322 research outputs found
Synthesis and Characterization of Homogeneous Water Oxidation Catalyst Containing Single Metal Site
The aim of this paper has been to design & synthesize Ru complexes for water oxidation catalyst & understood their catalytic mechanism. The main strategy has been to lower the oxidation potential of Ru complex &stabilizes their high valent state by introducing negatively charged ligand. So in this project we are going to synthesize mononuclear Ruthenium water oxidation catalyst for water oxidation, containing one tridentate ligand & one bidentate ligand & one water molecule. We used here Ruthenium based mononuclear complexes because of their favorable properties viz kinetic ligand-exchange, variable oxidation states and coordination numbers under physiological conditions. Since last two decades variety of transition metal complexes have been studied as catalysts for oxidation of water containing Mn, Fe, Co, Ir, Cu and Ru metals. Among the most effective of these catalysts are based on Ru (II)
Probabilistic progressive buckling of trusses
A three-bay, space, cantilever truss is probabilistically evaluated to describe progressive buckling and truss collapse in view of the numerous uncertainties associated with the structural, material, and load variables (primitive variables) that describe the truss. Initially, the truss is deterministically analyzed for member forces, and member(s) in which the axial force exceeds the Euler buckling load are identified. These member(s) are then discretized with several intermediate nodes and a probabilistic buckling analysis is performed on the truss to obtain its probabilistic buckling loads and respective mode shapes. Furthermore, sensitivities associated with the uncertainties in the primitive variables are investigated, margin of safety values for the truss are determined, and truss end node displacements are noted. These steps are repeated by sequentially removing the buckled member(s) until onset of truss collapse is reached. Results show that this procedure yields an optimum truss configuration for a given loading and for a specified reliability
Probabilistic assessment of space trusses subjected to combined mechanical and thermal loads
A three-bay, space, cantilever truss is probabilistically evaluated to quantify the range of uncertainties of buckling loads and member forces due to nonuniform thermal loads, applied loads and moments (mechanical loads), and combination of both. The truss members are assumed to be made from Aluminum tubes or high modulus graphite-fiber/intermediate modulus epoxy-matrix composite tubes. Cumulative distribution function results show that certain combinations of thermal loads with mechanical loads reduce the probabilistic buckling loads and increase the magnitude of the member axial forces for the aluminum truss. The same trend is observed for the composite truss as well, as however, the thermal effects on the probabilistic buckling loads and member axial forces are not as substantial as that for an aluminum truss. This can be attributed to the large differences in the values of coefficient of thermal expansion. Finally, the sensitivities associated with the uncertainties in the structural, material, and load variables (primitive variables) are investigated. They show that buckling loads and member axial forces are most sensitive to the uncertainties in spacial (geometry) variables
Probabilistic structural analysis of adaptive/smart/intelligent space structures
A three-bay, space, cantilever truss is probabilistically evaluated for adaptive/smart/intelligent behavior. For each behavior, the scatter (ranges) in buckling loads, vibration frequencies, and member axial forces are probabilistically determined. Sensitivities associated with uncertainties in the structure, material and load variables that describe the truss are determined for different probabilities. The relative magnitude for these sensitivities are used to identify significant truss variables that control/classify its behavior to respond as an adaptive/smart/intelligent structure. Results show that the probabilistic buckling loads and vibration frequencies increase for each truss classification, with a substantial increase for intelligent trusses. Similarly, the probabilistic member axial forces reduce for adaptive and intelligent trusses and increase for smart trusses
Calculation of Weibull strength parameters and Batdorf flow-density constants for volume- and surface-flaw-induced fracture in ceramics
The calculation of shape and scale parameters of the two-parameter Weibull distribution is described using the least-squares analysis and maximum likelihood methods for volume- and surface-flaw-induced fracture in ceramics with complete and censored samples. Detailed procedures are given for evaluating 90 percent confidence intervals for maximum likelihood estimates of shape and scale parameters, the unbiased estimates of the shape parameters, and the Weibull mean values and corresponding standard deviations. Furthermore, the necessary steps are described for detecting outliers and for calculating the Kolmogorov-Smirnov and the Anderson-Darling goodness-of-fit statistics and 90 percent confidence bands about the Weibull distribution. It also shows how to calculate the Batdorf flaw-density constants by uing the Weibull distribution statistical parameters. The techniques described were verified with several example problems, from the open literature, and were coded. The techniques described were verified with several example problems from the open literature, and were coded in the Structural Ceramics Analysis and Reliability Evaluation (SCARE) design program
A click away, night or day!
This poster session will focus on the presenter\u27s experience establishing access to library resources and services via Blackboard: library embedded in the virtual classroom. The relevant documents reside in the content system and are available to be linked from any course within Bb. Taking the library to where the students congregate has brought library awareness in faculty as well as students. The process was not quite easy, but the end result is, of course, positive and makes the effort well worth it
RIB-STIFFENED CORRUGATED SOIL-STEEL STRUCTURES .
The method of Finite Strip is modified and applied to the three dimensional analysis of rib stiffened soil-steel structures. The strips are oriented in the curved direction, so that the effect of stiffeners is determined by considering them as individual strips. The eccentricity of the stiffened section is incorporated in the displacement functions to satisfy the continuity of the shell between the strips. The surrounding soil is replaced by the spring analog model. The spring coefficients are dependent on the type and depth of soil and the direction of wall displacement. Displacement functions are developed to model a soil-steel structure during side filling and under the traffic loads. The developed formulation has been verified by the laboratory scale model tests as well as by prototype test results. It has been observed that the provision of stiffeners at closer spacing (say 1.0 m c/c) in the upper zone of the conduit has considerable effect in reducing the conduit deformation and the combined stresses during construction. However, if the stiffeners are widely spaced (say 2.75 m c/c or more) the bending load carrying capacity of the stiffened upper zone is increased but slightly when compared with the capacity of non-stiffened conduits. The practice of analysing the conduit as a plane structure is found to be approximately valid if the ratio of conduit radius (R) to stiffener spacing (S) is greater than 0.6. If S/R (LESSTHEQ) 0.2, the stiffeners are considered to be fully acting with the main shell, while for 0.2 \u3c S/R \u3c 0.6, the stiffeners are considered to be partially acting with the main shell. A simplified two-dimensional analysis procedures are suggested for stiffened soil-steel structures during and after backfilling. The failure tests of a laboratory scale model indicated that the stiffeners have considerable effect on the overall buckling of the conduit but little effect on the local buckling in the zone between the stiffeners, especially when localized live load is applied.Dept. of Civil and Environmental Engineering. Paper copy at Leddy Library: Theses & Major Papers - Basement, West Bldg. / Call Number: Thesis1986 .E543. Source: Dissertation Abstracts International, Volume: 47-05, Section: B, page: 2081. Thesis (Ph.D.)--University of Windsor (Canada), 1986
Pharmaceutical Stock Price Reactions to Price Constraint Threats and Firm-Level R&D Spending
Political pressure in the United States is again building to constrain pharmaceutical prices either directly or through legalized reimportation of lower-priced pharmaceuticals from foreign countries. This study uses the Clinton Administration's Health Security Act (HSA) of 1993 as a natural experiment to show how threats of price constraints affect firm-level R&D spending. We link events surrounding the HSA to pharmaceutical company stock price changes and then examine the cross-sectional relation between the stock price changes and subsequent unexpected R&D spending changes. Results show that the HSA had significant negative effects on firm stock prices and R&D spending. Conservatively, the HSA reduced R&D spending by $1.6 billion, even though it never became law. If the HSA had passed, and had many small firms not raised capital just prior to the HSA, the R&D effects could have been much larger.
Genetic manipulation of glial progenitors boosts oligodendrogenesis and myelination in the mammalian brain
Glia, once considered as mere ‘glue’ for the central nervous system (CNS), have now emerged as active participants in almost every aspect of nervous system development, homeostasis, and even disease. Among these, oligodendroglia, comprising of oligodendrocyte progenitor cells (OPCs) and mature oligodendrocytes (OLs) are responsible for myelinating the CNS. Additionally, recent discoveries have implicated these cells in other processes including phagocytosis, synaptogenesis, ability to influence neural activity, and even animal behaviour. OPCs originate during embryogenesis from neural stem cells, establish a non-overlapping grid-like pattern across CNS, and persist throughout life. They are also one of the most proliferative cell types within the brain, which differentiate into OLs. Given their widespread presence and multifaceted functions, it is not surprising that oligodendroglia are implicated in the pathogenesis of diseases such as Multiple Sclerosis (MS). MS is a highly prevalent demyelinating disease, characterised by a severe loss of OLs, neuronal atrophy, and disrupted neural circuits. Furthermore, the endogenous mechanisms of repair and regeneration fail, leading to progressive deterioration, including motor deficits and cognitive decline. Current clinical therapies mainly focus on slowing disease progression and alleviating symptoms. Therefore, there is an urgent need for the development of novel and improved regenerative therapies. My doctoral research focused on OPCs as a therapeutic avenue due to their stem-cell-like properties. By leveraging established links between cell cycle regulation and proliferation, my study aimed to specifically target G1 phase shortening through Cdk4 and CyclinD1 (4D) overexpression. To first evaluate its effect under physiological conditions, I employed a sophisticated triple transgenic mouse line that allows for spatiotemporal control of 4D overexpression in oligodendroglia. This approach led to an increase in OPC proliferation in the white and grey matter of the brain, effectively enhancing oligodendrogenesis. Subsequently, I tested the efficacy of 4D in a preclinical model of MS using cuprizone-induced demyelination. While no significant improvements in learning and memory functions were evident, a comprehensive analysis of cellular and functional effects of 4D will shed light on its mechanisms of action. Additionally, it is plausible that 4D might have positive outcomes on other aspects of behaviour; however, this requires further investigation. Altogether, the findings presented in this thesis introduce a novel tool aimed at augmenting endogenous oligodendrogenesis under physiological conditions and represent a significant step toward developing innovative therapeutic strategies for demyelinating disorders.:Table of Contents
CHAPTER 1: INTRODUCTION
1.1. HISTORY OF OLIGODENDROGLIA 1
1.2. OLIGODENDROGLIA DURING DEVELOPMENT 4
1.3. OLIGODENDROGLIA IN ADULTHOOD 7
1.3.1. OPCS – DENSITY AND FUNCTIONS 7
1.3.2. OLS – DENSITY AND FUNCTIONS 8
1.4. OLIGODENDROGLIAL HETEROGENEITY 11
1.4.1. OPCS 11
1.4.2. OLS 12
1.5. OPC CELL CYCLE DYNAMICS 14
1.5.1. QUANTIFICATION OF OPC CELL CYCLE LENGTH 15
1.5.2. FACTORS INFLUENCING OPC CELL CYCLE 16
1.6. MYELIN AND MYELINATION 19
1.6.1. STRUCTURE AND COMPOSITION 19
1.6.2. FUNCTIONS 20
1.7. OLIGODENDROGENESIS AND BEHAVIOUR 21
1.7.1. LEARNING AND MEMORY 21
1.7.2. OTHERS 23
1.8. OLIGODENDROGLIA IN DISEASE AND REGENERATION 24
1.9. MS 26
1.9.1. MOUSE MODELS OF MS 28
1.10. CURRENT THERAPIES FOR DEMYELINATING DISEASES 31
1.11. AIM OF THE PROJECT 33
CHAPTER 2: MATERIALS AND METHODS
2.1. MATERIALS 36
2.1.1. MOUSE STRAINS 36
2.1.2. GENOTYPING PRIMERS 36
2.1.3. BUFFERS AND SOLUTIONS 37
2.1.4. CHEMICALS AND KITS 38
2.1.5. ANTIBODIES 39
2.2. METHODS 40
2.2.1. ANIMALS 40
2.2.2. GENOTYPING 40
2.2.3. DRUG TREATMENTS 40
2.2.4. BEHAVIOUR TESTS 41
2.2.4.1. OFT 41
2.2.4.2. EPM 42
2.2.4.3. ROTAROD 42
2.2.4.4. RW/CW 42
2.2.4.5. MWM 43
2.2.4.6. BM 44
2.2.5. IMMUNOHISTOCHEMISTRY 46
2.2.6. IMAGE ACQUISITION AND CELLULAR QUANTIFICATION 46
2.2.8. STATISTICS 47
CHAPTER 3: RESULTS - PART I
CELLULAR AND BEHAVIOURAL EFFECTS OF GENETIC MANIPULATION OF CELL CYCLE OF OLIGODENDROCYTE PROGENITORS VIA CDK4/CYCLIND1 (4D) OVEREXPRESSION
3.1. CHARACTERISATION OF 4D OVEREXPRESSION MEDIATED BY TRIPLE TRANSGENIC MICE 48
3.2. 4D OVEREXPRESSION IN ADULT MICE INCREASES OPC PROLIFERATION IN CC AND CTX 49
3.3. 4D-INDUCED INCREASE IN OPC PROLIFERATION IS AGE-DEPENDENT 51
3.4. 4D OVEREXPRESSION INCREASES DENSITY OF OLS AND MYELIN IN CC AND CTX 52
3.5. 4D-INDUCED INCREASE IN OPC PROLIFERATION IS TEMPORALLY CORRELATED TO ACTIVATION OF 4D 53
3.6. 4D OVEREXPRESSION DOES NOT AFFECT ANXIETY-LIKE BEHAVIOUR ON THE OPEN FIELD AND ELEVATED PLUS MAZE TEST 55
3.7. 4D OVEREXPRESSION LEADS TO IMPAIRED LEARNING ON THE MORRIS WATER MAZE TEST 57
3.8. 4D OVEREXPRESSION NEGATIVELY IMPACTS RUNNING SPEEDS ON THE RUNNING/COMPLEX WHEEL TEST 59
3.9. 4D OVEREXPRESSION HAS A LONG-TERM NEGATIVE EFFECT ON RUNNING SPEEDS ON THE RUNNING/COMPLEX WHEEL TEST 61
CHAPTER 4: RESULTS - PART II
CELLULAR AND BEHAVIOURAL CHARACTERISATION OF CUPRIZONE-INDUCED
DEMYELINATION MODEL OF MULTIPLE SCLEROSIS
4.1. CUPRIZONE DIET LEADS TO OLIGODENDROCYTE LOSS AND DEMYELINATION ACROSS BRAIN REGIONS 64
4.2. TERMINATION OF CUPRIZONE DIET TRIGGERS SPONTANEOUS REGENERATION ACROSS BRAIN REGIONS 66
4.3. CUPRIZONE-INDUCED DEMYELINATION IMPAIRS LEARNING ON THE MORRIS WATER MAZE TEST 68
4.4. CUPRIZONE-INDUCED DEMYELINATION ADVERSELY AFFECTS BODY WEIGHT AND PERFORMANCE ON THE RUNNING/COMPLEX WHEEL TEST 70
CHAPTER 5: RESULTS - PART III
BEHAVIOURAL EFFECT OF 4D-INDUCED OLIGODENDROGENESIS IN THE MODEL OF CUPRIZONE-INDUCED DEMYELINATION
5.1. 4D OVEREXPRESSION BEFORE THE ONSET OF CUPRIZONE-INDUCED DEMYELINATION DOES NOT RESCUE COGNITIVE PERFORMANCE ON BARNES MAZE 73
5.2. 4D OVEREXPRESSION BEFORE THE ONSET OF CUPRIZONE-INDUCED DEMYELINATION DOES NOT RESCUE MOTOR PERFORMANCE ON THE RUNNING/COMPLEX WHEEL TEST 75
5.3. SIMULTANEOUS 4D OVEREXPRESSION AND CUPRIZONE-INDUCED DEMYELINATION DOES NOT RESCUE MOTOR PERFORMANCE ON THE RUNNING/COMPLEX WHEEL TEST 78
CHAPTER 6: DISCUSSION
6.1. CELLULAR IMPLICATIONS OF 4D OVEREXPRESSION UNDER PHYSIOLOGICAL CONDITIONS 81
6.2. BEHAVIOURAL IMPLICATIONS OF 4D OVEREXPRESSION UNDER PHYSIOLOGICAL CONDITIONS 85
6.3. 4D AS A THERAPEUTIC TOOL 88
6.4. CONCLUSIONS AND OUTLOOK 90
REFERENCES 93
ACKNOWLEDGEMENTS 124
APPENDIX I 125
APPENDIX II 12
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