Structure-activity relationships of alkylxanthines: alkyl chain elongation at the N1- or N7-position decreases cardiotonic activity in the isolated guinea pig heart

Relationships between the alkyl substitutions (C1-C6) and cardiac inotropic activities of xanthine derivatives were studied in isolated guinea pig heart muscles. Most of the alkylxanthines exhibited positive inotropic activity on the left atrium, which was increased with an elongation of alkyl chain at the N3-position but decreased by substitution of a long alkyl group at the N1- or N7-position of the xanthine skeleton. Although positive inotropic activity in the right ventricular papillary muscle was also increased by longer alkyl groups at the N3-position, the inotropic activity became negative with an increment in alkyl chain length at the N1- or N7-position. The positive inotropic activity of alkylxanthines was correlated with their inhibitory activity on the phosphodiesterase (PDE) III isoenzyme. Adenosine A1 antagonism and PDE IV inhibitory activity were also partly associated with the inotropic activity because H-89, an inhibitor of cyclic AMP-dependent protein kinase, diminished the positive inotropic action and potentiated the negative inotropic action. These results indicate that the positive inotropic activity of alkylxanthines becomes weak with elongation of alkyl chains at the N1- and N7-positions; In particular, xanthines having two long alkyl chains show a negative inotropic activity on the right ventricular papillary muscle, an effect that could not be elucidated from their cyclic AMP-dependent action.     

A 3-V, 2%-mW multibit current-mode ΣΔ DAC with 100 dBdynamic range

The area ratio of analog to digital for mixed-mode chip has been inversely proportional to the process design rule for a given dynamic range objective, in contradiction to the LSI trend. This paper presents a design approach to realize a high degree of size reduction with process design rules for analog circuitry and a signal processing architecture for digital circuitry. A five-level current-mode ΣΔ digital-to-analog converter (DAC) system reveals full scale total harmonic: distortion plus noise (THD+N) of -90 dB and dynamic-range of 100 dB at 3 V (low power of 22 mW). Analog-area down-scaling can be accomplished by this architecture to be 1.09 mm², using 0.6-μm double-poly double-metal (DPDM) CMOS. For the digital filter, a pipeline instruction sequence with multiplierless architecture also gives small area of 1.98 mm²     

Calbindin-D 28 kD and parvalbumin in the horizontal cells of rat retina during development

Restless legs syndrome (RLS) and periodic limb movements in sleep (PLMS) are disorders that are common and disturbing to uremic patients. The treatment of these is problematic. Eight patients on chronic hemodialysis and continuous peritoneal dialysis completed a double-blind placebo-controlled crossover study using incremental doses of pergolide up to 0.25 mg at bedtime for treatment of RLS and sleep disruption. Five patients (62.5%) noted subjective improvement in restless legs symptoms and sleep quality. Objective results were improved only slightly by treatment. The percentage of the first hour in bed during which leg movements occurred decreased from 20.5 +/- 6.0 to 11.5 +/- 3.3, p < 0.05. However, findings during sleep were less positive. The following measures were not significant between placebo and treatment: leg movements per hour of sleep [53.7 +/- 22.3 vs 35.8 +/- 11.8 (p = 0.2)]; and percentage of sleep time spent with leg movements [5.5% +/- 3.2 vs 4.4% +/- 1.4 (p = 0.37)]. Patients continued to have very disrupted sleep, and we could not document an objective improvement in sleep architecture. Thus, although pergolide at the dose of 0.25 mg at bedtime provided subjective improvement in symptoms of restless legs and quality of sleep, and objectively decreased leg movements during the first hour in bed, objectively sleep continued to be disrupted. In this small patient group, the response to pergolide was not uniform, and further investigation is required to test effectiveness at higher doses.     

Switching to Directional Antennas with Constant Increase in Radius and Hop Distance

For any angle α<2π, we show that any connected communication graph that is induced by a set P of n transceivers using omni-directional antennas of radius 1, can be replaced by a strongly connected communication graph, in which each transceiver in P is equipped with a directional antenna of angle α and radius r _dir, for some constant r _dir=r _dir(α). Moreover, the new communication graph is a c-spanner of the original graph, for some constant c=c(α), with respect to number of hops.     

Oxidation of synthetic triacylglycerols containing eicosapentaenoic and docosahexaenoic acids: Effect of oxidation system and triacylglycerol structure

Thirteen synthetic triacylglycerols (TAG) containing eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) were oxidized in the presence of 2,2′-azobis(2,4-dimethyl-valeronitrile) (AMVN) and 2,2′-azobis(2-amidinopropane)dihydrochloride (AAPH) as aqueous and nonaqueous radical initiators to investigate the influence of TAG structure and oxidation system on the oxidative stability of TAG that contain highly unsaturated fatty acids (HUFA). A 2:1 (mol/mol) mixture of trieicosapentaenoylglycerol and tripalmitoylglycerol was most susceptible to the AMVN-initiated oxidation among three types of TAG that contained EPA and palmitic acid (2:1, mol/mol). Compared with 1,2 (or 2,3)-dieicosapentaenoyl-3(or 1)-palmitoylglycerol (EEP) and 1,3-dieicosapentaenoyl-2-palmitoylglycerol (EPE), the oxidative rate of EEP was somewhat higher. A similar result was obtained for DHA-containing TAG. The oxidative rate of TAG that contained EPA and palmitic acid (1:2, mol/mol) showed a positive correlation with the amount of EPA in a single TAG molecule. Moreover, in the nonaqueous system, the oxidative rate of EPA-containing TAG was affected by unsaturation and carbon chainlength of constituent fatty acids. In the AAPH-initiated oxidation in the aqueous system, the oxidative rate of TAG with EPA and palmitic acid was higher with the increased quantity of EPA in a single TAG molecule. Also, constituent fatty acids modified the oxidative rate of EPA-containing TAG in an aqueous system. The glycerol position of EPA and DHA also affected the oxidative rate of the TAG. EPA and DHA located at the 1,2 (or 2,3)-position of glycerol were more oxidizable than those at the 1,3-position during AAPH-initiated oxidation. Thus, 1,2(or2,3)-dipalmitoyl-3(or 1)-eicosapentaenoylglycerol was oxidized faster than 1,3-dipalmitoyl-2-eicosapentaenoylglycerol. These observations suggest that the oxidative stability of TAG that contain HUFA could be modulated by the oxidation system and TAG structure.     

Evaluation of the wettability of spherical cement particle surfaces using penetration rate method

The wettability of cement particles is related to the fluidity of cement paste. This paper describes the mechanism of the higher fluidity imparted by the spherical cement particles in light of their wettability. In addition, the effects of gypsum on the wettability were also studied. This study has shown the following: (1) The weight of water and water-reducing agent solution penetrating the spherical cement powder bed is 24-150% higher than that for the ordinary Portland cement powder bed. This results in the improvement of the wettability of the particle surfaces of spherical cement. The high wettability of spherical cement contributes to its high fluidity. (2) The presence of many fine gypsum particles on the spherical cement particle surface reduces the wettability. (3) To prepare spherical cement, the optimum amount of gypsum added is determined by the acceleration of the formation of spherical particles and the wettability of particle surfaces.     

Solid/liquid extraction and isolation by molecular distillation of hydroxytyrosol from Olea europaea L. leaves

Molecular distillation, or short‐path distillation (SPD), is particularly appropriate for processing of low‐volatility compounds, which are easily altered at high temperature. Olea europaea L. leaves constitute an olive tree by‐product very interesting for their natural antioxidants content. In this research, molecular distillation technology has been applied to obtain high‐value‐added compounds by the SPD fractionation of an olive tree leaf extract. The process consists of two stages: (a) ethanolic extraction of the olive leaves, followed by incorporation of the extract into glycerine and (b) molecular distillation of the glycerine enriched in olive leaf extract compounds (terpenic and phenolic compounds). Four molecular distillation tests under different conditions were carried out. Results showed that 80.9% 3,4‐dihydroxy‐phenylethanol (hydroxytyrosol) was recovered from the glycerine admixture under a pressure of 1.50–2.00 mbar, a temperature of 190 °C and a feed rate of 15 mL/min.     

Application and limitation of neoadjuvant hormonal therapy for prostate cancer

Of 156 patients, 111 (clinical stage T1a-b; 21, T1c; 17, T2a-b; 36, T2c; 27, T3; 10) immediately underwent radical prostatectomy (surgery group), and 45 (clinical stage T1a-b; 8, T1c; 4, T2a-b; 10, T2c; 9, T3; 14) received neoadjuvant hormonal therapy (NHT group). NHT offered probability of increasing organ-confined cancer(OCC; pathological stage pT2 or lower N0M0) in the following group, which contains (a) patients who had moderately differentiated adenocarcinoma in the biopsy specimen and T2b or lower diseases, and (b) those who had well differentiated adenocarcinoma, T2c diseases and PSA levels of 10 ng/ml or higher, referred to as "OCC suitable criteria". Of 156 patients, 51 (33%) met OCC suitable criteria. In those cases, the proportion of OCC in NHT group was significantly higher than that in surgery group (11/12 (92%) vs. 16/39 (41%), p = 0.002). NHT is useful for increasing OCC in patients who meet OCC suitable criteria.     

Advection‐Based Function Matching on Surfaces

A tangent vector field on a surface is the generator of a smooth family of maps from the surface to itself, known as the flow. Given a scalar function on the surface, it can be transported, or advected, by composing it with a vector field's flow. Such transport is exhibited by many physical phenomena, e.g., in fluid dynamics. In this paper, we are interested in the inverse problem: given source and target functions, compute a vector field whose flow advects the source to the target. We propose a method for addressing this problem, by minimizing an energy given by the advection constraint together with a regularizing term for the vector field. Our approach is inspired by a similar method in computational anatomy, known as LDDMM, yet leverages the recent framework of functional vector fields for discretizing the advection and the flow as operators on scalar functions. The latter allows us to efficiently generalize LDDMM to curved surfaces, without explicitly computing the flow lines of the vector field we are optimizing for. We show two approaches for the solution: using linear advection with multiple vector fields, and using non‐linear advection with a single vector field. We additionally derive an approximated gradient of the corresponding energy, which is based on a novel vector field transport operator. Finally, we demonstrate applications of our machinery to intrinsic symmetry analysis, function interpolation and map improvement.