Synthesis and biological activity of homoarginine-containing opioid peptides.

Two tris-alkoxycarbonyl homoarginine derivatives, Boc-Har{omega,omega'-[Z(2Br)]2}-OH and Boc-Har{omega,omega'-[Z(2Cl)]2}-OH, were prepared by guanidinylation of Boc-Lys-OH, and used for the synthesis of neo-endorphins and dynorphins. The results were compared with that obtained in the synthesis in which Boc-Lys(Fmoc)-OH was incorporated into the peptide chain, and after removing Fmoc protection, the resulting peptide-resin was guanidinylated with N,N'-[Z(2Br)]2- or N,N'-[Z(2Cl)]2-S-methylisourea. The peptides were tested in the guinea-pig ileum (GPI) and mouse vas deferens (MVD) assays. The results indicated that replacement of Arg by Har may be a good avenue for the design of biologically active peptides with increased resistance to degradation by trypsin-like enzymes.     

The basic flow equations of electrophysiology in the presence of chemical reactions: I. Development of the equations

Starting from the basic flux equation, it is possible to obtain an integral form relating the current componentsI _i at an arbitrary pointr ₂ to the distribution of mobilities and concentrationsc _i, potential forces\(\bar \mu \), and chemical productivityp _i without any restrictive assumptions such as constant mobilities, constant field, steady state, or electrical neutrality. The equation is

$$\begin{gathered} I_i (r_2 ) = G_i (r_2 )\left[ {\Delta \bar \mu _i - \int_{r_1 }^{r_2 } {z_i } FA\left( {p_i - dc_i /dt} \right)\left( {\frac{1}{{G_i (r)}}} \right)dr} \right]; \hfill \\ G_i (r) = 1/\int_{r_1 }^r {\frac{{dr}}{{z_i^2 F^2 c_i u_i }}.} \hfill \\ \end{gathered} $$     

Local description of surface tension through thermodynamic and mechanical definitions

For a half century, the calculation of local pressure components and surface tension along the normal to the surface have been carried out using mechanical definitions. This has led to three principal definitions: Irving and Kirkwood, Harasima and Kirkwood–Buff. Recently, thermodynamic definitions based on the energy calculation have been introduced to compute the local properties. We propose here to compare both definitions for Lennard–Jones particles interacting through a truncated and shifted potential. For this, two locations of the pairwise interaction involved in the calculation of the local pressure components and surface tension within the thermodynamic routes are investigated. For the first time, we show that the thermodynamic definition suffers, to one least degree with respect to the mechanical definition, from the same ambiguity. From a numerical standpoint, thermodynamic definition is more simple and less computationally expensive. Therefore, with the complicated potential, the thermodynamic approach appears to be most interesting to compute macroscopic and local pressure and surface tension.     

Mathematical modelling of bone adaptation of the metacarpal subchondral bone in racehorses

In Thoroughbred racehorses, fractures of the distal limb are commonly catastrophic. Most of these fractures occur due to the accumulation of fatigue damage from repetitive loading, as evidenced by microdamage at the predilection sites for fracture. Adaptation of the bone in response to training loads is important for fatigue resistance. In order to better understand the mechanism of subchondral bone adaptation to its loading environment, we utilised a square root function defining the relationship between bone volume fraction \((f_{BM} )\) and specific surface \((S_v )\) of the subchondral bone of the lateral condyles of the third metacarpal bone (MCIII) of the racehorse, and using this equation, developed a mathematical model of subchondral bone that adapts to loading conditions observed in vivo. The model is expressed as an ordinary differential equation incorporating a formation rate that is dependent on strain energy density. The loading conditions applied to a selected subchondral region, i.e. volume of interest, were estimated based on joint contact forces sustained by racehorses in training. For each of the initial conditions of \(f_{BM} \) we found no difference between subsequent homoeostatic \(f_{BM} \) at any given loading condition, but the time to reach equilibrium differed by initial \(f_{BM} \) and loading condition. We found that the observed values for \(f_{BM} \) from the mathematical model output were a good approximation to the existing data for racehorses in training or at rest. This model provides the basis for understanding the effect of changes to training strategies that may reduce the risk of racehorse injury.     

Generation of ion-acoustic and magnetoacoustic waves in an RF helicon discharge

A study is made of the generation of ion-acoustic and magnetoacoustic waves in a discharge excited in an external magnetic field by an electromagnetic wave in the whistler frequency range (ω_LH ? ω ? ω_He, where ω_LH = $\sqrt {\omega _{He} \omega _{Hi} } $ and ω_He and ω_Hi are the electron and ion gyrofrequencies, respectively). The excitation of acoustic waves is attributed to the decay of a high-frequency hybrid mode forming a plasma waveguide into low-frequency acoustic waves and new high-frequency waves that satisfy both the decay conditions and the waveguide dispersion relations. The excitation of acoustic waves is resonant in character because the conditions for the generation of waveguide modes and for the occurrence of the corresponding nonlinear wave processes should be satisfied simultaneously. An unexpected effect is the generation of magnetoacoustic waves by whistlers. A diagnostic technique is proposed that allows one to determine the thermal electron velocity by analyzing decay conditions and dispersion relations for waves in the discharge channel.     

Effect of structural modification at carbon atom 1 of leukotriene B4 on the chemotactic and metabolic response of human neutrophils

Human neutrophils biosynthesize the chemoattractant leukotriene B4 (LTB4) and metabolize LTB4 to omega oxidative products 20-hydroxy-LTB4 (20-OH-LTB4) and 20-carboxy-LTB4 (20-COOH-LTB4). In this study, we prepared the C-1 methyl ester and N-methyl amide of LTB4 and then examined neutrophil chemotaxis and metabolism of these derivatives of LTB4. The results show that chemical modification of LTB4 at carbon atom 1 dramatically affects metabolism of the lipid molecule. The free acid form of LTB4 was taken up and metabolized by human neutrophils, while the methyl ester and N-methyl amide derivatives were poor substrates for omega oxidation. Although human neutrophils were poorly attracted to the methyl ester of LTB4, the amide derivative was a complete agonist of the neutrophil chemotactic response and displayed an ED50 for chemotaxis identical to that of LTB4. Therefore, we concluded that omega oxidation is not a requirement for the neutrophil chemotactic response induced by LTB4. These results also indicate that the N-methyl amide of LTB4 may be a useful ligand for the elucidation of molecular mechanisms operative in neutrophil chemotaxis to LTB4, since the C-1 derivative is not further metabolized. Two separate responses of human neutrophils are elicited by LTB4, resulting in both cellular activation and generation of omega oxidation products. It appears that putative receptors on the neutrophils can distinguish between LTB4 and certain derivatives that are structurally identical except for modification at the C-1 position (i.e., the methyl ester). LTB4 derivatives modified at the C-1 position do not undergo conversion to omega oxidation products by the neutrophil.     

Response to various shock loadings of the constant recycle-sludge-concentration activated-sludge process

The stability of the model of a completely mixed activated-sludge process holding the recycle sludge concentration, X_R, as a system constant subjected to pH, temperature, potassium cyanide, and phenol shock loading was investigated. Soft-drink bottling wastewater was used and maintained at 1000 mg/liter chemical oxygen demand (COD). The hydraulic ratio and recycle sludge concentration were maintained at 0.3 and 7000 mg/liter, respectively. An initial dilution rate of ¼ hr^?1 was maintained for pH and temperature shock loading, with ¼ and ? hr^?1 for KCN shock loading and ¼, ?, and \documentclass{article}\pagestyle{empty}\begin{document}$\frac{1}{16}$\end{document} hr^?1 for phenol shock loading. It was found that the present system could handle pH shock loading as low as 4.0 and as high as 10.4 without any serious disruption of biological solid concentration and filtrate COD. At pH 4.0 shock loading, filamentous organisms were predominant. Temperature shock loading could be handled from 23 to 36°C without any leakage of effluent filtrate COD. At 46°C temperature shock, a 14 hr period was required to recuperate to the new steady state and provided only 85% of COD removal efficiency. For KCN (50 mg/liger) and phenol (85 mg/liter) shock loading, the dilution rates should be lower than \documentclass{article}\pagestyle{empty}\begin{document}$\frac{1}{16}$\end{document} hr^?1 in order to shorten the transient period and improve the effluent quality. Biological kinetic constants included cell yield value, maximum growth rate, and the saturation constant, which was varied with the qualitative shock applied.     

Polarized fluorescence in an electric field. A model calculation with application to the geometry of the 2-hydroxy-4,4′-diamidinostilbene–DNA complex

Theoretical expressions are derived for the change in the polarized components of the fluorescence, resulting from the orientation of a rigid molecule bearing a chromophore with arbitrary angles for the absorption and transition moments \documentclass{article}\pagestyle{empty}\begin{document}$ \vec \mu _a $\end{document} and \documentclass{article}\pagestyle{empty}\begin{document}$ \vec \mu _e $\end{document} with respect to the molecular axis. The break in the symmetry relation H_V = V_H is related to the tilt angle between \documentclass{article}\pagestyle{empty}\begin{document}$ \vec \mu _a $\end{document} and \documentclass{article}\pagestyle{empty}\begin{document}$ \vec \mu _e $\end{document}. The theory is applied to a sonicated DNA–2-hydroxy-4,4′-diamidinostilbene complex, in the blue and red emission bands of this peculiar dye. Simultaneous measurements of linear dichroism and fluorescence lead to the determination of an angle of 47° between a fluorescent bound dye and the DNA axis, with no difference for the blue- and red-emitting species, but confirm the presence of nonfluorescent bound dye in a more perpendicular arrangement.     

A Combined Patch-Clamp and Electrorotation Study of the Voltage- and Frequency-Dependent Membrane Capacitance Caused by Structurally Dissimilar Lipophilic Anions

Interactions of structurally dissimilar anionic compounds with the plasma membrane of HEK293 cells were analyzed by patch clamp and electrorotation. The combined approach provides complementary information on the lipophilicity, preferential affinity of the anions to the inner/outer membrane leaflet, adsorption depth and transmembrane mobility. The anionic species studied here included the well-known lipophilic anions dipicrylamine (DPA⁻), tetraphenylborate (TPB⁻) and [W₂(CO)₁₀(S₂CH)]⁻, the putative lipophilic anion and three new heterocyclic W(CO)₅ derivatives. All tested anions partitioned strongly into the cell membrane, as indicated by the capacitance increase in patch-clamped cells. The capacitance increment exhibited a bell-shaped dependence on membrane voltage. The midpoint potentials of the maximum capacitance increment were negative, indicating the exclusion of lipophilic anions from the outer membrane leaflet. The adsorption depth of the large organic anions DPA⁻, TPB⁻ and increased and that of W(CO)₅ derivatives decreased with increasing concentration of mobile charges. In agreement with the patch-clamp data, electrorotation of cells treated with DPA⁻ and W(CO)₅ derivatives revealed a large dispersion of membrane capacitance in the kilohertz to megahertz range due to the translocation of mobile charges. In contrast, in the presence of TPB⁻ and no mobile charges could be detected by electrorotation, despite their strong membrane adsorption. Our data suggest that the presence of oxygen atoms in the outer molecular shell is an important factor for the fast translocation ability of lipophilic anions.     

A Bovine Babesiosis Model with Dispersion

Bovine Babesiosis (BB) is a tick borne parasitic disease with worldwide over 1.3 billion bovines at potential risk of being infected. The disease, also called tick fever, causes significant mortality from infection by the protozoa upon exposure to infected ticks. An important factor in the spread of the disease is the dispersion or migration of cattle as well as ticks. In this paper, we study the effect of this factor. We introduce a number, $\mathcal{P}$ , a “proliferation index,” which plays the same role as the basic reproduction number $\mathcal{R}_{0}$ with respect to the stability/instability of the disease-free equilibrium, and observe that $\mathcal{P}$ decreases as the dispersion coefficients increase. We prove, mathematically, that if $\mathcal{P}>1$ then the tick fever will remain endemic. We also consider the case where the birth rate of ticks undergoes seasonal oscillations. Based on data from Colombia, South Africa, and Brazil, we use the model to determine the effectiveness of several intervention schemes to control the progression of BB.     

Effect of feedback contingencies on the control of occipital alpha

Ten color transparencies were presented 30 times each to ten normal adults in response to changes in their occipital-parietal EEG's. By means of a feedback paradigm, detected alphas caused each slide to flash and stay on as long as alpha persisted, and then to turn off when alpha attenuated, according to four different contingency conditions. For half of the feedback trials, stimulus presentation depended on alpha detection in only one hemisphere and was not influenced by changes in the simultaneously recorded contralateral EEG. For the other feedback trials, stimulus presentation was bilaterally contingent. These contingency configurations were compared with sham feedback, a noncontingent condition during which slide presentation was controlled by a prerecorded tape. For both alpha and no-alpha, the ratio of mean duration over standard error was used as a quantification of the EEG response to visual stimulation. It was assumed that larger ratios indicated increased control of the EEG. Compared with the sham condition, all feedback contingencies produced greater ratios, and hence, improved control of the EEG. The highest ratios were obtained during unilateral feedback from the EEG in which the occurrence of alpha elicited the visual stimulus. The results show that contingency between a visual stimulus and the EEG is an important parameter with regard to experimental control of the EEG.     

Potential use of sulfite as a supplemental electron donor for wastewater denitrification

Biological denitrification typically requires the addition of a supplemental electron donor, which can add a significant operating expense to wastewater treatment facilities. Most common electron donors are organic, but reduced inorganic sulfur compounds (RISCs), such as sulfide (HS^?) and elemental sulfur (S⁰), may be more cost-effective. S⁰ is an inexpensive and well characterized electron donor, but it provides slow denitrification rates due to its low solubility. A lesser-known RISC is sulfite (\({\text{SO}}_{3}^{2 - }\)), which can be easily produced from S⁰ by a simple combustion process. Unlike S⁰, \({\text{SO}}_{3}^{2 - }\) is highly soluble, and therefore may provide higher denitrification rates. However, very little is known about microbial denitrification with \({\text{SO}}_{3}^{2 - }\). Also, \({\text{SO}}_{3}^{2 - }\) is a strong reductant that reacts abiotically with oxygen and has toxic effects on microorganisms. This paper reviews \({\text{SO}}_{3}^{2 - }\) in the environment, \({\text{SO}}_{3}^{2 - }\) chemistry, microbiology, toxicity, and its potential use for denitrification. Since \({\text{SO}}_{3}^{2 - }\) is an intermediate in the sulfur oxidation pathway of most sulfur-oxidizing microorganisms, it is an energetic electron donor and it should select for a \({\text{SO}}_{3}^{2 - }\)-oxidizing community. Our review of the literature, as well as our own lab experience, suggests that \({\text{SO}}_{3}^{2 - }\) can effectively serve as an electron donor for denitrification. Further research is needed to determine the kinetics of \({\text{SO}}_{3}^{2 - }\)-based denitrification, its toxic threshold for sulfur-oxidizing microorganisms, and its potential inhibition of sensitive species such as nitrifying microorganisms and potential formation of nitrous oxide. Its effect on sludge settling efficiency also should be explored.     

Theoretical Study of Sensitivity and Localized Surface Plasmon Resonance of Ag-Dielectric Core-Shell Multi-layered Nanosphere

Localized surface plasmon resonances (LSPRs) of Ag-dielectric-Ag multi-layered nanoshell are studied by quasi-static approximation and plasmon hybridization theory. Absorption properties of multi-layered nanoshell with the silver core and nanoshell separated by a dielectric layer exhibit strong coupling between the core and nanoshell. The result shows absorption spectrum of LSPRS is influenced by the refractive index of surrounding medium, the dielectric constant of middle dielectric layer, the thickness of inner core radius and outer shell layer. LSPR shift of the longest wavelength \(\left |\omega _{-}^{-}\right >\) is red-shifted with increasing the inner core radius. It is interesting to find that longer wavelength \(\left |\omega _{-}^{+}\right >\) mode is mainly effected by the ratio constant of the surrounding medium refractive index ε ₄ to the middle layer dielectric constant ε ₂. \(\left |\omega _{-}^{+}\right >\) mode takes place a blue-shift with increasing inner core radius when ε ₂ > ε ₄, a red-shift when ε ₂ < ε ₄, and no-shifting when ε ₂ = ε ₄. However, the influence of dielectric layer radius to \(\left |\omega _{-}^{+}\right >\) mode shows the different property as that of increasing the inner core radius. The underlying mechanisms are analyzed with the plasmon hybridization theory and the distribution of induced charge interaction between the inner core and outer shell. In addition, the influence of core radius, middle dielectric layer radius and outer shell radius to sensitivity of Ag-dielectric-Ag multi-layered nanoshell are also reported, a higher sensitivity could be gotten by adjusting geometrical parameters. Our theoretical study could give an easy way to analyze properties of the core-shell nanosphere based on plasmon hybridization theory and the induced charge interaction, and usefully broaden the applications in nano-optics.     

Retention of Dissolved Inorganic Nitrogen by Foliage and Twigs of Four Temperate Tree Species

Nitrogen (N) retention by tree canopies is believed to be an important process for tree nutrient uptake, and its quantification is a key issue in determining the impact of atmospheric N deposition on forest ecosystems. Due to dry deposition and retention by other canopy elements, the actual uptake and assimilation by the tree canopy is often obscured in throughfall studies. In this study, ¹⁵N-labeled solutions ( $ ^{15} {\text{NH}}_{4}^{ + } $ and $ ^{15} {\text{NO}}_{3}^{ - } $ ) were used to assess dissolved inorganic N retention by leaves/needles and twigs of European beech, pedunculate oak, silver birch, and Scots pine saplings. The effects of N form, tree species, leaf phenology, and applied $ {\text{NO}}_{3}^{ - } $ to $ {\text{NH}}_{4}^{ + } $ ratio on the N retention were assessed. Retention patterns were mainly determined by foliar uptake, except for Scots pine. In twigs, a small but significant ¹⁵N enrichment was detected for $ {\text{NH}}_{4}^{ + } $ , which was found to be mainly due to physicochemical adsorption to the woody plant surface. The mean $ {{^{15} {\text{NH}}_{4}^{ + } } \mathord{\left/ {\vphantom {{^{15} {\text{NH}}_{4}^{ + } } {^{15} {\text{NO}}_{3}^{ - } }}} \right. \kern-0em} {^{15} {\text{NO}}_{3}^{ - } }} $ retention ratio varied considerably among species and phenological stadia, which indicates that the use of a fixed ratio in the canopy budget model could lead to an over- or underestimation of the total N retention. In addition, throughfall water under each branch was collected and analyzed for $ ^{15} {\text{NH}}_{4}^{ + } $ , $ ^{15} {\text{NO}}_{3}^{ - } $ , and all major ions. Net throughfall of $ ^{15} {\text{NH}}_{4}^{ + } $ was, on average, 20 times higher than the actual retention of $ ^{15} {\text{NH}}_{4}^{ + } $ by the plant material. This difference in $ ^{15} {\text{NH}}_{4}^{ + } $ retention could not be attributed to pools and fluxes measured in this study. The retention of $ ^{15} {\text{NH}}_{4}^{ + } $ was correlated with the net throughfall of K⁺, Mg²⁺, Ca²⁺, and weak acids during leaf development and the fully leafed period, while no significant relationships were found for $ ^{15} {\text{NO}}_{3}^{ - } $ retention. This suggests that the main driving factors for $ {\text{NH}}_{4}^{ + } $ retention might be ion exchange processes during the start and middle of the growing season and passive diffusion at leaf senescence. Actual assimilation or abiotic uptake of N through leaves and twigs was small in this study, for example, 1–5% of the applied dissolved ¹⁵N, indicating that the impact of canopy N retention from wet deposition on forest productivity and carbon sequestration is likely limited.     

Synthesis and benzodiazepine receptor (omega receptor) affinities of 3-substituted derivatives of pyrrolo[2,3-c]pyridine-5-carboxylate, a novel class of omega1 selective ligands.

Based on the structure of ZK91296 (4d), a high affinity partial agonist of the central benzodiazepine (omega) receptor, a series of pyrrolo[2,3-c]pyridine-5-carboxylate derivatives having mainly aralkyl and aralkyloxy substituents at C-3 was synthesized. The in vitro binding affinities of these compounds for three subclasses of the omega receptor (omega1, omega2, omega5) were determined using rat brain tissue. Practically all of these compounds (except the diethyl ester derivative 22c) showed an approximately twofold selectivity for omega1 (IC50's in the 200-500 nM range) compared to omega2 receptors and practically no affinity for omega5 receptors. Compound 22c showed the highest affinity of all the compounds synthesized (IC50 = 70 nM for omega1 receptors) as well as a fivefold selectivity for omega1 versus omega2 receptors but also displayed significant binding to omega5 receptors (IC50 = 250 nM). The absence of appreciable binding of 4-methyl and 4-methoxymethyl derivatives to omega receptors, in contrast to beta-carbolines having these similarly located substituents, suggests that the pyrrolo[2,3-c]pyridine-5-carboxylates may be considered an entirely novel class of selective omega receptor ligands.     

An Error in the Calibration of Xylem-water Potential against Leaf-water Potential

An error occurs in the calibration of xylem pressure potential() against leaf-water potential () when the calibration is madeusing plant material in which the water stress has been inducedartificially after excision. The impostion of water stress afterexcision affects the determination more than it affects , consequentlythe relationship between these two indices of water stress isaltered. Care should be exercised to ensure that identical proceduresare adopted during . calibrations and during susbsequent fieldmeasurements of with the pressure-chamber apparatus.