Optimum design of composite prestressed concrete girder railway bridges

This paper deals with the formulation of design optimisation of pretsressed concrete bridges. The bridge is of a slab-on-girder type, hence modeled as an equivalent orthotropic plate. The whole bridge system is considered as a simply supported right angle plate. Following linear elastic behaviour, the governing fourth order differential equation of the plate for patch load is solved in order to find out load distribution on the girders forming the bridge as well as the deflections and internal forces at critical sections of the whole bridge. The optimisation problem is formulated for various cross sectional geometries including rectangular, symmetrical I, unsymmetrical I, box, T and inverted T sections. The design variables are the main cross sectional dimensions, prestressing force and tendon eccentricity. The objective function comprises the cost of concrete material, formwork and prestressing steel tendons. The constraint functions are set to satisfy design requirements as per British Standards for bridges (BS 5400). Nonlinear optimisation method based on sequential unconstrained minimisation technique (SUMT) is employed to achieve optimum bridge configuration for specific design parameters of span length, concrete compressive strength and railway loading patterns. A purpose built computer program is set up to carry out the solution of the design optimisation problem efficiently in terms of time and effort. A typical example of unsymmetrical I-section having a small bottom flange as compared to the top flange width with composite deck effect is presented. The results show that the total cost increases as the span increases due to the increase of the initial prestressing force. Furthermore, the total cost decreases as the concrete compressive strength increases in spite of the increasing of the prestressing force. This is due to decrease of the overall depth, top and bottom flange widths, hence leading to a smaller girder size. Such finding will encourage engineers to adopt high strength concrete for bridges as it will help reducing not only the initial cost but also the life cycle cost of the bridge over its entire life

On Cohomology Groups of Four-Dimensional Nilpotent Associative Algebras

تعد دراسة الزمر الكوهومولوجية واحدة من أكثر البحوث المكثفة والمثيرة  والتي قد  نشأت من التبولوجيا الجبرية. حيث يعتبرالبعد للزمر الكوهومولوجية على وجه الخصوص ثابت في غاية الفائدة ويلعب دورآ هامآ في التصنيف الهندسي للجبر التجميعي. هذا العمل يركز على تطبيقات الزمر الكوهومولوجية ذات الابعاد المنخفضة. في هذا الخصوص, الزمر الكوهومولوجية المنخفضة للجبر التجميعي عديم القوى ذات البعد الرابع تم وصفهاعلى شكل مصفوفة.The study of cohomology groups is one of the most intensive and exciting researches that arises from algebraic topology. Particularly, the dimension of cohomology groups is a highly useful invariant which plays a rigorous role in the geometric classification of associative algebras. This work focuses on the applications of low dimensional cohomology groups. In this regards, the cohomology groups of degree zero and degree one of nilpotent associative algebras in dimension four are described in matrix form

Stretch‐Induced Increase in Cardiac Contractility Is Independent of Myocyte Ca\u3csup\u3e2+\u3c/sup\u3e While Block of Stretch Channels by Streptomycin Improves Contractility After Ischemic Stunning

Stretching the cardiac left ventricle (LV) enhances contractility but its effect on myoplasmic [Ca2+] is controversial. We measured LV pressure (LVP) and [Ca2+] as a function of intra-LV stretch in guinea pig intact hearts before and after 15 min global stunning ± perfusion with streptomycin (STM), a stretch activated channel blocker. LV wall [Ca2+] was measured by indo-1 fluorescence and LVP by a saline-filled latex balloon inflated in 50 μL steps to stretch the LV. We implemented a mathematical model to interpret crossbridge dynamics and myofilament Ca2+ responsiveness from the instantaneous relationship between [Ca2+] and LVP ± stretching. We found that: (1) stretch enhanced LVP but not [Ca2+] before and after stunning in either control (CON) and STM groups, (2) after stunning [Ca2+] increased in both groups although higher in STM versus CON (56% vs. 39%), (3) STM-enhanced LVP after stunning compared to CON (98% vs. 76% of prestunning values), and (4) stretch-induced effects on LVP were independent of [Ca2+] before or after stunning in both groups. Mathematical modeling suggested: (1) cooperativity in cross-bridge kinetics and myofilament Ca2+ handling is reduced after stunning in the unstretched heart, (2) stunning results in depressed myofilament Ca2+ sensitivity in the presence of attached cross-bridges regardless of stretch, and (3) the initial mechanism responsible for increased contractility during stretch may be enhanced formation of cross-bridges. Thus stretch-induced enhancement of contractility is not due to increased [Ca2+], whereas enhanced contractility after stunning in STM versus CON hearts results from improved Ca2+ handling and/or enhanced actinomyosin cross-bridge cycling

Ranolazine Reduces Ca\u3csup\u3e2+\u3c/sup\u3e Overload and Oxidative Stress and Improves Mitochondrial Integrity to Protect Against Ischemia Reperfusion Injury in Isolated Hearts

Ranolazine is a clinically approved drug for treating cardiac ventricular dysrhythmias and angina. Its mechanism(s) of protection is not clearly understood but evidence points to blocking the late Na+ current that arises during ischemia, blocking mitochondrial complex I activity, or modulating mitochondrial metabolism. Here we tested the effect of ranolazine treatment before ischemia at the mitochondrial level in intact isolated hearts and in mitochondria isolated from hearts at different times of reperfusion. Left ventricular (LV) pressure (LVP), coronary flow (CF), and O2 metabolism were measured in guinea pig isolated hearts perfused with Krebs-Ringer’s solution; mitochondrial (m) O2 •−, Ca2+, NADH/FAD (redox state), and cytosolic (c) Ca2+ were assessed on-line in the LV free wall by fluorescence spectrophotometry. Ranolazine (5 μM), infused for 1min just before 30 min of global ischemia, itself did not change O2 •−, cCa2+, mCa2+ or redox state. During late ischemia and reperfusion (IR) O2 •− emission and m[Ca2+] increased less in the ranolazine group vs. the control group. Ranolazine decreased c [Ca2+] only during ischemia while NADH and FAD were not different during IR in the ranolazine vs. control groups. Throughout reperfusion LVP and CF were higher, and ventricular fibrillation was less frequent. Infarct size was smaller in the ranolazine group than the control group. Mitochondria isolated from ranolazinetreated hearts had mild resistance to permeability transition pore (mPTP) opening and less cytochrome c release than control hearts. Ranolazine may provide functional protection of the heart during IR injury by reducing cCa2+ and mCa2+ loading secondary to its effect to block the late Na+ current. Subsequently it indirectly reduces O2 •− emission, preserves bioenergetics, delays mPTP opening, and restricts loss of cytochrome c, thereby reducing necrosis and apoptosis

Enhanced Na\u3csup\u3e+\u3c/sup\u3e/H\u3csup\u3e+\u3c/sup\u3e Exchange During Ischemia and Reperfusion Impairs Mitochondrial Bioenergetics and Myocardial Function

Inhibition of Na+/H+ exchange (NHE) during ischemia reduces cardiac injury due to reduced reverse mode Na+/Ca2+ exchange. We hypothesized that activating NHE-1 at buffer pH 8 during ischemia increases mitochondrial oxidation, Ca2+ overload, and reactive O2 species (ROS) levels and worsens functional recovery in isolated hearts and that NHE inhibition reverses these effects. Guinea pig hearts were perfused with buffer at pH 7.4 (control) or pH 8 +/- NHE inhibitor eniporide for 10 minutes before and for 10 minutes after 35- minute ischemia and then for 110 minutes with pH 7.4 buffer alone. Mitochondrial NADH and FAD, [Ca2+], and superoxide were measured by spectrophotofluorometry. NADH and FAD were more oxidized, and cardiac function was worse throughout reperfusion after pH 8 versus pH 7.4, Ca2+ overload was greater at 10-minute reperfusion, and superoxide generation was higher at 30-minute reperfusion. The pH 7.4 and eniporide groups exhibited similar mitochondrial function, and cardiac performance was most improved after pH 7.4+eniporide. Cardiac function on reperfusion after pH 8+eniporide was better than after pH 8. Percent infarction was largest after pH 8 and smallest after pH 7.4+eniporide. Activation of NHE with pH 8 buffer and the subsequent decline in redox state with greater ROS and Ca2+ loading underlie the poor functional recovery after ischemia and reperfusion

Numerical solution for the time-Fractional Diffusion-wave Equations by using Sinc-Legendre Collocation Method

In this paper the numerical solution of fractional diffusion wave equation is proposed. The fractional derivative will be in the Caputo sense. The proposed method will be based on shifted Legendre collocation scheme and sinc function approximation for time and space respectively. The problem is reduced to the problem into a system of algebraic equations after implementing this method. For demonstrating the validity and applicability of the proposed numerical scheme some examples are presented. Keywords: Fractional diffusion equation, Sinc functions, shifted Legendre  polynomials, Collocation method

Adding ROS Scavengers to Cold K\u3csup\u3e+\u3c/sup\u3e Cardioplegia Reduces Superoxide Emission During 2 h Global Cold Cardiac Ischemia

We reported that the combination of reactive oxygen species (ROS) quenchers Mn(III) tetrakis (4-benzoic acid) porphyrin (MnTBAP), catalase, and glutathione (MCG) given before 2 hours cold ischemia better protected cardiac mitochondria against cold ischemia and warm reperfusion (IR)-induced damage than MnTBAP alone. Here, we hypothesize that high K+ cardioplegia (CP) plus MCG would provide added protection of mitochondrial bioenergetics and cardiac function against IR injury. Using fluorescence spectrophotometry, we monitored redox balance, ie reduced nicotinamide adenine dinucleotide and flavin adenine dinucleotide (NADH/FAD), superoxide (O2 •−), and mitochondrial Ca2+ (m[Ca2+]) in the left ventricular free wall. Guinea pig isolated hearts were perfused with either Krebs Ringer’s (KR) solution, CP, or CP + MCG, before and during 27°C perfusion followed immediately by 2 hours of global ischemia at 27°C. Drugs were washed out with KR at the onset of 2 hours 37°C reperfusion. After 120 minutes warm reperfusion, myocardial infarction was lowest in the CP + MCG group and highest in the KR group. Developed left ventricular pressure recovery was similar in CP and CP + MCG and was better than in the KR group. O2 •−, m[Ca2+], and NADH/FAD were significantly different between the treatment and KR groups. O2 •− was lower in CP + MCG than in the CP group. This study suggests that CP and ROS quenchers act in parallel to improve mitochondrial function and to provide protection against IR injury at 27°C

Identity and Function of a Cardiac Mitochondrial Small Conductance Ca2+-Activated K+ Channel Splice Variant

We provide evidence for location and function of a small conductance, Ca2+-activated K+ (SKCa) channel isoform 3 (SK3) in mitochondria (m) of guinea pig, rat and human ventricular myocytes. SKCa agonists protected isolated hearts and mitochondria against ischemia/reperfusion (IR) injury; SKCa antagonists worsened IR injury. Intravenous infusion of a SKCa channel agonist/antagonist, respectively, in intact rats was effective in reducing/enhancing regional infarct size induced by coronary artery occlusion. Localization of SK3 in mitochondria was evidenced by Western blot of inner mitochondrial membrane, immunocytochemical staining of cardiomyocytes, and immunogold labeling of isolated mitochondria. We identified a SK3 splice variant in guinea pig (SK3.1, aka SK3a) and human ventricular cells (SK3.2) by amplifying mRNA, and show mitochondrial expression in mouse atrial tumor cells (HL-1) by transfection with full length and truncated SK3.1 protein. We found that the N-terminus is not required for mitochondrial trafficking but the C-terminus beyond the Ca2+ calmodulin binding domain is required for Ca2+ sensing to induce mK+ influx and/or promote mitochondrial localization. In isolated guinea pig mitochondria and in SK3 overexpressed HL-1 cells, mK+ influx was driven by adding CaCl2. Moreover, there was a greater fall in membrane potential (ΔΨm), and enhanced cell death with simulated cell injury after silencing SK3.1 with siRNA. Although SKCa channel opening protects the heart and mitochondria against IR injury, the mechanism for favorable bioenergetics effects resulting from SKCa channel opening remains unclear. SKCa channels could play an essential role in restraining cardiac mitochondria from inducing oxidative stress-induced injury resulting from mCa2+ overload

Comparison of Cumulative Planimetry versus Manual Dissection to Assess Experimental Infarct Size in Isolated Hearts

Introduction Infarct size (IS) is an important variable to estimate cardiac ischemia/reperfusion injury in animal models. Triphenyltetrazolium chloride (TTC) stains viable cells red while leaving infarcted cells unstained. To quantify IS, infarcted and non-infarcted tissue is often manually dissected and weighed (IS-DW). An alternative is to measure infarcted areas by cumulative planimetry (IS-CP). Methods We prospectively compared these two methods in 141 Langendorff-prepared guinea pig hearts (1.44 ± 0.02 g) that were part of different studies on mechanisms of cardioprotection. Hearts were perfused with Krebs–Ringer\u27s and subjected to 30 min global ischemia after various cardioprotective treatments. Two hours after reperfusion hearts were cut into 6–7 transverse sections (3 mm) and stained for 5 min in 1% TTC and 0.1 M KH2PO4 buffer (pH 7.4, 38 °C). Each slice was first scanned and its infarcted area measured with Image 1.62 software (NIH). Infarctions in individual slices of each heart were averaged (IS-CP) on the basis of their weight. After scanning, IS-DW was determined by careful manual dissection of infarcted from non-infarcted tissue and measuring their respective total weight. Results We found limited tissue permeation of TTC in relation to the slice thickness leaving tissue in the center unstained, as well as significant cross-contamination of stained vs. unstained tissue after manual dissection. IS-CP and IS-DW ranged from 6.0 to 73.1% and 19.4 to 70.5%, respectively, and correlated as follows: IS-DW = (27.6 ± 1.4) + (0.518 ± 0.038) • IS-CP; r = 0.75 (Pearson), p \u3c 0.001. In addition, IS-CP correlated better with return of function after reperfusion like developed left ventricular pressure, contractility and relaxation, and myocardial oxygen consumption. Discussion Despite a good correlation between both methods, limited tissue permeation by TTC diffusion and limited precision in the ability to manually dissect stained from unstained tissue leads to an overestimation of infarct size by dissection and weighing compared to cumulative planimetry