The failing heart.

Cardiomyopathies are disorders affecting heart muscle that usually result in inadequate pumping of the heart. They are the most common cause of heart failure and each year kill more than 10,000 people in the United States. In recent years, there have been breakthroughs in understanding the molecular mechanisms involved in this group of conditions, with knowledge of the genetic basis for cardiomyopathies perhaps seeing the largest advance, enabling clinicians to devise improved diagnostic strategies and preparing the stage for new therapies.     

A calcium sensor in the sodium channel modulates cardiac excitability.

Sodium channels are principal molecular determinants responsible for myocardial conduction and maintenance of the cardiac rhythm. Calcium ions (Ca2+) have a fundamental role in the coupling of cardiac myocyte excitation and contraction, yet mechanisms whereby intracellular Ca2+ may directly modulate Na channel function have yet to be identified. Here we show that calmodulin (CaM), a ubiquitous Ca2+-sensing protein, binds to the carboxy-terminal 'IQ' domain of the human cardiac Na channel (hH1) in a Ca2+-dependent manner. This binding interaction significantly enhances slow inactivation-a channel-gating process linked to life-threatening idiopathic ventricular arrhythmias. Mutations targeted to the IQ domain disrupted CaM binding and eliminated Ca2+/CaM-dependent slow inactivation, whereas the gating effects of Ca2+/CaM were restored by intracellular application of a peptide modelled after the IQ domain. A naturally occurring mutation (A1924T) in the IQ domain altered hH1 function in a manner characteristic of the Brugada arrhythmia syndrome, but at the same time inhibited slow inactivation induced by Ca2+/CaM, yielding a clinically benign (arrhythmia free) phenotype.     

Abnormal pattern detected in fragile-X patients by pulsed-field gel electrophoresis.

The fragile-X syndrome is the most frequent inherited form of mental retardation, with an incidence of 1 in 1,500 males. It is characterized by the presence of a fragile site at Xq27.3 induced in vitro by folate deprivation or by inhibitors of deoxynucleotide synthesis. Its mode of inheritance is unusual for an X-linked trait, with incomplete penetrance in both males and females. Some phenotypically normal males transmit the mutation to all their daughters who rarely express any symptoms, but penetrance is high in sons and daughters of these carrier women. Genetic and physical mapping of the Xq27-q28 region has confirmed that the disease locus is located at or very near the fragile site. Hypotheses proposed to account for the abnormalities in the inheritance of the disease include sequence rearrangements by meiotic recombination or a mutation that affects reactivation of an inactive X chromosome during differentiation of female germ cells. To detect such rearrangements, or methylation changes that may reflect a locally inactive X chromosome, we used pulsed-field gel analysis of DNA from fragile-X patients with probes close to the fragile-X locus. The probe Do33 (DXS465) detected abnormal patterns in fragile-X patients, but not in normal controls or in non-expressing male transmitters.     

The detection of structural deformation errors in attitude determination

In the determination of the attitude parameters from a multi-antenna GPS array, one of the major assumptions is that the body frame is rigid at all times. If this assumption is not true then the derived attitude parameters will be in error. It is well known that in airborne platforms the wings often experience some displacement during flight, especially during periods of initializing maneouvres, such as taking off, landing,and banking. Often it is at these points in time that it is most critical to have the most precise attitude parameters.There are a number of techniques available for the detection of modeling errors.The CUSUM algorithm has successfully been implemented in the past to detect small persistent changes. In this paper the authors investigate different methods of generating the residuals, to be tested by the CUSUM algorithm, in an effort to determine which technique is best suited for the detection of structural deformation of an airborne platform. The methods investigated include monitoring the mean of the residuals generated from the difference between the known body frame coordinates, and those calculated from the derived attitude parameters. The generated residuals are then passed to a CUSUM algorithm to detect any small persistent changes. An alternative method involves transforming the generated residuals into the frequency domain through the use of the Fast Fourier Transform. The CUSUM algorithm is then used to detect any frequency changes. The final technique investigated involves transforming the generated residuals using the Haar wavelet. The wavelet coefficients are then monitored by the CUSUM algorithm in order to detect any significant change to the rigidity of the body frame.Detecting structural deformation, and quantifying the degree of deformation, during flight will ensure that these effects can be removed from the system, thus ensuring the most precise and reliable attitude parameter solutions. This paper, through a series ofsimulations, will assess the effectiveness of the above mentioned techniques for detecting structural deformation effects on a GPS multi-antenna array. These principles are then tested with experimental data.     

Comparison of the effects of different isomers of bicuculline infused in the preoptic area on male rat sexual behavior

Summary Intracerebral infusion of (+) bicuculline methiodide, but not of its (–) isomer, in the preoptic area, stimulated masculine sexual behavior in rat as evidenced by a decrease in the number of intromissions preceding ejaculation and a shortening of the ejaculation latency and postejaculatory interval. Data suggest a role of the GABAergic system in mediating masculine sexual behavior.Acknowledgments. Authors wish to thank Ms Elisabeth Wallin for excellent technical assistance and Ms Madelene Kröning for preparing the figures.     

Quantum Mechanics and Operational Probability Theory

We discuss a generalization of the standard notion of probability space and show that the emerging framework, to be called operational probability theory, can be considered as underlying quantal theories. The proposed framework makes special reference to the convex structure of states and to a family of observables which is wider than the familiar set of random variables: it appears as an alternative to the known algebraic approach to quantum probability.     

Comparative study of the karyotypes of two Egyptian species of bats,Taphozous perforatus andTaphozous nudiventris (Chiroptera: Mammalia)

A detailed karyotypic analysis of two Egyptian species of bats,Taphozous perforatus andTaphozous nudiventris, was made on the basis of conventional data and G-band patterns. No detectable karyotypic difference was found between the two species (2n=42, F.N. 64). By comparison of G-band patterns, some differences between the two species were seen in the corresponding autosomal pairs. These results are reported for the first time in Egypt.     

Nras loss induces metastatic conversion of Rb1-deficient neuroendocrine thyroid tumor

Mutations in the gene encoding the retinoblastoma tumor suppressor predispose humans and mice to tumor development. Here we have assessed the effect of Nras loss on tumor development in Rb1 heterozygous mice. Loss of one or two Nras alleles is shown to significantly reduce the severity of pituitary tumors arising in Rb1(+/-) animals by enhancing their differentiation. By contrast, C-cell thyroid adenomas occurring in Rb1(+/-) mice progress to metastatic medullary carcinomas after loss of Nras. In Rb1(+/-)Nras(+/-) animals, distant medullary thyroid carcinoma metastases are associated with loss of the remaining wild-type Nras allele. Loss of Nras in Rb1-deficient C cells results in elevated Ras homolog family A (RhoA) activity, and this is causally linked to the invasiveness and metastatic behavior of these cells. These findings suggest that the loss of the proto-oncogene Nras in certain cellular contexts can promote malignant tumor progression.     

新世纪图书馆员社会角色转换研究综述

就近几年图书馆界关于新世纪馆员意识转换及社会角色转换等方面的研究进行了综述，指出新时期的馆员要实现自我社会角色的转换，首先是要明确转换的必要性，然后采取有效的策略逐步地、系统地推进转换，才能取得较好的效果。     

The behavior of the homozygous and heterozygous sub-types of rats which are genetically-selected for diabetes insipidus: A comparison with Long Evans and Wistar stocks

Several aspects of spontaneous and conditioned behavior (food and water intake, locomotion and emotionality, passive and active avoidance acquisition and retention) of standard (albino and pigmented) rats, and rats heterozygous (HEDI) and homozygous (HODI) for diabetes insipidus, are reviewed. As would be expected, HODI rats have been repeatedly found to consume far more fluid than either HEDI or control rats. Pigmented rats appear to be more active than albinos. HODI rats exhibit less marked emotional responses than do control rats, among which the pigmented ones exhibit the highest emotionality. Light aversion is more evident in albino than in pigmented rats. No differences are found among HEDI, HODI and normal Long Evans rats. It is quite difficult to provide a clear-cut statement concerning inter-strain differences in passive avoidance behavior, possibly because of the variety of techniques employed. In any case, HODI rats do not perform worse than normal controls do. In one-way active avoidance paradigms, pigmented rats perform better than albinos, and the performance of HODI rats does not differ from that of controls. In two-way avoidance paradigms, albinos appear to outperform pigmented rats. Once again, there are no obvious differences between HODI and control animals.In addition to indicating that HODI rats may actually be less emotional than the other groups of rats reviewed here, the studies described once again fail to confirm the previously alleged functions of vasopressin in memory consolidation.