NMR Structure Implications of Enhanced Efficacy of Obestatin Fragment Analogs

Obestatin is a more recently discovered hormone that is encoded by the ghrelin gene and produced in the stomach and gut. We report NMR analysis on synthetic Obestatin (OB23), a 23 residue peptide, along with three overlapping fragments of the same in methanol solvent as a first step towards structure activity relationship. Selective substitutions on the promising N-terminal and middle fragments of obestatin have been carried out in order to improve the efficacy and potency. In the N-terminal fragment two peptides were obtained by the replacement of Gly (8) with a-aminoisobutyric acid (Aib, U) and Phe (F5) with Cyclohexylalanine (Cha). In case of the middle fragment both Gly (3) and Gly (8) were replaced with Aib residues. The rationale being, these unusual amino acids could provide protection from immediate degradation and aid structure stabilization. Our previous studies showed that the N-terminal and the middle fragment were unstructured and hence this substitution would directly evaluate the effect of structure on the activity of these fragment analogs. Detailed NMR analysis clearly demonstrates formation of helical secondary structure in all the peptide analogues and provides justification for relative activities reported by our group previously (Nagaraj et al. 2009).

Treatment efficacy of algae-based sewage treatment plants

Lagoons have been traditionally used in India for decentralized treatment of domestic sewage. These are cost effective as they depend mainly on natural processes without any external energy inputs. This study focuses on the treatment efficiency of algae-based sewage treatment plant (STP) of 67.65 million liters per day (MLD) capacity considering the characteristics of domestic wastewater (sewage) and functioning of the treatment plant, while attempting to understand the role of algae in the treatment. STP performance was assessed by diurnal as well as periodic investigations of key water quality parameters and algal biota. STP with a residence time of 14.3 days perform moderately, which is evident from the removal of total chemical oxygen demand (COD) (60 %), filterable COD (50 %), total biochemical oxygen demand (BOD) (82 %), and filterable BOD (70 %) as sewage travels from the inlet to the outlet. Furthermore, nitrogen content showed sharp variations with total Kjeldahl nitrogen (TKN) removal of 36 %; ammonium N (NH4-N) removal efficiency of 18 %, nitrate (NO3-N) removal efficiency of 22 %, and nitrite (NO2-N) removal efficiency of 57.8 %. The predominant algae are euglenoides (in facultative lagoons) and chlorophycean members (maturation ponds). The drastic decrease of particulates and suspended matter highlights heterotrophy of euglenoides in removing particulates.

Experimental assessment of concrete damage due to exposure to high temperature and efficacy of the repair system

The present study experimentally evaluates the performance of control (standard cylinder specimen), damaged (mechanical loading after thermal exposure) and repaired / retrofitted normal plain concrete cylinders using different repair schemes such as on use of FRP wraps, Geo-polymers, etc., to restore the capacity of damaged structural concrete elements. The control-companion specimen in the series provides the reference frame against which both, specimen damage levels were quantified and the benefits of a specimen repaired subsequent to damage were assessed.

Formulation of nanotized curcumin and demonstration of its antimalarial efficacy

Aim: The present study was conducted to overcome the disadvantages associated with the poor water solubility and low bioavailability of curcumin by synthesizing nanotized curcumin and demonstrating its efficacy in treating malaria. Materials and methods: Nanotized curcumin was prepared by a modified emulsion-diffusion-evaporation method and was characterized by means of transmission electron microscopy, atomic force microscopy, dynamic light scattering, Zetasizer, Fourier transform infrared spectroscopy, and differential thermal analysis. The novelty of the prepared nanoformulation lies in the fact that it was devoid of any polymeric matrices used in conventional carriers. The antimalarial efficacy of the prepared nanotized curcumin was then checked both in vitro and in vivo. Results: The nanopreparation was found to be non-toxic and had a particle size distribution of 20-50 nm along with improved aqueous dispersibility and an entrapment efficiency of 45%. Nanotized curcumin (half maximal inhibitory concentration IC50]: 0.5 mu M) was also found to be ten-fold more effective for growth inhibition of Plasmodium falciparum in vitro as compared to its native counterpart (IC50: 5 mu M). Oral bioavailability of nanotized curcumin was found to be superior to that of its native counterpart. Moreover, when Plasmodium berghei-infected mice were orally treated with nanotized curcumin, it prolonged their survival by more than 2 months with complete clearance of parasites in comparison to the untreated animals, which survived for 8 days only. Conclusion: Nanotized curcumin holds a considerable promise in therapeutics as demonstrated here for treating malaria as a test system.

Rollover-Preventive Force Synthesis at Active Suspensions in a Vehicle Performing a Severe Maneuver With Wheels Lifted Off

Among the intelligent safety technologies for road vehicles, active suspensions controlled by embedded computing elements for preventing rollover have received a lot of attention. The existing models for synthesizing and allocating forces in such suspensions are conservatively based on the constraints that are valid until no wheels lift off the ground. However, the fault tolerance of the rollover-preventive systems can be enhanced if the smart/active suspensions can intervene in the more severe situation in which the wheels have just lifted off the ground. The difficulty in computing control in the last situation is that the vehicle dynamics then passes into the regime that yields a model involving disjunctive constraints on the dynamics. Simulation of dynamics with disjunctive constraints in this context becomes necessary to estimate, synthesize, and allocate the intended hardware realizable forces in an active suspension. In this paper, we give an algorithm for the previously mentioned problem by solving it as a disjunctive dynamic optimization problem. Based on this, we synthesize and allocate the roll-stabilizing time-dependent active suspension forces in terms of sensor output data. We show that the forces obtained from disjunctive dynamics are comparable with existing force allocations and, hence, are possibly realizable in the existing hardware framework toward enhancing the safety and fault tolerance.

Enhanced Efficacy of Pluronic Copolymer Micelle Encapsulated SCR7 against Cancer Cell Proliferation(a)

5,6-Bis(benzylideneamino)-2-mercaptopyrimidin-4-ol (SCR7) is a new anti cancer molecule having capability to selectively inhibit non-homologous end joining (NHEJ), one of the DNA double strand break (DSB) repair pathways inside the cells. In spite of the promising potential as an anticancer agent, hydrophobicity of SCR7 decreases its bioavailability. Herein the entrapment of SCR7 in Pluronic copolymer is reported. The size of the aggregates was determined by transmission electron microscopy (TEM) and dynamic light scattering (DLS) which yields an average diameter of 23 nm. SCR7 encapsulated micelles (ES) were also characterized by small-angle neutron scattering (SANS). Evaluation of its biological properties by using a variety of techniques, including Trypan blue, MTT and Live-dead cell assays, reveal that encapsulated SCR7 can induce cytotoxicity in cancer cell lines, being more effective in breast cancer cell line. Encapsulated SCR7 treatment resulted in accumulation of DNA breaks within the cells, resulting in cell cycle arrest at G1 phase and activation of apoptosis. More importantly, we found approximate to 5 fold increase in cell death, when encapsulated SCR7 was used in comparison with SCR7 alone.

Aircraft Composite Structure Preventive Maintenance

In this paper, a methodology to reduce composite structure maintenance operational cost using SHM systems is adressed. Based on SHM real-time data, in-service structure lifetime prognostic and remaining useful lifetime (RUL) can be performed. Maintenance timetable can be therefore predicted by optimizing inspection times. A probabilistic ap-proach is combined with phenomenological fatigue damage models for composite mate-rials to perform maintenance cost-effectiveness of composite structure. A Monte Carlo method is used to estimate the probability of failure of composite structures and com-pute the average number of composite structure components to be replaced over the component lifetime. The replacement frequency of a given structure component over the aircraft lifetime is assessed. A first application of aeronautical composite structure maintenance is considered. Two composite models to predict the fatigue life and several laminates have been used. Our study shows that maintenance cost-effectiveness depends on material and fatigue loading applied.

Use of Sediment Bioassays to Verify Efficacy of Caulerpa taxifolia Eradication Treatments

Infestations of the marine macrophytic alga Caulerpa taxifolia were discovered in Agua Hedionda Lagoon, California in 2000. Rapid response actions included containment under pvc tarps coupled with injection of liquid sodium hypochlorite. To assess the efficacy of these treatments, replicated sediment cores were removed from representative treated sites and transferred to grow-out facilities. Similar cores from uninfested (control) sediments were removed, inoculated with viable explants of C. taxifolia and placed in grow-out facilities. Results from two sampling periods (1 year, 2 years post-treatment) showed that no viable C. taxifolia emerged in cores, and that inoculated “control” sediments supported normal growth. Eelgrass ( Zostera marina L.) seedlings emerged from native seed-banks in “treated” cores, which also supported growth of some invertebrates (annelid worms and hydroids). This study provided essential verification of C. taxifolia eradication efforts, and demonstrates the feasibility of incorporating quality control/quality assurance components in rapid response actions. Results of this study also suggest that seeds of eelgrass are viable for at least two years. (PDF has 9 pages.)

Comparative Efficacy of Diquat for Control of Two Members of the Hydrocharitaceae: Elodea and Hydrilla

The submersed plants hydrilla (Hydrilla verticillata (L.f.) Royle) and elodea (Elodea canadensis Rich.) are both members of the Hydrocharitaceae family and cause problems in waterways throughout the world. Diquat (6,7-dihydrodipyrido[1,2-α:2’,1’-c]pyrazinediium dibromide) is a contact herbicide used to control nuisance submersed and floating aquatic macrophytes. There is no readily available information in the literature on the control of elodea under various diquat concentration and exposure times (CET) and other than a study by Van et. al 1987, little on hydrilla. Since CET relationships are critical in controlling submersed plants in areas influenced by water exchange, this study was designed to evaluate the efficacy of diquat on hydrilla and elodea under various CET scenarios. (PDF has 3 pages.)

Efficacy and Residue Comparisons between Two Slow-release Formulations of Fluridone

Residue profiles and efficacy of Avast and Sonar, two slow release pellet formulations of fluridone {1-methyl-3-phenyl-5- [3-(trifluoromethyl)phenly]-4(1H)-pyridinone}, were compared in outdoor tanks. Hydrilla (Hydrilla verticillata (L.f.) Royle) and southern naiad (Najas guadalupensis (Sprengel) Magnus) were treated with a split application of 6, 12, 18 and 24 μg/l a.i. fluridone and the concentrations of both formulations compared over a 134-day period. Both pellet formulations exhibited very similar residues over time for each respective treatment, resulted in peak concentrations of fluridone 40 to 50 days after application, and effectively and similarly controlled southern naiad and hydrilla at all rates tested by 92 days after initial application. (PDF contains 3 pages.)

Influence of Foliar Exposure, Adjuvants, and Rain-free Period on the Efficacy of Glyphosate for Torpedograss Control

The proportion of torpedograss tissue exposed to glyphosate at application rates of 0.28, 0.56, 1.12, 2.24, and 4.48 kg/ha affected control as measured by regrowth. The effect of tissue exposure was more pronounced as application rate decreased. This study suggests that higher rates of glyphosate need to be used during higher water levels, when less torpedograss tissue is exposed to herbicide spray and lower rates may be used during periods of low water levels. Addition of the water conditioning agent Quest (R) (0.25% v/v) to glyphosate spray mixtures diminished the influence of simulated rain events following glyphosate application. Twelve other adjuvants did not influence the effect of simulated rain events.

Impacts of inorganic turbidity on diquat efficacy against Egeria densa

In clear water, diquat [6,7-dihydrodipyrido (1,2-1a:2',1'-c) pyrazinediium dibromide] provides excellent submersed Plant control at low concentrations, such as <0.5 mg active ingredient (ai) L-1: however. turbid water conditions can interfere with the activity and effectiveness of this herbicide. Little work has been done to examine what ranges of turbidity caused by different Suspended sediment types affect diquat efficacy against a target species. A growth chamber study was conducted rising diquat against the submersed macrophyte -egeria (Egeria densa Planch.) under a range Of turbid conditions. Two materials were used to create turbid beater conditions: 100% bentonite clay for a "worst-case" scenario and a natural partial-clav (20% clay). Results indicated that a high rate of diquat (2 mg ai L-1) controlled egeria under relatively low levels of turbidity (5-10 NTU) using bentonite clay: however. higher levels (25 to 50 NTU) of turbidity essentially blocked effectiveness of diquat when applied at all rates tested (0.5. 1, 2 mg ai L-1). When using a natural partial-clay sediment, rates of 1 to 2 mg ai L-1 diquat provided good control of egeria in moderately turbid water (15 NTU). Additional evaluations rising different clay types would be useful to determine the effect of inorganic turbidity oil diquat efficacy.

Carfentrazone-ethyl Pond Dissipation and Efficacy on Floating Plants

Carfentrazone-ethyl (CE) is a reduced risk herbicide that is currently being evaluated for the control of aquatic weeds. Greenhouse trials were conducted to determine efficacy of CE on water hyacinth ( Eichhornia crassipes (Mart.) Solms- Laub.), water lettuce ( Pistia stratiotes L.), salvinia ( Salvinia minima Baker) and landoltia (Landoltia punctata (G. Mey.) Les & D. J. Crawford ) . CE controlled water lettuce, water hyacinth and salvinia at rates less than the maximum proposed use rate of 224 g ha -1 . Water lettuce was the most susceptible to CE with an EC 90 of 26.9 and 33.0 g ha -1 in two separate trials. Water hyacinth EC 90 values were calculated to be 86.2 to 116.3 g ha -1 , and salvinia had a similar susceptibility to water hyacinth with an EC 90 of 79.1 g ha -1 . Landoltia was not adequately controlled at the rates evaluated. In addition, CE was applied to one-half of a 0.08 ha pond located in North Central, Florida to determine dissipation rates in water and hydrosoil when applied at an equivalent rate of 224 g ha -1 . The half-life of CE plus the primary metabolite, CE-chloropropionic acid, was calculated to be 83.0 h from the whole pond, and no residues were detected in water above the limit of quantification (5 μg L -1 ) 168 h after treatment. CE dissipated rapidly from the water column, did not occur in the sediment above the levels of quantification, and in greenhouse studies effectively controlled three species of aquatic weeds at relatively low rates.(PDF contains 6 pages.)

Influence of water temperature on the efficacy of diquat and endothall versus curlyleaf pondweed

determine the impact of water temperature on the efficacy of the contact herbicides diquat (6,7-dihydrodipyrido [1,2- α:2’,1’-c] pyrazinediium ion) and endothall (7-oxabicyclo [2.2.1] heptane-2,3-dicarboxylic acid) for control of the exotic nuisance species curlyleaf pondweed (Potamogeton crispus L.) across a range of water temperatures.