Association of the glycogen synthase locus on 19q13 with NIDDM in Pima Indians

Skeletal muscle glycogen synthase (encoded by GYS1 on chromosome 19q13.3) is the rate-limiting enzyme in insulin-mediated non-oxidative glucose disposal. Our previous studies have demonstrated an impairment of insulin-stimulated GYS1 activities in insulin-resistant Pima Indians, and associations of non-insulin-dependent diabetes mellitus (NIDDM) with the GYS1 locus were reported recently in Finnish and Japanese populations. We have performed linkage and association analyses of GYS1 and seven additional DNA markers on 19q with NIDDM, and with parameters of insulin action in the Pima Indians. We have found a significant association of NIDDM with GYS1 genotypes (p = 0.009), and with common GYS1 alleles (p = 0.022) in the Pima Indians. We have performed a detailed comparative analysis of the GYS1 gene, mRNA, and protein product in insulin-sensitive and insulin-resistant Pima Indians. No mutations in GYS1 coding sequences were detected; nor did we find alterations of GYS1 mRNA expression or of its basal enzymatic activity in insulin-resistant Pima Indians. These results contrasted with a 25% reduction of immunoreactive protein in insulin-resistant subjects as detected by Western blotting with an antibody specific for the C-terminal end of GYS1 (t-test p = 0.024; Wilcoxon's rank-sum test, p = 0.04). Because no mutations were detected in the DNA encoding this epitope, the difference in immunoreactivity may reflect post-translational modification(s) of the protein rather than a difference in the gene itself, or it could have occurred by chance. We conclude that our data do not indicate alterations in the GYS1 gene as the cause for the observed association, and that a different locus near GYS1 may be the contributing genetic element.     

Nonlinear black-box modeling in system identification: a unified overview

A nonlinear black-box structure for a dynamical system is a model structure that is prepared to describe virtually any nonlinear dynamics. There has been considerable recent interest in this area, with structures based on neural networks, radial basis networks, wavelet networks and hinging hyperplanes, as well as wavelet-transform-based methods and models based on fuzzy sets and fuzzy rules. This paper describes all these approaches in a common framework, from a user's perspective. It focuses on what are the common features in the different approaches, the choices that have to be made and what considerations are relevant for a successful system-identification application of these techniques. It is pointed out that the nonlinear structures can be seen as a concatenation of a mapping form observed data to a regression vector and a nonlinear mapping from the regressor space to the output space. These mappings are discussed separately. The latter mapping is usually formed as a basis function expansion. The basis functions are typically formed from one simple scalar function, which is modified in terms of scale and location. The expansion from the scalar argument to the regressor space is achieved by a radial- or a ridge-type approach. Basic techniques for estimating the parameters in the structures are criterion minimization, as well as two-step procedures, where first the relevant basis functions are determined, using data, and then a linear least-squares step to determine the coordinates of the function approximation. A particular problem is to deal with the large number of potentially necessary parameters. This is handled by making the number of ‘used’ parameters considerably less than the number of ‘offered’ parameters, by regularization, shrinking, pruning or regressor selection.     

Contrast-medium-induced ventricular fibrillation: arrhythmogenic mechanisms and the role of antiarrhythmic drugs in dogs

RATIONALE AND OBJECTIVES: Small electrolyte additions to a nonionic contrast medium reduce the risk of ventricular fibrillation (VF) during wedged catheter injection of a contrast medium. The current study was designed to further investigate contrast-medium-induced VF by studying the effect of pretreatment with different antiarrhythmic drugs. METHODS: During a simulated wedged catheter situation, iohexol was injected into the anterior descending branch of the left coronary artery in five open-chest, anesthetized dogs pretreated with lidocaine, propranolol, amiodarone, almokalant, or verapamil. RESULTS: Wedging the catheter for 60 sec did not induce VF. However, all 15 wedged catheter injections with iohexol induced VF within 28 sec (19 +/- 1 [mean +/- standard error of the mean]) despite pretreatment with antiarrhythmic drugs. Prior to VF, conduction was slowed and monophasic action potential duration lengthened in the contrast-medium-perfused myocardium, although no significant changes occurred in the control area. CONCLUSION: The combination of catheter wedging and long-lasting contrast medium injection has a high risk of causing VF. Although adding a small amount of electrolytes to nonionic contrast media can reduce the risk of VF, antiarrhythmic drug therapy may not have a protective effect.     

Congenital bilateral perisylvian syndrome

The congenital bilateral perisylvian syndrome is characterized by pseudobulbar palsy, moderate delay in mental and motor development and epilepsy. Three characteristic case stories are presented. Epileptic seizures are most frequently generalized: tonic, astatic, atypical absences and tonic-clonic seizures. Partial seizures are less frequent. Seizure control is often unsatisfactory. Neuroimaging demonstrates thickening of the cerebral cortex in the perisylvian area bilaterally; these changes together with the clinical picture establish the diagnosis. The etiology is unknown.     

Optic neuropathy resembling normal-pressure glaucoma in a teenager with congenital macrodiscs

We report a unique case of a renal transplant patient with a long-term nonprogressive human immunodeficiency virus type-1 (HIV-1) infection and who is asymptomatic despite sustained immunosuppression. Renal function is normal, and HIV infection was probably acquired through blood transfusion before the transplant. Nonprogression may be due either to an effective immune control of HIV replication or to particular genetic aspects of the virus. Several virological investigations were carried out to verify if she is infected with an attenuated virus strain. Results show an unusual combination of high and stable CD4 count, ongoing viral replication and elevated viral loads. Attempts to isolate the virus from plasma were unsuccessful, but isolation was possible from peripheral blood mononuclear cells, and the virus was shown to be non-syncytium-inducing. Sequence analysis of the nef gene revealed no mutation. This exceptional lack of progression of HIV infection under immunosuppressive therapy requires further investigation.     

Gastric antrectomy with selective gastric vagotomy does not influence gallbladder motility during interdigestive and postprandial periods

Fasting gastrointestinal motility and gallbladder motility during the interdigestive state and in the postprandial period was studied in eight patients who were operated for ulcer disease with an antrectomy and selective gastric vagotomy. Nocturnal motility recording revealed all three phases of the migrating motor complex (MMC) in all but one patient, where no phase III activity was recorded. In the rest of the patients 3-10 events with phase III activity were recorded. At scintigraphy ([75Se]HCAT) a cyclic gallbladder filling and emptying in relation to the MMC cycle was found. Episodes with emptying were confined to phase II and a total of 13 episodes with a median duration of 25 min (range 10-70 min) were observed. A median of 10.7% (6.1-17.7%) of the gallbladder contents was emptied. In a control group of eight healthy young men the values were 13.5 min (9-36 min) and 6.9% (3.7-31.1%), respectively. These differences were not significant. During the postprandial period, a lag period in gallbladder emptying of median 15 min (5-20 min) was observed when food ingestion took place during phase I of the MMC. Thereafter a gradual emptying occurred with a rate of 0.95% min (0.71-1.15%/min). In a control group of healthy young males, the lag period was 13.5 min (9-22.5 min) and the emptying rate 0.61%/min (0.08-0.77%/min). When food ingestion occurred during phase II of the MMC, the lag period of gallbladder emptying in the patient group was median 0 min (0-5 min) and the emptying rate was 0.77%/min (0.33-0.86%/min). The values in the control group were 0 min (-9 to 13.5 min) and 0.76%/min (0.54-2.25%/min), respectively. These differences between the patients and controls were not significant. In conclusion, antrectomy and selective gastric vagotomy do not influence fasting gastrointestinal motility or gallbladder motility during the interdigestive state or in the postprandial period.     

Auditory feedback in haptic collaborative interfaces

The combined effect of haptic and auditory feedback in shared interfaces on the cooperation between visually impaired and sighted persons is under-investigated. A central challenge for cooperating group members lies in obtaining a common understanding of the elements of the workspace and maintaining awareness of the other members' actions, as well as one's own, during the group work process. The aim of the experimental study presented here was to investigate if adding audio cues in a haptic and visual interface makes collaboration between a sighted and a blindfolded person more efficient. Results showed that task performance was significantly faster in the audio, haptic and visual feedback condition compared to the haptic and visual feedback condition. One special focus was also to study how participants utilize the auditory and haptic force feedback in order to obtain a common understanding of the workspace and to maintain an awareness of the group members' actions. Results from a qualitative analysis showed that the auditory and haptic feedback was used in a number of important ways to support the group members' action awareness and in the participants' grounding process.     

AZ31镁合金初始动态再结晶的临界条件研究

为确定AZ31镁合金初始动态再结晶的临界条件或临界应变，通过在变形温度范围473～623K、应变速率范围0．001-1 s^-1条件下进行等温压缩试验，利用所得数据并采用单参数方法，建立起AZ31镁合金初始动态再结晶的临界条件，即临界应变（εc）与变形条件（引入温度补偿应变速率因子即Zener-Hollomon参数）的定量关系，并对不同应变下合金微观组织的演变规律进行了研究。     

Study of the coupling reactions between electrochemically generated aromatic radical anions and methyl, alkyl and benzyl radicals

Alkyl radicals produced in the indirect reduction of alkyl halides or alkyldimethylsulfonium salts by electrochemically generated aromatic radical anions couple fast with the latter and alkylated or dialkylated dihydro compounds are formed. Rate constants measured for the coupling reaction between on one hand methyl, primary, secondary and tertiary alkyl radicals as well as benzyl and cumyl radicals and on the other hand a wide spectrum of electrochemically generated aromatic radical anions are found to be about 1×10⁹ M⁻¹ s⁻¹. Previous measurements of coupling rate constants for primary alkyl radicals have been re-evaluated since they were affected by the presence of an S_N2 reaction occurring between the alkyl halides used as radical precursors and the aromatic radical anions. New experiments are also included using alkyldimethylsulfonium salts as precursors in order to prevent such S_N2 artefacts. It is concluded that sterical hindrance does not play a significant role for the radical-radical anion coupling reactions. In general the rate constants for the coupling reactions are all close to 10⁹ M⁻¹ s⁻¹.