Mixed-Up-Ness or Entropy?

Mixed-up-ness can be traced to unpublished notes by Josiah Gibbs. Subsequently, the concept was developed independently, and under somewhat different names, by other investigators. The central idea of mixed-up-ness is that systems states can be organized in a hierarchy by their degree of mixed-up-ness. In its purest form, the organizing principle is independent of thermodynamic and statistical mechanics principles, nor does it imply irreversibility. Yet, Gibbs and subsequent investigators kept entropy as the essential concept in determining system evolution, thus retaining the notion that systems evolve from states of perfect "order" to states of total "disorder". Nevertheless, increasing mixed-up-ness is consistent with increasing entropy; however, there is no unique one-to-one connection between the two. We illustrate the notion of mixed-up-ness with an application to the permutation function of integer partitions and then formalize the notion of mixed-up-ness as a fundamental hierarchal principle, the law of mixed-up-ness (LOM), for non-thermodynamic systems.

Silica covered stannic oxide nanoparticles-an easily prepared robust substrate for optical sensors.

This paper describes a facile way to prepare a photophysically inert sensor substrate. Stannic oxide encapsulated silica nanoparticles with average diameters between 30 and 70 nm have been prepared by one-pot reverse-phase emulsion methodology. The constituents and core/shell morphology of the nanoparticles were demonstrated by electron microscopic technology, energy-dispersive x-ray spectroscopy, and x-ray photoelectron spectroscopy. X-ray diffraction was employed to provide additional constitutional and structural information. It has been shown that nanoparticles prepared by this method are optically clear in suspension. After anchoring optical indicators, this nanoparticle can be utilized as a sensor module both in biology and other analytical areas.

Molecular Recognition: Perspective and a New Approach.

This perspective presents an overview of approaches to the preparation of molecular recognition agents for chemical sensing. These approaches include chemical synthesis, using catalysts from biological systems, partitioning, aptamers, antibodies and molecularly imprinted polymers. The latter three approaches are general in that they can be applied with a large number of analytes, both proteins and smaller molecules like drugs and hormones. Aptamers and antibodies bind analytes rapidly while molecularly imprinted polymers bind much more slowly. Most molecularly imprinted polymers, formed by polymerizing in the presence of a template, contain a high level of covalent crosslinker that causes the polymer to form a separate phase. This results in a material that is rigid with low affinity for analyte and slow binding kinetics. Our approach to templating is to use predominantly or exclusively noncovalent crosslinks. This results in soluble templated polymers that bind analyte rapidly with high affinity. The biggest challenge of this approach is that the chains are tangled when the templated polymer is dissolved in water, blocking access to binding sites.

Stimuli-Responsive Templated Polymer as a Target Receptor for a Conformation-based Electrochemical Sensing Platform.

The use of highly crosslinked molecularly imprinted polymers as a synthetic target receptor has the limitations of restricted accessibility to the binding sites resulting in slow response time. Moreover, such artificial receptors often require additional transduction mechanisms to translate target binding events into measurable signals. Here, we propose the development of a single-chain stimuli-responsive templated polymer, without using any covalent interchain crosslinkers, as a target recognition element. The synthesized polymer chain exhibits preferential binding with the target molecule with which the polymer is templated. Moreover, upon specific target recognition, the polymer undergoes conformation change induced by its particular stimuli responsiveness, namely the target binding event. Such templated single-chain polymers can be attached to the electrode surface to implement a label-free electrochemical sensing platform. A target analyte, 4-nitrophenol (4-NP), was used as a template to synthesize a poly-N-isopropylacrylamide (PNIPAM)-based copolymer chain which was anchored to the electrode to be used as a selective receptor for 4-NP. The electrode surface chemistry analysis and the electrochemical impedance study reveal that the polymer concentration, the interchain interactions, and the Hofmeister effect play a major role in influencing the rate of polymer grafting as well as the morphology of the polymers grafted to the electrode. We also show that the specific binding between 4-NP and the copolymer results in a substantial change in the charge transfer kinetics at the electrode signifying the polymer conformation change.

Application of Voltage in Dynamic Light Scattering Particle Size Analysis.

Dynamic light scattering (DLS) is a common method for characterizing the size distribution of polymers, proteins, and other nano- and microparticles. Modern instrumentation permits measurement of particle size as a function of time and/or temperature, but currently there is no simple method for performing DLS particle size distribution measurements in the presence of applied voltage. The ability to perform such measurements would be useful in the development of electroactive, stimuli-responsive polymers for applications such as sensing, soft robotics, and energy storage. Here, a technique using applied voltage coupled with DLS and a temperature ramp to observe changes in aggregation and particle size in thermoresponsive polymers with and without electroactive monomers is presented. The changes in aggregation behavior observed in these experiments were only possible through the combined application of voltage and temperature control. To obtain these results, a potentiostat was connected to a modified cuvette in order to apply voltage to a solution. Changes in polymer particle size were monitored using DLS in the presence of constant voltage. Simultaneously, current data were produced, which could be compared with particle size data, to understand the relationship between current and particle behavior. The polymer poly(N-isopropylacrylamide) (pNIPAM) served as a test polymer for this technique, as pNIPAM's response to temperature is well-studied. Changes in the lower-critical solution temperature (LCST) aggregation behavior of pNIPAM and poly(N-isopropylacrylamide)-block-poly(ferrocenylmethyl methacrylate), an electrochemically active block-copolymer, in the presence of applied voltage are observed. Understanding the mechanisms behind such changes will be important when trying to achieve reversible polymer structures in the presence of applied voltage.

Insights on the Lower Critical Solution Temperature Behavior of pNIPAM in an Applied Electric Field.

Poly(N-isopropylacrylamide), or pNIPAM, is a free-radical polymer that is commonly studied for uses in surface coatings, tissue engineering, energy storage, biosensing, and more, due to its temperature responsiveness. pNIPAM is known to solubilize at temperatures below its lower critical solution temperature (LCST) and agglomerate above its LCST. This behavior has been shown to be reproducible and reversible. We confirmed this reversibility and the value of the LCST by performing dynamic light scattering (DLS) with a temperature sweep (increase and decrease). However, performing the same experiment under an applied voltage from copper electrodes, we observed a decrease in the LCST of pNIPAM and irreversible aggregation. Here we present preliminary data comparing the LCST behavior of pNIPAM in the presence of applied voltage using copper, aluminum, and carbon electrodes. We present data in support of the hypothesis that a phenomenon is occurring specifically with the use of copper electrodes that is altering pNIPAM LCST behavior.

A Cu(II) Indicator Platform Based on Cu(II) Induced Swelling that Changes the Extent of Fluorescein Self-Quenching.

In this study, we established a new fluorescent indicator platform. The responsive element consists of poly(N-isopropylacrylamide) nanospheres that include small percentages of fluorescein and a ligand, anilinodiacetate (phenylIDA). Nanosphere diameters were determined to be in the range from 50 to 90 nm by scanning electron microscopy. They were entrapped in a polyacrylamide gel to prevent nanosphere aggregation. At pH 6, the ligand is negatively charged in the absence of metal ions. Charge-charge repulsion causes the nanosphere to swell. Dynamic light scattering measurements show that these nanospheres do not shrink and aggregate at high temperature. Cu(II) binding neutralizes the charge causing the particles to shrink. This brings fluoresceins closer together, increasing the degree of self-quenching. The intensity decreases by 30% as Cu(II) concentration increases. To rule out the possibility that the observed decrease in intensity was due to Cu(II) quenching of fluorescence, we also added Zn(II) and observed a decrease in intensity. This approach can be adapted to sense different metal ions and different concentrations of Cu(II) by changing the ligand.

A Single-chain Templated Polymer-based Target Receptor as a New Platform for Label-free Selective Electrochemical Sensing.

We report a novel single-chain polymer-based chemical receptor that can be used for the label-free electrochemical detection of an analyte with high selectivity. The polymer was developed using poly-N-isopropylacrylamide (pNIPAM) as a backbone structure in addition to other functional monomers that are used to imprint the template molecule 4-nitrophenol. The polymer also contains a redox reporting monomers (ferrocene) which create a change in the electrochemical signal upon molecular recognition. We hypothesize that the analyte binding to the receptor causes the polymer conformation change from the extended to the collapsed phase. After anchoring the polymer-based receptors onto the surfaces of the gold electrode, when exposed to the analyte, the changes in the electrochemical signals were observed which confirmed the selective target binding as well as the polymer conformation change as a result.

Dynamic Aggregation of Poly-N-Isopropylacrylamide Characterized Using Second-Order Scattering.

A second-order scattering (SOS) method is presented for the characterization of aqueous particle suspensions undergoing aggregation. Scattering intensities are measured at 90° by a standard fluorimeter and referenced against dynamic light scattering (DLS) measurements to determine particle size increase in a metal-promoted aggregation process for 0.05 mg/mL aqueous poly-N-isopropylacrylamide (PNIPAm), MW ∼10 k g/mol. Particle size increases monotonically from 30 nm to 210 nm at temperature 308 K. A further validation of the SOS method was performed using monodisperse polystyrene reference particles sized at 52 nm, 101 nm, 151 nm, and 206 nm, which demonstrated the technique's accuracy to within 6% and its versatility with respect to sample composition. The technique is ideal for monitoring colloidal stability and macromolecular assembly and it can be performed at lower concentrations than are typically used in DLS.

Rapid, High Affinity Binding by a Fluorescein Templated Copolymer Combining Covalent, Hydrophobic, and Acid⁻Base Noncovalent Crosslinks.

A new type of biomimetic templated copolymer has been prepared by reverse addition fragmentation chain transfer polymerization (RAFT) in dioxane. The initial formulation includes the template fluorescein, N-isopropylacrylamide (NIPAM, 84 mol %), methacrylic acid (MAA, 5-mol %), 4-vinylpyridine (4-VP, 9 mmol %), and N,N′-methylenebis(acrylamide) (MBA, 2 mol %). PolyNIPAM is a thermosensitive polymer that comes out of aqueous solution above its lower critical solution temperature forming hydrophobic ‘crosslinks’. MAA and 4-VP interact in dioxane forming acid⁻base crosslinks. The excess 4-VP serves as a recognition monomer organizing around the template fluorescein to form a binding site that is held in place by the noncovalent and covalent crosslinks. The MBA is a covalent crosslinker. The RAFT agent in the resulting copolylmer was reduced to a thiol and attached to gold nanoparticles. The gold nanoparticle bound copolymer binds fluorescein completely in less than two seconds with an affinity constant greater than 108 M−1. A reference copolymer prepared with the same monomers by the same procedure binds fluorescein much more weakly.

Uptake of Neonicotinoid Insecticides by Water-Foraging Honey Bees (Hymenoptera: Apidae) Through Guttation Fluid of Winter Oilseed Rape.

The water-foraging activity of honey bees (Apis mellifera L.) on guttation fluid of seed-coated crops, such as winter oilseed rape (WOR; Brassica napus L.), has not yet been evaluated. We analyzed the uptake of active substances (a.s.) in guttation fluid by evaluating residues of honey-sac contents. In autumn, insecticide residues of up to 130 µg a.s. per liter were released in WOR guttation fluid; this concentration is noticeably lower than levels reported in guttation fluid of seed-coated maize. Until winter dormancy, the concentrations declined to <30 µg a.s. per liter. In spring, residues were linked to prewintered plants and declined steadily until flowering. The maximum release of residues in guttation fluid of seed-coated WOR occurs on the first leaves in autumn when the colonies' water demand decreases. For the first time, proof for the uptake of guttation fluid from seed-coated WOR by honey bees was provided by measuring residues in individual honey-sac contents. In total, 38 out of 204 samples (19%) showed residues of thiamethoxam at concentrations ranging from 0.3 to 0.95 µg per liter while the corresponding concentrations in guttation fluid of WOR varied between 3.6 to 12.9 µg thiamethoxam per liter. The amounts of thiamethoxam we found in the honey sacs of water-foraging honey bees were therefore below the thresholds in nectar and pollen that are considered to have negative effects on honey bees after chronic exposure.

Sensors Best Paper Award 2013.

Since 2011, Sensors has instituted an annual award to recognize outstanding papers that are related to sensing technologies and applications and meet the aims, scope and high standards of this journal. This year, nominations were made by the Section Editor-in-Chiefs of Sensors from among all the papers published in 2009. Reviews and full research articles were considered separately. We are pleased to announce that the following eight papers have won the Sensors Best Paper Award in 2013.

Fluorescent ratiometric indicators based on Cu(II)-induced changes in poly(NIPAM) microparticle volume.

Microparticles consisting of the thermal responsive polymer N-isopropyl acrylamide (polyNIPAM), a metal ion-binding ligand and a fluorophore pair that undergoes fluorescence resonance energy transfer (FRET) have been prepared and characterized. Upon the addition of Cu(II), the microparticles swell or contract depending on whether charge is introduced or neutralized on the polymer backbone. The variation in microparticle morphology is translated into changes in emission of each fluorophore in the FRET pair. By measuring the emission intensity ratio between the FRET pair upon Cu(II) addition, the concentration of metal ion in solution can be quantified. This ratiometric fluorescent indicator is the newest technique in an ongoing effort to use emission spectroscopy to monitor Cu(II) thermodynamic activity in environmental water samples.

Intermolecular approach to metal ion indicators based on polymer phase transitions coupled to fluorescence resonance energy transfer.

An approach to ratiometric fluorescence detection of quenching metal ions was devised by copolymerizing N-isopropylacrylamide with small percentages of bipyridine and amine monomers. The copolymer was divided into two portions. The amine group on one portion was functionalized with AlexaFluor555 (donor fluorophore) and the other with AlexaFluor647 (acceptor fluorophore). The indicator consists of a mixture of these two portions. Aggregation above the lower critical solution temperature (LCST) of this copolymer brings about a large increase in fluorescence resonance energy transfer (FRET). Addition of Cu(II) and other complexing metal ions to the aggregated copolymer introduces charge onto the backbone, causing the copolymer to redissolve with a resulting decrease in FRET. The ratio of acceptor to donor fluorescence varies with Cu(II) concentration. A plot of intensity ratio vs. pCu is sigmoidal with a log K(f) of 6.1 for the Cu(II)-bipyridine complex. The data are consistent with the formation of a 1 : 1 complex. The copolymer responds to higher concentrations of other transition metal ions. The selectivity for Cu(II) is consistent with the literature values for 1 : 1 formation constants for bipyridine with metal ions.

A ratiometric fluorescent metal ion indicator based on dansyl labeled poly(N-isopropylacrylamide) responds to a quenching metal ion.

The fluorescence emission of poly(N-isopropylacrylamide) (PNIPAM) covalently tagged with a 5-(dimethylamino)naphthalene-1-sulfonyl (dansyl) fluorophore and an iminodiacetic acid (IDA) chelator changes with temperature and with Cu(II) complexation. Increasing the temperature above the lower critical solution temperature (LCST) causes the polymer to collapse from a coil to a compact globule. This changes the environment experienced by the fluorophore causing a shift in maximum emission wavelength from 546 to 508 nm and an increase in the ratio of emission intensity at 508 nm to emission intensity at 546 nm from 0.70 to almost 1.40. Metal ions can be sensed by working at a temperature where the uncomplexed polymer is in an expanded state due to the charges on the ligand. Complexation with a metal ion such as Cu(II) neutralizes the charges on the ligand causing the polymer to collapse. At 35 °C, the emission intensity maximum shifted from 535 to 510 nm as Cu(II) concentration was increased and the intensity ratio increased from 0.84 to 1.28. By decoupling complexation from fluorescence, we have prepared a ratiometric fluorescent indicator for a metal ion that normally quenches fluorescence. The affinity for Cu(II) was found to be thermally tunable. The log apparent formation constants for the indicator-Cu(II) complex were estimated as the half way point in the intensity ratio vs. pCu curve. The values were determined to be 4.3 at 35 °C and 3.2 at 34 °C respectively.

Comparison of PDR brachytherapy and external beam radiation therapy in the case of breast cancer.

Pulsed dose rate brachytherapy (PDR) was compared to external beam radiation therapy (EBRT) in the case of breast cancer. The benefits were figured out by evaluation of dosimetric parameters and calculating the normal tissue complication probability (NTCP). PDR plans were set up for five randomly chosen left-sided breast cancer patients delivering a total dose of 50.4 Gy to the target (dose rate 0.8 Gy h(-1)). For EBRT five left-sided breast cancer patients were planned using 3D-conformal tangential photon beams with a prescribed total dose of 50 Gy (2 Gy/fraction) to the total breast volume. For plan ranking and NTCP calculation the physical dose was first converted into the biologically effective dose (BED) and then into the normalized total dose (NTD) using the linear quadratic model with an alpha/beta ratio of 3 Gy. In PDR the relative effectiveness (RE) was calculated for each dose bin of the differential dose volume histogram to get the BED. NTCPs were calculated for the ipsilateral lung and the heart as contoured on CT slices based on the Lyman model and the Kutcher reduction scheme. Dosimetric parameters as V(th) (percentage of the total volume exceeding a threshold dose) and Jackson's f(dam) (fraction of the organ damaged) were also used to figure out the benefits. The comparison of calculated NTCPs in PDR and EBRT showed no difference between these two modalities. All values were below 0.01%. f(dam) derived from EBRT was always higher (mean value 8.95% versus 1.21% for the lung). The mean V(10) and V(20) of the lung related to BED were 6.32% and 1.72% for PDR versus 11.72% and 9.59% for EBRT. When using dosimetric parameters as V(th) and f(dam), PDR was mostly superior to EBRT in respect of sparing normal tissues. NTCP calculation as a single method of modality ranking showed a lack of information, especially when normal tissue was exposed to low radiation doses.

Nitric oxide and endothelin after lipid apheresis - a pilot study.

OBJECTIVE: Patients with the heterozygous form of familial hypercholesterolemia (FH) display an early onset of atherosclerosis due to disturbed vascular-endothelial function. Whether the improvements of endothelial function after lipid apheresis are mediated by increased NO-production or by an altered turnover of vasoconstrictors such as ET-1 is still unknown. This was the onset of the present study. METHODS: Patients with FH and advanced atherosclerosis receiving regular LDL apheresis at 1 to 3 weeks were recruited. Lipids, L-arginine (L-Arg), L-hydroxyarginine (NHA), L-citrulline as well as big endothelin (Big-ET) and endothelin (ET-1) were measured after DALI, HELP and TheraSorb apheresis. RESULTS: 17 patients with severe FH aged 55.6 years (mean) received a total of 30 treatments. TC, LDL-C, HDL-C, TG and TC / HDL-C ratio were reduced (55, 70, 9, 48, and 52%; p<0.01) with no differences between apheresis systems. L-Arg was reduced after apheresis (HELP -18.0%, DALI -26.5%; Therasorb -7.6%) and returned to baseline after 2 h. Big-ET (p<0.01) and ET-1 were found to be increased directly and 2 hours after apheresis with HELP while transiently decreasing with DALI and Therasorb. CONCLUSION: Improvement of endothelial function after apheresis seems to have multifaceted causes. The further elucidation of the interrelationship between endothelial dysfunction and restricted NO synthesis, as addressed in this study by measuring L-NHA, L-Arg, L-Cit, ET-1 and Big-ET will be necessary in the future.

Glenoid labrum ossification and mechanical restriction of joint motion: extraosseous manifestations of melorheostosis.

We report a case of a 47-year-old man who presented with progressive loss of motion and pain in the right shoulder. Radiographs of the shoulder demonstrated dense ossification in the glenoid and humeral head with extension into the periarticular soft tissues. CT and MRI scans confirmed the radiographic findings and also revealed ossification of the glenoid labrum. A radiographic diagnosis of melorheostosis, an uncommon benign sclerosing bone dysplasia, was made. Because of the patient's severe symptomatology, he underwent total shoulder arthroplasty. Histological analysis of the resected masses was consistent with melorheostosis with a few areas covered by a cartilage cap. This case illustrates several uncommon but important features of melorheostosis, including mechanical obstruction of joint motion requiring joint replacement, ossification of the glenoid labrum, and cartilage-covering portions of the intra-articular masses, not to be confused with cartilage-producing tumors.

A pH sensor based on force generated by pH-dependent polymer swelling.

We have demonstrated the feasibility of a new type of pH sensor by combining a bead of porous lightly crosslinked diethanolamine derivatized poly(vinylbenzyl chloride) with a strain gauge, i.e. a pressure sensitive resistor. The polymer bead is toughened with Kraton G1652, a styrene-ethylene,butylene-styrene triblock copolymer. The sensor is constructed so that the shrunken form of the bead is held in contact with the strain gauge with a small force. Increases in the hydrogen ion concentration protonate the diethanolamine introducing a positive charge onto the polymer backbone. This results in an electrostatic swelling force that causes the polymer to swell. This is detected as a change in strain gauge resistance that is readout via a Wheatstone bridge. When the pH of 0.10 M buffers is changed from 10 to 4, the response time is 390 s for a bead that is 0.25 mm in diameter in the shrunken state. The response varies with the square of the bead radius. The magnitude of the response is highly correlated with the penetration modulus, a measure of the extent to which the bead resists deformation when subjected to an external force. The response to pH appears to be shifted by the application of pressure in the sensor. This instrumentally simple approach to sensing has the potential to be stable and long-lived if the polymer bead can undergo a large number of swelling/shrinking cycles without changing mechanical properties.

Passive synchronization of two independent laser oscillators with a Fabry-Perot modulator.

By optical modulation of the reflectivity of an intracavity nonlinear Fabry-Perot semiconductor mirror, the pulse train from a passively mode-locked picosecond Nd:YVO(4) laser oscillator is synchronized to an independent femtosecond-mode-locked Ti:sapphire laser. We obtain stable synchronized pulse trains at central wavelengths of 1064 and 850 nm, and the Ti:sapphire laser is still independently tunable over a large wavelength range. The tolerable cavity-length difference between the two laser oscillators exceeds 20mu;m .