The kinetics of endogenous decay, death and lysis for viable organic solids.

The long-term kinetic rates of solubilization/utilization of proteins, carbohydrates, and lipids in secondary solids from three municipal wastewater treatment plants were measured. Temperature, input sludge retention time (SRT₀), and terminal electron acceptor were used as control variables for two four-month digestion studies employing seven mixed batch reactors. Three types of adenosine triphosphate (ATP) measurements were used to differentiate between viable endogenous biomass, viable anaerobic/facultative biomass and intact non-viable solids. Solids solubilization was significantly affected by all three control variables. Temperature and terminal electron acceptor showed greater effects on solubilization than SRT₀. The effect of temperature was time-dependent and differed for the two types of secondary solids evaluated. Proteins were removed to the greatest extent, lipids to an extent comparable to that of volatile suspended solids (VSS), and carbohydrates were the most resistant component. Direct sample ATP or VSS measurements were poor indicators of the time-dependent potential of mixed microbial population for further waste stabilization. However, the analysis of the ratios of recovery ATP to sample ATP (ATP recovery ratio) provided more insights into the microbial behavior during sludge digestion. Under aerobic conditions, ATP recovery ratios generally increased with time. This result implied that during the initial phase of digestion the volatile solids consisted of a higher fraction of intact non-viable material, but after prolonged digestion the solids included a greater fraction of viable endogenous biomass. Under anaerobic conditions, ATP recovery ratios increased and then decreased with time, implying that the fermentative microbial fraction was highest at some intermediate point in the time frame employed. Four phase degradation patterns were observed in all cases, indicating an inability for any single equation to effectively model the long-term solubilization process

Design, synthesis, and biological evaluation of tumor-selective vascular disrupting agents, water-soluble amino acid prodrug conjugates, and bioreductively activatable prodrug conjugates targeting tumor hypoxia.

Selective targeting of tumor cells in comparison to healthy cells is vital in order to increase drug efficacy and reduce side effects to cancer patients. The underlying morphological and physiological differences between vasculature feeding healthy tissue versus tumor bearing tissue provides an opportunity to selectively target tumor vasculature as a promising therapeutic option for cancer treatment. Combretastatin A-1 (CA1) and combretastatin A-4 (CA4) are members of a family of inhibitors of tubulin polymerization which functions as tumor-selective vascular disrupting agents (VDAs). The success of clinical trials involving the phosphate prodrugs of CA1 and CA4 (CA1P and CA4P respectively) inspired the design, synthesis, and biological evaluation of structurally related benzosuberene analogues as potent VDAs. A phenolic benzosuberene analogue (referred to as KGP18) and its amino congener (referred to as KGP156) emerged as potential preclinical candidates because of their robust cytotoxicity (sub-nM to pM) against selected human cancer cell lines in vitro, and excellent tubulin inhibitory capabilities. A series of benzosuberene based analogues were synthesized in order to expand the relationship of structure to function in this class of anti-cancer agents. Also, a series of tri- and pentafluoro substituted amino-based combretastatin analogues were synthesized. In an effort to discover new VDAs with improved water solubility and bioavailability, various amino-acid producing conjugates (AAPCs) of potent amino-based combretastatin analogues were synthesized. The corresponding water-soluble hydrochloride salts of these AAPCs were investigated for their ability to be cleaved by the leucine aminopeptidase (LAP) enzyme through a collaborative effort with the Trawick Research Group (Baylor University). The glycinamide hydrochloride salt 2' CA4-amine were cleaved quantitatively by LAP, however only partial cleavage was evident for their serinamide and bis-serinamide counterparts. Since hypoxia is regarded as a hallmark of most solid tumors, a series of hypoxia-activated prodrugs [referred to as bioreductively activated producing onjugates (BCAPs)] of CA1 were synthesized regioselectively. These CA1-BAPCs are capable if being reduced by one or two-electron reductases, principally NAD(P)H cytochrome p450, cleaving the bioreductive trigger and releasing the cytotoxic drug in the hypoxic tumor microenvironment. A new and efficient synthetic methodology was explored to generate three nitrothiophene triggers from a common starting material

Design, synthesis, and biological evaluation of tumor-selective vascular disrupting agents, water-soluble amino acid prodrug conjugates, and bioreductively activatable prodrug conjugates targeting tumor hypoxia.

Selective targeting of tumor cells in comparison to healthy cells is vital in order to increase drug efficacy and reduce side effects to cancer patients. The underlying morphological and physiological differences between vasculature feeding healthy tissue versus tumor bearing tissue provides an opportunity to selectively target tumor vasculature as a promising therapeutic option for cancer treatment. Combretastatin A-1 (CA1) and combretastatin A-4 (CA4) are members of a family of inhibitors of tubulin polymerization which functions as tumor-selective vascular disrupting agents (VDAs). The success of clinical trials involving the phosphate prodrugs of CA1 and CA4 (CA1P and CA4P respectively) inspired the design, synthesis, and biological evaluation of structurally related benzosuberene analogues as potent VDAs. A phenolic benzosuberene analogue (referred to as KGP18) and its amino congener (referred to as KGP156) emerged as potential preclinical candidates because of their robust cytotoxicity (sub-nM to pM) against selected human cancer cell lines in vitro, and excellent tubulin inhibitory capabilities. A series of benzosuberene based analogues were synthesized in order to expand the relationship of structure to function in this class of anti-cancer agents. Also, a series of tri- and pentafluoro substituted amino-based combretastatin analogues were synthesized. In an effort to discover new VDAs with improved water solubility and bioavailability, various amino-acid producing conjugates (AAPCs) of potent amino-based combretastatin analogues were synthesized. The corresponding water-soluble hydrochloride salts of these AAPCs were investigated for their ability to be cleaved by the leucine aminopeptidase (LAP) enzyme through a collaborative effort with the Trawick Research Group (Baylor University). The glycinamide hydrochloride salt 2' CA4-amine were cleaved quantitatively by LAP, however only partial cleavage was evident for their serinamide and bis-serinamide counterparts. Since hypoxia is regarded as a hallmark of most solid tumors, a series of hypoxia-activated prodrugs [referred to as bioreductively activated producing onjugates (BCAPs)] of CA1 were synthesized regioselectively. These CA1-BAPCs are capable if being reduced by one or two-electron reductases, principally NAD(P)H cytochrome p450, cleaving the bioreductive trigger and releasing the cytotoxic drug in the hypoxic tumor microenvironment. A new and efficient synthetic methodology was explored to generate three nitrothiophene triggers from a common starting material

ELEVATIONAL DISTRIBUTION OF TREE DIVERSITY IN LOWER HIMALAYA: A CASE STUDY OF PHULCHOKI HILL, NEPAL

 Changes in tree species composition with elevation have been studied at three distinct altitudinal ranges on the basis of dominance, in sub-tropical and temperate forests on south slopes of Phulchoki hill, central part of lower Himalaya, Nepal. The greatest number of tree species was found in the low altitude (1600 m), followed by intermediate altitude (1950 m). The highest altitude (2650 m) contained only one distinct tree species (Oak). Site I has higher species diversity (Shannon Index: 2.1863, Evenness Index: 0.852) and density (5575 individual per hectare) dominated by Castonopsis indica, Quercus glauca, Myrica esculenta and myrsine capitellate. Site II has average species diversity (Shannon Index: 1.759, Evenness Index: 0.9) and an average density (2150 individual per hectare) dominated by Rhododendron arboretum, Castanopsis tribuloides and Quercus incana. At site III the forest is entirely dominated by Quercus semicarpifolia, a high altitude Oak. A linear trend of decreasing tree species diversity and density along with elevations was seen which might be because of intense afforestation by communities at lower elevation as site I and II under community managed forest and lower altitudinal ecozone with clear zonation of elevational vegetation types.International Journal of Environment Volume-4, Issue-3, June-August 2015Page: 130-139</p

A Hyperfluorinated Hydrophilic Molecule for Aqueous 19F MRI Contrast Media

Fluorine-19 (19F) magnetic resonance imaging (MRI) has the potential for a wide range of in vivo applications but is limited by lack of flexibility in exogenous probe formulation. Most 19F MRI probes are composed of perfluorocarbons (PFCs) or perfluoropolyethers (PFPEs) with intrinsic properties which limit formulation options. Hydrophilic organofluorine molecules can provide more flexibility in formulation options. We report herein a hyperfluorinated hydrophilic organoflourine, ET1084, with ∼24 wt. % 19F content. It dissolves in water and aqueous buffers to give solutions with ≥8 M 19F. 19F MRI phantom studies at 9.4T employing a 10-minute multislice multiecho (MSME) scan sequence show a linear increase in signal-to-noise ratio (SNR) with increasing concentrations of the molecule and a detection limit of 5 mM. Preliminary cytotoxicity and genotoxicity assessments suggest it is safe at concentrations of up to 20 mM