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Search Results: 1 - 10 of 1000 matches for " Paymaan Jafar-Nejad "
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Pharmacometabolomic Signature of Ataxia SCA1 Mouse Model and Lithium Effects
Bertrand Perroud, Paymaan Jafar-Nejad, William R. Wikoff, Jennifer R. Gatchel, Lu Wang, Dinesh K. Barupal, Juan Crespo-Barreto, Oliver Fiehn, Huda Y. Zoghbi, Rima Kaddurah-Daouk
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0070610
Abstract: We have shown that lithium treatment improves motor coordination in a spinocerebellar ataxia type 1 (SCA1) disease mouse model (Sca1154Q/+). To learn more about disease pathogenesis and molecular contributions to the neuroprotective effects of lithium, we investigated metabolomic profiles of cerebellar tissue and plasma from SCA1-model treated and untreated mice. Metabolomic analyses of wild-type and Sca1154Q/+ mice, with and without lithium treatment, were performed using gas chromatography time-of-flight mass spectrometry and BinBase mass spectral annotations. We detected 416 metabolites, of which 130 were identified. We observed specific metabolic perturbations in Sca1154Q/+ mice and major effects of lithium on metabolism, centrally and peripherally. Compared to wild-type, Sca1154Q/+ cerebella metabolic profile revealed changes in glucose, lipids, and metabolites of the tricarboxylic acid cycle and purines. Fewer metabolic differences were noted in Sca1154Q/+ mouse plasma versus wild-type. In both genotypes, the major lithium responses in cerebellum involved energy metabolism, purines, unsaturated free fatty acids, and aromatic and sulphur-containing amino acids. The largest metabolic difference with lithium was a 10-fold increase in ascorbate levels in wild-type cerebella (p<0.002), with lower threonate levels, a major ascorbate catabolite. In contrast, Sca1154Q/+ mice that received lithium showed no elevated cerebellar ascorbate levels. Our data emphasize that lithium regulates a variety of metabolic pathways, including purine, oxidative stress and energy production pathways. The purine metabolite level, reduced in the Sca1154Q/+ mice and restored upon lithium treatment, might relate to lithium neuroprotective properties.
The Protein O-glucosyltransferase Rumi Modifies Eyes Shut to Promote Rhabdomere Separation in Drosophila
Amanda R. Haltom equal contributor,Tom V. Lee equal contributor,Beth M. Harvey,Jessica Leonardi,Yi-Jiun Chen,Yang Hong,Robert S. Haltiwanger,Hamed Jafar-Nejad
PLOS Genetics , 2014, DOI: doi/10.1371/journal.pgen.1004795
Abstract: The protein O-glucosyltransferase Rumi/POGLUT1 regulates Drosophila Notch signaling by adding O-glucose residues to the Notch extracellular domain. Rumi has other predicted targets including Crumbs (Crb) and Eyes shut (Eys), both of which are involved in photoreceptor development. However, whether Rumi is required for the function of Crb and Eys remains unknown. Here we report that in the absence of Rumi or its enzymatic activity, several rhabdomeres in each ommatidium fail to separate from one another in a Notch-independent manner. Mass spectral analysis indicates the presence of O-glucose on Crb and Eys. However, mutating all O-glucosylation sites in a crb knock-in allele does not cause rhabdomere attachment, ruling out Crb as a biologically-relevant Rumi target in this process. In contrast, eys and rumi exhibit a dosage-sensitive genetic interaction. In addition, although in wild-type ommatidia most of the Eys protein is found in the inter-rhabdomeral space (IRS), in rumi mutants a significant fraction of Eys remains in the photoreceptor cells. The intracellular accumulation of Eys and the IRS defect worsen in rumi mutants raised at a higher temperature, and are accompanied by a ~50% decrease in the total level of Eys. Moreover, removing one copy of an endoplasmic reticulum chaperone enhances the rhabdomere attachment in rumi mutant animals. Altogether, our data suggest that O-glucosylation of Eys by Rumi ensures rhabdomere separation by promoting proper Eys folding and stability in a critical time window during the mid-pupal stage. Human EYS, which is mutated in patients with autosomal recessive retinitis pigmentosa, also harbors multiple Rumi target sites. Therefore, the role of O-glucose in regulating Eys may be conserved.
Negative Regulation of Notch Signaling by Xylose
Tom V. Lee,Maya K. Sethi equal contributor,Jessica Leonardi equal contributor,Nadia A. Rana equal contributor,Falk F. R. Buettner,Robert S. Haltiwanger,Hans Bakker,Hamed Jafar-Nejad
PLOS Genetics , 2013, DOI: 10.1371/journal.pgen.1003547
Abstract: The Notch signaling pathway controls a large number of processes during animal development and adult homeostasis. One of the conserved post-translational modifications of the Notch receptors is the addition of an O-linked glucose to epidermal growth factor-like (EGF) repeats with a C-X-S-X-(P/A)-C motif by Protein O-glucosyltransferase 1 (POGLUT1; Rumi in Drosophila). Genetic experiments in flies and mice, and in vivo structure-function analysis in flies indicate that O-glucose residues promote Notch signaling. The O-glucose residues on mammalian Notch1 and Notch2 proteins are efficiently extended by the addition of one or two xylose residues through the function of specific mammalian xylosyltransferases. However, the contribution of xylosylation to Notch signaling is not known. Here, we identify the Drosophila enzyme Shams responsible for the addition of xylose to O-glucose on EGF repeats. Surprisingly, loss- and gain-of-function experiments strongly suggest that xylose negatively regulates Notch signaling, opposite to the role played by glucose residues. Mass spectrometric analysis of Drosophila Notch indicates that addition of xylose to O-glucosylated Notch EGF repeats is limited to EGF14–20. A Notch transgene with mutations in the O-glucosylation sites of Notch EGF16–20 recapitulates the shams loss-of-function phenotypes, and suppresses the phenotypes caused by the overexpression of human xylosyltransferases. Antibody staining in animals with decreased Notch xylosylation indicates that xylose residues on EGF16–20 negatively regulate the surface expression of the Notch receptor. Our studies uncover a specific role for xylose in the regulation of the Drosophila Notch signaling, and suggest a previously unrecognized regulatory role for EGF16–20 of Notch.
Evaluation and Comparison of Using Low-Dose Aprotinin and Tranexamic Acid in CABG: a Double Blind Randomized Clinical Trial
Mohammad Hassan Ghaffari Nejad,Bahador Baharestani,Rostam Esfandiari,Jafar Hashemi
Journal of Tehran University Heart Center , 2012,
Abstract: Background: Cardiovascular operations are associated with an inherent bleeding tendency that sometimes leads to severe bleeding and transfusion requirement. Pharmacological intervention to minimize post-bypass bleeding and blood product transfusions has received increasing attention from both medical and economic viewpoints. Methods: This double-blind, randomized, placebo-controlled clinical trial recruited three groups of patients (each group consisting of 50 patients) undergoing on-pump coronary artery bypass graft surgery (CABG) and blindly randomized them to receive either low aprotinin, tranexamic acid, or placebo. The results were, subsequently, evaluated and compared between the groups. All the patients were operated on by one surgeon and the same surgery team. Results: The following variables were similar between the groups, and there was no statistically significant difference between the groups in terms of these variables: age (p value = 0.308), sex (p value = 0.973), hyperlipidemia (p value = 0.720), hypertension (p value = 0.786), smoking (p value = 0.72), and diabetes (p value = 0.960). The amounts of drainage from chest tubes were less in the aprotinin and tranexamic acid groups than the amount in the placebo group; the difference was statistically important (p value < 0.001). There was no statistically significant difference with respect to need for reoperation for bleeding between the three groups (p value = 0.998). Complications following surgery in the three groups were statistically the same and not significantly different. All the complications (myocardial infarction, pericardial effusion, neurological complication and renal complication) had a good course, and all the patients were discharged from the hospital uneventfully. There was no mortality in any group. Conclusions: Low-dose aprotinin and tranexamic acid can significantly reduce blood loss and transfusion requirement in CABG without importantly increasing mortality and morbidity.
Factors Associated With Premature Discharge of Patients With Psychosis Against Medical Advice
Seyed Ali Ahmadi Abhari,Mitra Monir Abbasi,P. Jafar Nejad,H. Zerrati
Iranian Journal of Psychiatry , 2006,
Abstract: Objective: This study was conducted to identify the characteristics of patients with psychosis who had escaped from hospital or were discharged prematurely and against medical advice. Method: We carried out this retrospective study on 72 patients with psychosis who were discharged prematurely over a 38-month period and compared them to 76 patients with psychosis who were discharged according to the physician’s order, as the control group. In addition to the demographic factors, we assessed the following: the patient’s and their care giver’s level of education, in hospital stay, suicidal idea and attempt, smoking, substance abuse, psychiatric diagnosis, arrest record, imprisonment, positive history of psychiatric disorder in the first degree family members, first episode of psychosis, admission with police assistance, unemployment, and escape history (from hospital, school, military service, home, work and prison). Results: The two groups of patients were comparable in regard to two factors: the in hospital stay, and a positive history of escape. The latter was defined as leaving home, quitting work, escaping from school and military service, and a positive history of escape from hospital. Conclusion: Irregular discharge of patients with psychosis seems to be predictable by their positive escape history, and therefore preventable. Irregular discharge is more likely in the first few days of hospital admission. There is also a great tendency towards irregular discharge when in hospital stay gets long.
A New Analytical Approach for Solving Nonlinear Boundary Value Problems in Finite Domains  [PDF]
Jafar Biazar, Behzad Ghanbari
Applied Mathematics (AM) , 2011, DOI: 10.4236/am.2011.28136
Abstract: Based on the homotopy analysis method (HAM), we propose an analytical approach for solving the following type of nonlinear boundary value problems in finite domain. In framework of HAM a convenient way to adjust and control the convergence region and rate of convergence of the obtained series solutions, by defining the so-called control parameter h , is provided. This paper aims to propose an efficient way of finding the proper values of h.Such values of parameter can be determined at the any order of approximations of HAM series solutions by solving of a nonlinear polynomial equation. Some examples of nonlinear initial value problems in finite domain are used to illustrate the validity of the proposed approach. Numerical results confirm that obtained series solutions agree very well with the exact solutions.
A Strong Method for Solving Systems of Integro-Differential Equations  [PDF]
Jafar Biazar, Hamideh Ebrahimi
Applied Mathematics (AM) , 2011, DOI: 10.4236/am.2011.29152
Abstract: The introduced method in this paper consists of reducing a system of integro-differential equations into a system of algebraic equations, by expanding the unknown functions, as a series in terms of Chebyshev wavelets with unknown coefficients. Extension of Chebyshev wavelets method for solving these systems is the novelty of this paper. Some examples to illustrate the simplicity and the effectiveness of the proposed method have been presented.
Locating Multiple Facilities in Convex Sets with Fuzzy Data and Block Norms  [PDF]
Jafar Fathali, Ali Jamalian
Applied Mathematics (AM) , 2012, DOI: 10.4236/am.2012.312267
Abstract: In this paper we study the problem of locating multiple facilities in convex sets with fuzzy parameters. This problem asks to find the location of new facilities in the given convex sets such that the sum of weighted distances between new facilities and existing facilities is minimized. We present a linear programming model for this problem with block norms, then we use it for problems with fuzzy data. We also do this for rectilinear and infinity norms as special cases of block norms.
Fuzzy Sliding Mode Observer for Vehicular Attitude Heading Reference System  [PDF]
Jafar Keighobadi, Parisa Doostdar
Positioning (POS) , 2013, DOI: 10.4236/pos.2013.43022
Abstract: In low-cost Attitude Heading Reference Systems (AHRS), the measurements made by Micro Electro-Mechanical Systems (MEMS) type sensors are affected by uncertainties, noises and unknown disturbances. In this paper, considering the robustness of sliding mode observers against structured and unstructured uncertainties, and also exogenous inputs, the process of design and implementation of a sliding mode observer (SMO) is proposed based on a linearized model of the AHRS. To decrease the chattering phenomenon is the main difficulty of the SMO. Through smoothing the discontinuity term, the tracking performance of the observer is attenuated. Boundary layer technique, for example, using a saturation term, is the common smoother to remove the chattering drawbacks. However, through poor tracking performance, the high range chattering could not be removed by this method. Therefore, a knowledge-based Mamdani-type fuzzy SMO (FSMO) is proposed to decrease the chattering effects intelligently, which in turn could obtain the high accuracy tracking performance of the SMO. Following proving the stability of the proposed SMOs based on direct Lyapunovs method, the performance of the proposed observers is compared with that of the extended Kalman filter through simulation and real experiments of an AHRS.
Matrix Operations Design Tool for FPGA and VLSI Systems  [PDF]
Semih Aslan, Jafar Saniie
Circuits and Systems (CS) , 2016, DOI: 10.4236/cs.2016.72005
Abstract: Embedded systems used in real-time applications require low power, less area and high computation speed. For digital signal processing, image processing and communication applications, data are often received at a continuously high rate. The type of necessary arithmetic functions and matrix operations may vary greatly among different applications. The RTL-based design and verification of one or more of these functions could be time-consuming. Some High Level Synthesis tools reduce this design and verification time but may not be optimal or suitable for low power applications. The design tool proposed in this paper can improve the design time and reduce the verification process. The design tool offers a fast design and verification platform for important matrix operations. These operations range from simple addition to more complex matrix operations such as LU and QR factorizations. The proposed platform can improve design time by reducing verification cycle. This tool generates Verilog code and its testbench that can be realized in FPGA and VLSI systems. The designed system uses MATLAB-based verification and reporting.
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