The search of small molecules with antipsychotic activity on the background of neurotensin

Tridecapeptide neurotensin (NT) is known to exert the neuroleptic-like effects in case of its intracerebral administration. The group of systemically active dipeptides , acylprolyltyrosines, was constructed on the background of NT. Methyl ester of N-caproyl-L-prolyl-L-tyrosine (Dilept) was chosen for further development. The paper is dealing with main principles of Dilept'design and with analysis of the experimental data concerning its effect on the "translational" model of schizophrenia--the deficit of prepulse inhibition of the acoustic startle-reaction caused by either dopamine-mimetic, apomorphine, or by the uncompetitive NMDA-blocker, ketamine. Dilept was shown to attenuate these deficits both in case ofintraperitoneal and peroral administration. Dilept is considered as a potential antipsychotic.     

Breeding without breeding: minimum fingerprinting effort with respect to the effective population size

We present a probabilistic model to minimize the fingerprinting effort associated with the implementation of the “breeding without breeding” scheme under partial pedigree reconstruction. Our approach is directed at achieving a declared target population’s minimum effective population size (N _e ), following the pedigree reconstruction and genotypic selection and is based on the graph theory algorithm. The primary advantage of the proposed method is to reduce the cost associated with fingerprinting before the implementation of the pedigree reconstruction for seed parent–offspring derived from breeding arboreta and production or natural populations. Stochastic simulation was conducted to test the method’s efficiency assuming a simple polygenic model and a single trait. Hypothetical population consisted of 30 parental trees that were paired at random (selfing excluded), resulting in 600 individuals (potential candidates for forwards selection). The male parentage was assumed initially unknown. The model was used to estimate the minimum genotyping sample size needed to reaching the prescribed N _e . Results were compared with the known pedigree data. The model was successful in revealing the true relationship pattern over the whole range of N _e . Two to three offspring entered genotyping to meet the N _e  = 2 while 41 to 43 were required to satisfy the N _e  = 14. Importantly, genetic gain was affected at the lower limits of the genotyping effort. Doubling the number of parents resulted in considerable reduction of the genotyping effort at higher N _e values.     

Nω-Hydroxyamino-α-amino acids as a new class of very strong inhibitors of arginases

 The effects of various compounds bearing an N-OH group such as N-hydroxy-guanidines, amidoximes, and hydroxylamines, on bovine and rat liver arginases was studied. Some of these compounds with an l-α-amino acid function at an appropriate distance from the N-OH group acted as strong competitive liver arginase inhibitors, displaying Ki values between 4 and 150 μM. Two compounds, N ^ε-hydroxy-l-lysine and N ^ω-hydroxy-d,l-indospicine, which exhibited Ki values of 4 and 20 μM (at pH 7.4), were the most potent inhibitors of arginase described to date. The distance between the α-amino acid and N-OH functions appeared to be crucial for potent inhibition of arginase, as N ^δ-hydroxy-l-ornithine, which has one -CH₂ group less than N ^ε-hydroxy-l-lysine, exhibited a 37-fold higher Ki value than N ^ε-hydroxy-l-lysine. Based on these results, a model for the interaction of N ^ω-hydroxyamino-l-α-amino acids with the arginase active site is proposed. This model involves the binding of the N-OH group of the inhibitors to the arginase Mn(II) center and suggests that N ^ε-hydroxy-l-lysine is a good transition state analog of arginase.     

Modelling nitrous oxide emission from water-logged soils of a spruce forest ecosystem using the biogeochemical model Wetland-DNDC

During the last decades, decision makers and policy have increasingly demanded for regional and national inventories of greenhouse gas emission, such as nitrous oxide (N₂O), to develop appropriate strategies and mitigation options. A potential way to derive large-scale estimates of N₂O emission is the use of process-based models, such as PnET-N-DNDC or Wetland-DNDC. While PnET-N-DNDC has been effectively applied for various upland forest ecosystems, the Wetland-DNDC model has not yet been validated with regard to N₂O emission. We calibrated and validated the Wetland-DNDC model on the basis of a 4-year field data set of two water-logged soils (Humic Gleysol and Histic Gleysol) of a spruce forest ecosystem. Model calibration by means of the Levenberg–Marquardt algorithm considerably improved the model performance for the period of calibration (2001–2002). The error variance was reduced by up to a factor of two and the modelling efficiency was increased from −1.24 to −0.15 (Humic Gleysol) and from −0.42 to 0.1 (Histic Gleysol). However, the model performance for the period of validation (2003–2004) and particularly for the extreme dry period in summer 2003 was not fully satisfying, notably with regard to the temporal pattern of the N₂O emission.     

A new model for relationship between irradiance and the rate of photosynthesis in <Emphasis Type="Italic">Oryza sativa</Emphasis>

The calculated maximum net photosynthetic rate (P _N) at saturation irradiance (I _m) of 1 314.13 μmol m⁻² s⁻¹ was 25.49 μmol(CO₂) m⁻² s⁻¹, and intrinsic quantum yield at zero irradiance was 0.103. The results fitted by nonrectangular hyperbolic model, rectangular hyperbolic method, binomial regression method, and the new model were compared. The maximum P _N values calculated by nonrectangular hyperbolic model and rectangular hyperbolic model were higher than the measured values, and the I _m calculated by nonrectangular hyperbolic model and rectangular hyperbolic model were less than measured values. Results fitted by new model showed that the response curve of P _N to I was nonlinear at low I for Oryza sativa, P _N increased nonlinearly with I below saturation value. Above this value, P _N decreased nonlinearly with I.     

Validation of density functional modeling protocols on experimental bis(μ-oxo)/μ-η<Superscript>2</Superscript>:η<Superscript>2</Superscript>-peroxo dicopper equilibria

The bis(μ-oxo)/μ-η²:η²-peroxo equilibria for seven supported Cu₂O₂ cores were studied with different hybrid and nonhybrid density functional theory models, namely, BLYP, mPWPW, TPSS, TPSSh, B3LYP, mPW1PW, and MPW1K. Supporting ligands 3,3′-iminobis(N,N-dimethylpropylamine), N,N,N′,N′,N″-pentamethyldipropylenetriamine, N-[2-(pyridin-2-yl)ethyl]-N,N,N′-trimethylpropane-1,3-diamine, bis[2-(2-pyridin-2-yl)ethyl]methylamine, bis[2-(4-methoxy-2-pyridin-2-yl)ethyl]methylamine, bis[2-(4-N,N-dimethylamino-2-pyridin-2-yl)ethyl]methylamine, and 1,4,7-triisopropyl-1,4,7-triazacyclononane were chosen on the basis of the availability of experimental data for comparison. Density functionals were examined with respect to their ability accurately to reproduce experimental properties, including, in particular, geometries and relative energies for the bis(μ-oxo) and side-on peroxo forms. While geometries from both hybrid and nonhybrid functionals were in good agreement with experiment, the incorporation of Hartree–Fock (HF) exchange in hybrid density functionals was found to have a large, degrading effect on predicted relative isomer energies. Specifically, hybrid functionals predicted the μ-η²:η²-peroxo isomer to be too stable by roughly 5–10 kcal mol⁻¹ for each 10% of HF exchange incorporated into the model. Continuum solvation calculations predict electrostatic effects to favor bis(μ-oxo) isomers by 1–4 kcal mol⁻¹ depending on ligand size, with larger ligands having smaller differential solvation effects. Analysis of computed molecular partition functions suggests that nonzero measured entropies of isomerization are likely to be primarily associated with interactions between molecular solutes and their first solvation shell. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Relationships between dynamics of nitrogen uptake and dry matter accumulation in maize crops. Determination of critical N concentration

The concept of critical nitrogen concentration(%N _c) has been proposed as the minimum%N in shoots required to produce the maximum aerial biomassat a given time. Several authors have shown that%N _c declines as a function of aerial biomassaccumulation (W) and the %N _c –W relationship has been proposed as a diagnostic tool of N statusin different crops, excluding maize. From data obtained in five nitrogenfertilisation experiments in irrigated maize crops, 26 critical data-pointswere selected with a precise statistical procedure. An allometric relationwas fitted and a critical %N−W relationshipmodel is proposed in maize as: If W < 1 t ha^-1%N _c = 3.40 If 1 t ha^-1≤ W ≤ 22 t ha^-1%N _c = 3.40(W)^−0.37 The model is applicable to maize crop development between emergenceand silking + 25 days. The model was tested and validated with dataobtained in a network of 17 N fertilisation experiments conducted inFrance under contrasting pedoclimatic conditions. In only nineout of 280 data-points (3.2%), the plant N status was mispredictedwhen ±5% error around %N _c wasallowed. A critical N uptake model (Nu_c, kg Nha^-1) is proposed as Nu_c = 34 (W)^0.63 A comparison between Nu_c and N uptake observedin N treatments giving the maximal grain yields has shown that maizecrops assimilate at least 30 kg N ha^-1 in a storage N poolat the silking stage. The significance of the critical%N−W and Nu−W relationships is discussed in relation to theoretical models proposed inwhole plant ecophysiology. Different relationships calculated betweenleaf area index and aerial biomass accumulation, and between N uptakeand leaf area were consistent with previous results for other crops.This strengthens the interest of the critical%N−W relationship for use as diagnostictool of nitrogen status in maize crops. This revised version was published online in June 2006 with corrections to the Cover Date.     

A model for relating troop size and home range area in a primate species

For relating troop size (N) and home range area (R), a simple model,QR=αN, whereQ denotes habitat quality and α is a constant, was examined using published field data forMacaca fuscata, M. mulatta andColobus guereza. In particular, theN-R direct proportionality of the model was tested for its validity and usefulness in comparison with a few less simple models. The implications of the present model are discussed in relation to bioenergetics and population dynamics.     

Production of N,N′-diacetylchitobiose from chitin using temperature-sensitive chitinolytic enzyme preparations of Aeromonas sp. GJ-18

Summary N,N′-diacetylchitobiose was produced from chitin as a major hydrolytic product by controlling the ratio of β-N-acetylglucosaminidase to N,N′-diacetylchitobiohydrolase activities in the crude enzyme preparation of Aeromonas sp. GJ-18. When the enzyme preparation was preincubated at 50 °C, β-N-acetylglucosaminidase was nearly inactivated, while the N,N′-diacetylchitobiohydrolase was still active. Thus, the composition of chitin oligosaccharides depended on the preincubation temperature of the crude enzyme preparations. Typically, after 7 days of incubation with the substrate chitin, 78.9 and 56.6% of N,N′-diacetylchitobiose yields were obtained from swollen α-chitin and powdered β-chitin, respectively, with enzyme preparations that had been pretreated at 50 °C for 60 min.     

Effect of histidine methylation on the recognition of OVA323-336 T-epitope: Synthesis of N-α-Fmoc-N-τ-methyl-L-histidine and its use for the synthesis of two histidine methylated analogues of OVA323-336

Summary N-α-Fmoc-N-τ-methyl-L-histidine was prepared in three steps fromN-α-Boc-L-histidine by treatment with methyliodine in DMF at−10°C, deprotection of theN-α position in pure TFA and subsequent reprotection by Fmoc-chloroformate in a 5% Na₂CO₃/dioxane mixture.N-α-Fmoc-N-τ-methyl-L-histidine was then used for the solid-phase synthesis of two analogues of the OVA_323–336 T-epitope, methylated on His₃₃₁ and on His_328/331, respectively. These peptides were tested for their ability to activate 3 DO-54.8 T-cell hybridoma when presented by fixed A-20.1.11 antigen presenting cells, and no significant difference was observed in IL-2 production.     

Biodegradation of <Emphasis Type="Italic">N</Emphasis>,<Emphasis Type="Italic">N</Emphasis> diethylaniline in a contaminated aquifer: laboratory- and field-scale evidences

The effectiveness of biosparging to mitigate N,N diethylaniline in aquifer was evaluated by measuring the time course of decrease in concentration of the aforementioned compound in aerobic microcosm experiments. The first-order kinetic constant for N,N diethylaniline aerobic biodegradation was estimated from microcosm data (0.037 ± 0.004 d⁻¹), and the value was consistent with the best-fitting value in the transport and reaction model of the aquifer (0.020 d⁻¹). Furthermore, the biodegradability of the compound was evaluated under anaerobic condition in microcosm experiments, which was supported by field modelling. There was no significant degradation in the anaerobic microcosm experiments, confirming the recalcitrance of N,N diethyl aniline under the aforementioned aquifer condition.     

Analyzing the performance of optical multistage interconnection networks with limited crosstalk

Analytical modeling techniques can be used to study the performance of optical multistage interconnection network (OMIN) effectively. MINs have assumed importance in recent times, because of their cost-effectiveness. An N×N MIN consists of a mapping from N processors to N memories, with log ₂ N stages of 2×2 switches with N/2 switches per stage. The interest is on the study of the performance of unbuffered optical multistage interconnection network using the banyan network. The uniform reference model approach is assumed for the purpose of analysis. In this paper the analytical modeling approach is applied to an N×N OMIN with limited crosstalk (conflicts between messages) up to (log ₂ N−1). Messages with switch conflicts satisfying the constraint of (log ₂ N−1) are allowed to pass in the same group, but in case of a link conflict, the message is routed in a different group. The analysis is performed by calculating the bandwidth and throughput of the network operating under a load l and allowing random traffic and using a greedy routing strategy. A number of equations are derived using the theory of probability and the performance curves are plotted. The results obtained show that the performance of the network improves by allowing limited crosstalk in the network.

Net Primary Production and Canopy Nitrogen in a Temperate Forest Landscape: An Analysis Using Imaging Spectroscopy, Modeling and Field Data

Understanding spatial patterns of net primary production (NPP) is central to the study of terrestrial ecosystems, but efforts are frequently hampered by a lack of spatial information regarding factors such as nitrogen availability and site history. Here, we examined the degree to which canopy nitrogen can serve as an indicator of patterns of NPP at the Bartlett Experimental Forest in New Hampshire by linking canopy nitrogen estimates from two high spectral resolution remote sensing instruments with field measurements and an ecosystem model. Predicted NPP across the study area ranged from less than 700 g m⁻² year⁻¹ to greater than 1300 g m⁻² year⁻¹ with a mean of 951 g m⁻² year⁻¹. Spatial patterns corresponded with elevation, species composition and historical forest management, all of which were reflected in patterns of canopy nitrogen. The relationship between production and elevation was nonlinear, with an increase from low- to mid-elevation deciduous stands, followed by a decline in upper-elevation areas dominated by evergreens. This pattern was also evident in field measurements and mirrored an elevational trend in foliar N concentrations. The increase in production from low-to mid-elevation deciduous stands runs counter to the generally accepted pattern for the northeastern U.S. region, and suggests an importance of moisture limitations in lower-elevation forests. Field measurements of foliar N, wood production and leaf litterfall were also used to evaluate sources of error in model estimates and to determine how predictions are affected by different methods of acquiring foliar N input data. The accuracy of predictions generated from remotely sensed foliar N approached that of predictions driven by field-measured foliar N. Predictions based on the more common approach of using aggregated foliar N for individual cover types showed reasonable agreement in terms of the overall mean, but were in poor agreement on a plot-by-plot basis. Collectively, these results suggest that variation in foliar N exerts an important control on landscape-level spatial patterns and can serve as an integrator of other underlying factors that influence forest growth rates.     

Mass–density relationship changes along salinity gradient in <Emphasis Type="Italic">Suaeda salsa</Emphasis> L.

Whether and why the biomass–density (M–N) scaling relationship varies along environmental gradients were continuously debated in theoretical ecology. In this study, how soil salinity stress affects on the M–N scaling relationship was investigated by using Suaeda salsa L. in beach of Dongtai, Jiangsu Province, China. The results showed that the exponent of the scaling relationship (b) of low salinity level (−1.259) was smaller than that of middle salinity level (−1.025), which in turn was smaller than that high salinity level (−0.698). The plant height–crown radius (H–r) scaling exponents (∂) decreased with increasing salinity stress, while the canopy coverage–density (C–N) scaling exponents (β) showed an inverse trend. The predict data (b) based on ∂ and β by using the geometric model were statistically indistinguishable from their observed values for the three salinity levels. Moreover, two resources utilization parameters (l mean from root to leaf, a total area of leaves) of metabolic theory, photosynthetic rate, and water-use efficiency were more advantageous to Suaeda salsa L. of high stress than to those of low salinity. Therefore, it was implied that the changes of M–N relationship along salinity gradients may be resulted from their different geometric morphologies and resource utilization in response to salinity stress.     

L-NAME administration prevents the inhibition of nucleotide hydrolysis by rat blood serum subjected to hyperargininemia

Summary. The main objective of the present study was to evaluate the in vivo and in vitro effect of Arg on serum nucleotide hydrolysis. The action of N^ω-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, on the effects produced by Arg was also examined. Sixty-day-old rats were treated with a single or a triple (with an interval of 1 h between each injection) intraperitoneal injection of saline (group I), Arg (0.8 g/kg) (group II), L-NAME (2.0 mg/kg or 20 mg/kg) (group III) or Arg (0.8 g/kg) plus L-NAME (2.0 mg/kg or 20 mg/kg) (group IV) and were killed 1 h later. The present results show that a triple Arg administration decreased ATP, ADP and AMP hydrolysis. Simultaneous injection of L-NAME (20 mg/kg) prevented such effects. Arg in vitro did not alter nucleotide hydrolysis. It is suggested that in vivo Arg administration reduces nucleotide hydrolysis in rat serum, probably through nitric oxide or/and peroxynitrite formation. Both are first authors.     

A maximum neural network approach for N-queens problems

 A novel neural network approach using the maximum neuron model is presented for N-queens problems. The goal of the N-queens problem is to find a set of locations of N queens on an N×N chessboard such that no pair of queens commands each other. The maximum neuron model proposed by Takefuji et al. has been applied to two optimization problems where the optimization of objective functions is requested without constraints. This paper demonstrates the effectiveness of the maximum neuron model for constraint satisfaction problems through the N-queens problem. The performance is verified through simulations in up to 500-queens problems on the sequential mode, the N-parallel mode, and the N ²-parallel mode, where our maximum neural network shows the far better performance than the existing neural networks. Received: 4 June 1996/Accepted in revised form: 13 November 1996     

Multilocus epistasis,linkage, and genetic variance in breeding populations with few parents

In a previous study of maize (Zea mays L.) populations formed from few parents, we found that estimates of genetic variances were inconsistent with a simple additive genetic model. Our objective in the current study was to determine how multilocus epistasis and linkage affect the loss of genetic variance in populations created from a small number of parents (N). In simulation experiments, F₂ individuals from the same single cross were intermated to form progeny populations from N = 1, 2, 4, and 8 parents. Additive gene effects and metabolic flux epistasis due to L = 10, 50, and 100 loci were modeled. For additive, additive-with-linkage, epistatic, and epistasis-with-linkage models, we estimated the ratio between total genetic variance in the progeny population (V _N ) and base population (V _B ) as well as the 95th (Δ_95%) and 75th (Δ_75%) percentile differences between the estimated V _N /V _B and the V _N /V _B expected for the additive model. The mean V _N /V _B ratio was lower under epistasis than under additivity, indicating that metabolic flux epistasis hastens the decline in genetic variance due to small N. In contrast, Δ_95% was higher with epistasis than with additivity across the different levels of N and L. Linkage had little effect on the mean V _N /V _B , whereas it increased Δ_95% and Δ_75% under both additivity and epistasis. Smaller N and L led to higher V _N /V _B particularly when epistasis was present. Overall, the results indicated that while metabolic flux epistasis led to a faster average decline in genetic variance, it also led to greater variability in this decline to the point that V _N /V _B was larger than expected in many populations.     

The influence of several changes in atmospheric states over semi-arid areas on the incidence of mental health disorders

The incidence of suicide attempts [Deliberate Self Harm (DSH); ICD-10: X60–X84] and psychotic attacks (PsA; ICD-10, F20–F29) in association with atmospheric states, typical for areas close to big deserts, was analyzed. A retrospective study is based on the 4,325 cases of DSH and PsA registered in the Mental Health Center (MHC) of Ben-Gurion University (Be’er-Sheva, Israel) during 2001–2003. Pearson and Spearman test correlations were used; the statistical significance was tested at p < 0.1. The influence of temperature and humidity on suicide attempts (N _SU ) and psychotic attacks (N _PS ) was weakly pronounced (p > 0.1). Correlation coefficients between N _SU and N _PS and speed WS of westerly wind reaches 0.3 (p < 0.05), while their dependence on easterly WS was weaker (p > 0.09). Variations in easterly wind direction WD influence N _SU and N _PS values (p < 0.04), but no corresponding correlation with westerly winds was found (p > 0.3). Obviously ,in transition areas located between different regions ,the main role of air streams in meteorological–biological impact can scarcely be exaggerated. An unstable balance in the internal state of a weather-sensitive person is disturbed when the atmospheric state is changed by specific desert winds, which can provoke significant perturbations in meteorological parameters. Results indicate the importance of wind direction, defining mainly the atmospheric situation in semi-arid areas: changes in direction of the easterly wind influence N _SU and N _PS , while changes in WS are important for mental health under westerly air streams. Obviously, N _SU and N _PS are more affected by the disturbance of weather from its normal state, for a given season, to which the local population is accustomed, than by absolute values of meteorological parameters.     

Micropropagation ofUraria picta, a medicinal plant, through axillary bud culture and callus regeneration

Summary Micropropagation ofUraria picta, a leguminous herb, was achieved through axillary bud culture and nodal callus culture. Bud break was best when nodes were cultured on Murashige and Skoog (1962) (MS) medium supplemented with 2.6 μM α-naphthalene acetic acid and 4.4 μM N⁶-benzyladenine. Optimum shoot multiplication was observed in adenine sulphate at 2.47 μM concentration. Competent callus was initiated around the nodal ring of the explant on the basal medium supplemented with cytokinins and auxin (α-naphthalene acetic acid and N⁶-benzyladenine), which regenerated into new profusely growing shoots on transferring to 0.13 μM N⁶-benzyladenine. Shoots elongated to 5 node length with 1.11 μM N⁶-benzyladenine were rooted on half-strength MS basal medium. The rooted plants were successfully established with 80% survival. About 400 such plants were transferred to the field.