Experimental and Theoretical Studies of the Environmental Sensitivity of the Absorption Spectra and Photochemistry of Nitenpyram and Analogs

Neonicotinoid (NN) pesticides have widespread use, largely replacing other pesticides such as the carbamates. Hence, there is a need to understand their environmental fates at a molecular level in various media, especially water. We report here the studies of a nitroenamine NN, nitenpyram (NPM), in aqueous solution where the absorption cross sections in the actinic region above 290 nm are observed to dramatically decrease compared to those in nonaqueous solvents. Quantum chemical calculations show that addition of a proton to the tertiary amine nitrogen in NPM breaks the conjugation in the chromophore, shifting the absorption to shorter wavelengths, consistent with experiment. However, surprisingly, adding a proton to the secondary amine nitrogen leads to its immediate transfer to the NO2 group, preserving the conjugation. This explains why the UV absorption of ranitidine (RAN), which has a similar chromophore but only secondary amine nitrogens, does not show a similar large blue shift in water. Photolysis quantum yields in aqueous NPM solutions were measured to be φ = 0.18 ± 0.07 at 254 nm, (9.4 ± 1.6) × 10-2 with broadband radiation centered at 313 nm and (5.2 ± 1.1) × 10-2 for broadband radiation centered at 350 nm (errors are 2σ). The major products in aqueous solutions are an imine that was also formed in the photolysis of the solid and a carboxylic acid derivative that is unique to the photolysis in water. Combining the larger quantum yields in water with the reduced absorption cross sections results in a calculated lifetime of NPM of only 5 min at a solar zenith angle of 35°, typical of 40°N latitude on April 1. The products do not absorb in the actinic region and hence will be long-lived with respect to photolysis

Commuting Quantum Circuits with Few Outputs are Unlikely to be Classically Simulatable

We study the classical simulatability of commuting quantum circuits with n input qubits and O(log n) output qubits, where a quantum circuit is classically simulatable if its output probability distribution can be sampled up to an exponentially small additive error in classical polynomial time. First, we show that there exists a commuting quantum circuit that is not classically simulatable unless the polynomial hierarchy collapses to the third level. This is the first formal evidence that a commuting quantum circuit is not classically simulatable even when the number of output qubits is exponentially small. Then, we consider a generalized version of the circuit and clarify the condition under which it is classically simulatable. Lastly, we apply the argument for the above evidence to Clifford circuits in a similar setting and provide evidence that such a circuit augmented by a depth-1 non-Clifford layer is not classically simulatable. These results reveal subtle differences between quantum and classical computation.Comment: 19 pages, 6 figures; v2: Theorems 1 and 3 improved, proofs modifie

A solar powered handheld plasma source for microbial decontamination applications

A fully portable atmospheric pressure air plasma system is reported to be suitable for the microbial decontamination of both surfaces and liquids. The device operates in quiescent air, and includes an integrated battery which is charged from a solar cell and weighs less than 750 g, making it highly amenable for a wide variety of applications beyond the laboratory. Using particle imaging velocimetry to visualise air flows around the device, the geometric configuration of the plasma generating electrodes was enhanced to induce a gas flow on the order of 0.5 m s-1 directed towards a sample placed downstream, thus improving the transport of plasma generated reactive species to the sample. The microbial decontamination efficiency of the system was assessed using potable water samples inoculated with common waterborne organisms Escherichia coli and Pseudomonas fluorescens. The reduction in the number of microorganisms was found to be in the range of 2-8 log and was strongly dependent on the plasma generation conditions

Evasion of a human cytomegalovirus entry inhibitor with potent cysteine reactivity is concomitant with the utilisation of a heparan sulfate proteoglycan independent route of entry

The dependence of viruses on the host cell to complete their replicative cycle renders cellular functions potential targets for novel anti-virals. We screened a panel of broad acting cellular ion channel inhibitors for activity against human cytomegalovirus (HCMV) and identified the voltage-gated chloride ion channel inhibitor 4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid (DIDS) as a potent inhibitor of HCMV replication. Time of addition studies demonstrated that DIDS inhibited entry via a direct interaction with the virion that impeded binding to the plasma membrane. Synthesis and analysis of pharmacological variants of DIDS suggested that intrinsic cysteine, and not lysine, reactivity was important for activity against HCMV.Although sequencing of a DIDS-resistant HCMV revealed enrichment of a mutation within UL100 (encoding for glycoprotein M) and a specific truncation of glycoprotein RL13, these did not explain the DIDS resistance phenotype. Specifically, only the introduction of the RL13 mutant partially pheno-copied the DIDS resistance phenotype. Serendipitously, the entry of DIDS-resistant HCMV also became independent of heparan sulfate proteoglycans (HSPGs) suggesting that evasion of DIDS lowered dependence on an initial interaction with HSPGs. Intriguingly, the DIDS-resistant virus demonstrated increased sensitivity to antibody neutralisation, which mapped, in part, to the presence of the gM mutation.Taken together the data characterise the anti-viral activity of a novel HCMV inhibitor that drives HCMV infection to occur independent of HSPGs and the generation of increased sensitivity to humoral immunity. The data also demonstrate that compounds with cysteine reactivity have the potential to act as anti-viral compounds against HCMV via direct engagement of virions.IMPORTANCE Human cytomegalovirus (HCMV) is major pathogen of non-immunocompetent individuals which remains in need of new therapeutic options. Here we have identified a potent antiviral compound (4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid, DIDS), its mechanism of action and the chemical properties required for its activity. In doing so, the data argue that cysteine-reactive compounds could have the capacity to be developed for anti-HCMV activity. Importantly, the data show that entry of DIDS resistant virus became independent of heparan sulfate proteoglycans (HSPGs) but, concomitantly, became more sensitive to neutralising antibody responses. This serendipitous observation suggests that retention of an interaction with HSPGs during the entry process in vivo may be evolutionarily advantageous through better evasion of humoral responses directed against HCMV virions

Stability of cluster solutions in a cooperative consumer chain model

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ Springer-Verlag Berlin Heidelberg 2012.We study a cooperative consumer chain model which consists of one producer and two consumers. It is an extension of the Schnakenberg model suggested in Gierer and Meinhardt [Kybernetik (Berlin), 12:30-39, 1972] and Schnakenberg (J Theor Biol, 81:389-400, 1979) for which there is only one producer and one consumer. In this consumer chain model there is a middle component which plays a hybrid role: it acts both as consumer and as producer. It is assumed that the producer diffuses much faster than the first consumer and the first consumer much faster than the second consumer. The system also serves as a model for a sequence of irreversible autocatalytic reactions in a container which is in contact with a well-stirred reservoir. In the small diffusion limit we construct cluster solutions in an interval which have the following properties: The spatial profile of the third component is a spike. The profile for the middle component is that of two partial spikes connected by a thin transition layer. The first component in leading order is given by a Green's function. In this profile multiple scales are involved: The spikes for the middle component are on the small scale, the spike for the third on the very small scale, the width of the transition layer for the middle component is between the small and the very small scale. The first component acts on the large scale. To the best of our knowledge, this type of spiky pattern has never before been studied rigorously. It is shown that, if the feedrates are small enough, there exist two such patterns which differ by their amplitudes.We also study the stability properties of these cluster solutions. We use a rigorous analysis to investigate the linearized operator around cluster solutions which is based on nonlocal eigenvalue problems and rigorous asymptotic analysis. The following result is established: If the time-relaxation constants are small enough, one cluster solution is stable and the other one is unstable. The instability arises through large eigenvalues of order O(1). Further, there are small eigenvalues of order o(1) which do not cause any instabilities. Our approach requires some new ideas: (i) The analysis of the large eigenvalues of order O(1) leads to a novel system of nonlocal eigenvalue problems with inhomogeneous Robin boundary conditions whose stability properties have been investigated rigorously. (ii) The analysis of the small eigenvalues of order o(1) needs a careful study of the interaction of two small length scales and is based on a suitable inner/outer expansion with rigorous error analysis. It is found that the order of these small eigenvalues is given by the smallest diffusion constant ε22.RGC of Hong Kon

UK medical students' perceptions, attitudes, and interest toward medical leadership and clinician managers

Background: We aimed to determine UK medical students’ perceptions and attitudes and interest toward medical leadership and clinician managers. Methods: A cross-sectional study was conducted during the academic year 2015–2016. An online questionnaire was distributed to 2,349 final-year students from 10 UK medical schools. Participants were asked to complete a 5-point Likert scale on their current perceptions, attitudes, and interest toward medical leadership and clinician managers. They were also asked to self-rate their leadership competences set by the Medical Leadership Competency Framework and to rate the quality of management and leadership training they received from their medical school. Results: In total, we received 114 complete responses. Only 7.9% of respondents were in agreement (strongly agree or agree) when asked whether they felt they were well informed about what a managerial position in medicine entails. When asked whether clinicians should influence managerial decisions within a clinical setting, 94.7% of respondents were in agreement with the statement. About 85% of respondents were in agreement that it is important for clinicians to have managerial or leadership responsibilities, with 63.2% of students in agreement that they would have liked more management or leadership training during medical school. Over half the respondents rated their management and leadership training they received during medical school as “very poor” or “poor” (54.4%). Conclusion: Our study suggests that UK medical students have an appetite for management and leadership training and appreciate its importance but feel that the training they are receiving is poor. This suggests that there is a gap between the demand for management and leadership training and the quality of training supplied by UK medical schools

Existence and Stability of a Spike in the Central Component for a Consumer Chain Model

We study a three-component consumer chain model which is based on Schnakenberg type kinetics. In this model there is one consumer feeding on the producer and a second consumer feeding on the first consumer. This means that the first consumer (central component) plays a hybrid role: it acts both as consumer and producer. The model is an extension of the Schnakenberg model suggested in \cite{gm,schn1} for which there is only one producer and one consumer. It is assumed that both the producer and second consumer diffuse much faster than the central component. We construct single spike solutions on an interval for which the profile of the first consumer is that of a spike. The profiles of the producer and the second consumer only vary on a much larger spatial scale due to faster diffusion of these components. It is shown that there exist two different single spike solutions if the feed rates are small enough: a large-amplitude and a small-amplitude spike. We study the stability properties of these solutions in terms of the system parameters. We use a rigorous analysis for the linearized operator around single spike solutions based on nonlocal eigenvalue problems. The following result is established: If the time-relaxation constants for both producer and second consumer vanish, the large-amplitude spike solution is stable and the small-amplitude spike solution is unstable. We also derive results on the stability of solutions when these two time-relaxation constants are small. We show a new effect: if the time-relaxation constant of the second consumer is very small, the large-amplitude spike solution becomes unstable. To the best of our knowledge this phenomenon has not been observed before for the stability of spike patterns. It seems that this behavior is not possible for two-component reaction-diffusion systems but that at least three components are required. Our main motivation to study this system is mathematical since the novel interaction of a spike in the central component with two other components results in new types of conditions for the existence and stability of a spike. This model is realistic if several assumptions are made: (i) cooperation of consumers is prevalent in the system, (ii) the producer and the second consumer diffuse much faster than the first consumer, and (iii) there is practically an unlimited pool of producer. The first assumption has been proven to be correct in many types of consumer groups or populations, the second assumption occurs if the central component has a much smaller mobility than the other two, the third assumption is realistic if the consumers do not feel the impact of the limited amount of producer due to its large quantity. This chain model plays a role in population biology, where consumer and producer are often called predator and prey. This system can also be used as a model for a sequence of irreversible autocatalytic reactions in a container which is in contact with a well-stirred reservoir

Genetic diversity among Toxoplasma gondii isolates from different hosts and geographical locations revealed by analysis of ROP13 gene sequences

Toxoplasma gondii can infect almost all the warm-blooded animals and human beings, causing serious public health problems and economic losses worldwide. Rhoptry protein 13 (ROP13) plays some roles in the invasion process of T. gondii. In this study, sequence variation in ROP13 gene among 14 T. gondii isolates from different geographical locations and hosts was examined. The ROP13 gene was amplified from individual isolates and sequenced. Results show that the length of the ROP13 sequences was 1203 bp. In total, there were 44 variable nucleotide positions in the ROP13 sequences, and sequence variations were 0.1 to 2.0% among the 14 examined T. gondii isolates, representing higher rate in transversion than in transition. Intra-specific nucleotide variations were mainly at the second codon positions. Phylogenetic analysis of the 14 examined T. gondii isolates indicate that the ROP13 sequence was not a suitable genetic marker to differentiate T. gondii isolates of different genotypes from different hosts and geographical regions. Low variation in ROP13 gene sequence may suggest that ROP13 gene could represent a good vaccine candidate against toxoplasmosis.Key words: Toxoplasma gondii, toxoplasmosis, rhpotry protein 13 (ROP13), sequence variation, phylogenetic analysis

Comparison of Two Mathematical Models for Greenhouse Gas Emission from Membrane Bioreactors

In this study two mathematical models (Model I and Model II), able to predict the nitrous oxide (N2O) and carbon dioxide (CO2) emission from an University Cape Town (UCT) \u2013 membrane bioreactor (MBR) plant, have been compared. Model I considers the N2O production only during the denitrification. Model II takes into account the two ammonia-oxidizing bacteria (AOB) formation pathways for N2O. Both models were calibrated adopting real data. Results highlight that Model II had a better capability of reproducing the measured data especially in terms of N2O model outputs. Indeed, the average efficiency related to the N2O model outputs was equal to 0.3 and 0.38 for Model I and Model II respectively

Peripheral neuropathy in HIV patients in sub-Saharan Africa failing first-line therapy and the response to second-line ART in the EARNEST trial.

Sensory peripheral neuropathy (PN) remains a common complication in HIV-positive patients despite effective combination anti-retroviral therapy (ART). Data on PN on second-line ART is scarce. We assessed PN using a standard tool in patients failing first-line ART and for 96 weeks following a switch to PI-based second-line ART in a large Randomised Clinical Trial in Sub-Saharan Africa. Factors associated with PN were investigated using logistic regression. Symptomatic PN (SPN) prevalence was 22 % at entry (N = 1,251) and was associated (p < 0.05) with older age (OR = 1.04 per year), female gender (OR = 1.64), Tuberculosis (TB; OR = 1.86), smoking (OR = 1.60), higher plasma creatinine (OR = 1.09 per 0.1 mg/dl increase), CD4 count (OR = 0.83 per doubling) and not consuming alcohol (OR = 0.55). SPN prevalence decreased to 17 % by week 96 (p = 0.0002) following similar trends in all study groups (p = 0.30). Asymptomatic PN (APN) increased over the same period from 21 to 29 % (p = 0.0002). Signs suggestive of PN (regardless of symptoms) returned to baseline levels by week 96. At weeks 48 and 96, after adjusting for time-updated associations above and baseline CD4 count and viral load, SPN was strongly associated with TB (p < 0.0001). In summary, SPN prevalence was significantly reduced with PI-based second-line therapy across all treatment groups, but we did not find any advantage to the NRTI-free regimens. The increase of APN and stability of PN-signs regardless of symptoms suggest an underlying trend of neuropathy progression that may be masked by reduction of symptoms accompanying general health improvement induced by second-line ART. SPN was strongly associated with isoniazid given for TB treatment