205 research outputs found

    Development of constitutive model for precast prestressed concrete segmental columns

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    The interest of using precast segmental columns in construction of concrete bridges has significantly increased in recent years. One research area of concrete bridges is the application of Precast Prestressed Concrete Segmental (PPCS) Column in any structural analysis software or FE program code. Modeling a PPCS column, which consists of various materials with interaction between them, is complicated and time-consuming. This research attempts to formulate the stiffness matrix of PPCS columns in order to form the constitutive model in linear form to evaluate the response of the columns. A two-dimensional finite element model is presented in the finite element package ANSYS. Parametric studies are conducted by finite element models to verify the constitutive models for the PPCS column with a different number of concrete segments. Comparison between the constitutive model and the FE program results indicates that the constitutive model is accurate enough to predict the deformation of the PPCS columns

    Derandomizing Codes for the Binary Adversarial Wiretap Channel of Type II

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    We revisit the binary adversarial wiretap channel (AWTC) of type II in which an active adversary can read a fraction rr and flip a fraction pp of codeword bits. The semantic-secrecy capacity of the AWTC II is partially known, where the best-known lower bound is non-constructive, proven via a random coding argument that uses a large number (that is exponential in blocklength nn) of random bits to seed the random code. In this paper, we establish a new derandomization result in which we match the best-known lower bound of 1H2(p)r1-H_2(p)-r where H2()H_2(\cdot) is the binary entropy function via a random code that uses a small seed of only O(n2)O(n^2) bits. Our random code construction is a novel application of pseudolinear codes -- a class of non-linear codes that have kk-wise independent codewords when picked at random where kk is a design parameter. As the key technical tool in our analysis, we provide a soft-covering lemma in the flavor of Goldfeld, Cuff and Permuter (Trans. Inf. Theory 2016) that holds for random codes with kk-wise independent codewords

    Polymorphisms of MTHFR and MTR genes are not related to susceptibility to childhood ALL in north India

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    Background:Acute lymphoblastic leukemia (ALL) is the most worldwide common type of childhood cancer. Methylenetetrahydrofolate reductase (MTHFR) and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR) participate in folate pathways and are known as critical factors for DNA integrity as well as DNA hypomethylation. The aim of this work is to investigate frequency of MTHFR (677C→T and 1298A→C) and MTR (2756A→G) polymorphisms and their interaction with respect to possible effect on risk of childhood ALL among North Indian population. Procedure: A case control study from has been conducted on bone marrow and peripheral blood samples from 125 ALL patients and 100 sex-age matched healthy controls using PCR-RFLP method. Results: No statistically significant differences were observed for different genotypes between patients and controls (p>0.05). Significant difference for the risk of ALL in individuals having genotype of MTHFR 677TT (OR=0.61, 95% CI=0.21–1.77) and MTHFR 1298CC (OR=0.56, 95% CI=0.18–1.68) was not observed. The correlation of SNP of MTR gene and risk of ALL was not observed, too. Conclusions: The differences in distribution of possible combined genotypes of MTHFR (677C→T, 1298A→C) and MTR (2756A→G) between ALL patients and controls were statistically insignificant

    The Evaluation of Growth, Yield and Physiological Responses of African Horned Cucumber (Cucumis metuliferus L.) to Deficit Irrigation

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    Introduction Water stress is the most prominent abiotic stress limiting agricultural crop growth and productivity. Deficit irrigation stress as a consequence of the progressive decrease in water availability has been a hot topic regarding food security during the last two decades. Growth and development of plants is influenced by reduction in turgor that results in decreased nutrient acquisition from dry soil. When water supply is limited, plant growth and yield is reduced and plant structure is modified by decreasing in leaf size. The effect of deficit irrigation on fruit yield and quality has been reported by numerous researchers with different results. In melon, deficit irrigation reduced marketable fruit number and yield, average fruit weight, fruit diameter and did not affect rind thickness and seed cavity, but increased total soluble solids content. Although the effects of water stress have been studied on growth and yield of different crops during the last years, recent information on the response of African horned cucumber yield and quality to deficit irrigation remains limited, particularly about the results of restricted water distributions in arid and sub-arid environments. The main goal of this study was to evaluate the effect of controlled deficit irrigation on growth, physiological parameters and yield and fruit quality of African horned cucumber.   Material and Methods Field experiment was performed based on a completely randomized block design with three irrigation regimes (60, 80 and 100 %ETc), whit three replications at Research Farm of University of Zanjan during the 2019. The African horned cucumber seeds were sown on 1th July 2020 at recommended spacing of 50 cm in row with 120 cm between rows. The irrigation system consisted of one drip line every crop row. The three irrigation levels were calculated based on actual evapotranspiration (ETc): (1) control, irrigated 100% crop water requirement, (2) deficit irrigation 80% ETc and (3) deficit irrigation 60% ETc. The Water requirement of the plant for control treatment was estimated using long-term average daily data of meteorological parameters recorded at Zanjan Meteorological Station and following relation. Before starting the differential irrigation at five-leaf stage, all treatments were supplied with similar amount of water to maximize stands and uniform crop establishment. During plant growth, the relative water content, proline content, electrolyte leakage, chlorophyll and carotenoids, P and K contents were measured. After fruit harvest, vine length of each plant, leaf dry weight and stem diameter were measured. The fruits were harvested when color changed from green to yellow. Fruit weight, fruit number per plant and fruit yield per plant was measured. Immediately after harvest, fruit firmness, total soluble solid, total phenols content, antioxidant capacity and vitamin C were determined.     Results and Discussion As the results showed water deficit stress significantly reduced plant length, chlorophyll content, and increased carotenoids content. Based on the findings, deficit irrigation caused a significant reduction in leaf relative water content. According to the results, phosphorus and potassium contents in African horned cucumber leaves decreased with deficit irrigation treatments. The highest P and K contents were found under irrigation 100 %ETc treatment. Drought stress and associated reduction in soil moisture can decrease plant nutrient uptake by reducing nutrient supply through mineralization. The proline content increased with the deficit irrigation treatments; in particular with sever deficit irrigation (60 %ETc). Mean comparisons of data showed that deficit irrigation led to a significant increase in electrolyte leakage compared to control. Water deficit stress caused significant reductions in yield. The highest fruit number per plant and yield were obtained under irrigation 100% ETc. The average fruit weigh significantly increased in response to increase water deficit stress. Deficit irrigation treatments significantly decreased vitamin C and fruit firmness. Significant differences among irrigation treatments were observed for total phenols and total soluble solid contents. The phenols and total soluble solid contents increased with the decrease of irrigation water applied. Antioxidant capacity was affected significantly by the irrigation treatments, and water deficit stress increased antioxidant capacity, which no significant difference was observed between irrigation 100 and 80 %ETc.   Conclusion Water deficit has been shown to adversely affect plant growth, fruit yield, and leaf water status of African horned cucumber, but led to increase the TSS and antioxidant capacity. According to the results, fruit yield reduced 13.9 % under irrigation 80% ETc compared to irrigation 100% ETc, However, water consumption was saved by 20% and improved fruit weight and fruit quality with increasing soluble solids and antioxidant capacity

    In vivo E2F reporting reveals efficacious schedules of MEK1/2–CDK4/6 targeting and mTOR–s6 resistance mechanisms

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    Targeting cyclin-dependent kinases 4/6 (CDK4/6) represents a therapeutic option in combination with BRAF inhibitor and/or MEK inhibitor (MEKi) in melanoma; however, continuous dosing elicits toxicities in patients. Using quantitative and temporal in vivo reporting, we show that continuous MEKi with intermittent CDK4/6 inhibitor (CDK4/6i) led to more complete tumor responses versus other combination schedules. Nevertheless, some tumors acquired resistance that was associated with enhanced phosphorylation of ribosomal S6 protein. These data were supported by phospho-S6 staining of melanoma biopsies from patients treated with CDK4/6i plus targeted inhibitors. Enhanced phospho-S6 in resistant tumors provided a therapeutic window for the mTORC1/2 inhibitor AZD2014. Mechanistically, upregulation or mutation of NRAS was associated with resistance in in vivo models and patient samples, respectively, and mutant NRAS was sufficient to enhance resistance. This study utilizes an in vivo reporter model to optimize schedules and supports targeting mTORC1/2 to overcome MEKi plus CDK4/6i resistance. SIGnIFICAnCE: Mutant BRAF and NRAS melanomas acquire resistance to combined MEK and CDK4/6 inhibition via upregulation of mTOR pathway signaling. This resistance mechanism provides the preclinical basis to utilize mTORC1/2 inhibitors to improve MEKi plus CDK4/6i drug regimens

    Spatial and temporal homogeneity of driver mutations in diffuse intrinsic pontine glioma.

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    Diffuse Intrinsic Pontine Gliomas (DIPGs) are deadly paediatric brain tumours where needle biopsies help guide diagnosis and targeted therapies. To address spatial heterogeneity, here we analyse 134 specimens from various neuroanatomical structures of whole autopsy brains from nine DIPG patients. Evolutionary reconstruction indicates histone 3 (H3) K27M-including H3.2K27M-mutations potentially arise first and are invariably associated with specific, high-fidelity obligate partners throughout the tumour and its spread, from diagnosis to end-stage disease, suggesting mutual need for tumorigenesis. These H3K27M ubiquitously-associated mutations involve alterations in TP53 cell-cycle (TP53/PPM1D) or specific growth factor pathways (ACVR1/PIK3R1). Later oncogenic alterations arise in sub-clones and often affect the PI3K pathway. Our findings are consistent with early tumour spread outside the brainstem including the cerebrum. The spatial and temporal homogeneity of main driver mutations in DIPG implies they will be captured by limited biopsies and emphasizes the need to develop therapies specifically targeting obligate oncohistone partnerships

    Atezolizumab-Induced Psoriasiform Drug Eruption Successfully Treated with Ixekizumab: A Case Report and Literature Review

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    Immune-related cutaneous adverse events (ircAE) are commonly seen with immune checkpoint inhibitors such as atezolizumab. Atezolizumab-induced psoriasis has been previously reported as an ircAE, especially in patients with pre-existing psoriasis. The severity of the reaction influences treatment of the cutaneous eruption. Biologics should be considered as a treatment option for severe refractory psoriasiform eruptions even in patients with complex medical conditions like chronic infections and malignancy. This is the first reported case of successful treatment of atezolizumab-induced psoriasiform eruption with ixekizumab, a neutralizing IL17A monoclonal antibody, to the best of our knowledge. Herein, we present a 63-year-old man with a history of human immunodeficiency virus and psoriasis who presented with atezolizumab-induced psoriasiform eruption while being treated for metastatic hepatocellular carcinoma. After initiating ixekizumab, atezolizumab was restarted without cutaneous eruption

    Demographic characteristics and the first program of colorectal cancer (CRC) screening in north of Iran (2016)

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    Background: Colorectal cancer (CRC) is one of the most common types of gastrointestinal cancers. This study aimed to determine the demographic characteristics and their relationships with the results of the first screening program for CRC in people over 50 years old in northern Iran. Methods: This cross-sectional study was conducted in 2016 on 924 eligible people over 50 years old. Initial screening was done by IFOBT and then colonoscopy was performed if the results were positive. The demographic characteristics of individuals including age, sex, place of residence, marital status, body mass index (BMI) and education level were investigated with the results of the colonoscopy and the test results. Results: The mean age of participants was 59.38 years, and the participation of women (57.0) and rural residents (54.2) were higher in the screening program. According to the demographic variables, age was considered as a strong independent predictor variable, so that the prevalence of positive test results was more than 2 times higher in subjects older than 70 compared with subjects aged �60 (OR =2.05; 95 CI, 1.18-3.55, P=0.010). Also, the chance of positive test result in the age group �55 years old was 23, with an increase of 64 in the age group above 75 years (P<0.001). Among the positive test subjects, 118 cases underwent colonoscopy. Conclusions: The prevalence of IFOBT positivity was increased with age. Therefore, given the aging population of the country, it is recommended to emphasize on the screening of older people in the general population. ©Journal of Gastrointestinal Oncology

    Neutrophilic Panniculitis Associated With Myelodysplastic Syndrome/Myeloproliferative Neoplasm: A Case Report and Literature Review

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    INTRODUCTION: Neutrophilic panniculitis (NP) is a rare subtype of neutrophilic dermatosis, a group of neutrophil-rich inflammatory skin disorders that can present in association with myeloid neoplasms. NP is defined by the presence of a neutrophilic infiltrate in the fat lobules of the subcutis in the absence of either infection or vasculitis. We herein describe a 65-year-old woman with a recent diagnosis of myelodysplastic syndrome/myeloproliferative neoplasm overlap syndrome (MDS/MPN) who abruptly developed painful, pruritic nodules consistent with NP. CASE PRESENTATION: A 65-year-old woman with MDS/MPN presented for evaluation of painful and pruritic nodules on her upper and lower extremities. A biopsy revealed a lobular neutrophilic infiltrate in the subcutis without evidence of microorganisms or vasculitis. The patient was diagnosed with NP and treated with oral prednisone. Within 1 month of treatment, she reported complete resolution of the nodules. DISCUSSION: Similar to other neutrophilic dermatoses, NP may arise in association with hematologic malignancies of myeloid origin, such as MDS/MPN. A literature review revealed that most cases of NP associated with MDS occur after the onset of MDS and respond to systemic corticosteroids, not antibiotics. Infection should be ruled out before initiating treatment with systemic steroids. CONCLUSION: Although the mechanism is still unknown, it is important for clinicians to be aware that NP is associated with MDS; thus, hematological malignancies should be investigated upon diagnosis of NP. Once diagnosed, NP is easily treated and has an excellent response to systemic corticosteroids

    Characterization and prognostic value of mutations in exons 5 and 6 of the p53 gene in patients with colorectal cancers in central Iran

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    Background/Aims: We aimed to investigate the relation-ships among various mutations of the p53 gene and their protein products, histological characteristics, and disease prognosis of primary colorectal cancer in Isfahan, central Iran. Methods: Sixty-one patients with colorectal adenocarcinoma were enrolled in the study. Mutations of the p53 gene were detected by single-stranded conformation polymorphism and DNA sequencing. The protein stability was evaluated by immunohistochemistry. Patients were followed up to 48 months. Results: Twenty-one point mutations in exons 5 and 6 were detected in the tumor specimens of 14 patients (23%). Of those, 81% and 9.5% were missense and nonsense mutations, respectively. There were also two novel mutations in the intronic region between exons 5 and 6. In 11 mutated specimens, protein stability and protein accumulation were identified. There was a relationship between the type of mutation and protein accumulation in exons 5 and 6 of the p53 gene. The presence of the mutation was associated with an advanced stage of cancer (trend, p&#60;0.009). Patients with mutated p53 genes had significantly lower survival rates than those with wild type p53 genes (p&#60;0.01). Conclusions: Mutations in exons 5 and 6 of the p53 gene are common genetic alterations in colorectal adenocarcinoma in central Iran and are associated with a poor prognosis of the disease
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