Pesticides as estrogen disruptors: QSAR for selective ERα and ERβ binding of pesticides

Evidence suggests that environmental exposure to estrogen-like compounds can cause adverse effects in humans and wildlife. The Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC) has advised screening of 87,000 compounds in the interest of human safety. This may best be accomplished by pre-screening using quantitative structure-activity relationship (QSAR) modelling. The present study aimed to develop in silico QSARs based on natural, semi-synthetic, synthetic, and phytoestrogens, to predict the potential estrogenic toxicity of pesticides. A diverse set of 170 compounds including steroidal-, synthetic- and phytoestrogens, as well as pesticides was used to construct the QSAR models using artificial neural networks (ANNs). Mean correlation coefficients between experimentally measured and predicted binding affinities were all greater than 0.7 and models had few false negative results, an important consideration for screening tools. This study demonstrated the utility of ANNs as QSAR models for pre-screening of potential endocrine disruptors.     

Sustained quantum coherence and entanglement in the avian compass

In artificial systems, quantum superposition and entanglement typically decay rapidly unless cryogenic temperatures are used. Could life have evolved to exploit such delicate phenomena? Certain migratory birds have the ability to sense very subtle variations in Earth's magnetic field. Here we apply quantum information theory and the widely accepted "radical pair" model to analyze recent experimental observations of the avian compass. We find that superposition and entanglement are sustained in this living system for at least tens of microseconds, exceeding the durations achieved in the best comparable man-made molecular systems. This conclusion is starkly at variance with the view that life is too "warm and wet" for such quantum phenomena to endure.     

Asymptotically optimal staffing of service systems with joint QoS constraints

We consider the problem of staffing large-scale service systems with multiple customer classes and multiple dedicated server pools under joint quality-of-service (QoS) constraints. We first analyze the case in which arrival rates are deterministic and the QoS metric is the probability a customer is queued, given by the Erlang-C formula. We use the Janssen–Van Leeuwaarden–Zwart bounds to obtain asymptotically optimal solutions to this problem. The second model considered is one in which the arrival rates are not completely known in advance (before the server staffing levels are chosen), but rather are known via a probability distribution. In this case, we provide asymptotically optimal solutions to the resulting stochastic integer program, leveraging results obtained for the case of deterministic arrivals.     

Microfluidic device for label-free measurement of platelet activation

In this work we demonstrate a new microfluidic method for the rapid assessment of platelet size and morphology in whole blood. The device continuously fractionates particles according to size by displacing them perpendicularly to the fluid flow direction in a micro-fabricated post array. Whole blood, labeled with the fluorescent, platelet specific, antibody PE-anti-CD41, was run through the device and the positions of fluorescent objects noted as they exited the array. From this, histograms of platelet size were created which show marked increases in size after exposure to thrombin or a temperature of 4 degrees C. We infer that the well known morphological changes that occur during activation are causing the observed increase in size.     

Structure, vibrational spectra, and unimolecular dissociation of gaseous 1-fluoro-1-phenethyl cations

The multiple CF bond character of PhCFMe (+) ions has been examined by means of theory, vibrational spectroscopy of the gaseous ions, and unimolecular decomposition chemistry. Atoms in Molecules analysis of DFT wave functions gives a CF bond order of n = 1.25 (as compared with n = 1.38 for Me 2CF (+), relative to n = 1 for fluoromethane and n = 2 for diatomic CF (+)), which is consistent with calculations of adiabatic CF stretching frequencies (nu CF). Experimental gas phase IR spectra, recorded by means of resonant multiphoton dissociation (IRMPD) using a free-electron laser connected to an FTICR mass spectrometer, show good agreement with predicted band positions for five deuterated isotopomers of PhCFMe (+). Metastable ion decompositions of deuterated analogues of PhCFMe (+) show the same HF/DF loss patterns as those produced by IRMPD. The evidence supports the conclusion that PhCFMe ions retain structural integrity until they become sufficiently excited to dissociate, whereupon they undergo intramolecular hydrogen scrambling that is competitive with HF/DF expulsion. Relative rates of hydrogen transposition and unimolecular dissociation are extracted from relative experimental fragment ion abundances. The predominant decomposition pathway is inferred to operate via a five-center transition state, as opposed to a four-center transition state for HF loss from gaseous Me 2CF (+).     

Convenient method for the functionalization of the 4- and 6-positions of the androgen skeleton

The preparation and reactivity of steroidal vinyldiazo compounds is reported, providing a convenient, substituent tolerant, chemo- and stereoselective entry into 4- and 6-substituted androgen analogues from a common precursor. Under dirhodium catalysis, O-H insertion occurs at the carbenoid site, leading to 4-substituted steroids, but under silver catalysis, O-H insertion occurs at the vinylogous position, leading to 6-substituted steroids.     

Accomplishing Accomplishment

The concepts of knowledge and accomplishment are duals. There are many parallels between them. In this paper I discuss the "AA" thesis, which is dual to the well known KK thesis. The KK thesis claims that if someone knows something, then she knows that she knows it. This is generally thought to be false, and there are powerful reasons for rejecting it. The AA thesis claims that if someone accomplishes something, then she accomplishes that she accomplishes it. I argue that this, too, is false, and that the reasons it is false parallel reasons for the falsity of the KK thesis.     

Detection of Trace Heavy Metal Ions Using Carbon Nanotube‐ Modified Electrodes

A sensitive voltammetric method for detection of trace heavy metal ions using chemically modified carbon nanotubes (CNTs) electrode surfaces is described. The CNTs were covalently modified with cysteine prior to casting on electrode surfaces. Cysteine is an amino acid with high affinities towards some heavy metals. In this assay, heavy metals ions accumulated on the cysteine‐modified CNT electrode surfaces prior to being subjected to differential pulse anodic stripping voltammetry analysis. The resulting peak currents were linearly related to the concentrations of the metal ions. The method was optimized with respect to accumulation time, reduction time and reduction potential. The detection limits were found to be 1 ppb and 15 ppb for Pb²⁺ and Cu²⁺ respectively. The technique was used for the detection of Pb²⁺ and Cu²⁺ in spiked lake water. The average recoveries of Pb²⁺ and Cu²⁺ were 96.2% and 94.5% with relative standard deviations of 8.43% and 7.53% respectively. The potential for simultaneous detection of heavy metal ions by the modified CNTs was also demonstrated.     

Reactions of atomic oxygen [O(3P)] with polymer films

The reactions of polymer films with oxygen atoms are reviewed. Emphasis is on work from this laboratory on polybutadienes having different amounts of 1,4 or 1,2 double bonds and their polyalkenamer homologues, on a polyimide (Kapton), and on a series of polyolefins with increasing fluorine content ranging from polyethylene (PE) to polytetrafluoroethylene (PTFE). Interest in this topic stems from a need to understand the mechanism(s) of surface erosion, or etching, that occurs in organic polymers when exposed to the low Earth orbital (LEO) environment, where ground-state atomic oxygen [O(³P)] is the most abundant constituent. The major findings for O atom reactions with the polyalkenamers were: (1) etch rates increase with decrease in -CH=CH-unsaturation, starting with 1,4-polybutadiene and reaching the maximum rate with PE or ethylene-propylene rubber; (2) in polybutadienes having both 1,4 and 1,2 double bonds, the rate of O(³P)-induced etching is lower the higher the 1,2 content; and (3) the reactions are confined to the polymer surface. Relative etch rates for various commercial polymer films (e.g., Kapton, Teflon, PE) exposed to O(³P) downstream from a low-pressure, radio-frequency O₂ plasma were compared with corresponding literature data for films exposed to O(³P) either during a Space Shuttle flight or in the plasma glow (where many species besides O(³P) are present). The use of O₂ discharge reactors – whether exposures are conducted “out of the glow” or “in the glow” – cannot serve as a routine, ground-based simulation of exposures of a polymer to the LEO environment. ESCA analysis of the surfaces of Kapton and other polymers, before and after reaction with O(³P), showed that there is a steady-state competition between surface recession and oxidation. In a series of fluorine-containing polyolefins exposed to O(³P), the maximum oxygen uptake increased regularly with decrease in fluorine content, ranging from a minimum in PTFE to a maximum in PE.