Cytochrome c-poly(acrylic acid) conjugates with improved peroxidase turnover number.

Cytochrome c-poly(acrylic acid) (cyt c-PAA) conjugates with 34-fold enchancement in peroxidase turnover number (kcat) are reported. Cyt c-PAA conjugates were prepared by carbodiimide coupling. PAA with molecular weight (Mw) ranging from 1.8k to 250k g mol-1 were employed, and the effect of PAA Mw on peroxiodase kinetics was assessed. The kcat value increased with increased Mw of PAA, ranging from 0.077(±0.002) s-1 in the absence of PAA to 2.66(±0.08) s-1 for the conjugate of cyt c with 250k PAA. Enzymatic activity studies over pH 6-8 indicated improved activity for cyt c-PAA conjugates at neutral or slightly alkaline pH. Examination of the cyt c heme spectroscopy in the presence of H2O2 revealed that formation of compound III, a reactive intermediate that leads to enzyme inactivation, was supressed in cyt c-PAA conjugates. Thus, we suggest the kcat enhancement can be attributed to acidification of the pH microenvironment and inhibition of the formation of a reactive intermediate that deactivates cyt c during the catalytic cycle.

3D-printed polymer antiresonant waveguides for short-reach terahertz applications.

In this work, we present a 3D-printed waveguide that provides effective electromagnetic guidance in the THz regime. The waveguide is printed using low-cost polycarbonate and a conventional fused deposition modeling printer. Light guidance in the hollow core is achieved through antiresonance, and it improves the energy effectively transported to the receiver compared to free space propagation. Our demonstration adds to the field of 3D-printed terahertz components, providing a low-cost way of guiding terahertz radiation.

Minimum size for a nanoscale temperature discriminator based on a thermochemical system.

What are the limits of size reduction for information processing devices based on chemical reactions? In this paper, we partially answer this question. We show that a thermochemical system can be used to design a discriminator of the parameters associated with oscillations of the ambient temperature. Depending on the amplitude and frequency of the oscillations, the system exhibits sharp transitions between different types of its time evolutions. This phenomenon can be used to discriminate between different parameter values describing the oscillating environment. We investigate the reliability of the thermochemical discriminator as a function of the number of molecules involved in the reactions. A stochastic model of chemical reactions and heat exchange with the neighborhood, in which the number of molecules explicitly appears, is introduced. For the selected values of the parameters, thermochemical discriminators operating with less than 10(5) molecules appear to be unreliable.

Chemical computing with reaction-diffusion processes.

Chemical reactions are responsible for information processing in living organisms. It is believed that the basic features of biological computing activity are reflected by a reaction-diffusion medium. We illustrate the ideas of chemical information processing considering the Belousov-Zhabotinsky (BZ) reaction and its photosensitive variant. The computational universality of information processing is demonstrated. For different methods of information coding constructions of the simplest signal processing devices are described. The function performed by a particular device is determined by the geometrical structure of oscillatory (or of excitable) and non-excitable regions of the medium. In a living organism, the brain is created as a self-grown structure of interacting nonlinear elements and reaches its functionality as the result of learning. We discuss whether such a strategy can be adopted for generation of chemical information processing devices. Recent studies have shown that lipid-covered droplets containing solution of reagents of BZ reaction can be transported by a flowing oil. Therefore, structures of droplets can be spontaneously formed at specific non-equilibrium conditions, for example forced by flows in a microfluidic reactor. We describe how to introduce information to a droplet structure, track the information flow inside it and optimize medium evolution to achieve the maximum reliability. Applications of droplet structures for classification tasks are discussed.

Temperature-driven coherence resonance and stochastic resonance in a thermochemical system.

We perform the stochastic analysis of a thermochemical system using a master equation which describes a chemical reaction and includes discrete and continuous temperature jumps. We study the time evolution of the system selecting the temperature of the thermostat as an easily tunable control parameter. Depending on the thermostat temperature, the system can be in an excitable, oscillatory, or stationary regime. Stochastic time series for the system temperature are generated and the distributions of interspike intervals are analyzed in the three dynamical regimes separated by a homoclinic bifurcation and a Hopf bifurcation. Different constructive roles of internal fluctuations are exhibited. A noise-induced transition is observed in the vicinity of the Hopf bifurcation. Coherence resonance and stochastic resonance are found in the oscillatory regime. In a range of thermostat temperatures, a nontrivial behavior of the highly nonlinear system is revealed by the existence of both a minimum and a maximum in the scaled standard deviation of interspike intervals as a function of particle number. This high sensitivity to system size illustrates that controlling dynamics in nanoreactors may remain a difficult task.

Information coding with frequency of oscillations in Belousov-Zhabotinsky encapsulated disks.

Information processing with an excitable chemical medium, like the Belousov-Zhabotinsky (BZ) reaction, is typically based on information coding in the presence or absence of excitation pulses. Here we present a new concept of Boolean coding that can be applied to an oscillatory medium. A medium represents the logical TRUE state if a selected region oscillates with a high frequency. If the frequency fails below a specified value, it represents the logical FALSE state. We consider a medium composed of disks encapsulating an oscillatory mixture of reagents, as related to our recent experiments with lipid-coated BZ droplets. We demonstrate that by using specific geometrical arrangements of disks containing the oscillatory medium one can perform logical operations on variables coded in oscillation frequency. Realizations of a chemical signal diode and of a single-bit memory with oscillatory disks are also discussed.

Therapeutic drug monitoring of nortriptyline in smoking cessation: a multistudy analysis.

Multiple, controlled clinical trials support the efficacy of nortriptyline as a smoking cessation agent. Although therapeutic plasma nortriptyline concentrations (PNCs) are known for the treatment of depression, little is known about PNCs in smoking cessation treatment. PNCs from three randomized, placebo-controlled smoking cessation trials (N=244) were analyzed both separately and pooled. PNCs normalized for dose and weight were associated with cigarettes per day and race, but not with sex or age. Greater smoking was associated with decreased normalized PNCs. In addition, both Asian and black populations had significantly higher normalized PNCs than the white populations. Weak and inconsistent associations between PNCs and self-reported side effects were observed. PNCs were linearly related to end of treatment and long-term biochemically verified smoking abstinence. Maximum therapeutic effects were observed over a range of plasma concentrations somewhat lower than those found effective for the treatment of depression.

Multiargument logical operations performed with excitable chemical medium.

Assuming that a pulse of excitation corresponds to the logical "true" state one can use a chemical medium for information processing and construct devices that execute the basic binary logical operations. Here we discuss direct chemical realizations of four argument logical functions equivalent to special types of McCulloch-Pitts neuron. We demonstrate that if a proper geometrical arrangement of excitable and nonexcitable areas is used then the construction of the considered devices can be much simpler than in the case where they are composed of chemical binary logical gates.

Sensing the distance to a source of periodic oscillations in a nonlinear chemical medium with the output information coded in frequency of excitation pulses.

A spatially distributed excitable chemical medium can collect and process information coded in the propagating pulses of excitation. We consider the problem of distance sensing with the use of a nonlinear chemical medium. We demonstrate that a sensor that can feel the distance separating it from a source of periodic excitations can be constructed by a proper geometrical arrangement of excitable and nonexcitable regions. The sensor returns information about the distance in the frequency of outgoing pulses. The sensor functionality is tested by simulations based on the Rovinsky-Zhabotinsky model. The results are confirmed in experiments performed for a ruthenium-catalyzed Belousov-Zhabotinsky reaction.

On one dimensional chemical diode and frequency generator constructed with an excitable surface reaction.

The oxidation of carbon monoxide on a Pt(110) surface is considered as a medium for chemical information processing in which bits of information are represented by traveling pulses of high oxygen coverage. Using numerical simulations for a model of CO oxidation we demonstrate that in such system one dimensional chemical signal diode can be realized by setting a proper profile of temperature. We also show that a pulse splitting can occur on a temperature inhomogeneity. The phenomenon of pulse splitting can be used to construct one dimensional generator of a train of pulses with adjustable frequency.

Derivation of a quantitative minimal model from a detailed elementary-step mechanism supported by mathematical coupling analysis.

Accurate experimental data increasingly allow the development of detailed elementary-step mechanisms for complex chemical and biochemical reaction systems. Model reduction techniques are widely applied to obtain representations in lower-dimensional phase space which are more suitable for mathematical analysis, efficient numerical simulation, and model-based control tasks. Here, we exploit a recently implemented numerical algorithm for error-controlled computation of the minimum dimension required for a still accurate reduced mechanism based on automatic time scale decomposition and relaxation of fast modes. We determine species contributions to the active (slow) dynamical modes of the reaction system and exploit this information in combination with quasi-steady-state and partial-equilibrium approximations for explicit model reduction of a novel detailed chemical mechanism for the Ru-catalyzed light-sensitive Belousov-Zhabotinsky reaction. The existence of a minimum dimension of seven is demonstrated to be mandatory for the reduced model to show good quantitative consistency with the full model in numerical simulations. We derive such a maximally reduced seven-variable model from the detailed elementary-step mechanism and demonstrate that it reproduces quantitatively accurately the dynamical features of the full model within a given accuracy tolerance.

T-shaped coincidence detector as a band filter of chemical signal frequency.

The construction of a reactor that works as a bandpass filter for a chemical signal is described and its potential applications are discussed. By a chemical signal we understand a train of concentration pulses propagating in a spatially distributed excitable medium.

Complex transformations of chemical signals passing through a passive barrier.

It has been recently observed that a passive barrier separating two excitable chemical media may transform the frequency of a train of incoming pulses. In this work we apply the FitzHugh-Nagumo-type model to study this phenomenon in a detailed way. Our numerical calculations demonstrate that at the barrier a periodic train of pulses may be transformed into a complex output signal. The ratio of frequencies of the output and the input signals, plotted as a function of the barrier's width or as a function of the input signal frequency, has a devil's-staircase-like shape.

Laminectomy versus percutaneous electrode placement for spinal cord stimulation.

OBJECTIVE: The purpose of this study was to compare the long-term effectiveness of spinal cord stimulation using laminectomy-style electrodes versus that using percutaneously implanted electrodes. METHODS: Forty-one patients underwent an initial trial period of spinal cord stimulation with temporary electrodes at Duke Medical Center between December 1992 and January 1998. A permanent system was implanted if trial stimulation reduced the patient's pain by more than 50%. Median long-term follow-up after permanent electrode placement was 34 months (range, 6-66 mo). Severity of pain was determined postoperatively by a disinterested third party using a visual analog scale and a modified outcome scale. RESULTS: Twenty-seven (66%) of the 41 patients participating in the trial had permanent electrodes placed. Visual analog scores decreased an average of 4.6 among patients in whom electrodes were placed via laminectomy in the thoracic region (two-tailed t test, P < 0.0001). Patients who underwent percutaneous placement of thoracic electrodes had an average decrease of 3.1 in their visual analog scores (two-tailed t test, P < 0.001). Electrodes placed through laminectomy furnished significantly greater long-term pain relief than did those placed percutaneously, as measured by a four-tier outcome grading scale (P = 0.02). CONCLUSION: Spinal cord stimulation is an effective treatment for chronic pain in the lower back and lower extremities that is refractory to conservative therapy. Electrodes placed via laminectomy in the thoracic region appear to be associated with significantly better long-term effectiveness than are electrodes placed percutaneously.

Do-not-resuscitate practices in the chronically critically ill.

OBJECTIVES: To determine the frequency of do-not-resuscitate (DNR) orders in the chronically critically ill; to identify the differences in clinical and demographic characteristics of chronically critically ill patients who have DNR orders and those who do not; to identify the differences in the cost of care between patients with and without DNR orders; and to identify the differences in DNR practices between an experimental special care unit and the traditional intensive care unit (ICU). DESIGN: Randomized, prospective design with a block randomization scheme. SUBJECTS: Two hundred twenty patients who met the following eligibility criteria for enrollment in a parent study of the special care unit: an ICU stay of at least 5 days, an absence of pulmonary artery monitoring, an absence of frequent titration of intravenous vasopressors, an Acute Physiology and Chronic Health Evaluation II score of less than 18, and a Therapeutic Intervention Scoring System score of less than 39. SETTING: A large, urban academic medical center. MEASURES: Clinical and demographic variables describing the study populations, mental status, and timing of DNR orders, mortality rates, and cost of hospitalization. RESULTS: There was no difference in the frequency of DNR orders between the special care unit versus the intensive care unit--although patients in the special care unit had a longer interval between hospital admission and initiation of the DNR order. DNR patients differed from non-DNR in that they were older, less likely to be married, and had a higher Acute Physiology and Chronic Health Evaluation II score on admission to the study. The mortality rate in the DNR group was 71% versus 6% in the non-DNR group. There was no difference in total costs. DNR patients were also more likely to have an impaired mental status on admission, and more likely to have deterioration in mental status by the time of discharge than the non-DNR patients.

The Duke experience with the nucleus caudalis DREZ operation.

The nucleus caudalis DREZ operation has been performed in three phases at Duke. Between 1982 and 1988 radiofrequency (RF) lesions were made in the trigeminal nucleus extending from the C2 root to the obex using a straight electrode. Complications include ipsilateral arm ataxia due to spinocerebellar tract injury and ipsilateral lower limb weakness from the pyramidal tract. The former occurred at least transiently in 90% of cases. The electrode employed from 1988 to 1989 had proximal insulation protecting the spinocerebellar tract. Since 1989 a ninety degree bend has been added to the electrode to allow better placement. Two electrodes are used to accommodate the shape of the caudalis nucleus. A total of 101 procedures have been performed. The newest electrodes were used in 46 procedures. Ataxia is recognized in 39%. Overall pain relief was excellent in 34% and good in 40%. In post herpetic neuralgia 71% enjoyed excellent or good relief. Indications include post herpetic neuralgia, deafferentation pain (anaesthesia dolorosa, post-tic dysesthesia, stroke, MS, gasserian tumour, Gamma Knife radiation injury), facial trauma/surgery, atypical facial pain, and migraine/cluster headache. A study to compare this operation to deep brain stimulation prospectively for the above indications has been initiated.

The Duke experience with nucleus caudalis DREZ coagulation.

The results of 46 nucleus caudalis DREZ coagulations performed at Duke in the preceding 5 years are reviewed retrospectively, with a mean follow-up of 32 months. Fifteen (38%) of 39 patients with complete data indicated that they would undergo the procedure again. Fifteen (38%) described improved quality of life. Outcome was fair or better in 18 (46%). Complications in the form of ataxia were present in 21 (54%).