Eightfold Decrease Research Articles

CD59 receptor targeted delivery of miRNA-1284 and cisplatin-loaded liposomes for effective therapeutic efficacy against cervical cancer cells

Co-delivery of two different therapeutics (miRNA-1284 and cisplatin (CDDP)) into the cancer cells in a single nanocarrier provides new dimension to the cancer treatment. In this study, we have designed the CD59sp-conjugated miRNA-1284/cisplatin(CDDP)-loaded liposomes for the enhanced therapeutic effect against cervical cancers. Compared with miRNA-1284/CDDP-loaded liposomes (LP-miCDDP), CD59 antibody-conjugated LP-miCDDP (CD/LP-miCDDP) showed a significantly higher cytotoxicity in HeLa cells. Notably, MiR-1284 showed a typical concentration-dependent cell killing effect in the cervical cancer cells owing to the downregulation of HMGB1. Flow cytometer analysis showed that CD/LP-miCDDP resulted in maximum apoptosis effect (~ 60%) compared to CDDP (~ 20%) or miR-1284 (~ 12%) treated cells indicating the superior anticancer effect in the cancer cells. Importantly, CD/LP-miCDDP significantly prolonged the blood circulation of encapsulated drug in rats with AUC(o-t) of CD/LP-miCDDP showed a 6.9 fold higher value than that of free CDDP. Similarly, CD/LP-miCDDP showed an eightfold decrease in the clearance (CL) and 3.6-fold higher t1/2 compared to that of free CDDP. Overall, results demonstrated that targeted and synergistic co-delivery of therapeutic components could be promising in cervical cancer therapy.

Drought tolerance induction in transgenic tobacco through RNA interference of BrDST71, a drought-responsive gene from Chinese cabbage

Because drought is a major environmental factor that causes serious agricultural problems, understanding the mechanisms and genetic bases underlying plant responses to drought stress is essential. Using the Brassica rapa 135 K microarray, BrDST71 gene was identified. BrDST71 expression in drought-tolerant Chinese cabbage showed an eight-fold decrease than in wild-type, and encodes a 362 amino acid protein containing a secretory peroxidase domain. Overexpression and RNAi vectors of BrDST71 were constructed and each vector was transformed into Nicotiana tabacum by the Agrobacterium-mediated transformation method. The expression level of BrDST71 and the phenotype were analyzed under drought condition. Transgenic lines with suppressed expression of BrDST71 showed more tolerance to drought stress compared to wild-type and overexpression transgenic lines. It showed that suppressing BrDST71 expression is correlated to better growth under drought conditions. Based on these results, we suggest that down-regulation of BrDST71 improves drought tolerance.

The use of covalent organic frameworks as template for conductive polymer synthesis and their sensor applications

In this study, the synthesis of a mesoporous crystalline covalent organic framework (COF) based on melamine and 1,4-dibromo butane as COF-1,4 and its use as a template for in situ synthesis of conductive polymers such as poly(Aniline) (PANi) and poly(Pyrrole) (PPy) within the pores were reported. The synthesized COF-1,4/conductive polymer semi-Interpenetrating Network (semi-IPN) composites were characterized via FT-IR spectroscopy and thermogravimetric analyzer (TGA), and the conductivities of the prepared composites were determined with an electrometer. It was found that upon the in situ synthesis of the conductive polymers such as PANi and PPy within COF-1,4, the conductivity of bare COF-1,4 was increased 3 million-fold for COF-1,4/PANi, and 500 thousand-fold for COF-1,4/PPy, respectively. Furthermore, the potential sensor applications of these COF-1,4/conductive polymer semi-IPN composites were investigated against HCl and NH3, and methyl orange (MO), and methylene blue (MB) dyes in aqueous solutions. The sensor studies revealed that the conductivity of bare COF-1,4 increased 20 and 7K-folds upon 15 min exposure to HCl and NH3 gases, respectively. Interestingly, an eightfold decrease in the conductivity of COF-1,4/PANi was observed upon 15 min exposure to NH3 gas vapor at ambient conditions. Also, the conductivities of prepared COF-1,4 and its conductive polymer composites changed after treatment with MO and MB dyes suggesting other potential sensor applications of these porous materials.

Identification of a Novel Polyamine Scaffold With Potent Efflux Pump Inhibition Activity Toward Multi-Drug Resistant Bacterial Pathogens.

We have previously reported the use of combinatorial chemistry to identify broad-spectrum antibacterial agents. Herein, we extend our analysis of this technology toward the discovery of anti-resistance molecules, focusing on efflux pump inhibitors. Using high-throughput screening against multi-drug resistant Pseudomonas aeruginosa, we identified a polyamine scaffold that demonstrated strong efflux pump inhibition without possessing antibacterial effects. We determined that these molecules were most effective with an amine functionality at R1 and benzene functionalities at R2 and R3. From a library of 188 compounds, we studied the properties of 5 lead agents in detail, observing a fivefold to eightfold decrease in the 90% effective concentration of tetracycline, chloramphenicol, and aztreonam toward P. aeruginosa isolates. Additionally, we determined that our molecules were not only active toward P. aeruginosa, but toward Acinetobacter baumannii and Staphylococcus aureus as well. The specificity of our molecules to efflux pump inhibition was confirmed using ethidium bromide accumulation assays, and in studies with strains that displayed varying abilities in their efflux potential. When assessing off target effects we observed no disruption of bacterial membrane polarity, no general toxicity toward mammalian cells, and no inhibition of calcium channel activity in human kidney cells. Finally, combination treatment with our lead agents engendered a marked increase in the bactericidal capacity of tetracycline, and significantly decreased viability within P. aeruginosa biofilms. As such, we report a unique polyamine scaffold that has strong potential for the future development of novel and broadly active efflux pump inhibitors targeting multi-drug resistant bacterial infections.

Ice-free Arctic projections under the Paris Agreement

Under the Paris Agreement, emissions scenarios are pursued that would stabilize the global mean temperature at 1.5–2.0 °C above pre-industrial levels, but current emission reduction policies are expected to limit warming by 2100 to approximately 3.0 °C. Whether such emissions scenarios would prevent a summer sea-ice-free Arctic is unknown. Here we employ stabilized warming simulations with an Earth System Model to obtain sea-ice projections under stabilized global warming, and correct biases in mean sea-ice coverage by constraining with observations. Although there is some sensitivity to details in the constraining method, the observationally constrained projections suggest that the benefits of going from 2.0 °C to 1.5 °C stabilized warming are substantial; an eightfold decrease in the frequency of ice-free conditions is expected, from once in every five to once in every forty years. Under 3.0 °C global mean warming, however, permanent summer ice-free conditions are likely, which emphasizes the need for nations to increase their commitments to the Paris Agreement.

Tailoring ion exchange membranes to enable low osmotic water transport and energy efficient electrodialysis

Ion exchange membranes have been applied for water desalination since the 1950s in a process called electrodialysis, ED. Parallel to the transport of ions across ion exchange membranes, water molecules are transported from diluate to concentrate compartments reducing ED efficiency. In this study tailor made meshed membranes were prepared by embedding polymeric meshes with significantly reduced open area into an ion conductive polymer. These membranes were characterized to assess their transport properties. It is shown that by changing mesh open area, material and surface properties, it is possible to significantly reduce osmotic water transport. Polyamide mesh embedded in a cation exchange polymer showed an eightfold decrease of the water mass transport coefficient. Unexpectedly, osmotic water transport was not affected when the same mesh material was embedded in an anion exchange polymer. A decrease of the osmotic water transport for meshed anion exchange membranes was achieved by using a polyethylene terephthalate mesh. Despite the associated electrical resistance increase, application of meshed membranes increased diluate yield and allowed for more energy efficient operation in case ED is confined to a low current density regime.

Spatiotemporal dynamics of the pollution of Al–Fe-humus podzols in the impact zone of a nonferrous metallurgical plant

The dependence of the level of contamination of the upper horizon of Al–Fe-humus podzols (Podzols Rustic) with heavy metals (Ni, Cu) on the distance from the Severonickel smelter (Monchegorsk, Murmansk oblast) was studied on a number of test plots in the medium-aged pine stands. It was found that metal concentrations in the soils could be reasonably approximated by the negative exponential function. In the buffer zone of the smelter, the concentrations of Ni and Cu exceed background values by 8–17 times; in the impact zone, by 50–100 times. The study of the dynamics of acid-soluble forms of Ni and Cu in the organic horizons of podzols on the key plots showed that the boundaries of polluted territory shift towards background regions despite the recent five–eightfold decrease in the emissions. The concentrations of heavy metals in the litter horizons continued to increase in the buffer zone. In the impact zone, their contamination remained at the very high level. Firm bounding of heavy metals in the organic horizon coupled with their continuing aerial input did not allow the beginning of the soil self-purification process, which might last for decades and centuries. Raster electron microscope and X-ray spectral microanalysis showed that particles (>85%) of the ashed matter of organic horizons from the background region, the buffer zone, and the impact zone is mainly represented by various soil-forming minerals and iron oxides (in particular, magnetite). In the samples from the impact zone, about 5% of the mineral particles had the surface morphology and chemical composition typical of dust particles emitted into the air by metal smelters. Most probably, these spherical particles represented magnetite Fe3O4 enriched in heavy metals (Cu, Ni).

Dnase1L3 trafficking is redirected from secretion to the nucleus in lupus-prone mice

Abstract Pediatric-onset Systemic Lupus Erythematosus (SLE) is linked to a deficiency of the endonuclease Dnase1L3. Dnase1L3 can function extracellularly as a barrier to transfection or localize to the nucleus of macrophages to cleave DNA during apoptosis, though the mechanism by which Dnase1L3 protects from pediatric-onset SLE is unknown. Two polygenic lupus murine models, MRL-lpr and NZB/W F1, bear the activity-reducing T89I mutation in Dnase1L3. Dnase1L3 T89I has an eight-fold decrease in barrier-to-transfection activity, while the endonuclease activity is only decreased two-fold compared to the wildtype, providing a tool with which to dissect Dnase1L3 trafficking in SLE. We hypothesized that Dnase1L3 T89I localizes to the nucleus, which decreases barrier-to-transfection activity and enhances SLE onset. We transfected HEK cells with wild type or T89I Dnase1L3, and determined the subcellular localization of Dnase1L3. We found that the majority of wild type Dnase1L3 is secreted from the cell, while Dnase1L3 T89I showed increased nuclear localization. Since Dnase1L3 alters inflammasome function, we tested whether inflammatory stimuli alter Dnase1L3 trafficking. LPS treatment of cells transfected with Dnase1L3 T89I reduced its nuclear localization. Altered Dnase1L3 trafficking may impair inflammasome function, since macrophages from NZB/W F1 mice secreted less IL-1β than wild type mice. Overall, the increase in nuclear localization of Dnase1L3 T89I suggests that barrier to transfection or extracellular nuclease activity may promote IL-1β release and protect against pediatric-onset SLE.

The use of acetone to enhance the infiltration of HA nanoparticles into a demineralized dentin collagen matrix

ObjectivesThis study investigates the role of acetone, as a carrier for nano-hydroxyapatite (nano-HA) in solution, to enhance the infiltration of fully demineralized dentin with HA nanoparticles (NPs). MethodsDentin specimens were fully demineralized and subsequently infiltrated with two types of water-based nano-HA solutions (one containing acetone and one without). Characterization of the dentin surfaces and nano-HA particles was performed using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The surface wettability and infiltration capacity of the nano-HA solutions were quantified by means of contact angle measurements and energy dispersive X-ray spectroscopy (EDS), respectively. Contact angle measurements were taken at baseline and repeated at regular intervals to assess the effect of acetone. The P and Ca levels of infiltrated dentin specimens were measured and compared to sound dentin and non-infiltrated controls. ResultsThe presence of acetone resulted in an eight-fold decrease in the contact angles of the nano-HA solutions recorded on the surface of demineralized dentin compared to nano-HA solutions without acetone (one-way ANOVA, p<0.05). Perfect wetting of the demineralized dentin surface was achieved 5min after the application of the nano-HA solution containing acetone. Infiltration of demineralized dentin with the nano-HA solution containing acetone restored the lost mineral content by 50%, whereas the mean mineralization values for P and Ca in dentin treated with the acetone-free nano-HA solution were less than 6%. SignificanceAcetone was shown to act as a vehicle to enhance the capacity to infiltrate demineralized dentin with HA NPs. The successful infiltration of dentin collagen with HA NPs provides a suitable scaffold, whereby the infiltrated HA NPs have the potential to act as seeds that may initiate heterogenous mineral growth when exposed to an appropriate mineral-rich environment.

Trends in Prevalence of Thyroid Cancer Over Three Decades: A Retrospective Cohort Study of 17,526 Surgical Patients.

IntroductionThyroid cancer (TC) incidence has been increasing in recent years. The aim of this study was to investigate our institution-based estimates of operative volumes for TC over the last three decades.Materials and methodsThis was a retrospective cohort study of patients undergoing thyroid surgery at our institution. Patient characteristics were reviewed in three subgroups: Group I (treated in 1981–1986), Group II (treated in 1987–2002), and Group III (treated in 2003–2012).ResultsTC was diagnosed in 1578/17,526 (9.0 %) thyroid operations. Incidence of TC increased from 3.7 % in Group I to 10.4 % in Group III (p < 0.001). Incidence of papillary TC increased form 40.6 % in Group I to 81.3 % in Group III (p < 0.001). In the latter group, 23.5 % of all papillary TCs were diagnosed in patients with Hashimoto’s disease. Meanwhile, incidence of anaplastic TC decreased from 16.2 % in Group I to 2.1 % in Group III patients (p < 0.001). pT1 tumors were diagnosed in 8.1 % Group I and 54.8 % Group III (p < 0.001), whereas pT4 tumors were identified in 40.5 % Group I, 2.4 % Group II, and 0.84 % Group III subjects (p < 0.001). pT3 tumors were found in 51.6 % Group I, whereas multifocal papillary TCs were found in 15.7 % Group III patients, the latter with a higher prevalence of pN1 stage (p < 0.001).ConclusionsThe following trends in surgical volume for TC were identified throughout the study period: a fivefold increase of thyroid operations for TC, a threefold increase in incidence of papillary TC, and an eightfold decrease in incidence of anaplastic TC. It is of interest that a significant increase in incidence of multifocal papillary TC in young female patients with Hashimoto’s disease was found over time.

Enhanced fixed-size parallel speedup with the Muskingum method using a trans-boundary approach and a large subbasins approximation

This study presents a new algorithm for parallel computation of river flow that builds on recent work demonstrating the relative independence of distant river reaches in the update step of the Muskingum method. The algorithm is designed to achieve enhanced fixed-size parallel speedup and uses a mathematical approximation applied at the boundaries of large subbasins. In order to use such an algorithm, a balanced domain decomposition method that differs from the traditional classifications of river reaches and subbasins and based on network topology is developed. An application of the algorithm and domain decomposition method to the Mississippi River Basin results in an eightfold decrease in computing time with 16 computing cores which is unprecedented for Muskingum-type algorithms applied in classic parallel-computing paradigms having a one-to-one relationship between cores and subbasins. An estimated 300 km between upstream and downstream reaches of subbasins guarantees the applicability of the algorithm in our study and motivates further investigation of domain decomposition methods.

End-User Mapping

Content Delivery Networks (CDNs) deliver much of the world's web, video, and application content on the Internet today. A key component of a CDN is the mapping system that uses the DNS protocol to route each client's request to a ``proximal'' server that serves the requested content. While traditional mapping systems identify a client using the IP of its name server, we describe our experience in building and rolling-out a novel system called end-user mapping that identifies the client directly by using a prefix of the client's IP address. Using measurements from Akamai's production network during the roll-out, we show that end-user mapping provides significant performance benefits for clients who use public resolvers, including an eight-fold decrease in mapping distance, a two-fold decrease in RTT and content download time, and a 30% improvement in the time-to-first byte. We also quantify the scaling challenges in implementing end-user mapping such as the 8-fold increase in DNS queries. Finally, we show that a CDN with a larger number of deployment locations is likely to benefit more from end-user mapping than a CDN with a smaller number of deployments.

Fast determination of octinoxate and oxybenzone uv filters in swimming pool waters by gas chromatography/mass spectrometry after solid‐phase microextraction

A fast gas chromatography/mass spectrometry method was developed and validated for the analysis of the potential endocrine disrupters octinoxate and oxybenzone in swimming pool water samples based on the solvent-free solid-phase microextraction technique. The low-pressure gas chromatography/mass spectrometry method used for the fast identification of UV filter substances was compared to a conventional method in terms of sensitivity and speed. The fast method proposed resulted in 2 min runs, leading to an eightfold decrease in the total analysis time and a sevenfold improvement in detection limits. The main parameters affecting the solid-phase microextraction process were also studied in detail and the optimized conditions were as follows: fiber coating, polyacrylate; extraction mode, direct immersion; extraction temperature, 25°C; sample volume, 5 mL; extraction time 45 min; pH 6.5. Under the optimized conditions, a linear response was obtained in the concentration range of 0.5-25 μg/L with correlation coefficients in the range 0.990-0.999. The limits of detection were 0.17-0.29 μg/L, and the recoveries were 80-83%. Combined method uncertainty was assessed and found to be less than 7% for both analytes for concentrations equal to or higher than 5 μg/L. Pool water samples were analyzed to demonstrate the applicability of the proposed method. Neither octinoxate nor oxybenzone were detected in the swimming pool water samples at concentrations above the respective limits of detection.

960 Exposure to Anti-TNFα Therapy in the Third Trimester of Pregnancy Is Not Associated With Increased Adverse Outcomes: Results From the PIANO Registry

Background: Patients with Inflammatory Bowel Disease (IBD) represent a population who are immunocompromised due to their underlying disease and the use of immunosuppressant medications. The Centers for Disease Control and Prevention (CDC) recommends an annual influenza vaccine and 1-2 doses of the pneumococcal vaccine in those on immunosuppressants as a preventive strategy. The efficacy and outcomes of these vaccinations in patients with IBD has been understudied. Our objective is to determine pneumococcal and influenza vaccination outcomes in patients with IBD. Methods: This was a retrospective study utilizing the Explorys database, an open private cloud based platform that electronically integrates non-identified patient data used by 14 major healthcare systems comprising 40 million patients. We included IBD patients (using ICD-9 code criteria) between the years 1999 and 2012 registered in Explorys. Vaccination was defined as receiving a single dose of each vaccine at any point of time during the study period. Results: Out of 21.6 million adults, 107,750 were identified to have IBD. 20.7% of these patients received an influenza vaccine and 3.6% received the pneumococcal vaccine. Medical co-morbidities in association with IBD (Table 1). Respiratory conditions in patients with IBD (Table 2). Discussion: Our study shows a dramatic decrease in overall respiratory infection rates in patients who have received the influenza and pneumococcal vaccines as compared to patients who have not. As noted in Table 2, there was a nine-fold decrease in influenza/common cold infection rate and an eight-fold decrease pneumonia infection rate who received their respective vaccine. Rates were determined by using the total number of IBD patients. In addition, presence of comorbidities such as diabetes, COPD or asthma may increase the risk of infection and also chances of vaccination, probably due to contact with additional medical providers. Conclusion: This is the first study performed to evaluate outcomes of vaccination in IBD patients. Until now, the literature has focused mainly on recommended immunization schedules and guidelines with no mention of outcomes. Given the significant reduction in overall infections in patients receiving the pneumoccoal and influenza vaccine demonstrated by our study, a renewed vigor needs to be maintained in educating patients and physicians on the importance of vaccinating this group of patients. Table 1: Influenza and pneumococcal vaccination rates in IBD patients with known co-morbidities

Redox and Oxygen Evolution Electrocatalytic Properties of Nafion and Single-Walled Carbon Nanotube/Hydrous Iron Oxide Composite Films

Novel Nafion and single-walled carbon nanotube composite hydrous iron oxide electrodes have been fabricated using a simple potential cycling methodology and are examined as oxygen evolution electrocatalyst films. Hydrous oxide materials prepared in this manner are typically quite amorphous in nature. Here, we show, using scanning electron microscopy and cyclic voltammetry, that a more uniform oxide growth can be achieved using a Nafion or carbon nanotube matrix as a template. This templated growth produces oxide films with unique surface morphologies and electrical properties. In particular, the composite films exhibit superior conductivity, as shown by electrochemical impedance spectroscopy, with up to eightfold decrease in charge transfer resistance. The ultimate result is an enhancement in the electrocatalytic performance of the hydrous Fe oxide film. Steady-state polarisation studies on the oxygen evolution reaction show a reduction in overpotential of up to 50 mV for the composite electrodes with a threefold increase in turnover frequency.

Detrimental effect of the 6 His C-terminal tag on YedY enzymatic activity and influence of the TAT signal sequence on YedY synthesis

BackgroundYedY, a molybdoenzyme belonging to the sulfite oxidase family, is found in most Gram-negative bacteria. It contains a twin-arginine signal sequence that is cleaved after its translocation into the periplasm. Despite a weak reductase activity with substrates such as dimethyl sulfoxide or trimethylamine N-oxide, its natural substrate and its role in the cell remain unknown. Although sequence conservation of the YedY family displays a strictly conserved hydrophobic C-terminal residue, all known studies on Escherichia coli YedY have been performed with an enzyme containing a 6 histidine-tag at the C-terminus which could hamper enzyme activity.ResultsIn this study, we demonstrate that the tag fused to the C-terminus of Rhodobacter sphaeroides YedY is detrimental to the enzyme’s reductase activity and results in an eight-fold decrease in catalytic efficiency. Nonetheless this C-terminal tag does not influence the properties of the molybdenum active site, as assayed by EPR spectroscopy. When a cleavable His-tag was fused to the N-terminus of the mature enzyme in the absence of the signal sequence, YedY was expressed and folded with its cofactor. However, when the signal sequence was added upstream of the N-ter tag, the amount of enzyme produced was approximately ten-fold higher.ConclusionOur study thus underscores the risk of using a C-terminus tagged enzyme while studying YedY, and presents an alternative strategy to express signal sequence-containing enzymes with an N-terminal tag. It brings new insights into molybdoenzyme maturation in R. sphaeroides showing that for some enzymes, maturation can occur in the absence of the signal sequence but that its presence is required for high expression of active enzyme.

ISAba825 controls the expression of the chromosomal b/aOXA-51-like and the plasmid borne blaOXA-58 gene in clinical isolates of Acinetobacter baumannii isolated from the USA

Four non-repetitive, clonally related (ST114), carbapenem-resistant Acinetobacter baumannii strains isolated in the USA were examined to understand the mechanisms of carbapenem resistance including screening for the presence of an insertion sequence upstream of the b/aOXA-51-like gene, which could be involved in the control and expression of the antibiotic-resistance gene. We observed that the main mechanisms of carbapenem resistance were the result of the over-expression of the b/aOXA-58-like and the b/aOXA-65 gene, both of which had the presence of ISAba825 upstream of the genes. The importance of this element was shown by isolating plasmid-cured isogenic strains that had lost the plasmid with the ISAba825-b/aOXA-58-like genes but during that same process also lost the chromosomal ISAba825 element present upstream of the b/aOXA-65 gene. A 16-fold decrease in minimum inhibitory concentration of imipenem and an eight-fold decrease in the minimum inhibitory concentration of meropenem were seen in the isogenic strains that lost the plasmid. The study presents the first report of ISAba825 simultaneously governing the b/aOXA-65 gene and the b/aOXA-58-like gene expression and also highlights the importance of this element in carbapenem-sensitive isogenic strains, which were once carbapenem resistant.

Identification of a Negative Allosteric Site on Human α4β2 and α3β4 Neuronal Nicotinic Acetylcholine Receptors

Acetylcholine-based neurotransmission is regulated by cationic, ligand-gated ion channels called nicotinic acetylcholine receptors (nAChRs). These receptors have been linked to numerous neurological diseases and disorders such as Alzheimer's disease, Parkinson's disease, and nicotine addiction. Recently, a class of compounds has been discovered that antagonize nAChR function in an allosteric fashion. Models of human α4β2 and α3β4 nicotinic acetylcholine receptor (nAChR) extracellular domains have been developed to computationally explore the binding of these compounds, including the dynamics and free energy changes associated with ligand binding. Through a blind docking study to multiple receptor conformations, the models were used to determine a putative binding mode for the negative allosteric modulators. This mode, in close proximity to the agonist binding site, is presented in addition to a hypothetical mode of antagonism that involves obstruction of C loop closure. Molecular dynamics simulations and MM-PBSA free energy of binding calculations were used as computational validation of the predicted binding mode, while functional assays on wild-type and mutated receptors provided experimental support. Based on the proposed binding mode, two residues on the β2 subunit were independently mutated to the corresponding residues found on the β4 subunit. The T58K mutation resulted in an eight-fold decrease in the potency of KAB-18, a compound that exhibits preferential antagonism for human α4β2 over α3β4 nAChRs, while the F118L mutation resulted in a loss of inhibitory activity for KAB-18 at concentrations up to 100 µM. These results demonstrate the selectivity of KAB-18 for human α4β2 nAChRs and validate the methods used for identifying the nAChR modulator binding site. Exploitation of this site may lead to the development of more potent and subtype-selective nAChR antagonists which may be used in the treatment of a number of neurological diseases and disorders.

Identification of a Tall Waterhemp (Amaranthus tuberculatus) Biotype Resistant to HPPD-Inhibiting Herbicides, Atrazine, and Thifensulfuron in Iowa

Seeds of a putative 4-hydroxyphenylpyruvate dioxygenase (HPPD)-inhibiting herbicide–resistant tall waterhemp biotype from Henry County, IA, were collected from a seed corn field in fall 2009 after plants were not controlled following a POST application of mesotrione plus atrazine. The response of this biotype to various herbicide modes of action was evaluated in greenhouse and field tests. Under greenhouse conditions, the suspect biotype showed an eightfold decrease in sensitivity to mesotrione with a 50% control rate of 21 g ha−1compared with 2.7 g ha−1for the susceptible biotype. The biotype also had a 10-fold decrease in sensitivity to atrazine and a 28-fold decrease in sensitivity to thifensulfuron. Under field conditions, tall waterhemp was not controlled POST at the label rate of 1,100 g ha−1of atrazine. Tall waterhemp control was less than 60% at the label rates of three commonly used POST HPPD-inhibiting herbicides in seed corn: 105 g ha−1of mesotrione, 92 g ha−1of tembotrione, or 18 g ha−1of topramezone. Thus, this new tall waterhemp biotype is resistant to three herbicide modes of action: HPPD inhibitors, photosystem-II inhibitors, and acetolactate synthase (ALS) inhibitors.

Spectroscopic evidence for nonradiative energy transfer between colloidal CdSe/ZnS nanocrystals and functionalized silicon substrates

We present the fabrication and properties of hybrid structures consisting of a monolayer of colloidal CdSe nanocrystals grafted on hydrogenated Si surfaces via amine modified carboxy-alkyl chain linkers. The wet chemical preparation ensures that Si surfaces are fully passivated with a negligible number of nonradiative surface state defects and that the separation between nanocrystals and Si is tightly controlled. An eightfold decrease in photoluminescence lifetime of nanocrystals on Si is observed as compared to glass. A quantitative analysis reveals that the nonradiative transfer from nanocrystals to Si is 65% efficient, demonstrating the potential of such hybrids for practical photovoltaic devices.