitous use of the Internet and social media by children and young people has had a dual effect. The first is to open a world of possibilities and promise that is characterized by the ability to consume and create content, connect with friends, explore and experiment. The second relates to risks such as unsolicited requests, sexual exploitation, cyberbullying and commercial exploitation. This duality poses significant difficulties for a generation of foster carers and social workers who have no childhood experience to draw on in terms of growing up using the Internet, social media and digital devices. This presentation is concerned with the findings of a small qualitative study about the use of digital devices and the Internet by care-experienced young people to stay in touch with their families and the way this was managed by foster carers and social workers using specific parental mediation strategies. The findings highlight that restrictive strategies were used by foster carers and endorsed by social workers. An argument is made for an approach that develops a series of balanced solutions that move foster carers from such restrictive approaches to those that are grounded in co-use and are interpretive in nature. Methods: Using a purposive sampling strategy, 12 triads consisting of care-experienced young people (aged 13-18 years), their foster carers and allocated social workers were recruited. All respondents undertook a semi-structured interview, with the young people detailing what social media apps and other devices they used to contact their families via an Ecomap. The foster carers and social workers shared details of the methods and approaches they used to manage digital devices and the Internet in general. Data analysis was performed using a Framework analytic method to explore the various attitudes, as well as complementary and contradictory perspectives of the young people, their foster carers and allocated social workers. Findings: The majority of foster carers made use of parental mediation strategies that erred on the side of typologies that included setting rules and regulations (restrictive), ad-hoc checking of a young person’s behavior and device (monitoring), and software used to limit or block access to inappropriate websites (technical). It was noted that minimal use was made by foster carers of parental mediation strategies that included talking about content (active/interpretive) or sharing Internet activities (co-use). Amongst the majority of the social workers, they also had a strong preference for restrictive approaches. Conclusions and implications: Trepidations on the part of both foster carers and social workers about the use of digital devices and the Internet meant that the parental strategies used were weighted more towards restriction, with little use made of approaches such as co-use and interpretative. This lack of balance calls for solutions that are grounded in co-use and an interpretive approach, both of which can be achieved through training and support, as well as wider policy change.Keywords: parental mediation strategies, risk, children in state care, online safety
Procedia PDF Downloads 6555 Evaluation of the Effect of Learning Disabilities and Accommodations on the Prediction of the Exam Performance: Ordinal Decision-Tree Algorithm
Abstract:
Providing students with learning disabilities (LD) with extra time to grant them equal access to the exam is a necessary but insufficient condition to compensate for their LD; there should also be a clear indication that the additional time was actually used. For example, if students with LD use more time than students without LD and yet receive lower grades, this may indicate that a different accommodation is required. If they achieve higher grades but use the same amount of time, then the effectiveness of the accommodation has not been demonstrated. The main goal of this study is to evaluate the effect of including parameters related to LD and extended exam time, along with other commonly-used characteristics (e.g., student background and ability measures such as high-school grades), on the ability of ordinal decision-tree algorithms to predict exam performance. We use naturally-occurring data collected from hundreds of undergraduate engineering students. The sub-goals are i) to examine the improvement in prediction accuracy when the indicator of exam performance includes 'actual time used' in addition to the conventional indicator (exam grade) employed in most research; ii) to explore the effectiveness of extended exam time on exam performance for different courses and for LD students with different profiles (i.e., sets of characteristics). This is achieved by using the patterns (i.e., subgroups) generated by the algorithms to identify pairs of subgroups that differ in just one characteristic (e.g., course or type of LD) but have different outcomes in terms of exam performance (grade and time used). Since grade and time used to exhibit an ordering form, we propose a method based on ordinal decision-trees, which applies a weighted information-gain ratio (WIGR) measure for selecting the classifying attributes. Unlike other known ordinal algorithms, our method does not assume monotonicity in the data. The proposed WIGR is an extension of an information-theoretic measure, in the sense that it adjusts to the case of an ordinal target and takes into account the error severity between two different target classes. Specifically, we use ordinal C4.5, random-forest, and AdaBoost algorithms, as well as an ensemble technique composed of ordinal and non-ordinal classifiers. Firstly, we find that the inclusion of LD and extended exam-time parameters improves prediction of exam performance (compared to specifications of the algorithms that do not include these variables). Secondly, when the indicator of exam performance includes 'actual time used' together with grade (as opposed to grade only), the prediction accuracy improves. Thirdly, our subgroup analyses show clear differences in the effect of extended exam time on exam performance among different courses and different student profiles. From a methodological perspective, we find that the ordinal decision-tree based algorithms outperform their conventional, non-ordinal counterparts. Further, we demonstrate that the ensemble-based approach leverages the strengths of each type of classifier (ordinal and non-ordinal) and yields better performance than each classifier individually.Keywords: actual exam time usage, ensemble learning, learning disabilities, ordinal classification, time extension
Procedia PDF Downloads 9854 A Comprehensive Survey of Artificial Intelligence and Machine Learning Approaches across Distinct Phases of Wildland Fire Management
Authors: Ursula Das, Manavjit Singh Dhindsa, Kshirasagar Naik, Marzia Zaman, Richard Purcell, Srinivas Sampalli, Abdul Mutakabbir, Chung-Horng Lung, Thambirajah Ravichandran
Abstract:
Wildland fires, also known as forest fires or wildfires, are exhibiting an alarming surge in frequency in recent times, further adding to its perennial global concern. Forest fires often lead to devastating consequences ranging from loss of healthy forest foliage and wildlife to substantial economic losses and the tragic loss of human lives. Despite the existence of substantial literature on the detection of active forest fires, numerous potential research avenues in forest fire management, such as preventative measures and ancillary effects of forest fires, remain largely underexplored. This paper undertakes a systematic review of these underexplored areas in forest fire research, meticulously categorizing them into distinct phases, namely pre-fire, during-fire, and post-fire stages. The pre-fire phase encompasses the assessment of fire risk, analysis of fuel properties, and other activities aimed at preventing or reducing the risk of forest fires. The during-fire phase includes activities aimed at reducing the impact of active forest fires, such as the detection and localization of active fires, optimization of wildfire suppression methods, and prediction of the behavior of active fires. The post-fire phase involves analyzing the impact of forest fires on various aspects, such as the extent of damage in forest areas, post-fire regeneration of forests, impact on wildlife, economic losses, and health impacts from byproducts produced during burning. A comprehensive understanding of the three stages is imperative for effective forest fire management and mitigation of the impact of forest fires on both ecological systems and human well-being. Artificial intelligence and machine learning (AI/ML) methods have garnered much attention in the cyber-physical systems domain in recent times leading to their adoption in decision-making in diverse applications including disaster management. This paper explores the current state of AI/ML applications for managing the activities in the aforementioned phases of forest fire. While conventional machine learning and deep learning methods have been extensively explored for the prevention, detection, and management of forest fires, a systematic classification of these methods into distinct AI research domains is conspicuously absent. This paper gives a comprehensive overview of the state of forest fire research across more recent and prominent AI/ML disciplines, including big data, classical machine learning, computer vision, explainable AI, generative AI, natural language processing, optimization algorithms, and time series forecasting. By providing a detailed overview of the potential areas of research and identifying the diverse ways AI/ML can be employed in forest fire research, this paper aims to serve as a roadmap for future investigations in this domain.Keywords: artificial intelligence, computer vision, deep learning, during-fire activities, forest fire management, machine learning, pre-fire activities, post-fire activities
Procedia PDF Downloads 6353 Finite Element Modeling of Global Ti-6Al-4V Mechanical Behavior in Relationship with Microstructural Parameters
Authors: Fatna Benmessaoud, Mohammed Cheikh, Vencent Velay, Vanessa Vedal, Farhad Rezai-Aria, Christine Boher
Abstract:
The global mechanical behavior of materials is strongly linked to their microstructure, especially their crystallographic texture and their grains morphology. These material aspects determine the mechanical fields character (heterogeneous or homogeneous), thus, they give to the global behavior a degree of anisotropy according the initial microstructure. For these reasons, the prediction of global behavior of materials in relationship with the microstructure must be performed with a multi-scale approach. Therefore, multi-scale modeling in the context of crystal plasticity is widely used. In this present contribution, a phenomenological elasto-viscoplastic model developed in the crystal plasticity context and finite element method are used to investigate the effects of crystallographic texture and grains sizes on global behavior of a polycrystalline equiaxed Ti-6Al-4V alloy. The constitutive equations of this model are written on local scale for each slip system within each grain while the strain and stress mechanical fields are investigated at the global scale via finite element scale transition. The beta phase of Ti-6Al-4V alloy modeled is negligible; its percent is less than 10%. Three families of slip systems of alpha phase are considered: basal and prismatic families with a burgers vector and pyramidal family with aKeywords: microstructural parameters, multi-scale modeling, crystal plasticity, Ti-6Al-4V alloy
Procedia PDF Downloads 12352 R&D Diffusion and Productivity in a Globalized World: Country Capabilities in an MRIO Framework
Authors: S. Jimenez, R.Duarte, J.Sanchez-Choliz, I. Villanua
Abstract:
There is a certain consensus in economic literature about the factors that have influenced in historical differences in growth rates observed between developed and developing countries. However, it is less clear what elements have marked different paths of growth in developed economies in recent decades. R&D has always been seen as one of the major sources of technological progress, and productivity growth, which is directly influenced by technological developments. Following recent literature, we can say that ‘innovation pushes the technological frontier forward’ as well as encourage future innovation through the creation of externalities. In other words, productivity benefits from innovation are not fully appropriated by innovators, but it also spread through the rest of the economies encouraging absorptive capacities, what have become especially important in a context of increasing fragmentation of production This paper aims to contribute to this literature in two ways, first, exploring alternative indexes of R&D flows embodied in inter-country, inter-sectorial flows of good and services (as approximation to technology spillovers) capturing structural and technological characteristic of countries and, second, analyzing the impact of direct and embodied R&D on the evolution of labor productivity at the country/sector level in recent decades. The traditional way of calculation through a multiregional input-output framework assumes that all countries have the same capabilities to absorb technology, but it is not, each one has different structural features and, this implies, different capabilities as part of literature, claim. In order to capture these differences, we propose to use a weight based on specialization structure indexes; one related with the specialization of countries in high-tech sectors and the other one based on a dispersion index. We propose these two measures because, as far as we understood, country capabilities can be captured through different ways; countries specialization in knowledge-intensive sectors, such as Chemicals or Electrical Equipment, or an intermediate technology effort across different sectors. Results suggest the increasing importance of country capabilities while increasing the trade openness. Besides, if we focus in the country rankings, we can observe that with high-tech weighted R&D embodied countries as China, Taiwan and Germany arose the top five despite not having the highest intensities of R&D expenditure, showing the importance of country capabilities. Additionally, through a fixed effects panel data model we show that, in fact, R&D embodied is important to explain labor productivity increases, in fact, even more that direct R&D investments. This is reflecting that globalization is more important than has been said until now. However, it is true that almost all analysis done in relation with that consider the effect of t-1 direct R&D intensity over economic growth. Nevertheless, from our point of view R&D evolve as a delayed flow and it is necessary some time to be able to see its effects on the economy, as some authors have already claimed. Our estimations tend to corroborate this hypothesis obtaining a gap between 4-5 years.Keywords: economic growth, embodied, input-output, technology
Procedia PDF Downloads 11751 Monitoring the Effect of Doxorubicin Liposomal in VX2 Tumor Using Magnetic Resonance Imaging
Authors: Ren-Jy Ben, Jo-Chi Jao, Chiu-Ya Liao, Ya-Ru Tsai, Lain-Chyr Hwang, Po-Chou Chen
Abstract:
Cancer is still one of the serious diseases threatening the lives of human beings. How to have an early diagnosis and effective treatment for tumors is a very important issue. The animal carcinoma model can provide a simulation tool for the study of pathogenesis, biological characteristics and therapeutic effects. Recently, drug delivery systems have been rapidly developed to effectively improve the therapeutic effects. Liposome plays an increasingly important role in clinical diagnosis and therapy for delivering a pharmaceutic or contrast agent to the targeted sites. Liposome can be absorbed and excreted by the human body, and is well known that no harm to the human body. This study aimed to compare the therapeutic effects between encapsulated (doxorubicin liposomal, LipoDox) and un-encapsulated (doxorubicin, Dox) anti-tumor drugs using Magnetic Resonance Imaging (MRI). Twenty-four New Zealand rabbits implanted with VX2 carcinoma at left thigh were classified into three groups: control group (untreated), Dox-treated group and LipoDox-treated group, 8 rabbits for each group. MRI scans were performed three days after tumor implantation. A 1.5T GE Signa HDxt whole body MRI scanner with a high resolution knee coil was used in this study. After a 3-plane localizer scan was performed, Three-Dimensional (3D) Fast Spin Echo (FSE) T2-Weighted Images (T2WI) was used for tumor volumetric quantification. And Two-Dimensional (2D) spoiled gradient recalled echo (SPGR) dynamic Contrast-enhanced (DCE) MRI was used for tumor perfusion evaluation. DCE-MRI was designed to acquire four baseline images, followed by contrast agent Gd-DOTA injection through the ear vein of rabbits. Afterwards, a series of 32 images were acquired to observe the signals change over time in the tumor and muscle. The MRI scanning was scheduled on a weekly basis for a period of four weeks to observe the tumor progression longitudinally. The Dox and LipoDox treatments were prescribed 3 times in the first week immediately after VX2 tumor implantation. ImageJ was used to quantitate tumor volume and time course signal enhancement on DCE images. The changes of tumor size showed that the growth of VX2 tumors was effectively inhibited for both LipoDox-treated and Dox-treated groups. Furthermore, the tumor volume of LipoDox-treated group was significantly lower than that of Dox-treated group, which implies that LipoDox has better therapeutic effect than Dox. The signal intensity of LipoDox-treated group is significantly lower than that of the other two groups, which implies that targeted therapeutic drug remained in the tumor tissue. This study provides a radiation-free and non-invasive MRI method for therapeutic monitoring of targeted liposome on an animal tumor model.Keywords: doxorubicin, dynamic contrast-enhanced MRI, lipodox, magnetic resonance imaging, VX2 tumor model
Procedia PDF Downloads 45450 A Complex Network Approach to Structural Inequality of Educational Deprivation
Authors: Harvey Sanchez-Restrepo, Jorge Louca
Abstract:
Equity and education are major focus of government policies around the world due to its relevance for addressing the sustainable development goals launched by Unesco. In this research, we developed a primary analysis of a data set of more than one hundred educational and non-educational factors associated with learning, coming from a census-based large-scale assessment carried on in Ecuador for 1.038.328 students, their families, teachers, and school directors, throughout 2014-2018. Each participating student was assessed by a standardized computer-based test. Learning outcomes were calibrated through item response theory with two-parameters logistic model for getting raw scores that were re-scaled and synthetized by a learning index (LI). Our objective was to develop a network for modelling educational deprivation and analyze the structure of inequality gaps, as well as their relationship with socioeconomic status, school financing, and student's ethnicity. Results from the model show that 348 270 students did not develop the minimum skills (prevalence rate=0.215) and that Afro-Ecuadorian, Montuvios and Indigenous students exhibited the highest prevalence with 0.312, 0.278 and 0.226, respectively. Regarding the socioeconomic status of students (SES), modularity class shows clearly that the system is out of equilibrium: the first decile (the poorest) exhibits a prevalence rate of 0.386 while rate for decile ten (the richest) is 0.080, showing an intense negative relationship between learning and SES given by R= –0.58 (p < 0.001). Another interesting and unexpected result is the average-weighted degree (426.9) for both private and public schools attending Afro-Ecuadorian students, groups that got the highest PageRank (0.426) and pointing out that they suffer the highest educational deprivation due to discrimination, even belonging to the richest decile. The model also found the factors which explain deprivation through the highest PageRank and the greatest degree of connectivity for the first decile, they are: financial bonus for attending school, computer access, internet access, number of children, living with at least one parent, books access, read books, phone access, time for homework, teachers arriving late, paid work, positive expectations about schooling, and mother education. These results provide very accurate and clear knowledge about the variables affecting poorest students and the inequalities that it produces, from which it might be defined needs profiles, as well as actions on the factors in which it is possible to influence. Finally, these results confirm that network analysis is fundamental for educational policy, especially linking reliable microdata with social macro-parameters because it allows us to infer how gaps in educational achievements are driven by students’ context at the time of assigning resources.Keywords: complex network, educational deprivation, evidence-based policy, large-scale assessments, policy informatics
Procedia PDF Downloads 11349 A Quality Index Optimization Method for Non-Invasive Fetal ECG Extraction
Authors: Lucia Billeci, Gennaro Tartarisco, Maurizio Varanini
Abstract:
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
Procedia PDF Downloads 27248 A Column Generation Based Algorithm for Airline Cabin Crew Rostering Problem
Authors: Nan Xu
Abstract:
In airlines, the crew scheduling problem is usually decomposed into two stages: crew pairing and crew rostering. In the crew pairing stage, pairings are generated such that each flight is covered by exactly one pairing and the overall cost is minimized. In the crew rostering stage, the pairings generated in the crew pairing stage are combined with off days, training and other breaks to create individual work schedules. The paper focuses on cabin crew rostering problem, which is challenging due to the extremely large size and the complex working rules involved. In our approach, the objective of rostering consists of two major components. The first is to minimize the number of unassigned pairings and the second is to ensure the fairness to crew members. There are two measures of fairness to crew members, the number of overnight duties and the total fly-hour over a given period. Pairings should be assigned to each crew member so that their actual overnight duties and fly hours are as close to the expected average as possible. Deviations from the expected average are penalized in the objective function. Since several small deviations are preferred than a large deviation, the penalization is quadratic. Our model of the airline crew rostering problem is based on column generation. The problem is decomposed into a master problem and subproblems. The mater problem is modeled as a set partition problem and exactly one roster for each crew is picked up such that the pairings are covered. The restricted linear master problem (RLMP) is considered. The current subproblem tries to find columns with negative reduced costs and add them to the RLMP for the next iteration. When no column with negative reduced cost can be found or a stop criteria is met, the procedure ends. The subproblem is to generate feasible crew rosters for each crew member. A separate acyclic weighted graph is constructed for each crew member and the subproblem is modeled as resource constrained shortest path problems in the graph. Labeling algorithm is used to solve it. Since the penalization is quadratic, a method to deal with non-additive shortest path problem using labeling algorithm is proposed and corresponding domination condition is defined. The major contribution of our model is: 1) We propose a method to deal with non-additive shortest path problem; 2) Operation to allow relaxing some soft rules is allowed in our algorithm, which can improve the coverage rate; 3) Multi-thread techniques are used to improve the efficiency of the algorithm when generating Line-of-Work for crew members. Here a column generation based algorithm for the airline cabin crew rostering problem is proposed. The objective is to assign a personalized roster to crew member which minimize the number of unassigned pairings and ensure the fairness to crew members. The algorithm we propose in this paper has been put into production in a major airline in China and numerical experiments show that it has a good performance.Keywords: aircrew rostering, aircrew scheduling, column generation, SPPRC
Procedia PDF Downloads 14147 Multivariate Ecoregion Analysis of Nutrient Runoff From Agricultural Land Uses in North America
Authors: Austin P. Hopkins, R. Daren Harmel, Jim A Ippolito, P. J. A. Kleinman, D. Sahoo
Abstract:
Field-scale runoff and water quality data are critical to understanding the fate and transport of nutrients applied to agricultural lands and minimizing their off-site transport because it is at that scale that agricultural management decisions are typically made based on hydrologic, soil, and land use factors. However, regional influences such as precipitation, temperature, and prevailing cropping systems and land use patterns also impact nutrient runoff. In the present study, the recently-updated MANAGE (Measured Annual Nutrient loads from Agricultural Environments) database was used to conduct an ecoregion-level analysis of nitrogen and phosphorus runoff from agricultural lands in the North America. Specifically, annual N and P runoff loads for cropland and grasslands in North American Level II EPA ecoregions were presented, and the impact of factors such as land use, tillage, and fertilizer timing and placement on N and P runoff were analyzed. Specifically we compiled annual N and P runoff load data (i.e., dissolved, particulate, and total N and P, kg/ha/yr) for each Level 2 EPA ecoregion and for various agricultural management practices (i.e., land use, tillage, fertilizer timing, fertilizer placement) within each ecoregion to showcase the analyses possible with the data in MANAGE. Potential differences in N and P runoff loads were evaluated between and within ecoregions with statistical and graphical approaches. Non-parametric analyses, mainly Mann-Whitney tests were conducted on median values weighted by the site years of data utilizing R because the data were not normally distributed, and we used Dunn tests and box and whisker plots to visually and statistically evaluate significant differences. Out of the 50 total North American Ecoregions, 11 were found that had significant data and site years to be utilized in the analysis. When examining ecoregions alone, it was observed that ER 9.2 temperate prairies had a significantly higher total N at 11.7 kg/ha/yr than ER 9.4 South Central Semi Arid Prairies with a total N of 2.4. When examining total P it was observed that ER 8.5 Mississippi Alluvial and Southeast USA Coastal Plains had a higher load at 3.0 kg/ha/yr than ER 8.2 Southeastern USA Plains with a load of 0.25 kg/ha/yr. Tillage and Land Use had severe impacts on nutrient loads. In ER 9.2 Temperate Prairies, conventional tillage had a total N load of 36.0 kg/ha/yr while conservation tillage had a total N load of 4.8 kg/ha/yr. In all relevant ecoregions, when corn was the predominant land use, total N levels significantly increased compared to grassland or other grains. In ER 8.4 Ozark-Ouachita, Corn had a total N of 22.1 kg/ha/yr while grazed grassland had a total N of 2.9 kg/ha/yr. There are further intricacies of the interactions that agricultural management practices have on one another combined with ecological conditions and their impacts on the continental aquatic nutrient loads that still need to be explored. This research provides a stepping stone to further understanding of land and resource stewardship and best management practices.Keywords: water quality, ecoregions, nitrogen, phosphorus, agriculture, best management practices, land use
Procedia PDF Downloads 7346 Photobleaching Kinetics and Epithelial Distribution of Hexylaminoleuilinate Induced PpIX in Rat Bladder Cancer
Authors: Sami El Khatib, Agnès Leroux, Jean-Louis Merlin, François Guillemin, Marie-Ange D’Hallewin
Abstract:
Photodynamic therapy (PDT) is a treatment modality based on the cytotoxic effect occurring on the target tissues by interaction of a photosensitizer with light in the presence of oxygen. One of the major advances in PDT can be attributed to the use of topical aminolevulinic (ALA) to induce Protoporphyrin IX (PpIX) for the treatment of early stage cancers as well as diagnosis. ALA is a precursor of the heme synthesis pathway. Locally delivered to the target tissue ALA overcomes the negative feedback exerted by heme and promotes the transient formation of PpIX in situ to reach critical effective levels in cells and tissue. Whereas early steps of the heme pathway occur in the cytosol, PpIX synthesis is shown to be held in the mitochondrial membranes and PpIX fluorescence is expected to accumulate in close vicinity of the initial building site and to progressively diffuse to the neighboring cytoplasmic compartment or other lipophylic organelles. PpIX is known to be highly reactive and will be degraded when irradiated with light. PpIX photobleaching is believed to be governed by a singlet oxygen mediated mechanism in the presence of oxidized amino acids and proteins. PpIX photobleaching and subsequent spectral phototransformation were described widely in tumor cells incubated in vitro with ALA solution, or ex vivo in human and porcine mucosa superfused with hexylaminolevulinate (hALA). PpIX photobleaching was also studied in vivo, using animal models such as normal or tumor mice skin and orthotopic rat bladder model. Hexyl aminolevulinate a more potent lipophilic derivative of ALA was proposed as an adjunct to standard cystoscopy in the fluorescence diagnosis of bladder cancer and other malignancies. We have previously reported the effectiveness of hALA mediated PDT of rat bladder cancer. Although normal and tumor bladder epithelium exhibit similar fluorescence intensities after intravesical instillation of two hALA concentrations (8 and 16 mM), the therapeutic response at 8mM and 20J/cm2 was completely different from the one observed at 16mM irradiated with the same light dose. Where the tumor is destroyed, leaving the underlying submucosa and muscle intact after an 8 mM instillation, 16mM sensitization and subsequent illumination results in the complete destruction of the underlying bladder wall but leaves the tumor undamaged. The object of the current study is to try to unravel the underlying mechanism for this apparent contradiction. PpIX extraction showed identical amounts of photosensitizer in tumor bearing bladders at both concentrations. Photobleaching experiments revealed mono-exponential decay curves in both situations but with a two times faster decay constant in case of 16mM bladders. Fluorescence microscopy shows an identical fluorescence pattern for normal bladders at both concentrations and tumor bladders at 8mM with bright spots. Tumor bladders at 16 mM exhibit a more diffuse cytoplasmic fluorescence distribution. The different response to PDT with regard to the initial pro-drug concentration can thus be attributed to the different cellular localization.Keywords: bladder cancer, hexyl-aminolevulinate, photobleaching, confocal fluorescence microscopy
Procedia PDF Downloads 398