Factors affecting the formation of FWUCs in institution building for PIMD in Cambodia: Two case studies

Irrigation programs / Participatory management / Farmer participation / Income / Institution building / Legal aspects / History

Improving agricultural productivity for poverty alleviation through integrated service provision with public-private sector partnerships: Examples and issues

Irrigation management / Crop production / Productivity / Constraints / Poverty / Farmers’ associations / Public sector / Private sector / Models / Food security / Sugarcane / Rice

Structures of Cl − (H 2 O) n and F − (H 2 O) n ( n =2,3,...,15) clusters. Molecular dynamics computer simulations

We have performed molecular dynamics calculations on Cl−(H2O) n and F−(H2O) n (n=2,3,...,15) clusters. The calculations show that the F− ion is solvated in these clusters, while Cl− remains attached to the water in the clusters. We also obtained the minimum energy structures for the Cl−(H2O) n and F−(H2O) n (n=6,7,8) clusters. From the comparison of these structures with the dynamical structures we conclude that the solvation of the F− ion is due to the entropy effect

Dynamics of ion solvation in a Stockmayer fluid

Molecular dynamics computer simulations were performed to study the dynamics of the ionic solvation in a Stockmayer fluid. The simulations show that the solvent relaxation proceeds in two time regimes. Most of the relaxation occurs in a short time period during which the relaxation process can be described by a gaussian function. The long time regime can be described by an exponential relaxation. The decay exponent of the relaxation function in this regime is the same as the exponent describing the decay of the single dipole correlation function. In addition, the contribution of the rotational and translational modes of the solvent to the energy relaxation was investigated. It was found that when the rotational mode is the dominant mode of the solvent motion the relaxation occurs from the outside-in, in accordance with the Onsager snowball picture. When the influence of the translational mode is increased the Onsager picture breaks down

Design and Synthesis of Selective Estrogen Receptor β Agonists and Their Pharmacology

Estrogens (17β-estradiol, E2) have garnered considerable attention in influencing cognitive process in relation to phases of the menstrual cycle, aging and menopausal symptoms. However, hormone replacement therapy can have deleterious effects leading to breast and endometrial cancer, predominantly mediated by estrogen receptor-alpha (ERα) the major isoform present in the mammary gland and uterus. Further evidence supports a dominant role of estrogen receptor-beta (ERβ) for improved cognitive effects such as enhanced hippocampal signaling and memory consolidation via estrogen activated signaling cascades. Creation of the ERβ selective ligands is challenging due to high structural similarity of both receptors. Thus far, several ERβ selective agonists have been developed, however, none of these have made it to clinical use due to their lower selectivity or considerable side effects. The research in this dissertation involved the design of non-steroidal ERβ selective agonists for hippocampal memory consolidation. The step-wise process to achieve the ultimate goal of this research includes: (1) design and synthesis of (4-hydroxyphenyl)cyclohexyl or cycloheptyl derivatives, (2) in vitro biological evaluation of synthesized compounds to identify highly potent and selective candidates, and (3) in vivo biological evaluation of selected candidates for hippocampal memory consolidation. Several (4-hydroxyphenyl)cyclohexyl or cycloheptyl derivatives were synthesized having structural alterations on both aromatic and cyclohexyl/heptyl ring scaffolds. ERβ agonist potency was initially evaluated in TR-FRET ERβ ligand binding assay and compounds having high potency were re-evaluated in functional cell based assays for potency and ERβ vs. ERα selectivity. Two compounds from each series, ISP 163-PK4 and ISP 358-2 were identified as most selective ERβ agonists. Both compounds revealed high metabolic stability, solubility and no cross reactivity towards other nuclear receptors. In vivo efficiency of ISP 358-2 was evaluated in ovariectomized mice (C57BL/6) with object recognition (OR) and object placement (OP) tasks. The results indicate improved memory consolidation at 100 pg/ hemisphere and 0.5 mg/Kg via DH infusion and IP injection respectively. The information learned from this project serves as a foundation for development of other cycloheptyl/hexyl based ERβ agonists or antagonists having acceptable pharmacological profiles

Stabilization energies of Cl − , Br − , and I − ions in water clusters

Molecular dynamics computer simulations were performed on clusters of Cl-(H20)n (n =2, ... ,15). From the simulations we calculated the stabilization energies of the anion in the cluster. These energies were compared with the values of stabilization energies obtained from the photodetachment spectra of X-(H20)n clusters (X=CI-, Br-, or 1-). The comparison confirms the hypothesis that the anion is attached to the water cluster

Kinetic Studies on Lactonization of Quinone Propionic Acid Derivatives for the Development of Redox Responsive Liposomes

ABSTRACT Stimuli-responsive liposome systems that utilize endogenous triggers of tumor microenvironment have generated great attention in recent drug delivery research. Among such formulations, redox-responsive liposomes seem highly promising for cancer treatment due to their potential to release high drug concentrations upon reduction (by reductase enzymes). The research described in this thesis involved the evaluation of kinetics of trimethyl-lock quinone propionic acid reduction and lactonization, which accounts for payload release from trimethyl-lock quinone propionic acid-decorated liposomes. To achieve the ultimate goal of this research, several trimethyl-lock quinone propionic acid-based amide compounds were synthesized and characterized. Kinetic studies were carried out with 1H NMR spectroscopy under different experimental conditions, and time-resolved 1H NMR spectra were used to evaluate the kinetic rate constant (k) and half-life time (t½) values for the lactonization (cyclization) reaction. Upon reduction, five different quinone ring-substituted quinone propionic acid-ethanolamine derivatives have shown distinct cyclization rates, representing the influence of ring substituent on lactonization. Tertiary amides, and organic solution conditions, slow down the cyclization process, whereas buffer conditions and higher temperature enhanced the trimethyl-lock lactonization. The outcome of this research can be utilized to optimize redox-responsive trimethyl-lock quinone propionic acid based liposomes, as well as other effective target delivery systems, in order to achieve efficient payload release