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Sökning: WFRF:(Khan Rasheed)

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1.
  • Ahmad, Shafqat, et al. (författare)
  • Physical activity, smoking, and genetic predisposition to obesity in people from Pakistan : the PROMIS study
  • 2015
  • Ingår i: BMC Medical Genetics. - : BioMed Central. - 1471-2350. ; 16
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Multiple genetic variants have been reliably associated with obesity-related traits in Europeans, but little is known about their associations and interactions with lifestyle factors in South Asians.Methods: In 16,157 Pakistani adults (8232 controls; 7925 diagnosed with myocardial infarction [MI]) enrolled in the PROMIS Study, we tested whether: a) BMI-associated loci, individually or in aggregate (as a genetic risk score - GRS), are associated with BMI; b) physical activity and smoking modify the association of these loci with BMI. Analyses were adjusted for age, age(2), sex, MI (yes/no), and population substructure.Results: Of 95 SNPs studied here, 73 showed directionally consistent effects on BMI as reported in Europeans. Each additional BMI-raising allele of the GRS was associated with 0.04 (SE = 0.01) kg/m(2) higher BMI (P = 4.5 x 10(-14)). We observed nominal evidence of interactions of CLIP1 rs11583200 (P-interaction = 0.014), CADM2 rs13078960 (P-interaction = 0.037) and GALNT10 rs7715256 (P-interaction = 0.048) with physical activity, and PTBP2 rs11165643 (P-interaction = 0.045), HIP1 rs1167827 (P-interaction = 0.015), C6orf106 rs205262 (P-interaction = 0.032) and GRID1 rs7899106 (P-interaction = 0.043) with smoking on BMI.Conclusions: Most BMI-associated loci have directionally consistent effects on BMI in Pakistanis and Europeans. There were suggestive interactions of established BMI-related SNPs with smoking or physical activity.
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  • Khan, Yusra Habib, et al. (författare)
  • Barriers and facilitators of childhood COVID-19 vaccination among parents : A systematic review
  • 2022
  • Ingår i: Frontiers in Pediatrics. - : Frontiers Media S.A.. - 2296-2360. ; 10
  • Forskningsöversikt (refereegranskat)abstract
    • BackgroundThe acceptance of vaccination against COVID-19 among parents of young children plays a significant role in controlling the current pandemic. A wide range of factors that influence vaccine hesitancy in adults has been reported worldwide, but less attention has been given to COVID-19 vaccination among children. Vaccine hesitancy is considered a major challenge in achieving herd immunity, and it is more challenging among parents as they remain deeply concerned about their child's health. In this context, a systematic review of the current literature is inevitable to assess vaccine hesitancy among parents of young children to ensure a successful ongoing vaccination program.MethodA systematic search of peer-reviewed English literature indexed in Google Scholar, PubMed, Embase, and Web of science was performed using developed keywords between 1 January 2020 and August 2022. This systematic review included only those studies that focused on parental concerns about COVID-19 vaccines in children up to 12 years without a diagnosis of COVID-19. Following PRISMA guidelines, a total of 108 studies were included. The quality appraisal of the study was performed by Newcastle-Ottawa Scale (NOS).ResultsThe results of 108 studies depict that vaccine hesitancy rates differed globally with a considerably large number of factors associated with it. The highest vaccine hesitancy rates among parents were reported in a study from the USA (86.1%) and two studies from Saudi Arabia (> 85%) and Turkey (89.6%). Conversely, the lowest vaccine hesitancy rates ranging from 0.69 and 2% were found in two studies from South Africa and Switzerland, respectively. The largest study (n = 227,740) was conducted in Switzerland while the smallest sample size (n = 12) was represented by a study conducted in the USA. The most commonly reported barriers to childhood vaccination were mothers' lower education level (N = 46/108, 43%), followed by financial instability (N = 19/108, 18%), low confidence in new vaccines (N = 13/108, 12%), and unmonitored social media platforms (N = 5/108, 4.6%). These factors were significantly associated with vaccine refusal among parents. However, the potential facilitators for vaccine uptake among respondents who intended to have their children vaccinated include higher education level (N = 12/108, 11%), followed by information obtained through healthcare professionals (N = 9/108, 8.3%) and strong confidence in preventive measures taken by the government (N = 5/81, 4.6%).ConclusionThis review underscores that parents around the globe are hesitant to vaccinate their kids against COVID-19. The spectrum of factors associated with vaccine hesitancy and uptake varies across the globe. There is a dire need to address vaccine hesitancy concerns regarding the efficacy and safety of approved vaccines. Local context is inevitable to take into account while developing programs to reduce vaccine hesitancy. There is a dire need to devise strategies to address vaccine hesitancy among parents through the identification of attributing factors.
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3.
  • Khattak, Muhammad Uzair, et al. (författare)
  • MaPLe: Multi-modal Prompt Learning
  • 2023
  • Ingår i: 2023 IEEE/CVF CONFERENCE ON COMPUTER VISION AND PATTERN RECOGNITION (CVPR). - : IEEE COMPUTER SOC. - 9798350301298 - 9798350301304 ; , s. 19113-19122
  • Konferensbidrag (refereegranskat)abstract
    • Pre-trained vision-language (V-L) models such as CLIP have shown excellent generalization ability to downstream tasks. However, they are sensitive to the choice of input text prompts and require careful selection of prompt templates to perform well. Inspired by the Natural Language Processing (NLP) literature, recent CLIP adaptation approaches learn prompts as the textual inputs to ne-tune CLIP for downstream tasks. We note that using prompting to adapt representations in a single branch of CLIP (language or vision) is sub-optimal since it does not allow the exibility to dynamically adjust both representation spaces on a downstream task. In this work, we propose Multi-modal Prompt Learning (MaPLe) for both vision and language branches to improve alignment between the vision and language representations. Our design promotes strong coupling between the vision-language prompts to ensure mutual synergy and discourages learning independent uni-modal solutions. Further, we learn separate prompts across different early stages to progressively model the stage-wise feature relationships to allow rich context learning. We evaluate the effectiveness of our approach on three representative tasks of generalization to novel classes, new target datasets and unseen domain shifts. Compared with the state-of-the-art method Co-CoOp, MaPLe exhibits favorable performance and achieves an absolute gain of 3.45% on novel classes and 2.72% on overall harmonic-mean, averaged over 11 diverse image recognition datasets. Our code and pre-trained models are available at https://github.com/muzairkhattak/multimodal-prompt-learning.
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  • Maaz, Muhammad, et al. (författare)
  • Class-Agnostic Object Detection with Multi-modal Transformer
  • 2022
  • Ingår i: COMPUTER VISION, ECCV 2022, PT X. - Cham : SPRINGER INTERNATIONAL PUBLISHING AG. - 9783031200793 - 9783031200809 ; , s. 512-531
  • Konferensbidrag (refereegranskat)abstract
    • What constitutes an object? This has been a long-standing question in computer vision. Towards this goal, numerous learning-free and learning-based approaches have been developed to score objectness. However, they generally do not scale well across new domains and novel objects. In this paper, we advocate that existing methods lack a top-down supervision signal governed by human-understandable semantics. For the first time in literature, we demonstrate that Multi-modal Vision Transformers (MViT) trained with aligned image-text pairs can effectively bridge this gap. Our extensive experiments across various domains and novel objects show the state-of-the-art performance of MViTs to localize generic objects in images. Based on the observation that existing MViTs do not include multi-scale feature processing and usually require longer training schedules, we develop an efficient MViT architecture using multi-scale deformable attention and late vision-language fusion. We show the significance of MViT proposals in a diverse range of applications including open-world object detection, salient and camouflage object detection, supervised and self-supervised detection tasks. Further, MViTs can adaptively generate proposals given a specific language query and thus offer enhanced interactability.
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  • Rasheed, Hanoona, et al. (författare)
  • Fine-tuned CLIP Models are Efficient Video Learners
  • 2023
  • Ingår i: 2023 IEEE/CVF CONFERENCE ON COMPUTER VISION AND PATTERN RECOGNITION, CVPR. - : IEEE COMPUTER SOC. - 9798350301298 - 9798350301304 ; , s. 6545-6554
  • Konferensbidrag (refereegranskat)abstract
    • Large-scale multi-modal training with image-text pairs imparts strong generalization to CLIP model. Since training on a similar scale for videos is infeasible, recent approaches focus on the effective transfer of image-based CLIP to the video domain. In this pursuit, new parametric modules are added to learn temporal information and inter-frame relationships which require meticulous design efforts. Furthermore, when the resulting models are learned on videos, they tend to overfit on the given task distribution and lack in generalization aspect. This begs the following question: How to effectively transfer image-level CLIP representations to videos? In this work, we show that a simple Video Fine-tuned CLIP (ViFi-CLIP) baseline is generally sufficient to bridge the domain gap from images to videos. Our qualitative analysis illustrates that the framelevel processing from CLIP image-encoder followed by feature pooling and similarity matching with corresponding text embeddings helps in implicitly modeling the temporal cues within ViFi-CLIP. Such fine-tuning helps the model to focus on scene dynamics, moving objects and inter-object relationships. For low-data regimes where full fine-tuning is not viable, we propose a bridge and prompt approach that first uses fine-tuning to bridge the domain gap and then learns prompts on language and vision side to adapt CLIP representations. We extensively evaluate this simple yet strong baseline on zero-shot, base-to-novel generalization, few-shot and fully supervised settings across five video benchmarks. Our code and pre-trained models are available at https://github.com/muzairkhattak/ViFi-CLIP.
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  • Shaker, Abdelrahman, et al. (författare)
  • SwiftFormer: Efficient Additive Attention for Transformer-based Real-time Mobile Vision Applications
  • 2023
  • Ingår i: 2023 IEEE/CVF INTERNATIONAL CONFERENCE ON COMPUTER VISION (ICCV 2023). - : IEEE COMPUTER SOC. - 9798350307184 - 9798350307191 ; , s. 17379-17390
  • Konferensbidrag (refereegranskat)abstract
    • Self-attention has become a defacto choice for capturing global context in various vision applications. However, its quadratic computational complexity with respect to image resolution limits its use in real-time applications, especially for deployment on resource-constrained mobile devices. Although hybrid approaches have been proposed to combine the advantages of convolutions and self-attention for a better speed-accuracy trade-off, the expensive matrix multiplication operations in self-attention remain a bottleneck. In this work, we introduce a novel efficient additive attention mechanism that effectively replaces the quadratic matrix multiplication operations with linear element-wise multiplications. Our design shows that the key-value interaction can be replaced with a linear layer without sacrificing any accuracy. Unlike previous state-of-the-art methods, our efficient formulation of self-attention enables its usage at all stages of the network. Using our proposed efficient additive attention, we build a series of models called "Swift-Former" which achieves state-of-the-art performance in terms of both accuracy and mobile inference speed. Our small variant achieves 78.5% top-1 ImageNet-1K accuracy with only 0.8 ms latency on iPhone 14, which is more accurate and 2 faster compared to MobileViT-v2. Our code and models: https://tinyurl.com/5ft8v46w
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  • Alam, Mahmood, et al. (författare)
  • Performance analysis of microchannel heat sink with ribbed pinfins
  • 2024
  • Ingår i: International Journal of Heat and Fluid Flow. - : Elsevier BV. - 0142-727X .- 1879-2278. ; 109
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper presents a numerical study investigating the effect of ribbed pinfins on the thermal–hydraulic performance of a microchannel heat sink. A three-dimensional numerical model of a single rectangular microchannel with rectangular pinfins having ribs on them is developed, and simulations are performed for different rib configurations under laminar flow conditions with deionized water as the coolant. The study is conducted in two parts. The first part examines the influence of varying numbers of ribs on the pinfins while maintaining a constant rib width. The results show that increasing the number of ribs initially enhances heat transfer, with the case having two ribs (R2) exhibiting the highest Nusselt number ratio and lowest thermal resistance, up to 16 % lower than the nonribbed case (R0). However, a further increase in the number of ribs leads to a decrease in heat transfer performance due to the reduced cross-sectional area for heat conduction through the ribs. Moreover, the highest performance factor is exhibited by the case consisting of seven ribs (R7). The second part explores the impact of varying rib width, using the optimal R7 configuration based on the performance factor from the first part. The results indicate that increasing the rib width significantly improves heat transfer, with the widest rib case (W7) achieving up to a 25 % increase in Nusselt number compared to a plain microchannel. The study provides insights into the design of efficient microchannel heat sinks with ribbed pinfins for effective cooling of high-heat-flux electronic devices.
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12.
  • Grövdal, Michael, et al. (författare)
  • Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy
  • 2010
  • Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 150:3, s. 293-302
  • Tidskriftsartikel (refereegranskat)abstract
    • This prospective Phase II study is the first to assess the feasibility and efficacy of maintenance 5-azacytidine for older patients with high-risk myelodysplastic syndrome (MDS), chronic myelomonocytic leukaemia and MDS-acute myeloid leukaemia syndromes in complete remission (CR) after induction chemotherapy. Sixty patients were enrolled and treated by standard induction chemotherapy. Patients that reached CR started maintenance therapy with subcutaneous azacytidine, 5/28 d until relapse. Promoter-methylation status of CDKN2B (P15 ink4b), CDH1 and HIC1 was examined pre-induction, in CR and 6, 12 and 24 months post CR. Twenty-four (40%) patients achieved CR after induction chemotherapy and 23 started maintenance treatment with azacytidine. Median CR duration was 13.5 months, >24 months in 17% of the patients, and 18-30.5 months in the four patients with trisomy 8. CR duration was not associated with CDKN2B methylation status or karyotype. Median overall survival was 20 months. Hypermethylation of CDH1 was significantly associated with low CR rate, early relapse, and short overall survival (P = 0.003). 5-azacytidine treatment, at a dose of 60 mg/m(2) was well tolerated. Grade III-IV thrombocytopenia and neutropenia occurred after 9.5 and 30% of the cycles, respectively, while haemoglobin levels increased during treatment. 5-azacytidine treatment is safe, feasible and may be of benefit in a subset of patients.
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13.
  • Grövdal, Michael, et al. (författare)
  • Negative effect of DNA hypermethylation on the outcome of intensive chemotherapy in older patients with high-risk myelodysplastic syndromes and acute myeloid leukemia following myelodysplastic syndrome
  • 2007
  • Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 13:23, s. 7107-7112
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Promoter hypermethylation of, for example, tumor-suppressor genes, is considered to be an important step in cancerogenesis and a negative risk factor for survival in patients with myelodysplastic syndromes (MDS); however, its role for response to therapy has not been determined. This study was designed to assess the effect of methylation status on the outcome of conventional induction chemotherapy. EXPERIMENTAL DESIGN: Sixty patients with high-risk MDS or acute myeloid leukemia following MDS were treated with standard doses of daunorubicin and 1-beta-d-arabinofuranosylcytosine. Standard prognostic variables and methylation status of the P15(ink4b) (P15), E-cadherin (CDH), and hypermethylated in cancer 1 (HIC) genes were analyzed before treatment. RESULTS: Forty percent of the patients achieved complete remission (CR). CR rate was lower in patients with high WBC counts (P = 0.03) and high CD34 expression on bone marrow cells (P = 0.02). Whereas P15 status alone was not significantly associated with CR rate (P = 0.25), no patient with hypermethylation of all three genes achieved CR (P = 0.03). Moreover, patients with CDH methylation showed a significantly lower CR rate (P = 0.008), and CDH methylation retained its prognostic value also in the multivariate analysis. Hypermethylation was associated with increased CD34 expression, but not with other known predictive factors for response, such as cytogenetic profile. CONCLUSIONS: We show for the first time a significant effect of methylation status on the outcome of conventional chemotherapy in high-risk MDS and acute myelogenous leukemia following MDS. Provided confirmed in an independent study, our results should be used as a basis for therapeutic decision-making in this patient group.
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14.
  • Jabeen, Rida, et al. (författare)
  • General construction of efficient circular partially strongly-balanced repeated measurements designs
  • 2022
  • Ingår i: Communications in statistics. Simulation and computation. - : Informa UK Limited. - 0361-0918 .- 1532-4141. ; , s. 1-11
  • Tidskriftsartikel (refereegranskat)abstract
    • Residual effects in repeated measurements design (RMDs) leads to wrong estimation of direct treatment effects. Minimal strongly balanced RMDs are preferred to balance out the residual effects. The partially strongly balanced designs form an important family of RMDs which provide designs where minimal strongly balanced RMDs do not exist. In this article, a general construction of efficieint circular partially strongly-balanced RMDs is given in periods of k different sizes which produces these designs in periods of equal sizes, two different sizes, three different sizes, …, by putting k = 1, 2, 3, …, respectively. 
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17.
  • Khan, Abid, et al. (författare)
  • Construction of minimal circular nearly strongly balanced repeated measurements designs and their conversion
  • 2023
  • Ingår i: Communications in statistics. Simulation and computation. - : Informa UK Limited. - 0361-0918 .- 1532-4141. ; 52:12, s. 5749-5758
  • Tidskriftsartikel (refereegranskat)abstract
    • Repeated measurements designs (RMDs) are very useful and economical but unfortunately, with the use of RMDs, a major source of bias is arisen, that is the carry over effect. Minimal designs which are strongly and nearly strongly balanced, are preferred to estimate the direct and carry over effects independently. In this article, some new classes of minimal circular nearly strongly balanced RMDs are constructed in periods of two and three different sizes which can be converted directly into minimal circular balanced and minimal strongly balanced which are highly efficient.
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18.
  • Khan, Majid, et al. (författare)
  • Forecasting the strength of graphene nanoparticles-reinforced cementitious composites using ensemble learning algorithms
  • 2024
  • Ingår i: Results in Engineering (RINENG). - : Elsevier B.V.. - 2590-1230. ; 21
  • Tidskriftsartikel (refereegranskat)abstract
    • Integrating nanomaterials into concrete is a promising solution to improve concrete strength and durability. However, the intricacies of such nanoscale cementitious composites are highly complex. Traditional regression models encounter limitations in capturing these intricate compositions to provide accurate and reliable estimations. This study focuses on developing robust prediction models for the compressive strength (CS) of graphene nanoparticle-reinforced cementitious composites (GrNCC) through machine learning (ML) algorithms. Three ML models, bagging regressor (BR), decision tree (DT), and AdaBoost regressor (AR), were employed to predict CS based on a comprehensive dataset of 172 experimental values. Seven input parameters, including graphite nanoparticle (GrN) diameter, water-to-cement ratio (wc), GrN content (GC), ultrasonication (US), sand content (SC), curing age (CA), and GrN thickness (GT), were considered. The models were trained with 70 % of the data, and the remaining 30 % of the data was used for testing the models. Statistical metrics such as mean absolute error (MAE), root mean square error (RMSE) and correlation coefficient (R) were employed to assess the predictive accuracy of the models. The DT and AR models demonstrated exceptional accuracy, yielding high correlation coefficients of 0.983 and 0.979 for training, and 0.873 and 0.822 for testing, respectively. Shapley Additive exPlanation (SHAP) analysis highlighted the influential role of curing age and GrN thickness (GT), positively impacting CS, while an increased water-to-cement ratio (w/c) negatively affected CS. This study showcases the efficacy of ML techniques in accurately predicting CS of graphene nanoparticle-modified concrete, offering a swift and cost-effective approach for assessing nanomaterial impact on concrete strength and reducing reliance on time-consuming and expensive experiments.
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19.
  • Khan, Rasheed (författare)
  • DNA methylation and 5-azacytidine in myelodysplastic syndromes : pharmacodynamic, mechanistic and clinical studies
  • 2007
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Promoter DNA hypermethylation and hence silencing of e.g. tumour suppressor genes is considered to be an important step in carcinogenesis and has been associated with poor outcome in patients with myelodysplastic syndromes (MDS). In contrast to many other chemotherapeutic agents, the DNA hypomethylating compound 5-azacytidine has a positive therapeutic effect in patients with high-risk myelodysplastic syndromes (MDS), however, the lack of knowledge about its mechanism of action hampers clinical development of the drug. The first aim of the thesis was to assess the pharmocodynamic properties of 5-azacytidine, and the mechanism of 5-azacytidine-induced apoptosis as well as its link with DNA methylation. Secondly, we investigated the role of gene-specific methylation status for the outcome of induction chemotherapy in a cohort of patients high-risk MDS and MDS-AML, and assessed global and gene-specific (p15INK4B) methylation patterns in another cohort of patients with low and intermediate-risk MDS. 5-azacytidine induced dose-dependent hypomethylation and growth inhibition, as well as a complex pattern of apoptotic mechanisms regulated by multiple and separate pathways. Furthermore, we demonstrated a possible link between apoptosis and hypomethylation. We showed that optimal cellular effects of 5-azacytidine could be achieved by shorter exposure times than expected. Translated to shorter treatment duration in patients, this may eventually lead to superior and more cost-effective and convenient clinical treatment schedules. P15INK4B methylation plus methylation of CDH or HIC gene was more frequent in patients with conventional high-risk features, such as adverse karyoptype and high percentage of marrow blasts. DNA hypermethylation of multiple surrogate genes correlated with the percentage of blasts and marrow CD34 expression, but not with the degree of inefficient haematopoiesis. We demonstrated a significant negative impact of promoter methylation status on the outcome of conventional induction chemotherapy in high-risk MDS and MDS-AML, a finding that may have significant impact on the clinical management of patients with high-risk myeloid disease. Global and gene-specific DNA methylation pattern in MDS correlated with each other in the sense that more advanced MDS, characterized by p15INK4B methylation showed higher global DNA methylation than those with unmethylated p15INK4B. Global methylation status did not correlate with conventional risk factors, but was more pronounced in patients with severe erythroid failure. Patients with stable disease maintained their global DNA methylation level over time, and disease progression was associated with an increase in global DNA methylation in only half of the cases. To conclude, these studies provide important knowledge about the cellular mechanisms of 5-azacytidine and role of DNA methylation in patients with MDS and MDS-AML.
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20.
  • Khan, Umar Hasan, et al. (författare)
  • Localization of Compact Circularly Polarized RFID Tag Using ToA Technique
  • 2017
  • Ingår i: Radioengineering. - : SPOLECNOST PRO RADIOELEKTRONICKE INZENYRSTVI. - 1210-2512 .- 1805-9600. ; 26:1, s. 147-153
  • Tidskriftsartikel (refereegranskat)abstract
    • A compact, flexible crossed-dipole circularly polarized antenna using commercially available paper substrate is presented which caters North American frequency band. The crossed-dipoles have meandered lines for reduction of size as well as increased inductivity in the antenna. Dipoles have asymmetric T-shaped rectangular endings to provide the required compactness. Two semicircles are induced between the orthogonal dipoles and meandering matching structure to accomplish circular polarization excitation. Good impedance matching with the chip is achieved through a modified meander line matching structure. The proposed design dimensions are 32 x 32 x 0.4 mm(3). Systematic analysis revealed the results comprising circular polarization 3dB-AR bandwidth of 12 MHz (908-920 MHz) and power transmission coefficient bandwidth of 36 MHz (900-936 MHz). Time delay between interrogating signal and backscattered signal is measured and relative distance is calculated. Linear Least Square (LLS) method is applied to approximate the position of tag in interrogation area. The proposed tag is placed at known locations and its position is measured to analyze accuracy of the method by simulating the positioning algorithm code in MATLAB. Six valid tag positions 0.5-2 m read range and 0 degrees-150 degrees angular resolution has been investigated.
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  • Mahmood, Rashid, et al. (författare)
  • Assessment of antidiabetic potential and phytochemical profiling of Rhazya stricta root extracts
  • 2020
  • Ingår i: BMC Complementary Medicine and Therapies. - : Springer Nature. - 2662-7671. ; 20:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Diabetes mellitus is a chronic disease characterized by hyperglycemia that may occur due to genetic, environmental or lifestyle factors. Natural remedies have been used to treat diabetes since long and many antidiabetic compounds of varied efficacies have been isolated from medicinal plants. Rhazya stricta has been used for decades for the treatment of diabetes mellitus and associated ailments. Considering the folkloric use of R. stricta against diabetes, it was aimed to investigate the effectiveness of its root extracts against diabetes through in vitro assays and in vivo studies using animal model along with phytochemical profiling through GCMS. Methods: Various fractions of Rhazya stricta obtained through column chromatography were evaluated for a variety of assays including a-glucosidase, Dipeptidyl peptidase-IV (DPP-IV), beta-secretase and Glucagon-like peptide-1 (GLP-1) secretion studies. For the in vivo studies the alloxan-induced diabetic mice were treated with root extracts and blood glucose levels, HbA1C, and other biochemical markers along with the histological study of the liver were done. The phytochemical identification was performed using an Agilent 7890B GC coupled to a 7010 Triple Quadrupole (MS/MS) system. GraphPad Prism software version 5.01 was used for statistical analysis. Results: Majority of the extract fractions showed excellent results against diabetes by inhibiting enzymes DPP-IV (Up to 61%) and beta-secretase (Up to 83%) with IC50s 979 pg/ml and 169 mu g/ml respectively with increase in the GLP1 secretion. The results of in vivo studies indicated a marked reduction in blood glucose and HbA1c levels along with positive effects on other parameters like lipid profile, liver functions and renal functions of extract-treated mice as compared to control. The histological examination of the liver demonstrated hepatoprotective effects against diabetes led changes and various classes of phytochemicals were also identified through GCMS in different fractions. Conclusion: The results revealed strong antidiabetic activity of R. stricta root with the potential to protect body organs against diabetic changes. Moreover, a variety of phytochemicals has also been identified through GCMS that might be responsible for the antidiabetic potential of Rhazya stricta root.
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23.
  • Masson, Kristina, et al. (författare)
  • A role of Gab2 association in Flt3 ITD mediated Stat5 phosphorylation and cell survival.
  • 2009
  • Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 146, s. 193-202
  • Tidskriftsartikel (refereegranskat)abstract
    • Summary The haematopoietic growth factor receptor Flt3 has been implicated as major cause of transformation in acute myeloid leukaemia. Intracellular signals mediated by wild-type Flt3 are involved in cell differentiation and survival whereas signalling via the mutant Flt3 ITD (internal tandem duplication) promotes enhanced cell growth. In this study, we identified tyrosines 768, 955 and 969 of Flt3 as phosphorylation sites and mediators of growth factor receptor binding protein 2 (Grb2) interaction, leading to the association of Grb2 associated binder 2 (Gab2) and contributing to proliferation and survival. Ba/F3 cells were transfected with either the wild-type Flt3 or the ITD, with or without a triple mutation of the Grb2 binding sites, and characterised in terms of proliferation and viability. Interestingly, the Flt3 ITD promoted increased survival but after introducing the triple mutation, this phenotype was lost. When looking into different downstream pathways, this effect was mainly caused by decreased phosphoinositide 3-kinase and Stat5 signalling, and the Flt3 ITD carrying the Grb2 binding mutations showed less Akt and Stat5 activation compared to the regular Flt3 ITD receptor. These findings not only reveal novel phosphorylation sites in Flt3 but contribute to the understanding of the molecular mechanism by which Flt3 ITD functions in pathological conditions.
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24.
  • Nawaz, Saima, et al. (författare)
  • Polyaniline inside the pores of high surface area mesoporous silicon as composite electrode material for supercapacitors
  • 2022
  • Ingår i: RSC Advances. - : ROYAL SOC CHEMISTRY. - 2046-2069. ; 12:27, s. 17228-17236
  • Tidskriftsartikel (refereegranskat)abstract
    • Mesoporous silicon (mSi) obtained by the magnesiothermic reduction of mesoporous silica was used to deposit polyaniline (PANI) in its pores, the composite was tested for its charge storage application for high performance supercapacitor electrodes. The mesoporous silica as confirmed by Small Angle X-ray Scattering (SAXS) has a Brunauer-Emmett-Teller (BET) surface area of 724 m(2)g(-1) and mean pore size of 5 nm. After magnesiothermic reduction to mSi, the BET surface area is reduced to 348 m(2)g(-1) but the mesoporousity is retained with a mean pore size of 10 nm. The BET surface area of mesoporous silicon is among the highest for porous silicon prepared/reduced from silica. In situ polymerization of PANI inside the pores of mSi was achieved by controlling the polymerization conditions. As a supercapacitor electrode, the mSi-PANI composite exhibits better charge storage performance as compared to pure PANI and mesoporous silica-PANI composite electrodes. Enhanced electrochemical performance of the mSi-PANI composite is attributed to the high surface mesoporous morphology of mSi with a network structure containing abundant mesopores enwrapped by an electrochemically permeable polyaniline matrix.
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  • Nikpay, Majid, et al. (författare)
  • A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease
  • 2015
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:10, s. 1121-1121
  • Tidskriftsartikel (refereegranskat)abstract
    • Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of similar to 185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 million low-frequency (0.005 < MAF < 0.05) variants. In addition to confirming most known CAD-associated loci, we identified ten new loci (eight additive and two recessive) that contain candidate causal genes newly implicating biological processes in vessel walls. We observed intralocus allelic heterogeneity but little evidence of low-frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD, showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size.
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26.
  • Peden, John F., et al. (författare)
  • A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease
  • 2011
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 43:4, s. 339-344
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies have identified 11 common variants convincingly associated with coronary artery disease (CAD)(1-7), a modest number considering the apparent heritability of CAD(8). All of these variants have been discovered in European populations. We report a meta-analysis of four large genome-wide association studies of CAD, with similar to 575,000 genotyped SNPs in a discovery dataset comprising 15,420 individuals with CAD (cases) (8,424 Europeans and 6,996 South Asians) and 15,062 controls. There was little evidence for ancestry-specific associations, supporting the use of combined analyses. Replication in an independent sample of 21,408 cases and 19,185 controls identified five loci newly associated with CAD (P < 5 x 10(-8) in the combined discovery and replication analysis): LIPA on 10q23, PDGFD on 11q22, ADAMTS7-MORF4L1 on 15q25, a gene rich locus on 7q22 and KIAA1462 on 10p11. The CAD-associated SNP in the PDGFD locus showed tissue-specific cis expression quantitative trait locus effects. These findings implicate new pathways for CAD susceptibility.
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27.
  • Rasheed, H. M. Kashif, et al. (författare)
  • Efficient circular repeated measurements designs strongly balanced to control carryover effects
  • 2024
  • Ingår i: Communications in statistics. Simulation and computation. - 0361-0918 .- 1532-4141.
  • Tidskriftsartikel (refereegranskat)abstract
    • In experiments related to agriculture, psychology, medicine, animal sciences, pharmacology, and other fields, repeated measurements designs (RMDs) are utilized which are economical design. However, the use of these designs may result in carryover effects, which are the primary cause of bias. Balanced or strongly balanced RMDs can control these effects. Strongly balanced RMDs estimate the direct effects and carryover effects independently; therefore, these designs have an edge over the balanced RMDs. In this article, therefore, some general procedures are presented to obtain minimal circular strongly and nearly strongly balanced RMDs in periods of k different sizes with high efficiency of Separability and of carryover effects.
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28.
  • Razumovskaya, Elena, et al. (författare)
  • Oncogenic flt3 receptors display different specificity and kinetics of autophosphorylation.
  • 2009
  • Ingår i: Experimental Hematology. - : Elsevier BV. - 1873-2399 .- 0301-472X. ; 37, s. 979-989
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Fms-like tyrosine kinase-3 (FLT3), a growth factor receptor normally expressed in hematopoietic progenitor cells, has been shown to have an important role in the development of acute myeloid leukemia due to activating mutations. FLT3 mutations are found in approximately one third of AML patients and correlate with a poor prognosis, thus making the FLT3 receptor a potential therapeutic target. The aim of the investigation is to analyze the kinetics and specificity of FLT3 autophosphorylation in wild-type FLT3 as well as in the oncogenic FLT3 mutants. METHODS: We have used Ba/F3 cells stably expressing either wild-type, ITD or D835Y mutants of FLT3 in order to compare the site selectivity of tyrosine phosphorylation sites. By the use of a panel of phospho-specific antibodies directed against potential tyrosine phosphorylation sites in FLT3, we identified several novel phosphorylation sites in FLT3 and studied the kinetics and specificity of ligand-induced phosphorylation in living cells. RESULTS: Eight phosphorylated tyrosines (pY589, pY591, pY599, pY726, pY768, pY793, pY842 and pY955) were investigated and shown to be differentially phosphorylated in the wild-type versus the mutated receptors. Furthermore, we show that tyrosines 726, 793 and 842 are novel phosphorylation sites of FLT3 in intact cells. CONCLUSION: In this study, we have looked at the site-specific phosphorylation in the wild-type FLT3 in comparison to the mutants found in AML. We observed not only quantitative changes but more importantly, qualitative differences in the phosphorylation patterns of the wild-type and the mutated FLT3 receptors, which might enhance the understanding of the mechanisms by which FLT3 contributes to AML in patients with mutations in FLT3.
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29.
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30.
  • Riaz, Muhammad, et al. (författare)
  • Construction of efficient classes of circular balanced repeated measurements designs with R
  • 2024
  • Ingår i: Communications in Statistics - Theory and Methods. - 0361-0926 .- 1532-415X.
  • Tidskriftsartikel (refereegranskat)abstract
    • Pharmacology, medicine, psychology, and the animal sciences all employ repeated measurement designs (RMDs). However, RMDs may experience carryover effects, which are the primary cause of bias in treatment effect estimation. In order to eliminate the carryover effects for odd v (the number of treatments), minimal circular balanced and strongly balanced repeated measurement designs (RMDs) are the ones that should be used. The minimal circular partially balanced and weakly balanced RMDs are used for even v. In order to obtain these important classes of minimal circular RMDs in periods of equal, two, and three different sizes, an R-based algorithm is developed in this article. The newly developed algorithm has made so simple the construction of balanced RMDs and their generalized classes. As a result, it is a novel piece of research.
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