A model of ocular dominance column development by competition for trophic factor

Recent experimental evidence has shown that application of certain neurotrophic factors (NTs) to the developing primary visual cortex prevents the development of ocular dominance (OD) columns. One interpretation of this result is that afferents from the lateral geniculate nucleus compete for postsynaptic trophic factor in an activity-dependent manner. Application of excess trophic factor eliminates this competition, thereby preventing OD column formation. We present a model of OD column development, incorporating Hebbian synaptic modification and activity-driven competition for NT, which accounts for both normal OD column development as well as the prevention of that development when competition is removed. In the "control" situation, when available NT is below a critical amount, OD columns form normally. These columns form without weight normalization procedures and in the presence of positive inter-eye correlations. In the "experimental" case, OD column development is prevented in a local neighborhood in which excess NT has been added. Our model proposes a biologically plausible mechanism for competition between neural populations that is motivated by several pieces of experimental data, thereby accounting for both normal and experimentally perturbed conditions.     

能源管理：更高效的第一步（第二部分）

这一系列的文章,将给出一些例子--关于工程师如何在工厂内部几乎不增加开支的前提下找到能源浪费的根源。第一部分（2009年5月刊）关注的是工厂、设备用电、电机和驱动;第二部分将关注能源重用以及专项节能方案。     

Instrumentation of the patellar osteotomy in total knee arthroplasty. The relationship of patellar thickness and lateral retinacular release

This study investigates the influence of patellar thickness in total knee arthroplasty (TKA) with routine patellar resurfacing on the rate of lateral retinacular release. A study group comprised of 121 TKAs using surgical instrumentation allowing a measured resection of the patella was compared with a control group comprised of 100 TKAs using an "eye-ball" technique for patellar resurfacing without particular attention to patellar thickness. A composite without patellar thickness equal to or slightly less than the original patella was attempted in the study group. The average thickness difference of the patella in the study group was -1.58 mm. Lateral retinacular release for patellar maltracking was performed in 12.4% of knees in the study group compared with 55% of knees in the control group. The variation in patellar thickness in this series often led to a residual bone thickness < 15 mm. No clinical problems have been observed to date.     

Selective screening for abdominal aortic aneurysm

Coagulase-negative staphylococci (CNS) are common causes of infection in patients undergoing chronic ambulatory peritoneal dialysis (CAPD). Their ability to survive intracellularly within peritoneal macrophages and to persist within the peritoneum during antibiotic therapy has led to the development of drug resistance during treatment. Strains of Staphylococcus epidermidis (SE) and Staphytococcus haemolyticus (SH) have been isolated from patients with CAPD during treatment with ciprofloxacin. The respective MIC values pre-and post-therapy were SE-0.25 and 128 mg/L and SH-0.50 and 64 mg/L. The susceptibility of each isolate to opsonophagocytosis was measured in vitro using isolated polymorphonuclear leucocytes (PMN) derived from fresh human blood donations. The bacteria were radiolabelled during growth, opsonised in either 1 or 10% serum and their uptake measured No differences were seen between the pre- and post therapy isolates when using 10% serum as opsonic source (18 vs. 21%); with 1% serum the corresponding values were lower (5 and 8% respectively). Similarly their ability to generate a respiratory burst as measured by chemiluminescence (CL) in the phagocytic cells was not diminished in the strains which had developed resistance to ciprofloxacin. The mean CL response to the strains isolated at outset of therapy ranged from 0.35-0.45 cpsc, and to the resistant strains following therapy from 0.36-0.50 cpsc. It is clear from the present investigation that although the bacterial strain became at least 10 times more resistant to ciprofloxacin during therapy, no change in their susceptibility to phagocytosis occurred refuting the idea that the emergence of drug resistant strains during therapy results in "super-bugs" of greater virulence.     

Contribution of PO2, P50, and Hb to changes in arteriovenous O2 content during exercise in heart failure

Arteriovenous O2 content (a-vCO2) differences increase during exercise in normal subjects through several mechanisms including PO2, O2 pressure at which hemoglobin (Hb) is half saturated with O2 (P50), and Hb concentration changes. The present study was undertaken to evaluate how much these biochemical changes are relevant to a-vCO2 difference through exercise in patients with heart failure. Twenty-seven patients with congestive heart failure [10 patients in functional class A (peak exercise O2 uptake >20 ml x kg-1 x min-1), 9 in class B (20-15 ml x kg-1 x min-1), and 8 in class C (15-10 ml x kg-1 x min-1)] underwent a cardiopulmonary exercise test with once-per-minute simultaneous blood sampling from the pulmonary and systemic arteries for determination of Hb, PO2, PCO2, pH, O2 content (CO2), Hb saturation and lactic acid (pulmonary artery only), and calculation of P50. Analysis of data was done at six exercise stages: the first at rest, the last at peak exercise, and the second to the fifth at one-, two-, three-, and four-fifths of O2 consumption increase. a-vCO2 difference at peak exercise was 14.3 +/- 2.1, 16.9 +/- 2.4, and 14.7 +/- 2.1 (SD) ml/dl in class A, B, and C patients, respectively. The contribution of Hb, P50, and PO2 changes to the increments of a-vCO2 difference during exercise was 21, 17, and 63%, respectively; the only interclass difference observed was for P50, which plays a greater role in a-vCO2 difference in class A. Hb changes act mainly at the arterial site, whereas P50 and PO2 act at the venous site. Hb increase was constant through the test, venous P50 increase was greater above anaerobic threshold, and venous PO2 reduction was most remarkable at the onset of exercise; in class C patients, no venous PO2 change was recorded in the second half of exercise. Thus a-vCO2 difference increase during exercise is notable in patients with heart failure but unrelated to the severity of the syndrome. Hb, P50, and, to the greatest degree, PO2 changes participate in the increment of a-vCO2 difference. In class C patients, the lack of PO2 reduction in the second half of exercise suggests the achievement of a "whole body critical venous PO2."     

Intraoperative determination of small intestinal viability following ischemic injury: a prospective, controlled trial of two adjuvant methods (Doppler and fluorescein) compared with standard clinical judgment

Two adjuvant techniques for the intraoperative assessment of small intestinal viability were compared with standard clinical judgment in a prospective, controlled study of 71 ischemic bowel segments in 28 consecutive patients operated on for acute intestinal ischemic disease. Each segment was independently assessed 15 minutes after surgical correction of the underlying lesion by: 1) standard clinical judgment; 2) Doppler-detected pulsatile mural blood flow; and 3) fluorescein ultraviolet fluorescence pattern. Viability endpoint for each segment was determined objectively by patient follow-up or "blinded" microscopic evaluation of histologically unequivocal resection specimens using criteria established by previous animal studies. Seventeen histologically equivocal specimens were excluded from the final results. Standard clinical judgment proved moderately accurate overall (89%) but would have led to a relatively high rate (46%) of unnecessary bowel resection. The Doppler technique did not increase accuracy in any category of evaluation. The fluorescein fluorescent pattern was correct in all 54 determinant bowel segments, and proved more sensitive specific, predictive, and significantly more accurate overall than either standard clinical judgment or the Doppler method. This controlled study suggests that the fluorescein technique is the method of choice for the prediction of small intestinal recovery following ischemic injury.     

Quasielastic light-scattering studies of aqueous biliary lipid systems. Mixed micelle formation in bile salt-lecithin solutions

From measurements of the autocorrelation function and time-averaged intensity of light scattered from aqueous bile salt-lecithin solutions, we deduced the mean hydrodynamic radius (Rh), shape, and polydispersity of bile salt-lecithin mixed micelles as functions of bile salt species, lecithin to bile salt (L/BS) molar ratio, total lipid concentration (0.625-10 g/dL), temperature (20-60 degrees C), and NaCl concentration (0.15-0.6 M). Our data suggest that at low L/BS ratios (0 to approximately 0.6) simple bile salt micelles coexist in varying proportions with minimum-sized mixed micelles (Rh, 18-35 A). These solutions are highly polydisperse and display features dependent upon the particular bile salt species. At high L/BS ratios (greater than 0.6), only mixed micelles are present, and their sizes increase markedly (Rh, 20 leads to 300 A) with increases in L/BS ratio and appear to diverge as the lecithin-bile salt phase limit is approached. The shape of the mixed micelles as deduced from light-scattering measurements and confirmed by transmission electron microscopy is disklike. The radii of the disks, however, are not compatible with Small's model of mixed micellar structure [Small, D.M. (1967a) Gastroenterology 52, 607-a1 but are consistent with a new model proposed here in which bile salts and lecithin interact to form a mixed bilayer disk which is surrounded on its perimeter by bile salts. The inclusion of bile salts in a fixed stoichiometry within the interior of the bilayers is shown to provide a quantitative explanation for the divergence of the mixed micellar sizes, their temperature dependence, and the origin of the lecithin-bile salt phase limit. The influence of total lipid concentration on both mixed micellar size and the lecithin-bile salt phase limit is explained by the "mixed disk" model by taking account of the equilibrium between mixed micelles and bile salt monomers in the intermicellar solution. By use of this concept, deductions of the intermicellar bile salt concentration in taurocholate-lecithin solutions are made and are shown to vary as a function of mixed micellar size and temperature. The range of values obtained, 3-6 mM, is comparable in magnitude to the critical micellar concentration of the pure bile salt.     

Dynamics of membrane excitability determine interspike interval variability: a link between spike generation mechanisms and cortical spike train statistics

We propose a biophysical mechanism for the high interspike interval variability observed in cortical spike trains. The key lies in the nonlinear dynamics of cortical spike generation, which are consistent with type I membranes where saddle-node dynamics underlie excitability (Rinzel & Ermentrout, 1989). We present a canonical model for type I membranes, the theta-neuron. The theta-neuron is a phase model whose dynamics reflect salient features of type I membranes. This model generates spike trains with coefficient of variation (CV) above 0.6 when brought to firing by noisy inputs. This happens because the timing of spikes for a type I excitable cell is exquisitely sensitive to the amplitude of the suprathreshold stimulus pulses. A noisy input current, giving random amplitude "kicks" to the cell, evokes highly irregular firing across a wide range of firing rates; an intrinsically oscillating cell gives regular spike trains. We corroborate the results with simulations of the Morris-Lecar (M-L) neural model with random synaptic inputs: type I M-L yields high CVs. When this model is modified to have type II dynamics (periodicity arises via a Hopf bifurcation), however, it gives regular spike trains (CV below 0.3). Our results suggest that the high CV values such as those observed in cortical spike trains are an intrinsic characteristic of type I membranes driven to firing by "random" inputs. In contrast, neural oscillators or neurons exhibiting type II excitability should produce regular spike trains.     

Junctional tachycardia during radiofrequency ablation of the slow pathway in patients with AV nodal reentrant tachycardia: effects of autonomic blockade

BACKGROUND: Exogenous surfactant treatment of hyaline membrane disease is known to modify the pattern of radiological changes on the chest radiograph. OBJECTIVES: To analyse and attempt to explain the radiological changes observed after exogenous surfactant treatment. Materials and methods. Thirty-nine premature infants with typical hyaline membrane disease. RESULTS: Transient asymmetrical clearing with better aeration of the right lung in the absence of malposition of the tip of the endotracheal tube was observed in nine cases (23 %). This asymmetry was patchy in one case. It was due to a complication of mechanical ventilation in three cases [pneumothorax (n = 2) and pneumomediastinum (n = 1)]. In the other six cases, asymmetrical clearing could be related to the anatomical position of the right main bronchus, which facilitates distribution of surfactant to the right lung. However, the course of these premature infants was similar to that of infants with symmetrical chest radiological findings after treatment. CONCLUSIONS: Asymmetrical clearing of chest radiographs, sometimes patchy, after surfactant treatment requires exclusion of pneumothorax or infection but has no influence on clinical outcome.     

Protease evolution in Streptomyces griseus. Discovery of a novel dimeric enzymes

This report describes the cloning and sequencing of a novel protease gene derived from Streptomyces griseus. Also described is the heterologous expression of the gene in Bacillus subtilis and characterization of the gene product. The sprD gene encodes a prepro mature protease of 392 amino acids tentatively named S. griseus protease D (SGPD). A significant component of the enzyme preregion was found to be homologous with the mitochondrial import signal of hsp60. The sprD gene was subcloned into an Escherichia coli/B. subtilis shuttle vector system such that the pro mature portion of SGPD was fused in frame with the promoter, ribosome binding site, and signal sequences of subtilisin. The gene fusion was subsequently expressed in B. subtilis DB104, and active protease was purified. SGPD has a high degree of sequence homology to previously described S. griseus proteases A, B, C, and E and the alpha-lytic protease of Lysobacter enzymogenes, but unlike all previously characterized members of the chymotrypsin superfamily, the recombinant SGPD forms a stable alpha 2 dimer. The amino acid sequence of the protein in the region of the specificity pocket is similar to that of S. griseus proteases A, B, and C. The purified enzyme was found to have a primary specificity for large aliphatic or aromatic amino acids. Nucleotide sequence data were used to construct a phylogenetic tree using a method of maximum parsimony which reflects the relationships and potentially the lineage of the chymotrypsin-like proteases of S. griseus.