Search results for: Omicron variant

Authors: Sven Tackenberg, Sönke Duckwitz, Andreas Petz, Christopher M. Schlick

Abstract:

This paper introduces an extension to the well-established Resource-Constrained Project Scheduling Problem (RCPSP) to apply it to complex maintenance problems. The problem is to assign technicians to a team which has to process several tasks with multi-level skill requirements during a work shift. Here, several alternative activities for a task allow both, the temporal shift of activities or the reallocation of technicians and tools. As a result, switches from one valid work process variant to another can be considered and may be selected by the developed evolutionary algorithm based on the present skill level of technicians or the available tools. An additional complication of the observed scheduling problem is that the locations of the construction sites are only temporarily accessible during a day. Due to intensive rail traffic, the available time slots for maintenance and repair works are extremely short and are often distributed throughout the day. To identify efficient working periods, a first concept of a Bayesian network is introduced and is integrated into the extended RCPSP with pre-emptive and non-pre-emptive tasks. Thereby, the Bayesian network is used to calculate the probability of a maintenance task to be processed during a specific period of the shift. Focusing on the domain of maintenance of the railway infrastructure in metropolitan areas as the most unproductive implementation process at construction site, the paper illustrates how the extended RCPSP can be applied for maintenance planning support. A multi-criteria evolutionary algorithm with a problem representation is introduced which is capable of revising technician-task allocations, whereas the duration of the task may be stochastic. The approach uses a novel activity list representation to ensure easily describable and modifiable elements which can be converted into detailed shift schedules. Thereby, the main objective is to develop a shift plan which maximizes the utilization of each technician due to a minimization of the waiting times caused by rail traffic. The results of the already implemented core algorithm illustrate a fast convergence towards an optimal team composition for a shift, an efficient sequence of tasks and a high probability of the subsequent implementation due to the stochastic durations of the tasks. In the paper, the algorithm for the extended RCPSP is analyzed in experimental evaluation using real-world example problems with various size, resource complexity, tightness and so forth.

Keywords: maintenance management, scheduling, resource constrained project scheduling problem, genetic algorithms

Procedia PDF Downloads 228

Authors: F. Ghani, T. S. O’Donovan

Abstract:

Today, the global solar thermal market is dominated by two collector types; the flat plate and evacuated tube collector. With regards to the number of installations worldwide, the evacuated tube collector is the dominant variant primarily due to the Chinese market but the flat plate collector dominates both the Australian and European markets. The market share of the evacuated tube collector is, however, growing in Australia due to a common belief that this collector type is ‘more efficient’ and, therefore, the better choice for hot water applications. In this study, we investigate this issue further to assess the validity of this statement. This was achieved by methodically comparing the performance and economics of several solar thermal systems comprising of; a low-performance flat plate collector, a high-performance flat collector, and an evacuated tube collector coupled with a storage tank and pump. All systems were simulated using the commercial software package Polysun for four climate zones in Australia to take into account different weather profiles in the study and subjected to a thermal load equivalent to a household comprising of four people. Our study revealed that the energy savings and payback periods varied significantly for systems operating under specific environmental conditions. Solar fractions ranged between 58 and 100 per cent, while payback periods range between 3.8 and 10.1 years. Although the evacuated tube collector was found to operate with a marginally higher thermal efficiency over the selective surface flat plate collector due to reduced ambient heat loss, the high-performance flat plate collector outperformed the evacuated tube collector on thermal yield. This result was obtained as the flat plate collector possesses a significantly higher absorber to gross collector area ratio over the evacuated tube collector. Furthermore, it was found for Australian regions operating with a high average solar radiation intensity and ambient temperature, the lower performance collector is the preferred choice due to favorable economics and reduced stagnation temperature. Our study has provided additional insight into the thermal performance and economics of the two prevalent solar thermal collectors currently available. A computational investigation has been carried out specifically for the Australian climate due to its geographic size and significant variation in weather. For domestic hot water applications were fluid temperatures between 50 and 60 degrees Celsius are sought, the flat plate collector is both technically and economically favorable over the evacuated tube collector. This research will be useful to system design engineers, solar thermal manufacturers, and those involved in policy to encourage the implementation of solar thermal systems into the hot water market.

Keywords: solar thermal, energy analysis, flat plate, evacuated tube, collector performance

Procedia PDF Downloads 207

Authors: Mohammad Ali Al Qatawneh, Bespalchuk Pavel Ivanovich

Abstract:

Computer navigation has been introduced in total knee arthroplasty to improve the accuracy of the procedure. Computer navigation improves the accuracy of bone resection in the coronal and sagittal planes. It was also noted that it normalizes the rotational alignment of the femoral component and fully assesses and balances the deformation of soft tissues in the coronal plane. The work is devoted to the advantages of using computer navigation technology in total knee arthroplasty in 62 patients (11 men and 51 women) suffering from gonarthrosis, aged 51 to 83 years, operated using a computer navigation system, followed up to 3 years from the moment of surgery. During the examination, the deformity variant was determined, and radiometric parameters of the knee joints were measured using the Knee Society Score (KSS), Functional Knee Society Score (FKSS), and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) scales. Also, functional stress tests were performed to assess the stability of the knee joint in the frontal plane and functional indicators of the range of motion. After surgery, improvement was observed in all scales; firstly, the WOMAC values decreased by 5.90 times, and the median value to 11 points (p < 0.001), secondly KSS increased by 3.91 times and reached 86 points (p < 0.001), and the third one is that FKSS data increased by 2.08 times and reached 94 points (p < 0.001). After TKA, the axis deviation of the lower limbs of more than 3 degrees was observed in 4 patients at 6.5% and frontal instability of the knee joint just in 2 cases at 3.2%., The lower incidence of sagittal instability of the knee joint after the operation was 9.6%. The range of motion increased by 1.25 times; the volume of movement averaged 125 degrees (p < 0.001). Computer navigation increases the accuracy of the spatial orientation of the endoprosthesis components in all planes, reduces the variability of the axis of the lower limbs within ± 3 °, allows you to achieve the best results of surgical interventions, and can be used to solve most basic tasks, allowing you to achieve excellent and good outcomes of operations in 100% of cases according to the WOMAC scale. With diaphyseal deformities of the femur and/or tibia, as well as with obstruction of their medullary canal, the use of computer navigation is the method of choice. The use of computer navigation prevents the occurrence of flexion contracture and hyperextension of the knee joint during the distal sawing of the femur. Using the navigation system achieves high-precision implantation for the endoprosthesis; in addition, it achieves an adequate balance of the ligaments, which contributes to the stability of the joint, reduces pain, and allows for the achievement of a good functional result of the treatment.

Keywords: knee joint, arthroplasty, computer navigation, advantages

Procedia PDF Downloads 83

Authors: Dercan Gencbas, Hatice Bebis, Sue Moorhead

Abstract:

In the nursing process, many of the nursing classification systems were created to be used in international. From these, NANDA-I, Nursing Outcomes Classification (NOC) and Nursing Interventions Classification (NIC). In this direction, the main objective of this study is to establish a model for caregivers in hospitals and communities in Turkey and to ensure that nursing outputs are assessed by NOC-based measures. There are many scales to measure Urinary Incontinence (UI), which is very common in children, in old age, vaginal birth, NOC scales are ideal for use in the nursing process for comprehensive and holistic assessment, with surveys available. For this reason, the purpose of this study is to evaluate the validity of the NOC outputs and indicators used for UI NANDA-I. This research is a methodological study. In addition to the validity of scale indicators in the study, how much they will contribute to recovery after the nursing intervention was assessed by experts. Scope validations have been applied and calculated according to Fehring 1987 work model. According to this, nursing inclusion criteria and scores were determined. For example, if experts have at least four years of clinical experience, their score was 4 points or have at least one year of the nursing classification system, their score was 1 point. The experts were a publication experience about nursing classification, their score was 1 point, or have a doctoral degree in nursing, their score was 2 points. If the expert has a master degree, their score was 1 point. Total of 55 experts rated Fehring as a “senior degree” with a score of 90 according to the expert scoring. The nursing interventions to be applied were asked to what extent these indicators would contribute to recovery. For coverage validity tailored to Fehring's model, each NOC and NOC indicator from specialists was asked to score between 1-5. Score for the significance of indicators was from 1=no precaution to 5=very important. After the expert opinion, these weighted scores obtained for each NOC and NOC indicator were classified as 0.8 critical, 0.8 > 0.5 complements, > 0.5 are excluded. In the NANDA-I / NOC / NIC system (guideline), 5 NOCs proposed for nursing diagnoses for UI were proposed. These outputs are; Urinary Continence, Urinary Elimination, Tissue Integrity, Self CareToileting, Medication Response. After the scales are translated into Turkish, the weighted average of the scores obtained from specialists for the coverage of all 5 NOCs and the contribution of nursing initiatives exceeded 0.8. After the opinions of the experts, 79 of the 82 indicators were calculated as critical, 3 of the indicators were calculated as supplemental. Because of 0.5 > was not obtained, no substance was removed. All NOC outputs were identified as valid and usable scales in Turkey. In this study, five NOC outcomes were verified for the evaluation of the output of individuals who have received nursing knowledge of UI and variant types. Nurses in Turkey can benefit from the outputs of the NOC scale to perform the care of the elderly incontinence.

Keywords: nursing outcomes, content validity, nursing diagnosis, urinary incontinence

Procedia PDF Downloads 121

Authors: M. Chukhryaeva, R. Skhalyakho, J. Kagazegeva, E. Pocheshkhova, L. Yepiskopossyan, O. Balanovsky, E. Balanovska

Abstract:

The Middle East is crossroad of different populations at different times. The Kurds are of particular interest in this region. Historical sources suggested that the origin of the Kurds is associated with Medes. Therefore, it was especially interesting to compare gene pool of Kurds with other supposed descendants of Medes-Tats. Yezidis are ethno confessional group of Kurds. Yezidism as a confessional teaching was formed in the XI-XIII centuries in Iraq. Yezidism has caused reproductively isolation of Yezidis from neighboring populations for centuries. Also, isolation helps to retain Yezidian caste system. It is unknown how the history of Yezidis affected its genу pool because it has never been the object of researching. We have examined the Y-chromosome variation in Yezidis and Kurdish males to understand their gene pool. We collected DNA samples from 90 Yezidi males and 24 Kurdish males together with their pedigrees. We performed Y-STR analysis of 17 loci in the samples collected (Yfiler system from Applied Biosystems) and analysis of 42 Y-SNPs by real-time PCR. We compared our data with published data from other Kurdish groups and from European, Caucasian, and West Asian populations. We found that gene pool of Yezidis contains haplogroups common in the Middle East (J-M172(xM67,M12)- 24%, E-M35(xM78)- 9%) and in South Western Asia (R-M124- 8%) and variant with wide distribution area - R-M198(xM458- 9%). The gene pool of Kurdish has higher genetic diversity than Yezidis. Their dominants haplogroups are R-M198- 20,3 %, E-M35- 9%, J-M172- 9%. Multidimensional scaling also shows that the Kurds and Yezidis are part of the same frontier Asian cluster, which, in addition, included Armenians, Iranians, Turks, and Greeks. At the same time, the peoples of the Caucasus and Europe form isolated clusters that do not overlap with the Asian clusters. It is noteworthy that Kurds from our study gravitate towards Tats, which indicates that most likely these two populations are descendants of ancient Medes population. Multidimensional scaling also reveals similarity between gene pool of Yezidis, Kurds with Armenians and Iranians. The analysis of Yezidis pedigrees and their STR variability did not reveal a reliable connection between genetic diversity and caste system. This indicates that the Yezidis caste system is a social division and not a biological one. Thus, we showed that, despite many years of isolation, the gene pool of Yezidis retained a common layer with the gene pool of Kurds, these populations have common spectrum of haplogroups, but Yezidis have lower genetic diversity than Kurds. This study received primary support from the RSF grant No. 16-36-00122 to MC and grant No. 16-06-00364 to EP.

Keywords: gene pool, haplogroup, Kurds, SNP and STR markers, Yezidis

Procedia PDF Downloads 203

Authors: Osman Adiguzel

Abstract:

Shape memory effect is a peculiar property exhibited by certain alloy systems and based on martensitic transformation, and shape memory properties are closely related to the microstructures of the material. Shape memory effect is linked with martensitic transformation, which is a solid state phase transformation and occurs with the cooperative movement of atoms by means of lattice invariant shears on cooling from high-temperature parent phase. Lattice twinning and detwinning can be considered as elementary processes activated during the transformation. Thermally induced martensite occurs as martensite variants, in self-accommodating manner and consists of lattice twins. Also, this martensite is called the twinned martensite or multivariant martensite. Deformation of shape memory alloys in martensitic state proceeds through a martensite variant reorientation. The martensite variants turn into the reoriented single variants with deformation, and the reorientation process has great importance for the shape memory behavior. Copper based alloys exhibit this property in metastable β- phase region, which has DO3 –type ordered lattice in ternary case at high temperature, and these structures martensiticaly turn into the layered complex structures with lattice twinning mechanism, on cooling from high temperature parent phase region. The twinning occurs as martensite variants with lattice invariant shears in two opposite directions, <110 > -type directions on the {110}- type plane of austenite matrix. Lattice invariant shear is not uniform in copper based ternary alloys and gives rise to the formation of unusual layered structures, like 3R, 9R, or 18R depending on the stacking sequences on the close-packed planes of the ordered lattice. The unit cell and periodicity are completed through 18 atomic layers in case of 18R-structure. On the other hand, the deformed material recovers the original shape on heating above the austenite finish temperature. Meanwhile, the material returns to the twinned martensite structures (thermally induced martensite structure) in one way (irreversible) shape memory effect on cooling below the martensite finish temperature, whereas the material returns to the detwinned martensite structure (deformed martensite) in two-way (reversible) shape memory effect. Shortly one can say that the microstructural mechanisms, responsible for the shape memory effect are the twinning and detwinning processes as well as martensitic transformation. In the present contribution, x-ray diffraction, transmission electron microscopy (TEM) and differential scanning calorimetry (DSC) studies were carried out on two copper-based ternary alloys, CuZnAl, and CuAlMn.

Keywords: shape memory effect, martensitic transformation, twinning and detwinning, layered structures

Procedia PDF Downloads 426

Authors: J. Van Engeland, C. Lavigne, S. De Jaeger

Abstract:

In the light of the transition towards a more circular economy, recovery of products, parts or materials will gain in importance. Additionally, the EU proximity principle related to waste management and emissions generated by transporting large amounts of end-of-life products, shift attention to local recovery networks. The Flemish inter-communal cooperation for municipal solid waste management Meetjesland (IVM) is currently investigating the set-up of such a network. More specifically, the network encompasses the recycling of polyvinyl chloride (PVC), which is collected in separate containers. When these containers are full, a truck should transport them to the processor which can recycle the PVC into new products. This paper proposes a model to optimize the container collection. The containers are located at different Civic Amenity sites (CA sites) in a certain region. Since people can drop off their waste at these CA sites, the containers will gradually fill up during a planning horizon. If a certain container is full, it has to be collected and replaced by an empty container. The collected waste is then transported to a single processor. To perform this collection and transportation of containers, the responsible firm has a set of vehicles stationed at a single depot and different personnel crews. A vehicle can load exactly one container. If a trailer is attached to the vehicle, it can load an additional container. Each day of the planning horizon, the different crews and vehicles leave the depot to collect containers at the different sites. After loading one or two containers, the crew has to drive to the processor for unloading the waste and to pick up empty containers. Afterwards, the crew can again visit sites or it can return to the depot to end its collection work for that day. All along the collection process, the crew has to respect the opening hours of the sites. In order to allow for some flexibility, a crew is allowed to wait a certain amount of time at the gate of a site until it opens. The problem described can be modelled as a variant to the PVRP-TW (Periodic Vehicle Routing Problem with Time Windows). However, a vehicle can at maximum load two containers, hence only two subsequent site visits are possible. For that reason, we will refer to the model as a model for building tactical waste collection schemes. The goal is to a find a schedule describing which crew should visit which CA site on which day to minimize the number of trucks and the routing costs. The model was coded in IBM CPLEX Optimization studio and applied to a number of test instances. Good results were obtained, and specific suggestions concerning route and truck costs could be made. For a large range of input parameters, collection schemes using two trucks are obtained.

Keywords: container collection, crew scheduling, mixed integer linear programming, waste management

Procedia PDF Downloads 127

Authors: Adekeye Joshua Temitope

Abstract:

“Transgender” presents a complexion of ambiguity in the African context and it remains a contested topography in the discourse of sexual identity. The casts and stigmatisations towards transgender unveils vital facts and intricacies often ignored in the academic communities; the problems and oppressions of given sex/gender system, the constrain of monogamy and ignorance of fluidity of human sexuality thereby generating dual discords of “enforced heterosexual” and “unavoidable homosexual.” The African culture voids transgender movements and perceive same-sex sexual behavior as “taboo or bad habits” and this provide reasonable explanations for the failure of asserting for the sexual rights in GLBT movement in most discourse on sexuality in the African context. However, we could not deny the real existence of active flowing and fluidity of human sexuality even though its variants could be latent. The incessant consciousness of the existence of transgender practices in Africa either in form of bisexual desire or bisexual behavior with or without sexual identity, including people who identify themselves as bisexual opens up the vision for us to reconsider and reexamine what constitutes such ambiguity and controversy of transgender identity at present time. The notion of identity politics in gay, lesbian, and transgender community has its complexity and debates in its historical development. This paper analyses the representation of the historical trajectory of transgender practices by presenting the dynamic transition of how people cognize transgender practices under different historical conditions since the understanding of historical transition of bisexual practices would be very crucial and meaningful for gender/sexuality liberation movement at present time and in the future. The paper did a juxtaposition of the trajectories of bisexual practices between Anglo-American world and Africa, as it has certain similarities and differences within diverse historical complexities. The similar condition is the emergence of gay identity under the influence of capitalism but within different cultural context. Therefore, the political economy of each cultural context plays very important role in understanding the formation of sexual identities historically and its development and influence for the GLBT movement afterwards and in the future. By reexamining Kinsey’s categorization and applying Klein’s argument on individual’s sexual orientation this paper is poised to break the given and fixed connection among sexual behavior/sexual orientation/sexual identity, on the other hand to present the potential fluidity of human sexuality by reconsidering and reexamining the present given sex/gender system in our world. The paper concludes that it is obligatory for the essentialist and exclusionary trend at this historical moment since gay and lesbian communities in Africa need to clearly demonstrate and voice for themselves under the nuances of gender/sexuality liberation.

Keywords: heterosexual, homosexual, identity politics, queer politics, transgender

Procedia PDF Downloads 304

Authors: Peter Burggräf, Matthias Dannapfel, Hanno Voet, Patrick-Benjamin Bök, Jérôme Uelpenich, Julian Hoppe

Abstract:

The increasing digitalization of value chains can help companies to handle rising complexity in their processes and thereby reduce the steadily increasing planning and control effort in order to raise performance limits. Due to technological advances, companies face the challenge of smart value chains for the purpose of improvements in productivity, handling the increasing time and cost pressure and the need of individualized production. Therefore, companies need to ensure quick and flexible decisions to create self-optimizing processes and, consequently, to make their production more efficient. Lean production, as the most commonly used paradigm for complexity reduction, reaches its limits when it comes to variant flexible production and constantly changing market and environmental conditions. To lift performance limits, which are inbuilt in current value chains, new methods and tools must be applied. Digitalization provides the potential to derive these new methods and tools. However, companies lack the experience to harmonize different digital technologies. There is no practicable framework, which instructs the transformation of current value chains into digital pervasive value chains. Current research shows that a connection between lean production and digitalization exists. This link is based on factors such as people, technology and organization. In this paper, the introduced method for the determination of digitally pervasive value chains takes the factors people, technology and organization into account and extends existing approaches by a new dimension. It is the first systematic approach for the digital transformation of lean production and consists of four steps: The first step of ‘target definition’ describes the target situation and defines the depth of the analysis with regards to the inspection area and the level of detail. The second step of ‘analysis of the value chain’ verifies the lean-ability of processes and lies in a special focus on the integration capacity of digital technologies in order to raise the limits of lean production. Furthermore, the ‘digital evaluation process’ ensures the usefulness of digital adaptions regarding their practicability and their integrability into the existing production system. Finally, the method defines actions to be performed based on the evaluation process and in accordance with the target situation. As a result, the validation and optimization of the proposed method in a German company from the electronics industry shows that the digital transformation of current value chains based on lean production achieves a raise of their inbuilt performance limits.

Keywords: digitalization, digital transformation, Industrie 4.0, lean production, value chain

Procedia PDF Downloads 308

Authors: Satria B. Mahathma, Asri Hendrawati

Abstract:

Background: Diabetes mellitus (DM) is a metabolic disorder syndrome characterized by chronic hyperglycemia. The number of people with diabetes rose from 108 million in 1980 to 422 million in 2014. In general, almost 90% of the prevalence of DM is type 2 DM which marked by insulin resistance and decreased receptor sensitivity. Aside from conventional antidiabetic therapy, the utilization of medicinal plants as alternative medicine has beneficial effects in diabetic patients. Flavonoid contents in radish leaves such as quercetin, pelargonidin, and kaempferol are thought to have antidiabetic activity on decreasing blood glucose levels by tricyclic nucleotide modulation of pancreatic beta cells and ameliorating insulin resistance. This study aimed to determine the effect of variant concentration of radish leaves ethanol extract on blood glucose levels in diabetic rats. Method: This study used pretest-posttest control group design by using 16 male Wistar rats which were induced type-2 diabetic by streptozotocin 60 mg/kg BW-nicotinamide 120 mg/kg BW intraperitoneally. Rats who had developed type-2 DM later divided randomly into 4 groups; negative control received placebo, positive control received glibenclamide 5 mg/kg BW/day, rats intervention I and intervention II received 100% and 50% of radish leaves ethanol extract, respectively. Treatments were administered orally for four weeks. The blood glucose levels were measured using the Enzymatic Colorimetric Test “GOD-PAP”. Data were analyzed by the dependent t-test for pretest-posttest intervention difference and one-way ANOVA followed by post hoc test to determine the significant difference of each treatment to obtain the significant data. Result: The result revealed that intervention group had lower blood glucose levels mean than control group which the lowest was intervention II group (negative control: 540,9 ± 191,7 mg/dl, positive control: 494, 97 ± 64,91 mg/dl, intervention I: 301,92 ± 165,70 mg/dl, and intervention II group: 276,1 ± 139,02 mg/dl. Intervention II group had the highest antidiabetic activity, followed by the intervention I group with the amount of decrease in blood glucose levels were -151,85 ± 77,43 mg/dl and -11,08 ± 186,62 mg/dl, however negative and positive control group didn’t have antidiabetic activity. The dependent t-test result showed there is a significant difference in decreasing blood glucose levels in the intervention II pretest-posttest intervention (p=0,03) while the other group didn’t. Data analyzed by one-way ANOVA also revealed the intervention II group significantly declined blood glucose levels compared to the negative and positive control group (p = 0,033 and p=0,032, respectively). Conclusion: There is a significant effect of radish leaves ethanol extract on blood glucose levels in streptozotocin-nicotinamide-induced diabetic rats with the optimal therapeutic effect at a concentration of 50%.

Keywords: blood glucose levels, medicinal plant, radish leaves, type-2 diabetes mellitus

Procedia PDF Downloads 131

Authors: Ponghyung Lee

Abstract:

This study seeks to investigate the variations occurring to Korean consonantal variations center around laryngeal features of the concerned sounds, to the exclusion of others. Our fundamental premise is that the weak contrast associated with concerned segments might be held accountable for the oscillation of the status quo of the concerned consonants. What is more, we assume that an array of notions as a measure of communicative efficiency of linguistic units would be significantly influential on triggering those variations. To this end, we have tried to compute the surprisal, entropic contribution, and relative contrastiveness associated with Korean obstruent consonants. What we found therein is that the Information-theoretic perspective is compelling enough to lend support our approach to a considerable extent. That is, the variant realizations, chronologically and stylistically, prove to be profoundly affected by a set of Information-theoretic factors enumerated above. When it comes to the biblical proper names, we use Georgetown University CQP Web-Bible corpora. From the 8 texts (4 from Old Testament and 4 from New Testament) among the total 64 texts, we extracted 199 samples. We address the issue of laryngeal feature variations associated with Korean obstruent consonants under the presumption that the variations stem from the weak contrast among the triad manifestations of laryngeal features. The variants emerge from diverse sources in chronological and stylistic senses: Christianity biblical texts, ordinary casual speech, the shift of loanword adaptation over time, and ideophones. For the purpose of discussing what they are really like from the perspective of Information Theory, it is necessary to closely look at the data. Among them, the massive changes occurring to loanword adaptation of proper nouns during the centennial history of Korean Christianity draw our special attention. We searched 199 types of initially capitalized words among 45,528-word tokens, which account for around 5% of total 901,701-word tokens (12,786-word types) from Georgetown University CQP Web-Bible corpora. We focus on the shift of the laryngeal features incorporated into word-initial consonants, which are available through the two distinct versions of Korean Bible: one came out in the 1960s for the Protestants, and the other was published in the 1990s for the Catholic Church. Of these proper names, we have closely traced the adaptation of plain obstruents, e. g. /b, d, g, s, ʤ/ in the sources. The results show that as much as 41% of the extracted proper names show variations; 37% in terms of aspiration, and 4% in terms of tensing. This study set out in an effort to shed light on the question: to what extent can we attribute the variations occurring to the laryngeal features associated with Korean obstruent consonants to the communicative aspects of linguistic activities? In this vein, the concerted effects of the triad, of surprisal, entropic contribution, and relative contrastiveness can be credited with the ups and downs in the feature specification, despite being contentiousness on the role of surprisal to some extent.

Keywords: entropic contribution, laryngeal feature variation, relative contrastiveness, surprisal

Procedia PDF Downloads 123

Authors: Spira A., Marabelle A., Kientop D., Moser E., Mumm J.

Abstract:

Background: Both interleukin-2 (IL-2) and interleukin-10 (IL-10) have been extensively studied for their stimulatory function on T cells and their potential to obtain sustainable tumor control in RCC, melanoma, lung, and pancreatic cancer as monotherapy, as well as combination with PD-1 blockers, radiation, and chemotherapy. While approved, IL-2 retains significant toxicity, preventing its widespread use. The significant efforts undertaken to uncouple IL-2 toxicity from its anti-tumor function have been unsuccessful, and early phase clinical safety observed with PEGylated IL-10 was not met in a blinded Phase 3 trial. Deka Biosciences has engineered a novel molecule coupling wild-type IL-2 to a high affinity variant of Epstein Barr Viral (EBV) IL-10 via a scaffold (scFv) that binds to epidermal growth factor receptors (EGFR). This patented molecule, termed DK210 (EGFR), is retained at high levels within the tumor microenvironment for days after dosing. In addition to overlapping and non-redundant anti-tumor function, IL-10 reduces IL-2 mediated cytokine release syndrome risks and inhibits IL-2 mediated T regulatory cell proliferation. Methods: DK210 (EGFR) is being evaluated in an open-label, dose-escalation (Phase 1) study with 5 (0.025-0.3 mg/kg) monotherapy dose levels and (expansion cohorts) in combination with PD-1 blockers, or radiation or chemotherapy in patients with advanced solid tumors overexpressing EGFR. Key eligibility criteria include 1) confirmed progressive disease on at least one line of systemic treatment, 2) EGFR overexpression or amplification documented in histology reports, 3) at least a 4 week or 5 half-lives window since last treatment, and 4) excluding subjects with long QT syndrome, multiple myeloma, multiple sclerosis, myasthenia gravis or uncontrolled infectious, psychiatric, neurologic, or cancer disease. Plasma and tissue samples will be investigated for pharmacodynamic and predictive biomarkers and genetic signatures associated with IFN-gamma secretion, aiming to select subjects for treatment in Phase 2. Conclusion: Through successful coupling of wild-type IL-2 with a high affinity IL-10 and targeting directly to the tumor microenvironment, DK210 (EGFR) has the potential to harness IL-2 and IL-10’s known anti-cancer promise while reducing immunogenicity and toxicity risks enabling safe concomitant cytokine treatment with other anti-cancer modalities.

Keywords: cytokine, EGFR over expression, interleukine-2, interleukine-10, clinical trial

Procedia PDF Downloads 84

Authors: Thao Nguyen, Maximiliano Hyon, Sany Rajagukguk, Anna Melkonyan

Abstract:

Introduction: Type 2 Diabetes is a well-established risk factor for severe SARS-CoV-2 infection. Uncontrolled hyperglycemia in patients with established or newly diagnosed diabetes is associated with poor outcomes, including increased mortality and hospital length of stay. Objectives: Our study aims to compare three different glycemic management strategies and their association with clinical outcomes in patients hospitalized for moderate to severe SARS-CoV-2 infection. Identifying optimal glycemic management strategies will improve the quality of patient care and improve their outcomes. Method: This is a retrospective observational study on patients hospitalized at Adventist Health White Memorial with severe SARS-CoV-2 infection from 11/1/2020 to 02/28/2021. The following inclusion criteria were used: positive SARS-CoV-2 PCR test, age >18 yrs old, diabetes or random glucose >200 mg/dL on admission, oxygen requirement >4L/min, and treatment with glucocorticoids. Our exclusion criteria included: ICU admission within 24 hours, discharge within five days, death within five days, and pregnancy. The patients were divided into three glycemic management groups: Group 1, managed solely by the Primary Team, Group 2, by Pharmacy; and Group 3, by Endocrinologist. Primary outcomes were average glucose on Day 5, change in glucose between Days 3 and 5, and average insulin dose on Day 5 among groups. Secondary outcomes would be upgraded to ICU, inpatient mortality, and hospital length of stay. For statistics, we used IBM® SPSS, version 28, 2022. Results: Most studied patients were Hispanic, older than 60, and obese (BMI >30). It was the first CV-19 surge with the Delta variant in an unvaccinated population. Mortality was markedly high (> 40%) with longer LOS (> 13 days) and a high ICU transfer rate (18%). Most patients had markedly elevated inflammatory markers (CRP, Ferritin, and D-Dimer). These, in combination with glucocorticoids, resulted in severe hyperglycemia that was difficult to control. Average glucose on Day 5 was not significantly different between groups primary vs. pharmacy vs. endocrine (220.5 ± 63.4 vs. 240.9 ± 71.1 vs. 208.6 ± 61.7 ; P = 0.105). Change in glucose from days 3 to 5 was not significantly different between groups but trended towards favoring the endocrinologist group (-26.6±73.6 vs. 3.8±69.5 vs. -32.2±84.1; P= 0.052). TDD insulin was not significantly different between groups but trended towards higher TDD for the endocrinologist group (34.6 ± 26.1 vs. 35.2 ± 26.4 vs. 50.5 ± 50.9; P=0.054). The endocrinologist group used significantly more preprandial insulin compared to other groups (91.7% vs. 39.1% vs. 65.9% ; P < 0.001). The pharmacy used more basal insulin than other groups (95.1% vs. 79.5% vs. 79.2; P = 0.047). There were no differences among groups in the clinical outcomes: LOS, ICU upgrade, or mortality. Multivariate regression analysis controlled for age, sex, BMI, HbA1c level, renal function, liver function, CRP, d-dimer, and ferritin showed no difference in outcomes among groups. Conclusion: Given high-risk factors in our population, despite efforts from the glycemic management teams, it’s unsurprising no differences in clinical outcomes in mortality and length of stay.

Keywords: glycemic management, strategies, hospitalized, SARS-CoV-2, outcomes

Procedia PDF Downloads 444

Authors: Mohammed AL-Hasani

Abstract:

The Pandemic COVID-19 altered the daily habits and affected the functional performance of the cities after this crisis leaving remarkable impacts on many metropolises worldwide. It is so obvious that having more densification in the city leads to more threats altering this main approach that was called for achieving sustainable development. The main goal to achieve resiliency in the cities, especially in forcing risks, is to deal with a planning system that is able to resist, absorb, accommodate and recover from the impacts that had been affected. Many Cities in London, Wuhan, New York, and others worldwide carried different planning approaches and varied in reaction to safeguard the impacts of the pandemic. The cities globally varied from the radiant pattern predicted by Le Corbusier, or having multi urban centers more like the approach of Frank Lloyd Wright’s Broadacre City, or having linear growth or gridiron expansion that was common by Doxiadis, compact pattern, and many other hygiene patterns. These urban patterns shape the spatial distribution and Identify both open and natural spaces with gentrified and gentrifying areas. This crisis paid attention to reassess many planning approaches and examine the existing urban patterns focusing more on the aim of continuity and resiliency in managing the crises within the rapid transformation and the power of market forces. According to that, this paper hypothesized that those urban planning patterns determine the method of reaction in assuring quarantine for the inhabitance and the performance of public services and need to be updated through carrying out an innovative urban management system and adopt further resilience patterns in prospective urban planning approaches. This paper investigates the adaptivity and resiliency of variant urban planning patterns regarding selected cities worldwide that affected by COVID-19 and their role in applying certain management strategies in controlling the pandemic spread, finding out the main potentials that should be included in prospective planning approaches. The examination encompasses the spatial arrangement, blocks definition, plots arrangement, and urban space typologies. This paper aims to investigate the urban patterns to deliberate also the debate between densification as one of the more sustainable planning approaches and disaggregation tendency that was followed after the pandemic by restructuring and managing its application according to the assessment of the spatial distribution and urban patterns. The biggest long-term threat to dense cities proves the need to shift to online working and telecommuting, creating a mixture between using cyber and urban spaces to remobilize the city. Reassessing spatial design and growth, open spaces, urban population density, and public awareness are the main solutions that should be carried out to face the outbreak in our current cities that should be managed from global to tertiary levels and could develop criteria for designing the prospective cities

Keywords: COVID-19, densification, resiliency, urban patterns

Procedia PDF Downloads 126

Authors: Pavlina Capkova, Josef Srovnal, Vera Becvarova, Marie Trkova, Zuzana Capkova, Andrea Stefekova, Vaclava Curtisova, Alena Santava, Sarka Vejvalkova, Katerina Adamova, Radek Vodicka

Abstract:

ASDs are heterogeneous and complex developmental diseases with a significant genetic background. Recurrent CNVs are known to be a frequent cause of ASD. These CNVs can have, however, a variable expressivity which results in a spectrum of phenotypes from asymptomatic to ID/DD/ASD. ASD is associated with ID in ~75% individuals. Various platforms are used to detect pathogenic mutations in the genome of these patients. The performed study is focused on a determination of the frequency of pathogenic mutations in a group of ASD patients and a group of ID/DD patients using various strategies along with a comparison of their detection rate. The possible role of the origin of these mutations in aetiology of ASD was assessed. The study included 35 individuals with ASD and 68 individuals with ID/DD (64 males and 39 females in total), who underwent rigorous genetic, neurological and psychological examinations. Screening for pathogenic mutations involved karyotyping, screening for FMR1 mutations and for metabolic disorders, a targeted MLPA test with probe mixes Telomeres 3 and 5, Microdeletion 1 and 2, Autism 1, MRX and a chromosomal microarray analysis (CMA) (Illumina or Affymetrix). Chromosomal aberrations were revealed in 7 (1 in the ASD group) individuals by karyotyping. FMR1 mutations were discovered in 3 (1 in the ASD group) individuals. The detection rate of pathogenic mutations in ASD patients with a normal karyotype was 15.15% by MLPA and CMA. The frequencies of the pathogenic mutations were 25.0% by MLPA and 35.0% by CMA in ID/DD patients with a normal karyotype. CNVs inherited from asymptomatic parents were more abundant than de novo changes in ASD patients (11.43% vs. 5.71%) in contrast to the ID/DD group where de novo mutations prevailed over inherited ones (26.47% vs. 16.18%). ASD patients shared more frequently their mutations with their fathers than patients from ID/DD group (8.57% vs. 1.47%). Maternally inherited mutations predominated in the ID/DD group in comparison with the ASD group (14.7% vs. 2.86 %). CNVs of an unknown significance were found in 10 patients by CMA and in 3 patients by MLPA. Although the detection rate is the highest when using CMA, recurrent CNVs can be easily detected by MLPA. CMA proved to be more efficient in the ID/DD group where a larger spectrum of rare pathogenic CNVs was revealed. This study determined that maternally inherited highly penetrant mutations and de novo mutations more often resulted in ID/DD without ASD in patients. The paternally inherited mutations could be, however, a source of the greater variability in the genome of the ASD patients and contribute to the polygenic character of the inheritance of ASD. As the number of the subjects in the group is limited, a larger cohort is needed to confirm this conclusion. Inherited CNVs have a role in aetiology of ASD possibly in combination with additional genetic factors - the mutations elsewhere in the genome. The identification of these interactions constitutes a challenge for the future. Supported by MH CZ – DRO (FNOl, 00098892), IGA UP LF_2016_010, TACR TE02000058 and NPU LO1304.

Keywords: autistic spectrum disorders, copy number variant, chromosomal microarray, intellectual disability, karyotyping, MLPA, multiplex ligation-dependent probe amplification

Procedia PDF Downloads 346

Authors: Christina Y. P. Ting

Abstract:

Migration is a global phenomenon with movements of migrants from developed and developing countries to the host societies. Migrants have changed the host countries’ demography – its population structure and also its ethnic cultural diversity. Acculturation of migrants in terms of their adoption of the host culture is seen as important to ensure that they ‘fit into’ their adopted country so as to participate in everyday public life. However, this research found that the increase of the China-born migrants’ post-migration consumption level had impact on Australia’s environment reflected not only because of their adoption of elements of the host culture, but also retention of aspects of Chinese culture – indicating that the influence of bi-culturalism was in operation. This research, which was based on the face-to-face interview with 61 China-born migrants in the suburb of Box Hill, Melbourne, investigated the pattern of change in the migrants’ consumption upon their settlement in Australia. Using an ecological footprint calculator, their post-migration footprints were found to be larger than pre-migration footprint. The uniquely-derived CALD (Culturally and Linguistically Diverse) Index was used to measure individuals’ strength of connectedness to ethnic culture. Multi-variant analysis was carried out to understand which independent factors that influence consumption best explain the change in footprint (which is the difference between pre-and post-migration footprints, as a dependent factor). These independent factors ranged from socio-economic and demographics to the cultural context, that is, the CALD Index and indicators of acculturation. The major findings from the analysis were: Chinese culture (as measured by the CALD Index) and indicators of acculturation such as length of residency and using English in communications besides the traditional factors such as age, income and education level made significant contributions to the large increase in the China-born group’s post-migration consumption level. This paper as part of a larger study found that younger migrants’ large change in their footprint were related to high income and low level of education. This group of migrants also practiced bi-cultural consumption in retaining ethnic culture and adopting the host culture. These findings have importantly highlighted that for a host society to tackle environmental crisis, governments need not only to understand the relationship between age and consumption behaviour, but also to understand and embrace the migrants’ ethnic cultures, which may act as bridges and/or fences in relationships. In conclusion, for governments to deal with national issues such as environmental crisis within a cultural diverse population, it necessitates an understanding of age and aspects of ethnic culture that may act as bridges and fences. This understanding can aid in putting in place policies that enable the co-existence of a hybrid of the ethnic and host cultures in order to create and maintain a harmonious and secured living environment for population groups.

Keywords: bicultural consumer, CALD index, consumption, ethnic culture, migrants

Procedia PDF Downloads 240

Authors: Hamed Movahedi, Nicolas Bovet, Henning Friis Poulsen

Abstract:

Following the advent of the Industrial Revolution, there has been a significant increase in the extraction and utilization of hydrocarbon and fossil fuel resources. However, a new era has emerged, characterized by a shift towards sustainable practices, namely the reduction of carbon emissions and the promotion of renewable energy generation. Given the substantial number of mature oil and gas wells that have been developed inside the petroleum reservoir domain, it is imperative to establish an environmental strategy and adopt appropriate measures to effectively seal and decommission these wells. In general, the cement plug serves as a material for plugging purposes. Nevertheless, there exist some scenarios in which the durability of such a plug is compromised, leading to the potential escape of hydrocarbons via fissures and fractures within cement plugs. Furthermore, cement is often not considered a practical solution for temporary plugging, particularly in the case of well sites that have the potential for future gas storage or CO2 injection. The Danish oil and gas industry has promising potential as a prospective candidate for future carbon dioxide (CO2) injection, hence contributing to the implementation of carbon capture strategies within Europe. The primary reservoir component consists of chalk, a rock characterized by limited permeability. This work focuses on the development and characterization of a novel hydrogel variant. The hydrogel is designed to be injected via a low-permeability reservoir and afterward undergoes a transformation into a high-viscosity gel. The primary objective of this research is to explore the potential of this hydrogel as a new solution for effectively plugging well flow. Initially, the synthesis of polyacrylamide was carried out using radical polymerization inside the confines of the reaction flask. Subsequently, with the application of the Hoffman rearrangement, the polymer chain undergoes partial amination, facilitating its subsequent reaction with the crosslinker and enabling the formation of a hydrogel in the subsequent stage. The organic crosslinker, glutaraldehyde, was employed in the experiment to facilitate the formation of a gel. This gel formation occurred when the polymeric solution was subjected to heat within a specified range of reservoir temperatures. Additionally, a rheological survey and gel time measurements were conducted on several polymeric solutions to determine the optimal concentration. The findings indicate that the gel duration is contingent upon the starting concentration and exhibits a range of 4 to 20 hours, hence allowing for manipulation to accommodate diverse injection strategies. Moreover, the findings indicate that the gel may be generated in environments characterized by acidity and high salinity. This property ensures the suitability of this substance for application in challenging reservoir conditions. The rheological investigation indicates that the polymeric solution exhibits the characteristics of a Herschel-Bulkley fluid with somewhat elevated yield stress prior to solidification.

Keywords: polyacrylamide, hofmann rearrangement, rheology, gel time

Procedia PDF Downloads 73

Authors: Olasunkanmi Olapeju

Abstract:

A large chunk of global population are not yet connected to water borne faecal management systems that rely on flush mechanisms and sewers networks that are linked with a central treatment plant. Only about 10% of sub-Saharan African countries are connected to central sewage systems. In Nigeria, majority of the population do not only depend on on-plot sanitation systems, a huge chunk do not also have access to safe and improved toilets. Apart from the organizational challenges and technical capacity, the other major factors that account for why faecal waste management is yet unimproved in developing countries are faulty planning frameworks that fail to maintain balance between urbanization dynamics and infrastructures, and misconceptions about what modern sanitation is all about. In most cases, the quest to implement developmental patterns that integrate modern sewers based sanitation systems have huge financial and political costs. Faecal waste management in poor countries largely lacks the needed political attention and budgetary prioritization. Yet, the on-plot sanitation systems being mainly relied upon the need to be managed in a manner that is sustainable and healthy, pending when development would embrace a more sustainable off-site central sewage system. This study is aimed at investigating existing strategies for managing on-plot sanitation systems’ faecal waste in Ogun state, Nigeria, with the aim of recommending sustainable sanitation management systems. The study adopted the convergent parallel variant of the mixed-mode technique, which involves the adoption of both quantitative and qualitative method of data collection. Adopting a four-level multi-stage approach, which is inclusive of all political divisions in the study area, a total of 330 questionnaires were respectively administered in the study area. Moreover, the qualitative data adopted the purposive approach in scoping down to 33 key informants. SPSS software (Version 22.0) was employed for descriptively analysis. The study shows that about 52% of households adopt the non-recovery management (NRM) means of burying their latrines with sand sludge shrinkage with chemicals such as carbides. The dominance of the non-recovery management means seriously constrains the quest for faecal resource recovery. Essentially, the management techniques adopted by households depend largely on the technology of their sanitary containments, emptying means available, the ability of households to pay for the cost of emptying, and the social acceptability of the reusability of faecal waste, which determines faecal resource recoverability. The study suggests that there is a need for municipal authorities in the study area to urgently intervene in the sanitation sector and consider it a key element of the planning process. There is a need for a comprehensive plan that would ensure a seamless transition to the adoption of a modern sanitation management system.

Keywords: faecal, management, planning, waste, sanitation, sustainability

Procedia PDF Downloads 100

Authors: Zubair Ahmed, Andrea Barbieri

Abstract:

The need to reduce energy consumption has prompted a considerable research effort for developing alternative energy-efficient lighting systems to replace conventional light sources (i.e., incandescent and fluorescent lamps). Organic light emitting device (OLED) technology offers the distinctive possibility to fabricate large area flat devices by vacuum or solution processing. Lanthanide β-diketonates complexes, due to unique photophysical properties of Ln(III) ions, have been explored as emitting layers in OLED displays and in solid-state lighting (SSL) in order to achieve high efficiency and color purity. For such applications, the excellent photoluminescence quantum yield (PLQY) and stability are the two key points that can be achieved simply by selecting the proper organic ligands around the Ln ion in a coordination sphere. Regarding the strategies to enhance the PLQY, the most common is the suppression of the radiationless deactivation pathways due to the presence of high-frequency oscillators (e.g., OH, –CH groups) around the Ln centre. Recently, a different approach to maximize the PLQY of Ln(β-DKs) has been proposed (named 'Escalate Coordination Anisotropy', ECA). It is based on the assumption that coordinating the Ln ion with different ligands will break the centrosymmetry of the molecule leading to less forbidden transitions (loosening the constraints of the Laporte rule). The OLEDs based on such complexes are available, but with low efficiency and stability. In order to get efficient devices, there is a need to develop some new Ln complexes with enhanced PLQYs and stabilities. For this purpose, the Ln complexes, both visible and (NIR) emitting, of variant coordination structures based on the various fluorinated/non-fluorinated β-diketones and O/N-donor neutral ligands were synthesized using a one step in situ method. In this method, the β-diketones, base, LnCl₃.nH₂O and neutral ligands were mixed in a 3:3:1:1 M ratio in ethanol that gave air and moisture stable complexes. Further, they were characterized by means of elemental analysis, NMR spectroscopy and single crystal X-ray diffraction. Thereafter, their photophysical properties were studied to select the best complexes for the fabrication of stable and efficient OLEDs. Finally, the OLEDs were fabricated and investigated using these complexes as emitting layers along with other organic layers like NPB,N,N′-Di(1-naphthyl)-N,N′-diphenyl-(1,1′-biphenyl)-4,4′-diamine (hole-transporting layer), BCP, 2,9-Dimethyl-4,7-diphenyl-1,10-phenanthroline (hole-blocker) and Alq3 (electron-transporting layer). The layers were sequentially deposited under high vacuum environment by thermal evaporation onto ITO glass substrates. Moreover, co-deposition techniques were used to improve charge transport in the devices and to avoid quenching phenomena. The devices show strong electroluminescence at 612, 998, 1064 and 1534 nm corresponding to ⁵D₀ →⁷F₂(Eu), ²F₅/₂ → ²F₇/₂ (Yb), ⁴F₃/₂→ ⁴I₉/₂ (Nd) and ⁴I1₃/₂→ ⁴I1₅/₂ (Er). All the devices fabricated show good efficiency as well as stability.

Keywords: electroluminescence, lanthanides, paramagnetic NMR, photoluminescence

Procedia PDF Downloads 111

Authors: Dinara F. Gaynutdinova, Vladimir Ya Modorsky, Nikolay A. Shevelev

Abstract:

The problem under research is that of unpredictable modes occurring in two-stage centrifugal hydraulic pump as a result of hydraulic processes caused by vibrations of structural components. Numerical, analytical and experimental approaches are considered. A hypothesis was developed that the problem of unpredictable pressure decrease at the second stage of centrifugal pumps is caused by cavitation effects occurring upon vibration. The problem has been studied experimentally and theoretically as of today. The theoretical study was conducted numerically and analytically. Hydroelastic processes in dynamic “liquid – deformed structure” system were numerically modelled and analysed. Using ANSYS CFX program engineering analysis complex and computing capacity of a supercomputer the cavitation parameters were established to depend on vibration parameters. An influence domain of amplitudes and vibration frequencies on concentration of cavitation bubbles was formulated. The obtained numerical solution was verified using CFM program package developed in PNRPU. The package is based on a differential equation system in hyperbolic and elliptic partial derivatives. The system is solved by using one of finite-difference method options – the particle-in-cell method. The method defines the problem solution algorithm. The obtained numerical solution was verified analytically by model problem calculations with the use of known analytical solutions of in-pipe piston movement and cantilever rod end face impact. An infrastructure consisting of an experimental fast hydro-dynamic processes research installation and a supercomputer connected by a high-speed network, was created to verify the obtained numerical solutions. Physical experiments included measurement, record, processing and analysis of data for fast processes research by using National Instrument signals measurement system and Lab View software. The model chamber end face oscillated during physical experiments and, thus, loaded the hydraulic volume. The loading frequency varied from 0 to 5 kHz. The length of the operating chamber varied from 0.4 to 1.0 m. Additional loads weighed from 2 to 10 kg. The liquid column varied from 0.4 to 1 m high. Liquid pressure history was registered. The experiment showed dependence of forced system oscillation amplitude on loading frequency at various values: operating chamber geometrical dimensions, liquid column height and structure weight. Maximum pressure oscillation (in the basic variant) amplitudes were discovered at loading frequencies of approximately 1,5 kHz. These results match the analytical and numerical solutions in ANSYS and CFM.

Keywords: computing experiment, hydroelasticity, physical experiment, vibration

Procedia PDF Downloads 243

Authors: N. Manjunatha, K. T. Rangswamy, N. Nagaraju, H. A. Prameela, P. Rudraswamy, M. Krishnareddy

Abstract:

The identification of virus in cowpea especially potyviruses is confusing. Even though there are several studies on viruses causing diseases in cowpea, difficult to distinguish based on symptoms and serological detection. The differentiation of potyviruses considering as a constraint, the present study is initiated for molecular characterization, host plant resistance and epidemiology of the BCMV infecting cowpea. The etiological agent causing cowpea mosaic was identified as Bean Common Mosaic Virus (BCMV) on the basis of RT-PCR and electron microscopy. An approximately 750bp PCR product corresponding to coat protein (CP) region of the virus and the presence of long flexuous filamentous particles measuring about 952 nm in size typical to genus potyvirus were observed under electron microscope. The characterized virus isolate genome had 10054 nucleotides, excluding the 3’ terminal poly (A) tail. Comparison of polyprotein of the virus with other potyviruses showed similar genome organization with 9 cleavage sites resulted in 10 functional proteins. The pairwise sequence comparison of individual genes, P1 showed most divergent, but CP gene was less divergent at nucleotide and amino acid level. A phylogenetic tree constructed based on multiple sequence alignments of the polyprotein nucleotide and amino acid sequences of cowpea BCMV and potyviruses showed virus is closely related to BCMV-HB. Whereas, Soybean variant of china (KJ807806) and NL1 isolate (AY112735) showed 93.8 % (5’UTR) and 94.9 % (3’UTR) homology respectively with other BCMV isolates. This virus transmitted to different leguminous plant species and produced systemic symptoms under greenhouse conditions. Out of 100 cowpea genotypes screened, three genotypes viz., IC 8966, V 5 and IC 202806 showed immune reaction in both field and greenhouse conditions. Single marker analysis (SMA) was revealed out of 4 SSR markers linked to BCMV resistance, M135 marker explains 28.2 % of phenotypic variation (R2) and Polymorphic information content (PIC) value of these markers was ranged from 0.23 to 0.37. The correlation and regression analysis showed rainfall, and minimum temperature had significant negative impact and strong relationship with aphid population, whereas weak correlation was observed with disease incidence. Path coefficient analysis revealed most of the weather parameters exerted their indirect contributions to the aphid population and disease incidence except minimum temperature. This study helps to identify specific gaps in knowledge for researchers who may wish to further analyse the science behind complex interactions between vector-virus and host in relation to the environment. The resistant genotypes identified are could be effectively used in resistance breeding programme.

Keywords: cowpea, epidemiology, genotypes, virus

Procedia PDF Downloads 230

Authors: Liam Fassam, Pouria Liravi, Jacquie Bridgman

Abstract:

Introduction: The way we travel is rapidly changing, car ownership and use are declining among young people and those residents in urban areas. Also, the increasing role and popularity of sharing economy companies like Uber highlight a movement towards consuming transportation solutions as a service [Mobility of a Service]. This research looks to bridge the knowledge gap that exists between city mobility, smart cities, sharing economy and social entrepreneurship business models. Understanding of this subject is crucial for smart city design, as access to affordable transport has been identified as a contributing factor to social isolation leading to issues around health and wellbeing. Methodology: To explore the current fit vis-a-vis transportation business models and social impact this research undertook a comparative analysis between a systematic literature review and a Delphi study. The systematic literature review was undertaken to gain an appreciation of the current academic thinking on ‘social entrepreneurship and smart city mobility’. The second phase of the research initiated a Delphi study across a group of 22 participants to review future opinion on ‘how social entrepreneurship can assist city mobility sharing models?’. The Delphi delivered an initial 220 results, which once cross-checked for duplication resulted in 130. These 130 answers were sent back to participants to score importance against a 5-point LIKERT scale, enabling a top 10 listing of areas for shared user transports in society to be gleaned. One further round (4) identified no change in the coefficient of variant thus no further rounds were required. Findings: Initial results of the literature review returned 1,021 journals using the search criteria ‘social entrepreneurship and smart city mobility’. Filtering allied to ‘peer review’, ‘date’, ‘region’ and ‘Chartered associated of business school’ ranking proffered a resultant journal list of 75. Of these, 58 focused on smart city design, 9 on social enterprise in cityscapes, 6 relating to smart city network design and 3 on social impact, with no journals purporting the need for social entrepreneurship to be allied to city mobility. The future inclusion factors from the Delphi expert panel indicated that smart cities needed to include shared economy models in their strategies. Furthermore, social isolation born by costs of infrastructure needed addressing through holistic A-political social enterprise models, and a better understanding of social benefit measurement is needed. Conclusion: In investigating the collaboration between key public transportation stakeholders, a theoretical model of social enterprise transportation models that positively impact upon the smart city needs of reduced transport poverty and social isolation was formed. As such, the research has identified how a revised business model of Mobility of a Service allied to a social entrepreneurship can deliver impactful measured social benefits associated to smart city design existent research.

Keywords: social enterprise, collaborative transportation, new models of ownership, transport social impact

Procedia PDF Downloads 136

Authors: Laura Gleason, Sahithi Talasila, Lauren Banner, Ladan Afifi, Neda Nikbakht

Abstract:

Primary cutaneous anaplastic large cell lymphoma (pcALCL) accounts for 9% of all cutaneous T-cell lymphomas. pcALCL is classically characterized as a solitary papulonodule that often enlarges, ulcerates, and can be locally destructive, but overall exhibits an indolent course with overall 5-year survival estimated to be 90%. Distinguishing pcALCL from systemic ALCL (sALCL) is essential as sALCL confers a poorer prognosis with average 5-year survival being 40-50%. Although extremely rare, there have been several cases of ALK-positive ALCL diagnosed on skin biopsy without evidence of systemic involvement, which poses several challenges in the classification, prognostication, treatment, and follow-up of these patients. Objectives: We present a case of cutaneous ALK-positive ALCL without evidence of systemic involvement, and a narrative review of the literature to further characterize that ALK-positive ALCL limited to the skin is a distinct variant with a unique presentation, history, and prognosis. A 30-year-old woman presented for evaluation of an erythematous-violaceous papule present on her right chest for two months. With the development of multifocal disease and persistent lymphadenopathy, a bone marrow biopsy and lymph node excisional biopsy were performed to assess for systemic disease. Both biopsies were unrevealing. The patient was counseled on pursuing systemic therapy consisting of Brentuximab, Cyclophosphamide, Doxorubicin, and Prednisone given the concern for sALCL. Apropos of the patient we searched for clinically evident, cutaneous ALK-positive ALCL cases, with and without systemic involvement, in the English literature. Risk factors, such as tumor location, number, size, ALK localization, ALK translocations, and recurrence, were evaluated in cases of cutaneous ALK-positive ALCL. The majority of patients with cutaneous ALK-positive ALCL did not progress to systemic disease. The majority of cases that progressed to systemic disease in adults had recurring skin lesions and cytoplasmic localization of ALK. ALK translocations did not influence disease progression. Mean time to disease progression was 16.7 months, and significant mortality (50%) was observed in those cases that progressed to systemic disease. Pediatric cases did not exhibit a trend similar to adult cases. In both the adult and pediatric cases, a subset of cutaneous-limited ALK-positive ALCL were treated with chemotherapy. All cases treated with chemotherapy did not progress to systemic disease. Apropos of an ALK-positive ALCL patient with clinical cutaneous limited disease in the histologic presence of systemic markers, we discussed the literature data, highlighting the crucial issues related to developing a clinical strategy to approach this rare subtype of ALCL. Physicians need to be aware of the overall spectrum of ALCL, including cutaneous limited disease, systemic disease, disease with NPM-ALK translocation, disease with ALK and EMA positivity, and disease with skin recurrence.

Keywords: anaplastic large cell lymphoma, systemic, cutaneous, anaplastic lymphoma kinase, ALK, ALCL, sALCL, pcALCL, cALCL

Procedia PDF Downloads 78

Authors: Mariia A. Parfenenko, Ilya S. Dantsev, Sergei V. Bochenkov, Natalia V. Vinogradova, Olga S. Groznova, Victoria Yu. Voinova

Abstract:

Introduction: Autism is the most common neurodevelopmental disorder. Autism is characterized by difficulties in social interaction and adherence to stereotypic behavioral patterns and frequently co-occurs with epilepsy, intellectual disabilities, connective tissue disorders, and other conditions. CHD8 codes for chromodomain-helicase-DNA-binding protein 8 - a chromatin remodeler that regulates cellular proliferation and neurodevelopment in embryogenesis. CHD8 is one of the genes most frequently involved in autism. Patients and methods: 2 unrelated male patients, P3 and P12, aged 3 and 12 years old, underwent whole genome sequencing, which determined that they both had different likely pathogenic variants, both previously undescribed in literature. Sanger sequencing later determined that P12 inherited the variant from his affected mother. Results: P3 and P12 presented with autism, a developmental delay, ataxia, sleep disorders, overgrowth, and macrocephaly, as well as other clinical features typically present in patients with causative variants in CHD8. The mother of P12 also has autistic traits, as well as ataxia, hypotonia, sleep disorders, and other symptoms. However, P3 and P12 also have different cardiac abnormalities. P3 had signs of a repolarization disorder: a flattened T wave in the III and aVF derivations and a negative T wave in the V1-V2 derivations. He also had structural valve anomalies with associated regurgitation, local contractility impairment of the left ventricular, and diastolic dysfunction of the right ventricle. Meanwhile, P12 had Wolff-Parkinson-White syndrome and underwent radiofrequency ablation at the age of 2 years. At the time of observation, P12 had mild sinus arrhythmia and an incomplete right bundle branch block, as well as arterial hypertension. Discussion: Cardiac abnormalities were not previously reported in patients with causative variants in CHD8. The underlying mechanism for the formation of those abnormalities is currently unknown. However, the two hypotheses are either a disordered interaction with CHD7 – another chromodomain remodeler known to be directly involved in the cardiophenotype of CHARGE syndrome – a rare condition characterized by coloboma, heart defects and growth abnormalities, or the disrupted functioning of CHD8 as an A-Kinase Anchoring Protein, which are known to modulate cardiac function. Conclusion: We observed 2 unrelated autistic males with likely pathogenic variants in CHD8 that presented with typical symptoms of CHD8-related neurodevelopmental disorder, as well as cardiac abnormalities. Cardiac abnormalities have, until now, been considered uncharacteristic for patients with causative variants in CHD8. Further accumulation of data, including experimental evidence of the involvement of CHD8 in heart formation, will elucidate the mechanism underlying the cardiophenotype of those patients. Acknowledgements: Molecular genetic testing of the patients was made possible by the Charity Fund for medical and social genetic aid projects «Life Genome.»

Keywords: autism spectrum disorders, chromodomain-helicase-DNA-binding protein 8, neurodevelopmental disorder, cardio phenotype

Procedia PDF Downloads 81

Authors: Margarita Ivanova, Julia Dao, Andrew Friedman, Neil Kasaci, Rekha Gopal, Ozlem Goker-Alpan

Abstract:

In Fabry disease (FD), α-galactosidase A (α-Gal A) deficiency leads to the accumulation of globotriaosylceramide (Lyso-Gb3 and Gb3), triggering a pathologic cascade that causes the severity of organs damage. The heart is one of the several organs with high sensitivity to the α-Gal A deficiency. A subgroup of patients with significant residual of α-Gal A activity with primary cardiac involvement is occasionally referred to as “cardiac variant.” The cardiovascular complications are most frequently encountered, contributing substantially to morbidity, and are the leading cause of premature death in male and female patients with FD. The deposition of Lyso-Gb-3 and Gb-3 within the myocardium affects cardiac function with resultant progressive cardiovascular pathology. Gb-3 and Lyso-Gb-3 accumulation at the cellular level trigger a cascade of events leading to end-stage fibrosis. In the cardiac tissue, Lyso-Gb-3 deposition is associated with the increased release of inflammatory factors and transforming growth factors. Infiltration of lymphocytes and macrophages into endomyocardial tissue indicates that inflammation plays a significant role in cardiac damage. Moreover, accumulated data suggest that chronic inflammation leads to multisystemic FD pathology even under enzyme replacement therapy (ERT). NF-κB activation plays a subsequent role in the inflammatory response to cardiac dysfunction and advanced heart failure in the general population. TNFalpha/NF-κB signaling protects the myocardial evoking by ischemic preconditioning; however, this protective effect depends on the concentration of TNF-α. Thus, we hypothesize that TNF-α is a critical factor in determining the grade of cardio-pathology. Cardiac hypertrophy corresponds to the expansion of the coronary vasculature to maintain a sufficient supply of nutrients and oxygen. Coronary activation of angiogenesis and fibrosis plays a vital role in cardiac vascularization, hypertrophy, and tissue remodeling. We suggest that the interaction between the inflammatory pathways and cardiac vascularization is a bi-directional process controlled by secreted cytokines and growth factors. The co-coordination of these two processes has never been explored in FD. In a cohort of 40 patients with FD, biomarkers associated with inflammation and cardio hypertrophic remodeling were studied. FD patients were categorized into three groups based on LVmass/DSA, LVEF, and ECG abnormalities: FD with no cardio complication, FD with moderate cardio complication, and severe cardio complication. Serum levels of NF-kB, TNFalpha, Il-6, Il-2, MCP1, ING-gamma, VEGF, IGF-1, TGFβ, and FGF2 were quantified by enzyme-linked immunosorbent assays (ELISA). Among the biomarkers, MCP-1, INF-gamma, VEGF, TNF-alpha, and TGF-beta were elevated in FD patients. Some of these biomarkers also have the potential to correlate with cardio pathology in FD. Conclusion: The study provides information about the role of inflammatory pathways and biomarkers of cardio hypertrophic remodeling in FD patients. This study will also reveal the mechanisms that link intracellular accumulation of Lyso-GB-3 and Gb3 to the development of cardiomyopathy with myocardial thickening and resultant fibrosis.

Keywords: biomarkers, Fabry disease, inflammation, growth factors

Procedia PDF Downloads 78

Authors: Ferzat Anka

Abstract:

Many types of problems can be solved using traditional analytical methods. However, these methods take a long time and cause inefficient use of resources. In particular, different approaches may be required in solving complex and global engineering problems that we frequently encounter in real life. The bigger and more complex a problem, the harder it is to solve. Such problems are called Nondeterministic Polynomial time (NP-hard) in the literature. The main reasons for recommending different metaheuristic algorithms for various problems are the use of simple concepts, the use of simple mathematical equations and structures, the use of non-derivative mechanisms, the avoidance of local optima, and their fast convergence. They are also flexible, as they can be applied to different problems without very specific modifications. Thanks to these features, it can be easily embedded even in many hardware devices. Accordingly, this approach can also be used in trend application areas such as IoT, big data, and parallel structures. Indeed, the metaheuristic approaches are algorithms that return near-optimal results for solving large-scale optimization problems. This study is focused on the new metaheuristic method that has been merged with the chaotic approach. It is based on the chaos theorem and helps relevant algorithms to improve the diversity of the population and fast convergence. This approach is based on Chimp Optimization Algorithm (ChOA), that is a recently introduced metaheuristic algorithm inspired by nature. This algorithm identified four types of chimpanzee groups: attacker, barrier, chaser, and driver, and proposed a suitable mathematical model for them based on the various intelligence and sexual motivations of chimpanzees. However, this algorithm is not more successful in the convergence rate and escaping of the local optimum trap in solving high-dimensional problems. Although it and some of its variants use some strategies to overcome these problems, it is observed that it is not sufficient. Therefore, in this study, a newly expanded variant is described. In the algorithm called Ex-ChOA, hybrid models are proposed for position updates of search agents, and a dynamic switching mechanism is provided for transition phases. This flexible structure solves the slow convergence problem of ChOA and improves its accuracy in multidimensional problems. Therefore, it tries to achieve success in solving global, complex, and constrained problems. The main contribution of this study is 1) It improves the accuracy and solves the slow convergence problem of the ChOA. 2) It proposes new hybrid movement strategy models for position updates of search agents. 3) It provides success in solving global, complex, and constrained problems. 4) It provides a dynamic switching mechanism between phases. The performance of the Ex-ChOA algorithm is analyzed on a total of 8 benchmark functions, as well as a total of 2 classical and constrained engineering problems. The proposed algorithm is compared with the ChoA, and several well-known variants (Weighted-ChoA, Enhanced-ChoA) are used. In addition, an Improved algorithm from the Grey Wolf Optimizer (I-GWO) method is chosen for comparison since the working model is similar. The obtained results depict that the proposed algorithm performs better or equivalently to the compared algorithms.

Keywords: optimization, metaheuristic, chimp optimization algorithm, engineering constrained problems

Procedia PDF Downloads 71

Authors: Pawel Martynowicz

Abstract:

Vibrations are a crucial problem for slender structures such as towers, masts, chimneys, wind turbines, bridges, high buildings, etc., that is why most of them are equipped with vibration attenuation or fatigue reduction solutions. In this work, a slender structure (i.e., wind turbine tower-nacelle model) equipped with nonlinear, semiactive tuned vibration absorber(s) is analyzed. For this study purposes, magnetorheological (MR) dampers are used as semiactive actuators. Several optimal-based approaches to structural vibration attenuation are investigated against the standard ‘ground-hook’ law and passive tuned vibration absorber(s) implementations. The common approach to optimal control of nonlinear systems is offline computation of the optimal solution, however, so determined open loop control suffers from lack of robustness to uncertainties (e.g., unmodelled dynamics, perturbations of external forces or initial conditions), and thus perturbation control techniques are often used. However, proper linearization may be an issue for highly nonlinear systems with implicit relations between state, co-state, and control. The main contribution of the author is the development as well as numerical and experimental verification of the Pontriagin maximum-principle-based vibration control concepts that produce directly actuator control input (not the demanded force), thus force tracking algorithm that results in control inaccuracy is entirely omitted. These concepts, including one-step optimal control, quasi-optimal control, and optimal-based modified ‘ground-hook’ law, can be directly implemented in online and real-time feedback control for periodic (or semi-periodic) disturbances with invariant or time-varying parameters, as well as for non-periodic, transient or random disturbances, what is a limitation for some other known solutions. No offline calculation, excitations/disturbances assumption or vibration frequency determination is necessary, moreover, all of the nonlinear actuator (MR damper) force constraints, i.e., no active forces, lower and upper saturation limits, hysteresis-type dynamics, etc., are embedded in the control technique, thus the solution is optimal or suboptimal for the assumed actuator, respecting its limitations. Depending on the selected method variant, a moderate or decisive reduction in the computational load is possible compared to other methods of nonlinear optimal control, while assuring the quality and robustness of the vibration reduction system, as well as considering multi-pronged operational aspects, such as possible minimization of the amplitude of the deflection and acceleration of the vibrating structure, its potential and/or kinetic energy, required actuator force, control input (e.g. electric current in the MR damper coil) and/or stroke amplitude. The developed solutions are characterized by high vibration reduction efficiency – the obtained maximum values of the dynamic amplification factor are close to 2.0, while for the best of the passive systems, these values exceed 3.5.

Keywords: magnetorheological damper, nonlinear tuned vibration absorber, optimal control, real-time structural vibration attenuation, wind turbines

Procedia PDF Downloads 119

Authors: Jiri Cecrdle

Abstract:

This paper describes the concept of the W-WING whirl flutter aeroelastic demonstrator. Whirl flutter is the specific case of flutter that accounts for the additional dynamic and aerodynamic influences of the engine rotating parts. The instability is driven by motion-induced unsteady aerodynamic propeller forces and moments acting in the propeller plane. Whirl flutter instability is a serious problem that may cause the unstable vibration of a propeller mounting, leading to the failure of an engine installation or an entire wing. The complicated physical principle of whirl flutter required the experimental validation of the analytically gained results. W-WING aeroelastic demonstrator has been designed and developed at Czech Aerospace Research Centre (VZLU) Prague, Czechia. The demonstrator represents the wing and engine of the twin turboprop commuter aircraft. Contrary to the most of past demonstrators, it includes a powered motor and thrusting propeller. It allows the changes of the main structural parameters influencing the whirl flutter stability characteristics. Propeller blades are adjustable at standstill. The demonstrator is instrumented by strain gauges, accelerometers, revolution-counting impulse sensor, sensor of airflow velocity, and the thrust measurement unit. Measurement is supported by the in house program providing the data storage and real-time depiction in the time domain as well as pre-processing into the form of the power spectral densities. The engine is linked with a servo-drive unit, which enables maintaining of the propeller revolutions (constant or controlled rate ramp) and monitoring of immediate revolutions and power. Furthermore, the program manages the aerodynamic excitation of the demonstrator by the aileron flapping (constant, sweep, impulse). Finally, it provides the safety guard to prevent any structural failure of the demonstrator hardware. In addition, LMS TestLab system is used for the measurement of the structure response and for the data assessment by means of the FFT- and OMA-based methods. The demonstrator is intended for the experimental investigations in the VZLU 3m-diameter low-speed wind tunnel. The measurement variant of the model is defined by the structural parameters: pitch and yaw attachment stiffness, pitch and yaw hinge stations, balance weight station, propeller type (duralumin or steel blades), and finally, angle of attack of the propeller blade 75% section (). The excitation is provided either by the airflow turbulence or by means of the aerodynamic excitation by the aileron flapping using a frequency harmonic sweep. The experimental results are planned to be utilized for validation of analytical methods and software tools in the frame of development of the new complex multi-blade twin-rotor propulsion system for the new generation regional aircraft. Experimental campaigns will include measurements of aerodynamic derivatives and measurements of stability boundaries for various configurations of the demonstrator.

Keywords: aeroelasticity, flutter, whirl flutter, W WING demonstrator

Procedia PDF Downloads 90

Authors: M. A. C. S. Sampath Fernando, James M. Curran, Renate Meyer

Abstract:

Model assessment, in the Bayesian context, involves evaluation of the goodness-of-fit and the comparison of several alternative candidate models for predictive accuracy and improvements. In posterior predictive checks, the data simulated under the fitted model is compared with the actual data. Predictive model accuracy is estimated using information criteria such as the Akaike information criterion (AIC), the Bayesian information criterion (BIC), the Deviance information criterion (DIC), and the Watanabe-Akaike information criterion (WAIC). The goal of an information criterion is to obtain an unbiased measure of out-of-sample prediction error. Since posterior checks use the data twice; once for model estimation and once for testing, a bias correction which penalises the model complexity is incorporated in these criteria. Cross-validation (CV) is another method used for examining out-of-sample prediction accuracy. Leave-one-out cross-validation (LOO-CV) is the most computationally expensive variant among the other CV methods, as it fits as many models as the number of observations. Importance sampling (IS), truncated importance sampling (TIS) and Pareto-smoothed importance sampling (PSIS) are generally used as approximations to the exact LOO-CV and utilise the existing MCMC results avoiding expensive computational issues. The reciprocals of the predictive densities calculated over posterior draws for each observation are treated as the raw importance weights. These are in turn used to calculate the approximate LOO-CV of the observation as a weighted average of posterior densities. In IS-LOO, the raw weights are directly used. In contrast, the larger weights are replaced by their modified truncated weights in calculating TIS-LOO and PSIS-LOO. Although, information criteria and LOO-CV are unable to reflect the goodness-of-fit in absolute sense, the differences can be used to measure the relative performance of the models of interest. However, the use of these measures is only valid under specific circumstances. This study has developed 11 models using normal, log-normal, gamma, and student’s t distributions to improve the PCR stutter prediction with forensic data. These models are comprised of four with profile-wide variances, four with locus specific variances, and three which are two-component mixture models. The mean stutter ratio in each model is modeled as a locus specific simple linear regression against a feature of the alleles under study known as the longest uninterrupted sequence (LUS). The use of AIC, BIC, DIC, and WAIC in model comparison has some practical limitations. Even though, IS-LOO, TIS-LOO, and PSIS-LOO are considered to be approximations of the exact LOO-CV, the study observed some drastic deviations in the results. However, there are some interesting relationships among the logarithms of pointwise predictive densities (lppd) calculated under WAIC and the LOO approximation methods. The estimated overall lppd is a relative measure that reflects the overall goodness-of-fit of the model. Parallel log-likelihood profiles for the models conditional on equal posterior variances in lppds were observed. This study illustrates the limitations of the information criteria in practical model comparison problems. In addition, the relationships among LOO-CV approximation methods and WAIC with their limitations are discussed. Finally, useful recommendations that may help in practical model comparisons with these methods are provided.

Keywords: cross-validation, importance sampling, information criteria, predictive accuracy

Procedia PDF Downloads 386

Authors: Antonela Matana, Dubravka Brdar, Vesela Torlak, Marijana Popovic, Ivana Gunjaca, Ozren Polasek, Vesna Boraska Perica, Maja Barbalic, Ante Punda, Caroline Hayward, Tatijana Zemunik

Abstract:

Parathyroid hormone (PTH) plays a critical role in the regulation of bone mineral metabolism and calcium homeostasis. Higher PTH levels are associated with heart failure, hypertension, coronary artery disease, cardiovascular mortality and poorer bone health. A twin study estimated that 60% of the variation in PTH concentrations is genetically determined. Only one GWAS of PTH concentration has been reported to date. Identified loci explained 4.5% of the variance in circulating PTH, suggesting that additional genetic variants remain undiscovered. Therefore, the aim of this study was to identify novel genetic variants associated with PTH levels in a general population. We have performed a GWAS meta-analysis on 2596 individuals originating from three Croatian cohorts: City of Split and the Islands of Korčula and Vis, within a large-scale project of “10,001 Dalmatians”. A total of 7 411 206 variants, imputed using the 1000 Genomes reference panel, with minor allele frequency ≥ 1% and Rsq ≥ 0.5 were analyzed for the association. GWAS within each data set was performed under an additive model, controlling for age, gender and relatedness. Meta-analysis was conducted using the inverse-variance fixed-effects method. Furthermore, to identify sex-specific effects, we have conducted GWAS meta-analyses analyzing males and females separately. In addition, we have performed biological pathway analysis. Four SNPs, representing one locus, reached genome-wide significance. The most significant SNP was rs11099476 on chromosome 4 (P=1.15x10-8), which explained 1.14 % of the variance in PTH. The SNP is located near the protein-coding gene RASGEF1B. Additionally, we detected suggestive association with SNPs, rs77178854 located on chromosome 2 in the DPP10 gene (P=2.46x10-7) and rs481121 located on chromosome 1 (P=3.58x10-7) near the GRIK1 gene. One of the top hits detected in the main meta-analysis, intron variant rs77178854 located within DPP10 gene, reached genome-wide significance in females (P=2.21x10-9). No single locus was identified in the meta-analysis in males. Fifteen biological pathways were functionally enriched at a P<0.01, including muscle contraction, ion homeostasis and cardiac conduction as the most significant pathways. RASGEF1B is the guanine nucleotide exchange factor, known to be associated with height, bone density, and hip. DPP10 encodes a membrane protein that is a member of the serine proteases family, which binds specific voltage-gated potassium channels and alters their expression and biophysical properties. In conclusion, we identified 2 novel loci associated with PTH levels in a general population, providing us with further insights into the genetics of this complex trait.

Keywords: general population, genome-wide association analysis, parathyroid hormone, single nucleotide polymorphisms.

Procedia PDF Downloads 222