Outward currents in smooth muscle cells isolated from sheep mesenteric lymphatics.

1. The patch-clamp technique was used to measure membrane currents in isolated smooth muscle cells dispersed from sheep mesenteric lymphatics. Depolarizing steps positive to -30 mV evoked rapid inward currents followed by noisy outward currents. 2. Nifedipine (1 microM) markedly reduced the outward current, while Bay K 8644 (1 microM) enhanced it. Up to 90% of the outward current was also blocked by iberiotoxin (Kd = 36 nM). 3. Large conductance (304 +/- 15 pS, 7 cells), Ca(2+)- and voltage-sensitive channels were observed during single-channel recordings on inside-out patches using symmetrical 140 mM K+ solutions (at 37 degrees C). The voltage required for half-maximal activation of the channels (V1/2) shifted in the hyperpolarizing direction by 146 mV per 10-fold increase in [Ca2+]i. 4. In whole-cell experiments a voltage-dependent outward current remained when the Ca(2+)-activated current was blocked with penitrem A (100 nM). This current activated at potentials positive to -20 mV and demonstrated the phenomenon of voltage-dependent inactivation (V1/2 = -41 +/- 2 mV, slope factor = 18 +/- 2 mV, 5 cells). 6. Tetraethylammonium (TEA; 30 mM) reduced the voltage-dependent current by 75% (Kd = 3.3 mM, 5 cells) while a maximal concentration of 4-aminopyridine (4-AP; 10 mM) blocked only 40% of the current. TEA alone had as much effect as TEA and 4-AP together, suggesting that there are at least two components to the voltage-sensitive K+ current. 7. These results suggest that lymphatic smooth muscle cells generate a Ca(2+)-activated current, largely mediated by large conductance Ca(2+)-activated K+ channels, and several components of voltage-dependent outward current which resemble 'delayed rectifier' currents in other smooth muscle preparations.

Arching action in high strength concrete slabs

The corrosion of reinforcement in bridge deck slabs has been the cause of major deterioration and high costs in repair and maintenance.This problem could be overcome by reducing the amount of reinforcement and/or altering the location.This is possible because, in addition to the strength provided by the reinforcement, bridge deck slabs have an inherent strength due to the in-plane arching forces set up as a result of restraint provided by the slab boundary conditions. This is known as arching action or Compressive Membrane Action (CMA). It has been recognised for some time that laterally restrained slabs exhibit strengths far in excess of those predicted by most design codes but the phenomenon has not been recognised by the majority of bridge design engineers. This paper presents the results of laboratory tests on fifteen reinforced concrete slab strips typical of a bridge deck slab and compares them to predicted strengths using the current codes and CMA theory. The tests showed that the strength of laterally restrained slabs is sensitive to both the degree of external lateral restraint and the concrete compressive strength.The tests particularly highlighted the benefits in strength obtained from very high strength concrete slabs. The theory extends the existing knowledge of CMA in slabs with concrete compressive strengths up to 100 N/mm[2] and promotes more economical and durable bridge deck construction by utilising the benefits of high strength concrete.

Serviceability of bridge deck slabs with arching action

The deterioration of infrastructure, such as bridges, has been one of the major challenges facing both the designers and the owners of such utilities. Sustainable development and a climate of increasing commercialism has led to a requirement for more accurate means of structural analysis. Bridge assessment is one area where this is particularly relevant. It has been known for some time that bridge deck slabs have inherent enhanced strength due to the presence of arching or compressive membrane action (CMA) but only in recent years has there been some acceptance of a rational treatment of this phenomenon for design and assessment purposes. To use the benefits of arching action, this paper presents the results of tests carried out on a reinforced-concrete beam and slab bridge in Northern Ireland that incorporated novel reinforcement type and position. The research was aimed at extending previous laboratory tests on 1/3scale bridge deck edge panels. The measured crack widths and deflections have been compared with the current code requirements.

Delayed failure of a deep cutting in lodgement till

Recent research on the delayed failure of cuttings in clay clearly recognises and predicts progressive delayed failure of deep cuttings. This is due to a combination of strain-softening, weathering, dissipation of negative excess pore water pressure generated at the time of excavation, and frequent occurrence of prolonged periods of wet weather. There have been several slope failures of this kind in Northern Ireland. This paper discusses a case study based on a failure of a deep cutting, excavated at a slope of 1 in 2, on the A1 near Dromore (County Down) in Northern Ireland. The cutting was in lodgement till, a stiff, heavily overconsolidated clay. The failure occurred approximately 30 years after the cutting was excavated, following a prolonged period of heavy rainfall. An analysis of the failure, together with laboratory test data on soil samples taken from the site, confirmed that by using long-term soil strength parameters the factor of safety of this slope was unity. The conclusion of the analysis is that slopes excavated in this soil should be designed (and assessed) on long-term strength parameters.

The effect of rudder angle on the scouring action produced by the propeller wash of a manoeuvring ship

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Chemical ablation of gastric inhibitory polypeptide receptor action by daily (Pro3) GIP administration improves glucose tolerance and ameliorates insulin resistance and abnormalities of islet structure in obesity-diabetes.

Glucose-dependent insulinotropic polypeptide (gastric inhibitory polypeptide [GIP]) is an important incretin hormone secreted by endocrine K-cells in response to nutrient ingestion. In this study, we investigated the effects of chemical ablation of GIP receptor (GIP-R) action on aspects of obesity-related diabetes using a stable and specific GIP-R antagonist, (Pro3)GIP. Young adult ob/ob mice received once-daily intraperitoneal injections of saline vehicle or (Pro3)GIP over an 11-day period. Nonfasting plasma glucose levels and the overall glycemic excursion (area under the curve) to a glucose load were significantly reduced (1.6-fold; P <0.05) in (Pro3)GIP-treated mice compared with controls. GIP-R ablation also significantly lowered overall plasma glucose (1.4-fold; P <0.05) and insulin (1.5-fold; P <0.05) responses to feeding. These changes were associated with significantly enhanced (1.6-fold; P <0.05) insulin sensitivity in the (Pro3)GIP-treated group. Daily injection of (Pro3)GIP reduced pancreatic insulin content (1.3-fold; P <0.05) and partially corrected the obesity-related islet hypertrophy and ß-cell hyperplasia of ob/ob mice. These comprehensive beneficial effects of (Pro3)GIP were reversed 9 days after cessation of treatment and were independent of food intake and body weight, which were unchanged. These studies highlight a role for GIP in obesity-related glucose intolerance and emphasize the potential of specific GIP-R antagonists as a new class of drugs for the alleviation of insulin resistance and treatment of type 2 diabetes.