Search results for: functional mutations

Authors: Nouha Bouayed Abdelmoula, Rim Louati, Nawel Abdellaoui, Balkiss Abdelmoula, Oldez Kaabi, Walid Smaoui, Samir Aloulou

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Background and Aims: Cardiofaciocutaneous syndrome (CFC) is an autosomal dominant disorder with the vast majority of cases arising by a new mutation of BRAF, MEK1, MEK2, or rarely, KRAS genes. Here, we report a rare Tunisian case of CFC syndrome for whom we identify SOS1 mutation. Methods: Genomic DNA was obtained from peripheral blood collected in an EDTA tube and extracted from leukocytes using the phenol/chloroform method according to standard protocols. High resolution melting (HRM) analysis for screening of mutations in the entire coding sequence of PTPN11 was conducted first. Then, HRM assays to look for hot spot mutations coding regions of the other genes of the RAS-MAPK pathway (RAt Sarcoma viral oncogene homolog Mitogen-Activated Protein Kinases Pathway): SOS1, SHOC2, KRAS, RAF1, KRAS, NRAS, CBL, BRAF, MEK1, MEK2, HRAS, and RIT1, were applied. Results: Heterozygous SOS1 point mutation clustered in exon 10, which encodes for the PH domain of SOS1, was identified: c.1655 G > A. The patient was a 9-year-old female born from a consanguineous couple. She exhibited pulmonic valvular stenosis as congenital heart disease. She had facial features and other malformations of Noonan syndrome, including macrocephaly, hypertelorism, ptosis, downslanting palpebral fissures, sparse eyebrows, a short and broad nose with upturned tip, low-set ears, high forehead commonly associated with bitemporal narrowing and prominent supraorbital ridges, short and/or webbed neck and short stature. However, the phenotype is also suggestive of CFC syndrome with the presence of more severe ectodermal abnormalities, including curly hair, keloid scars, hyperkeratotic skin, deep plantar creases, and delayed permanent dentition with agenesis of the right maxillary first molar. Moreover, the familial history of the patient revealed recurrent brain malignancies in the paternal family and epileptic disease in the maternal family. Conclusions: This case report of an overlapping RASopathy associated with SOS1 mutation and familial history of brain tumorigenesis is exceptional. The evidence suggests that RASopathies are truly cancer-prone syndromes, but the magnitude of the cancer risk and the types of cancer partially overlap.

Keywords: cardiofaciocutaneous syndrome, CFC, SOS1, brain cancer, germline mutation

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Authors: Jun-ya Nagase, Toshiyuki Satoh, Norihiko Saga, Koichi Suzumori

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In recent years, Japanese society has been aging, engendering a labour shortage of young workers. Robots are therefore expected to perform tasks such as rehabilitation, nursing elderly people, and day-to-day work support for elderly people. The pneumatic balloon actuator is a rubber artificial muscle developed for use in a robot hand in such environments. This actuator has a long stroke, and a high power-to-weight ratio compared with the present pneumatic artificial muscle. Moreover, the dynamic characteristics of this actuator resemble those of human muscle. This study evaluated characteristics of force control of balloon actuator using a predictive functional control (PFC) system with disturbance observer. The predictive functional control is a model-based predictive control (MPC) scheme that predicts the future outputs of the actual plants over the prediction horizon and computes the control effort over the control horizon at every sampling instance. For this study, a 1-link finger system using a pneumatic balloon actuator is developed. Then experiments of PFC control with disturbance observer are performed. These experiments demonstrate the feasibility of its control of a pneumatic balloon actuator for a robot hand.

Keywords: disturbance observer, pneumatic balloon, predictive functional control, rubber artificial muscle

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Authors: Hee-Young Song

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Background and objectives: In 2011, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations proposed a multidimensional assessment of patients’ conditions that included both functional parameters and patient-reported outcomes, with the aim to provide a comprehensive assessment of the disease, thus meeting both the needs of the patient and the role of the physician. However, few studies have evaluated patient-reported outcomes as well as objective functional assessments among individuals with chronic obstructive pulmonary disease (COPD) in clinical practice in Korea. This study was undertaken to explore the relationship between functional status assessed by the 6-minute walking distance (MWD) test and subjective health status reported by stable patients with COPD residing in community. Methods: A cross-sectional descriptive study was conducted with 118 stable COPD patients aged 69.4 years old and selected by a convenient sampling from an outpatient department of pulmonology in a tertiaryhospitals. The 6-MWD test was conducted according to standardized instructions. Participants also completed a constructed questionnaire including general characteristics, smoking history, dyspnea by modified medical research council (mMRC) scale, and health status by COPD assessment test (CAT). Anthropometric measurements were performed for body mass index (BMI). Medical records were reviewed to obtain disease-related characteristics including duration of the disease and forced expiratory volume in 1 second (FEV1). Data were analyzed using PASW statistics 20.0. Results: Mean FEV1% of participants was 63.51% and mean 6-MWD and CAT scores were 297.54m and 17.7, respectively. The 6-MWD and CAT showed significant negative correlations (r= -.280, p=.002); FEV1 and CAT did as well correlations (r= -.347, p < .001). Conclusions: Findings suggest that the better functional status an individual with COPD has, the better subjective health status is, and provide the support for using patient-reported outcomes along with functional parameters to facilitate comprehensive assessment of COPD patients in real clinical practices.

Keywords: chronic obstructive pulmonary disease, COPD assessment test, functional status, patient-reported outcomes

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Authors: Katyana A. Vert-Pre, James T. Thorson, Thomas Trancart, Eric Feunteun

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In marine ecosystems, spatial and temporal species structure is an important component of ecosystems’ response to anthropological and environmental factors. Although spatial distribution patterns and fish temporal series of abundance have been studied in the past, little research has been allocated to the joint dynamic spatio-temporal functional patterns in marine ecosystems and their use in multispecies management and conservation. Each species represents a function to the ecosystem, and the distribution of these species might not be random. A heterogeneous functional distribution will lead to a more resilient ecosystem to external factors. Applying a Vector-Autoregressive Spatio-Temporal (VAST) model for count data, we estimate the spatio-temporal distribution, shift in time, and abundance of 140 species of the Eastern English Chanel, Bay of Biscay and Mediterranean Sea. From the model outputs, we determined spatio-temporal clusters, calculating p-values for hierarchical clustering via multiscale bootstrap resampling. Then, we designed a functional map given the defined cluster. We found that the species distribution within the ecosystem was not random. Indeed, species evolved in space and time in clusters. Moreover, these clusters remained similar over time deriving from the fact that species of a same cluster often shifted in sync, keeping the overall structure of the ecosystem similar overtime. Knowing the co-existing species within these clusters could help with predicting data-poor species distribution and abundance. Further analysis is being performed to assess the ecological functions represented in each cluster.

Keywords: cluster distribution shift, European marine ecosystems, functional distribution, spatio-temporal model

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Authors: Bartłomiej K. Sołtysik, Agnieszka Guligowska, Łukasz Kroc, Małgorzata Pigłowska, Elizavetta Fife, Tomasz Kostka

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Introduction: Functional capacity is one of the basic determinants of health in older age. Functional capacity may be influenced by multiple disorders, including cardiovascular and metabolic diseases. Nevertheless, there is relatively little evidence regarding the association of functional status and cardiometabolic risk factors. Aim: The aim of this research is to check possible association between functional capacity and cardiovascular risk factor in a group of younger seniors. Materials and Methods: The study group consisted of 300 participants aged 60-65 years (50% were women). Total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), glucose, uric acid, body mass index (BMI), waist-to-height ratio (WHtR) and blood pressure were measured. Smoking status and physical activity level (by Seven Day Physical Activity Recall Questionnaire ) were analysed. Functional status was assessed with the Timed Up and Go (TUG) Test. The data were compared according to gender, and then separately for both sexes regarding prolonged TUG score (>7 s). The limit of significance was set at p≤0.05 for all analyses. Results: Women presented with higher serum lipids and longer TUG. Men had higher blood pressure, glucose, uric acid, the prevalence of hypertension and history of heart infarct. In women group, those with prolonged TUG displayed significantly higher obesity rate (BMI, WHTR), uric acid, hypertension and ischemic heart disease (IHD), but lower physical activity level, TC or LDL-C. Men with prolonged TUG were heavier smokers, had higher TG, lower HDL and presented with higher prevalence of diabetes and IHD. Discussion: This study shows association between functional status and risk profile of cardiometabolic disorders. In women, the relationship of lower functional status to cardiometabolic diseases may be mediated by overweight/obesity. In men, locomotor problems may be related to smoking. Higher education level may be considered as a protective factor regardless of gender.

Keywords: cardiovascular risk factors, functional capacity, TUG test, seniors

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Authors: Binod Duwadi

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This article examines the language and literacy practices of English Code-mixing in Nepalese Classroom. Situating the study within an ecological framework, a systematic functional linguistic (SFL) approach was used to analyze students writing in two Neplease schools. Data collection included interviews with teachers, classroom observations, instructional materials, and focal students’ writing samples. Data analyses revealed vastly different language ecologies between the schools owing to sharp socioeconomic stratification, the structural organization of schools, and the pervasiveness of standard language ideology, with stigmatizes English code mixing (ECM) and privileges Standard English in schools. Functional analysis of students’ writing showed that the nature of the writing tasks at the schools created different affordances for exploiting lexicogrammatically choices for meaning making-enhancing them in the case of one school but severely restricting them in the case of another- perpetuating the academic disadvantage for code mixing speakers. Recommendations for structural and attitudinal changes through teacher training and implementation of approaches that engage students’ bidialectal competence for learning are made as important first steps towards addressing educational inequities in Nepalese schools.

Keywords: code-mixing, ecological perspective, systematic functional approach, language and identity

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Authors: Fatemeh Safdari, Amirnaser Shamkhali, Gholamabbas Parsafar

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Carbon nanostructures are of great importance in academic research and industry, which can be mentioned to chemical sensors, catalytic processes, pharmaceutical and environmental issues. Common point in all of these applications is the occurrence of adsorption of molecules on these structures. Important carbon nanostructures in this case are mainly nanotubes and graphene. To modify pure graphene, recently, many experimental and theoretical studies have carried out to investigate of metal adsorption on graphene. In this work, the adsorption of CO molecules on pure graphene and on metal adatom on graphene surface has been simulated based on density functional theory (DFT). All calculations were performed by PBE functional and Troullier-Martins pseudopotentials. Density of states (DOS) for graphene-CO, graphen and CO around the Fermi energy has been moved and very small mixing occured which implies the physisorption of CO on the bare graphen surface. While, the results have showed that CO adsorption on transition-metal adatom on graphene surface is chemisorption.

Keywords: adsorption, density functional theory, graphene, metal adatom

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Authors: Adilah Abdul Ghapor, Yong Zulina Zubairi, A. H. M. R. Imon

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Missing value problem is common in statistics and has been of interest for years. This article considers two modern techniques in handling missing data for linear functional relationship model (LFRM) namely the Expectation-Maximization (EM) algorithm and Expectation-Maximization with Bootstrapping (EMB) algorithm using three performance indicators; namely the mean absolute error (MAE), root mean square error (RMSE) and estimated biased (EB). In this study, we applied the methods of imputing missing values in two types of LFRM namely the full model of LFRM and in LFRM when the slope is estimated using a nonparametric method. Results of the simulation study suggest that EMB algorithm performs much better than EM algorithm in both models. We also illustrate the applicability of the approach in a real data set.

Keywords: expectation-maximization, expectation-maximization with bootstrapping, linear functional relationship model, performance indicators

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Authors: Timothy William Lawrence

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The goal of this paper is to research and categorize the four basic verb types found in the Spanish descriptive grammar book Método de los Relojes using verb clauses as representation as found in M.A.K. Halliday's Systemic-Functional Grammar with the purpose of establishing theoretical along with syntactical parallels and deviations between English and Spanish. Results confirm theoretical correlations exist therefore leading to an analysis of English grammar syntax resulting in delineating commonalities and differences from Spanish. Corpora searches were carried out on different patterns of syntactical structures confirming divergences in verb syntax, making it possible to establish parameters to adapt English verbs to the criteria of the four basic Método de los Relojes verb types.

Keywords: corpus studies, Método de los Relojes, structural-functional grammar, verb syntax

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Authors: M. Volpini, D. Alves, A. Horta, M. Borges, P. Reis

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The gait pattern in people that present motor limitations foment the demand for auxiliary locomotion devices. These artifacts for movement assistance vary according to its shape, size and functional features, following the clinical applications desired. Among the ortheses of lower limbs, the ankle-foot orthesis aims to improve the ability to walk in people with different neuromuscular limitations, although they do not always answer patients' expectations for their aesthetic and functional characteristics. The purpose of this study is to explore the possibility of using new design in additive manufacturer to reproduce the shape and functional features of a ankle-foot orthesis in an efficient and modern way. Therefore, this work presents a study about the performance of the mechanical forces through the analysis of finite elements in an ankle-foot orthesis. It will be demonstrated a study of distribution of the stress on the orthopedic device in orthostatism and during the movement in the course of patient's walk.

Keywords: additive manufacture, new designs, orthoses, finite elements

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Authors: Maryam Vaezi

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In this study, the Functional Theory of Political Campaign Discourse has been applied in order to investigate the 2016 Clinton-Trump presidential debates. All three kinds of utterances (acclaims, attacks, and defenses) were produced by the candidates supporting the usefulness of the Functional Theory of Political Campaign Discourse for the analysis of the presidential debates as a type of political discourse. Attacks comprised 45% of the candidates’ utterances, followed by acclaims at 33%; defenses were the least common function at 22%. The candidate from the Democratic Party, Hillary Clinton, acclaimed more, whereas the Republican Party presidential candidate, Donald Trump, attacked more. Simple denial was the most common form of defense used by the candidates. Both candidates directed more of their utterances to policy (past deeds, future plans, and general goals) than character (personal qualities, leadership abilities, and ideals). Analyzing debates in terms of the functions performed by the candidates to increase their desirability and chance of winning the election, can lead to a better understanding of these significant political events as well as other forms of political discourse.

Keywords: acclaim, attack, defend, character, Democratic Party, Donald Trump, Hillary Clinton, policy, presidential debates, Republican Party

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Authors: Paul W. Murray

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This research explores the relationship between leadership style and continuous improvement (CI) teams. CI teams have several features that are not always found in other types of teams, including multi-functional members, short time period for performance, positive and actionable results, and exposure to senior leadership. There is not only one best style of leadership for these teams. Instead, it is important to select the best leadership style for the situation. The leader must have the flexibility to change styles and the skill to use the chosen style effectively in order to ensure the team’s success.

Keywords: leadership style, lean manufacturing, teams, cross-functional

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Authors: Yakup Ulusu, Numan Eczacıoğlu, İsa Gökçe, Helen Waller, Jeremy H. Lakey

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Besides having the appropriate amino acid sequence to perform the function of proteins, it is important to have correct conformation after this sequence to process. To consist of this conformation depends on the amino acid sequence at the primary structure, hydrophobic interaction, chaperones and enzymes in charge of folding etc. Misfolded proteins are not functional and tend to be aggregated. Cysteine originating disulfide cross-links make stable this conformation of functional proteins. When two of the cysteine amino acids come side by side, disulfide bond is established that forms a cystine bridge. Due to this feature cysteine plays an important role on the formation of three-dimensional structure of many proteins. There are two cysteine amino acids (C44, C69) in the Tol-A-III protein. Unlike protein disulfide bonds from within his own, any non-specific cystine bridge causes a change in the three dimensional structure of the protein. Proteins can be expressed in various host cells as directly or fusion (chimeric). As a result of overproduction of the recombinant proteins, aggregation of insoluble proteins in the host cell can occur by forming a crystal structure called inclusion body. In general fusion proteins are produced for provide affinity tags to make proteins more soluble and production of some toxic proteins via fusion protein expression system like pTolT. Proteins can be modified by using a site-directed mutagenesis. By this way, creation of non-specific disulfide crosslinks can be prevented at fusion protein expression system via the present cysteine replaced by another amino acid such as serine, glycine or etc. To do this, we need; a DNA molecule that contains the gene that encodes for the target protein, required primers for mutation to be designed according to site directed mutagenesis reaction. This study was aimed to be replaced cysteine encoding codon TGT with serine encoding codon AGT. For this sense and reverse primers designed (given below) and used site-directed mutagenesis reaction. Several new copy of the template plasmid DNA has been formed with above mentioned mutagenic primers via polymerase chain reaction (PCR). PCR product consists of both the master template DNA (wild type) and the new DNA sequences containing mutations. Dpn-l endonuclease restriction enzyme which is specific for methylated DNA and cuts them to the elimination of the master template DNA. E. coli cells obtained after transformation were incubated LB medium with antibiotic. After purification of plasmid DNA from E. coli, the presence of the mutation was determined by DNA sequence analysis. Developed this new plasmid is called PtolT-δ.

Keywords: site directed mutagenesis, Escherichia coli, pTolT, protein expression

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Authors: Alok Raghav, Jamal Ahmad

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Background: Serum albumin glycation and advanced glycation end products (AGE) formation correlates in diabetes and its associated complications. Extensive modified human serum albumin is used to study the biochemical, electrochemical and functional properties in hyperglycemic environment with relevance to diabetes. We evaluate Spectroscopic, side chain modifications, amino acid analysis, biochemical and functional group properties in four glucose modified samples. Methods: A series four human serum albumin samples modified with glucose was characterized in terms of amino acid analysis, spectroscopic properties and side chain modifications. The diagnostic technique employed incorporates UV Spectroscopy, Fluorescence Spectroscopy, biochemical assays for side chain modifications, amino acid estimations. Conclusion: Glucose modified human serum albumin confers AGE formation causes biochemical and functional property that depend on the reactivity of glucose and its concentration used for in-vitro glycation. A biochemical and functional characterization of modified albumin in-vitro produced AGE product that will be useful to interpret the complications and pathophysiological significance in diabetes.

Keywords: glycation, diabetes, human serum albumin, biochemical and electrochemical characterization

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Authors: Efstratios Karavasilis, Foteini Christidi, Georgios Velonakis, Agapi Plousi, Kalliopi Platoni, Nikolaos Kelekis, Ioannis Evdokimidis, Efstathios Efstathopoulos

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Introduction: Advanced structural and functional neuroimaging techniques contribute to the study of anatomical and functional brain connectivity and its role in the pathophysiology and symptoms’ heterogeneity in several neurodegenerative disorders, including multiple sclerosis (MS). Aim: In the present study, we applied multiparametric neuroimaging techniques to investigate the structural and functional cortico-cerebellar changes in MS patients. Material: We included 51 MS patients (28 with clinically isolated syndrome [CIS], 31 with relapsing-remitting MS [RRMS]) and 51 age- and gender-matched healthy controls (HC) who underwent MRI in a 3.0T MRI scanner. Methodology: The acquisition protocol included high-resolution 3D T1 weighted, diffusion-weighted imaging and echo planar imaging sequences for the analysis of volumetric, tractography and functional resting state data, respectively. We performed between-group comparisons (CIS, RRMS, HC) using CAT12 and CONN16 MATLAB toolboxes for the analysis of volumetric (cerebellar gray matter density) and functional (cortico-cerebellar resting-state functional connectivity) data, respectively. Brainance suite was used for the analysis of tractography data (cortico-cerebellar white matter integrity; fractional anisotropy [FA]; axial and radial diffusivity [AD; RD]) to reconstruct the cerebellum tracts. Results: Patients with CIS did not show significant gray matter (GM) density differences compared with HC. However, they showed decreased FA and increased diffusivity measures in cortico-cerebellar tracts, and increased cortico-cerebellar functional connectivity. Patients with RRMS showed decreased GM density in cerebellar regions, decreased FA and increased diffusivity measures in cortico-cerebellar WM tracts, as well as a pattern of increased and mostly decreased functional cortico-cerebellar connectivity compared to HC. The comparison between CIS and RRMS patients revealed significant GM density difference, reduced FA and increased diffusivity measures in WM cortico-cerebellar tracts and increased/decreased functional connectivity. The identification of decreased WM integrity and increased functional cortico-cerebellar connectivity without GM changes in CIS and the pattern of decreased GM density decreased WM integrity and mostly decreased functional connectivity in RRMS patients emphasizes the role of compensatory mechanisms in early disease stages and the disintegration of structural and functional networks with disease progression. Conclusions: In conclusion, our study highlights the added value of multimodal neuroimaging techniques for the in vivo investigation of cortico-cerebellar brain changes in neurodegenerative disorders. An extension and future opportunity to leverage multimodal neuroimaging data inevitably remain the integration of such data in the recently-applied mathematical approaches of machine learning algorithms to more accurately classify and predict patients’ disease course.

Keywords: advanced neuroimaging techniques, cerebellum, MRI, multiple sclerosis

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Authors: N. Lebga, Kh. Bouamama, K. Kassali

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We report first-principles calculation results on the structural and elastic properties of ZnS x Se1−x alloy for which we employed the virtual crystal approximation provided with the ABINIT program. The calculations done using density functional theory within the local density approximation and employing the virtual-crystal approximation, we made a comparative study between the numerical results obtained from ab-initio calculation using ABINIT or Wien2k within the Density Functional Theory framework with either Local Density Approximation or Generalized Gradient approximation and the pseudo-potential plane-wave method with the Hartwigzen Goedecker Hutter scheme potentials. It is found that the lattice parameter, the phase transition pressure, and the elastic constants (and their derivative with respect to the pressure) follow a quadratic law in x. The variation of the elastic constants is also numerically studied and the phase transformations are discussed in relation to the mechanical stability criteria.

Keywords: density functional theory, elastic properties, ZnS, ZnSe,

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Authors: Josip Karuc, Marjeta Mišigoj-Duraković, Goran Marković, Vedran Hadžić, Michael J. Duncan, Hrvoje Podnar, Maroje Sorić

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As a part of the CRO-PALS longitudinal study, this investigation aimed to examine the association between different levels of physical activity (PA) and movement quality in 16-years old school children. The total number of participants in this research was 725. Movement quality was assessed via the Functional Movement Screen (FMSTM), and the PA level was estimated using the School Health Action, Planning, and Evaluation System (SHAPES) questionnaire. In addition, body fat and socioeconomic status (SES) were assessed. In order to investigate the association between total FMS score and different levels of PA, multilevel modeling was employed for boys (n=359) and girls (n=366) separately. All models were adjusted for age, body fat, and SES. Among boys, MVPA, MPA, and VPA were not significant predictors of the total FMS score (β=0.000, p=0.78; β=-0.002, p=0.455; β=0.004, p=0.158, respectively). On the contrary, among girls, VPA and MVPA showed significant effects on the total FMS score (β=0.011, p=0.001, β=0.005, p=0.006, respectively). The findings of this research provide evidence that the intensity of PA is a minor but relevant factor in describing the association between PA and movement quality in adolescent girls but not in boys. This means that the PA level does not guarantee optimal functional movement patterns. Therefore, practicing functional movement patterns in an isolated manner and at moderate to vigorous intensity could be beneficial in order to reduce the risk of injury incidence and potential orthopedic abnormalities in later life. This work was supported by the Croatian Science Foundation, grant no: IP-2016-06-9926 and grant no: DOK-2018-01-2328.

Keywords: functional movement screen, fundamental movement patterns, movement quality, pediatric

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Authors: Bui Phuong Linh, Yuki Sakakibara, Ryuto Tanaka, Elizabeth H. Pigney, Taishi Hashiguchi

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Non-alcoholic steatohepatitis (NASH) is a chronic liver disease, often associated with type II diabetes, which sometimes progresses to more serious conditions such as liver fibrosis and hepatocellular carcinoma (HCC). NASH has become an important health problem worldwide, buttherapeutic agents for NASH have not yet been approved, and animal models with high clinical correlation are required. TheSTAM™ mouse shows the same pathological progression as human NASH patients and has been widely used for both drug efficacy and basic research, such as lipid profiling and gut microbiota research. In this study, we analyzed the RNA-seq data of STAM™mice at each pathological stage (steatosis, steatohepatitis, liver fibrosis, and HCC) and examined the clinical correlation at the genetic level. NASH was induced in male mice by a single subcutaneous injection of 200 µg streptozotocin solution 2 days after birth and feeding with high fat dietafter 4 weeks of age. The mice were sacrificed and livers collected at 6, 8, 10, 12, 16, and 20 weeks of age. For liver samples, the left lateral lobe was snap frozen in liquid nitrogen and stored at -80˚C for RNA-seq analysis. Total RNA of the cells was isolated using RNeasy mini kit. The gene expression of the canonical pathways in NASH progression from steatosis to hepatocellular carcinoma were analyzed, such as immune system process, oxidation-reduction process, lipid metabolic process. Moreover, since it has been reported that genetic traits are involved in the development of NASH-HCC, we next analyzed the genetic mutations in the STAM™mice. The number of individuals showing mutations in Mtorinvolved in Insulin signaling increases as the disease progresses, especially in the liver cancer phase. These results indicated a clinical correlation of gene profiles in the STAM™mouse.

Keywords: steatosis, non-alcoholic steatohepatitis, fibrosis, hepatocellular carcinoma, RNA-seq

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Authors: P. Aarumugam, N. Krishnamoorthy, K. Gunasekaran

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The mosquitoes with loss of minimum three legs especially the hind legs have the negative impact on the survival hood of mosquitoes. Three days old unfed adult female laboratory strain was selected in each generation against sublethal dosages (0.004%, 0.005%, 0.007% and 0.01%) of deltamethrin upto 40 generations. Impregnated papers with acetone were used for control. Every fourth generation, survived mosquitoes were observed for functional mortality. Hind legs lost were significantly (P< 0.05) higher in treated than the controls up to generation 24, thereafter no significant lost. In contrary, no significant forelegs lost among exposed mosquitoes. Middle legs lost were also not significant in the exposed mosquitoes except first generation (F1). The field strain (Chennai) did not show any significant loss of legs (fore or mid or hind) compared to the control. The selection pressure on mosquito population influences strong natural selection to develop various adaptive mechanisms.

Keywords: Anopheles stephensi, deltamethrin, functional mortality, synthetic pyrethroids

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Authors: Dicle Aydın, Süheyla Büyükşahin Sıramkaya

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Conservation concept gained importance especially in 19th century, it found value with the change and developments lived globally. Basic values in the essence of the concept are important in the continuity of historical and cultural fabrics which have character special to them. Reuse of settlements and spaces carrying historical and cultural values in the frame of socio-cultural and socio-economic conditions is related with functional value. Functional dimension of reuse signifies interrogation of the usage potential of the building with a different aim other than its determined aim. If a building carrying historical and cultural values cannot be used with its own function because of environmental, economical, structural and functional reasons, it is advantageous to maintain its reuse from the point of environmental ecology. By giving a new function both a requirement of the society is fulfilled and a culture entity is conserved because of its functional value. In this study, functional dimension of reuse is exemplified in Antalya Kaleiçi where has a special location and importance with its natural, cultural and historical heritage characteristics. Antayla Kaleiçi settlement preserves its liveliness as a touristic urban fabric with its almost fifty thousand years of past, traditional urban form, civil architectural examples of 18th–19th century reflecting the life style of the region and monumental buildings. The civil architectural examples in the fabric have a special character formed according to Mediterranean climate with their outer sofa (open or closed), one, two or three storey, courtyards and oriels. In the study reuse of five civil architectural examples as boutique hotel by forming a whole with their environmental arrangements is investigated, it is analyzed how the spatial requirements of a boutique hotel are fulfilled in traditional dwellings. Usage of a cultural entity as a boutique hotel is evaluated under the headlines of i.functional requirement, ii.satisfactoriness of spatial dimensions, iii.functional organization. There are closed and open restaurant, kitchen, pub, lobby, administrative offices in the hotel with 70 bed capacity and 28 rooms in total. There are expansions to urban areas on second and third floors by the means of oriels in the hotel surrounded by narrow streets in three directions. This boutique hotel, formed by unique five different dwellings having similar plan scheme in traditional fabric, is different with its structure opened to outside and connected to each other by the means of courtyards, and its outside spaces which gained mobility because of the elevation differences in courtyards.

Keywords: reuse, adaptive reuse, functional dimension of reuse, traditional dwellings

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Authors: Emanuela Chiarella, Annamaria Aloisio, Nisticò Clelia, Maria Mesuraca

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ZNF521 is a stem cell-associated transcription co-factor, that plays a crucial role in the homeostatic regulation of the stem cell compartment in the hematopoietic, osteo-adipogenic, and neural system. In normal hematopoiesis, primary human CD34+ hematopoietic stem cells display typically a high expression of ZNF521, while its mRNA levels rapidly decrease when these progenitors progress towards erythroid, granulocytic, or B-lymphoid differentiation. However, most acute myeloid leukemias (AMLs) and leukemia-initiating cells keep high ZNF521 expression. In particular, AMLs are often characterized by chromosomal translocations involving the Mixed Lineage Leukemia (MLL) gene, which MLL gene includes a variety of fusion oncogenes arisen from genes normally required during hematopoietic development; once they are fused, they promote epigenetic and transcription factor dysregulation. The chromosomal translocation t(9;11)(p21-22;q23), fusing the MLL gene with AF9 gene, results in a monocytic immune phenotype with an aggressive course, frequent relapses, and a short survival time. To better understand the dysfunctional transcriptional networks related to genetic aberrations, AML gene expression profile datasets were queried for ZNF521 expression and its correlations with specific gene rearrangements and mutations. The results showed that ZNF521 mRNA levels are associated with specific genetic aberrations: the highest expression levels were observed in AMLs involving t(11q23) MLL rearrangements in two distinct datasets (MILE and den Boer); elevated ZNF521 mRNA expression levels were also revealed in AMLs with t(7;12) or with internal rearrangements of chromosome 16. On the contrary, relatively low ZNF521 expression levels seemed to be associated with the t(8;21) translocation, that in turn is correlated with the AML1-ETO fusion gene or the t(15;17) translocation and in AMLs with FLT3-ITD, NPM1, or CEBPα double mutations. Invitro, we found that the enforced co-expression of ZNF521 in cord blood-derived CD34+ cells induced a significant proliferative advantage, improving MLL-AF9 effects on the induction of proliferation and the expansion of leukemic progenitor cells. Transcriptome profiling of CD34+ cells transduced with either MLL-AF9, ZNF521, or a combination of the two transgenes highlighted specific sets of up- or down-regulated genes that are involved in the leukemic phenotype, including those encoding transcription factors, epigenetic modulators, and cell cycle regulators as well as those engaged in the transport or uptake of nutrients. These data enhance the functional cooperation between ZNF521 and MA9, resulting in the development, maintenance, and clonal expansion of leukemic cells. Finally, silencing of ZNF521 in MLL-AF9-transformed primary CD34+ cells inhibited their proliferation and led to their extinction, as well as ZNF521 silencing in the MLL-AF9+ THP-1 cell line resulted in an impairment of their growth and clonogenicity. Taken together, our data highlight ZNF521 role in the control of self-renewal and in the immature compartment of malignant hematopoiesis, which, by altering the gene expression landscape, contributes to the development and/or maintenance of AML acting in concert with the MLL-AF9 fusion oncogene.

Keywords: AML, human zinc finger protein 521 (hZNF521), mixed lineage leukemia gene (MLL) AF9 (MLLT3 or LTG9), cord blood-derived hematopoietic stem cells (CB-CD34+)

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Authors: Ruchi, A. M. Acu, Purshottam N. Agrawal

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The purpose of this paper to introduce the Durrmeyer type modification of q-generalized-Bernstein operators which include the Bernstein polynomials in the particular α = 0. We investigate the rate of convergence by means of the Lipschitz class and the Peetre’s K-functional. Also, we define the bivariate case of Durrmeyer type modification of q-generalized-Bernstein operators and study the degree of approximation with the aid of the partial modulus of continuity and the Peetre’s K-functional. Finally, we introduce the GBS (Generalized Boolean Sum) of the Durrmeyer type modification of q- generalized-Bernstein operators and investigate the approximation of the Bögel continuous and Bögel differentiable functions with the aid of the Lipschitz class and the mixed modulus of smoothness.

Keywords: Bögel continuous, Bögel differentiable, generalized Boolean sum, Peetre’s K-functional, Lipschitz class, mixed modulus of smoothness

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Authors: Yahia Massinissa, Yahia Mouloud

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Cystic fibrosis (CF), the most common lethal genetic disease in the Europe population, is caused by mutations in the transmembrane conductance regulator gene (CFTR). It affects most organs including an epithelial tissue, base of hydroelectrolytic transepithelial transport, notably that aerial ways, the pancreas, the biliary ways, the intestine, sweat glands and the genital tractus. The gene whose anomalies are responsible of the cystic fibrosis codes for a protein Cl channel named CFTR (cystic fibrosis transmembrane conductance regulator) that exercises multiple functions in the cell, one of the most important in control of sodium and chlorine through epithelia. The deficient function translates itself notably by an abnormal production of viscous secretion that obstructs the execrator channels of this target organ: one observes then a dilatation, an inflammation and an atrophy of these organs. It also translates itself by an increase of the concentration in sodium and in chloride in sweat, to the basis of the sweat test. In order to do a phenotypical and genotypical diagnosis at a part of the Algerian population, our survey has been carried on 16 patients with evocative symptoms of the cystic fibrosis at that the clinical context has been confirmed by a sweat test. However, anomalies of the CFTR gene have been determined by electrophoresis in gel of polyacrylamide of the PCR products (polymerase chain reaction), after enzymatic digestion, then visualized to the ultraviolet (UV) after action of the ethidium bromide. All mutations detected at the time of our survey have already been identified at patients attained by this pathology in other populations of the world. However, the important number of found mutation with regard to the one of the studied patients testifies that the origin of this big clinical variability that characterizes the illness in the consequences of an enormous diversity of molecular defects of the CFTR gene.

Keywords: cystic fibrosis, CFTR gene, polymorphism, algerian population, sweat test, genotypical diagnosis

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Authors: Debesh R. Roy

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The fundamental issue in understanding the origin and growth mechanism of nanomaterials, from a fundamental unit is a big challenging problem to the scientists. Recently, an immense attention is generated to the researchers for prediction of exceptionally stable atomic cluster units as the building units for future smart materials. The present study is a systematic investigation on the stability and electronic properties of a series of bimetallic (semiconductor-alkaline earth) clusters, viz., BxMg3 (x=1-5) is performed, in search for exceptional and/ or unusual stable motifs. A very popular hybrid exchange-correlation functional, B3LYP as proposed by A. D. Becke along with a higher basis set, viz., 6-31+G[d,p] is employed for this purpose under the density functional formalism. The magic stability among the concerned clusters is explained using the jellium model. It is evident from the present study that the magic stability of B4Mg3 cluster arises due to the jellium shell closure.

Keywords: atomic clusters, density functional theory, jellium model, magic clusters, smart nanomaterials

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Authors: Youn-Sung Kim, Hye-Mi Kim, Sang-Hoon Seo, Jaden Cha

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This International standard IEC 61508 sets out a generic approach for all safety lifecycle activities for systems comprised of electrical/electronic/programmable electronic (E/E/PE) elements that are used to perform safety functions. The control unit in stage control system is safety related facilities to control state and speed for stage system running, and it performs safety-critical function by stage control system. The controller unit is part of safety loops corresponding to the IEC 61508 and classified as logic part in the safety loop. In this paper, we analyze using FMEDA (Failure Mode Effect and Diagnostic Analysis) to verification for fault tolerance methods and functional safety of control unit. Moreover, we determined SIL (Safety Integrity Level) for control unit according to the safety requirements defined in IEC 61508-2 based on an analyzed functional safety.

Keywords: safety function, failure mode effect, IEC 61508-2, diagnostic analysis, stage control system

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Authors: Lydia Tan, Philippe Lemey, Lieselot Houspie, Marco Viveen, Darren Martin, Frank Coenjaerts

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Introduction: Human respiratory syncytial virus (hRSV) is the leading cause of severe respiratory tract infections in infants under the age of two. Genomic substitutions and related evolutionary dynamics of hRSV are of great influence on virus transmission behavior. The evolutionary patterns formed are due to a precarious interplay between the host immune response and RSV, thereby selecting the most viable and less immunogenic strains. Studying genomic profiles can teach us which genes and consequent proteins play an important role in RSV survival and transmission dynamics. Study design: In this study, genetic diversity and evolutionary rate analysis were conducted on 36 RSV subgroup B whole genome sequences and 37 subgroup A genome sequences. Clinical RSV isolates were obtained from nasopharyngeal aspirates and swabs of children between 2 weeks and 5 years old of age. These strains, collected during epidemic seasons from 2001 to 2011 in the Netherlands and Belgium by either conventional or 454-sequencing. Sequences were analyzed for genetic diversity, recombination events, synonymous/non-synonymous substitution ratios, epistasis, and translational consequences of mutations were mapped to known 3D protein structures. We used Bayesian statistical inference to estimate the rate of RSV genome evolution and the rate of variability across the genome. Results: The A and B profiles were described in detail and compared to each other. Overall, the majority of the whole RSV genome is highly conserved among all strains. The attachment protein G was the most variable protein and its gene had, similar to the non-coding regions in RSV, more elevated (two-fold) substitution rates than other genes. In addition, the G gene has been identified as the major target for diversifying selection. Overall, less gene and protein variability was found within RSV-B compared to RSV-A and most protein variation between the subgroups was found in the F, G, SH and M2-2 proteins. For the F protein mutations and correlated amino acid changes are largely located in the F2 ligand-binding domain. The small hydrophobic phosphoprotein and nucleoprotein are the most conserved proteins. The evolutionary rates were similar in both subgroups (A: 6.47E-04, B: 7.76E-04 substitution/site/yr), but estimates of the time to the most recent common ancestor were much lower for RSV-B (B: 19, A: 46.8 yrs), indicating that there is more turnover in this subgroup. Conclusion: This study provides a detailed description of whole RSV genome mutations, the effect on translation products and the first estimate of the RSV genome evolution tempo. The immunogenic G protein seems to require high substitution rates in order to select less immunogenic strains and other conserved proteins are most likely essential to preserve RSV viability. The resulting G gene variability makes its protein a less interesting target for RSV intervention methods. The more conserved RSV F protein with less antigenic epitope shedding is, therefore, more suitable for developing therapeutic strategies or vaccines.

Keywords: drug target selection, epidemiology, respiratory syncytial virus, RSV

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Authors: Nicolas Haber

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The study addresses the conceptual design of Product-Service Systems (PSSs) as a means of innovating solutions with the aim of reducing the environmental load of conventional product based solutions. Functional approaches targeting PSS solutions are developed in instinctive methods within the constraints of the setting in which they are conceived. Adopting morphological matrices in designing PSS concepts allows a thorough understanding of the settings, stakeholders, and functional requirements. Additionally, such a methodology is robust and adaptable to product-oriented, use-oriented and result-oriented systems. The research is based on a functional decomposition of the task in a similar way as in product design; while extended to include service components, providers, and receivers, while assessing the adaptability and homogeneity of the selected components and actors. A use-oriented concept is presented via a practical case study at an agricultural boom-sprayer manufacturer to demonstrate the effectiveness of the morphological approach to justify its viability. Additionally, a life cycle analysis is carried out in order to evaluate the environmental advantages inherited in a PSS solution versus a conventional solution. In light of the applications presented, the morphological approach appears to be a valid and generic tactic to conceiving integrated solutions whilst capturing the interrelations between the actors and elements of an integrated product-service system.

Keywords: conceptual design, design for sustainability, functional decomposition, product-service systems

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Authors: D. S. Palimkar

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The FRIGDI (functional random integrodifferential inclusion) seems to be new and includes several known random differential inclusions already studied in the literature as special cases have been discussed in the literature for various aspects of the solutions. In this paper, we prove the existence result for FIGDI under the non-convex case of multi-valued function involved in it.Using random fixed point theorem of B. C. Dhage and caratheodory condition. This result is new to the theory of differential inclusion.

Keywords: caratheodory condition, random differential inclusion, random solution, integro-differential inclusion

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Authors: A. Kellou, L. Rouaiguia, L. Rabahi

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In the present work, the atomic hydrogen absorption trend in the GdNi5 and GdNi4Cu rare earth compounds within the hexagonal CaCu5 type of crystal structure (space group P6/mmm) is investigated. The density functional theory (DFT) combined with the generalized gradient approximation (GGA) is used to study the site preference of atomic hydrogen at 0K. The octahedral and tetrahedral interstitial sites are considered. The formation energies and structural properties are determined in order to evaluate hydrogen effects on the stability of the studied compounds. The energetic diagram of hydrogen storage is established and compared in GdNi5 and GdNi4Cu. The magnetic properties of the selected compounds are determined using spin polarized calculations. The obtained results are discussed with and without hydrogen addition taking into account available theoretical and experimental results.

Keywords: density functional theory, hydrogen storage, rare earth compounds, structural and magnetic properties

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Authors: Dong Tran, Thanh Dac Van, Ly Le

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Hemagglutinin (HA) and Neuraminidase (NA) play an important role in host immune evasion across influenza virus evolution process. The correlation between HA and NA evolution in respect to epitopic evolution and drug interaction has yet to be investigated. In this study, combining of sequence to structure evolution and statistical analysis on epitopic/binding site specificity, we identified potential therapeutic features of HA and NA that show specific antibody binding site of HA and specific binding distribution within NA active site of current inhibitors. Our approach introduces the use of sequence variation and molecular interaction to provide an effective strategy in establishing experimental based distributed representations of protein-protein/ligand complexes. The most important advantage of our method is that it does not require complete dataset of complexes but rather directly inferring feature interaction from sequence variation and molecular interaction. Using correlated sequence analysis, we additionally identified co-evolved mutations associated with maintaining HA/NA structural and functional variability toward immunity and therapeutic treatment. Our investigation on the HA binding specificity revealed unique conserved stalk domain interacts with unique loop domain of universal antibodies (CR9114, CT149, CR8043, CR8020, F16v3, CR6261, F10). On the other hand, NA inhibitors (Oseltamivir, Zaninamivir, Laninamivir) showed specific conserved residue contribution and similar to that of NA substrate (sialic acid) which can be exploited for drug design. Our study provides an important insight into rational design and identification of novel therapeutics targeting universally recognized feature of influenza HA/NA.

Keywords: influenza virus, hemagglutinin (HA), neuraminidase (NA), sequence evolution

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