Differential modes of nuclear localization signal (NLS) recognition by three distinct classes of NLS receptors

The targeting of karyophilic proteins to nuclear pores is mediated via the formation of a nuclear pore-targeting complex, through the interaction of nuclear localization signal (NLS) with its NLS receptor. Recently, a novel human protein, Qip1, was identified from a yeast two-hybrid system with DNA helicase Q1. This study demonstrates that Qip1 is a novel third class of NLS receptor that efficiently recognizes the NLS of the helicase Q1. Moreover, the data obtained in this study show that the specific interaction between Qip1 and the NLS of the helicase Q1 requires its upstream sequence of the minimal essential NLS. By using purified recombinant proteins alone in the digitonin-permeabilized cell-free transport system, it was demonstrated that the two known human NLS receptors, Rch1 and NPI-1, are able to transport all the tested NLS substrates into the nucleus, while Qip1 most efficiently transports the helicase Q1-NLS substrates, which contain its upstream sequence in so far as we have examined the system. Furthermore, in HeLa cell crude cytosol, it was found that endogenous Rch1 binds to all the tested NLS substrates, while the binding of endogenous NPI-1 is restricted to only some NLSs, despite the fact that NPI-1 itself shows binding activity to a variety of NLSs. These results indicate that at least three structurally and functionally distinct NLS receptors exist in the human single cell population, and suggest that the nuclear import of karyophilic proteins may be controlled in a complex manner at the NLS recognition step by the existence of a variety of NLS receptors with various specificities to each NLS.     

Excessive closure of the right eye: a new sign of infarction in the territory of the ipsilateral right middle cerebral artery

In right middle cerebral territory infarction a new sign, excessive closure of the right eye ipsilateral to the lesion and mild closure of the left eye on command, was noted. The excessive ipsilateral eye closure was not observed on spontaneous eye closure.     

Correlates and prognosis in relation to intellectual dysfunction in a community-residing elderly population

To estimate the risk factors for intellectual dysfunction and examine its prognosis in a community-residing (non-institutionalized) elderly population, a randomly selected sample of 1,473 elderly people aged 65 years and over living in S city, Osaka Prefecture, was studied in October 1992, and data were obtained from 1,383, a response rate of 93.9%. A cohort of 1,383 was followed for 42 months and follow-up was completed for 1,300 (94.0%). The main results were as follows: 1) The prevalence of intellectual dysfunction did not differ significantly between sexes, and there was an increasing prevalence of intellectual dysfunction with age in both sexes. The prevalence of severe intellectual dysfunction was found to increase highly at age 85 and over. 2) By univariate analysis, odds ratios for age older than 75 years, low Activities of Daily Living (ADL), urinary and fecal incontinence, and no participation in social activities were significantly higher than 1 in any level of mild, moderate, and severe intellectual dysfunction. In the multivariate analysis using logistic regression, age older than 75 years and urinary and fecal incontinence showed significant higher odds ratios than 1 for severe intellectual dysfunction, and low ADL and treatment for hypertension also showed significant higher odds ratios than 1 for moderate intellectual dysfunction. 3) From analysis using the Kaplan-Meier method, the cumulative survival rates decreased with a decline in intellectual functioning in both age groups of 65-74 and 75 years and older. 4) Application of the Cox proportional hazards model resulted in adjusted hazard ratio for severe intellectual dysfunction of 1.79 (95% confidence interval, 1.02-3.12), controlling for other factors such as sex, age, general health status, incontinence and social activities.     

Interference of Mesoscopic Particles: Quantum–Classical Transition

We analyze the double slit interference of a mesoscopic particle. We calculate the visibility of the interference pattern in the far field case, introduce a characteristic temperature that defines the onset to decoherence and scrutinize the conditions that must be satisfied for an interference experiment to be possible.     

ILU factorization well suited to the vector processor using a variant of the 5-point difference scheme

The implementation on the vector processor of Incomplete LU factorization in the Preconditioned Conjugate Gradient method and other Preconditioned CG-like methods for the numerical solutions of the partial differential equations is discussed. For sufficient vectorization, a variant of the standard 5-point difference scheme for 2-dimensional problems is introduced. The convergence property of ILU factorization for this variant is examined in comparison with that vectorized with the usual hyperplane ordering method for the standard 5-point difference scheme on the vector processor. The efficiency and effectiveness of this factorization for the variant of the difference scheme is demonstrated through several computational experiments.     

Alteration of substrate specificity of cholesterol oxidase from Streptomyces sp. by site-directed mutagenesis

Despite the structural similarities between cholesterol oxidasefrom Streptomyces and that from Brevibacterium, both enzymesexhibit different characteristics, such as catalytic activity,optimum pH and temperature. In attempts to define the molecularbasis of differences in catalytic activity or stability, substitutionsat six amino acid residues were introduced into cholesteroloxidase using site-directed mutagenesis of its gene. The aminoacid substitutions chosen were based on structural comparisonsof cholesterol oxidases from Streptomyces and Brevibacterium.Seven mutant enzymes were constructed with the following aminoacid substitutions: L117P, L119A, L119F, V145Q, Q286R, P357Nand S379T. All the mutant enzymes exhibited activity with theexception of that with the L117P mutation. The resulting V145Qmutant enzyme has low activities for all substrates examinedand the S379T mutant enzyme showed markedly altered substratespecificity compared with the wild-type enzyme. To evaluatethe role of V145 and S379 residues in the reaction, mutantswith two additional substitutions in V145 and four in S379 wereconstructed. The mutant enzymes created by the replacement ofV145 by Asp and Glu had much lower catalytic efficiency forcholesterol and pregnenolone as substrates than the wild-typeenzyme. From previous studies and this study, the V145 residueseems to be important for the stability and substrate bindingof the cholesterol oxidase. In contrast, the catalytic efficiencies(k_cat/K_m) of the S379T mutant enzyme for cholesterol and pregnenolonewere 1.8- and 6.0-fold higher, respectively, than those of thewild-type enzyme. The enhanced catalytic efficiency of the S379Tmutant enzyme for pregnenolone was due to a slightly high k_catvalue and a low K_m value. These findings will provide severalideas for the design of more powerful enzymes that can be appliedto clinical determination of serum cholesterol levels and assterol probes.     

Photocatalytic Activity of a TiO<Subscript>2</Subscript> Photocatalyst Doped with C<Superscript>4+</Superscript> and S<Superscript>4+</Superscript> Ions Having a Rutile Phase Under Visible Light

C⁴⁺ and S⁴⁺-codoped titanium dioxide (TiO₂) having a rutile phase was prepared. By doping C⁴⁺ and S⁴⁺ ions into a TiO₂ lattice, the absorption edge of rutile TiO₂ powder was largely shifted from 400 to 700 nm. 2-Methylpyridine and methyleneblue were photocatalytically oxidized at high efficiency on C⁴⁺ and S⁴⁺-doped TiO₂ under visible light at a wavelength longer than 5 nm.     

Extended operation for T4 lung carcinoma

PURPOSE: The study objective was to determine an "optimal" individual pressure support (PS) level for beginning weaning with PS ventilation in patients with chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: Eleven COPD patients intubated and ventilated for acute respiratory failure and judged ready for weaning were studied. The technique consisted of lowering the PS level from a point that was characteristic for each patient and measurable under controlled mechanical ventilation, after setting the ventilator as recommended for COPD patients judged ready for weaning, that is, peak inflation pressure (PIP). This determination was based mainly on exploring the diaphragm with an electromyographic technique by defining the optimal PS level as the lowest PS level associated with no EMG evidence of diaphragmatic stress. Diaphragmatic electromyographic activity (diEMG) was recorded by a bipolar esophageal electrode (Disa-Denmark), and the high-frequency electrical component/low-frequency ratio (H/L) was calculated. The reference H/L was determined during a few spontaneous ventilatory cycles. Muscle stress was defined as a greater than 20% reduction in H/L compared with the reference value. RESULTS: Optimal PS levels ranged from 4 to 24 cm H2O with a mean of 14+/-6 cm H2O. Two patients with optimal PS level at 4 cm H2O did not require weaning and were quickly extubated. For the nine other patients, optimal PS levels were found to be 70% of PIP; in none was it necessary during weaning to use PS levels higher than individual optimal PS levels. CONCLUSIONS: Optimal PS level established with diEMG monitoring seems to be a useful index for beginning weaning in the PS ventilation mode in COPD patients. The hypothesis of beginning weaning with a PS level equal to 70% of PIP needs to be tested.     

Outdoor autonomous navigation using SURF features

In this article, we propose a speeded-up robust features (SURF)-based approach for outdoor autonomous navigation. In this approach, we capture environmental images using an omni-directional camera and extract features of these images using SURF. We treat these features as landmarks to estimate a robot’s self-location and direction of motion. SURF features are invariant under scale changes and rotation, and are robust under image noise, changes in light conditions, and changes of viewpoint. Therefore, SURF features are appropriate for the self-location estimation and navigation of a robot. The mobile robot navigation method consists of two modes, the teaching mode and the navigation mode. In the teaching mode, we teach a navigation course. In the navigation mode, the mobile robot navigates along the teaching course autonomously. In our experiment, the outdoor teaching course was about 150 m long, the average speed was 2.9 km/h, and the maximum trajectory error was 3.3 m. The processing time of SURF was several times shorter than that of scale-invariant feature transform (SIFT). Therefore, the navigation speed of the mobile robot was similar to the walking speed of a person.     

Effects of hematocrit variations on cerebral blood flow and oxygen transport in ischemic cerebrovascular disease

The contribution of hematocrit (Ht) changes on cerebral blood flow (CBF) and brain oxygenation in ischemic cerebrovascular disease is still controversial. In the present study, effects of Ht variations of CBF and oxygen delivery were investigated in patients with ischemic cerebrovascular disease. CBF was measured by the Xe-133 intracarotid injection method in 27 patients, whose diagnoses included completed stroke, reversible ischemic neurological deficit, and transient ischemic attack. Ht values in the patients ranged from 31 to 53%. There was a significant inverse correlation between CBF and Ht in these Ht ranges. Oxygen delivery, i.e., the product of arterial oxygen content and CBF, increased with Ht elevation and reached the maximum level in the Ht range of 40-45% and then declined. The CBF-Ht and oxygen transport-Ht relations observed in our study were similar to those in the glass-tube model studies by other workers rather than to those in intact animal experiments. From these results, it is conceivable that in ischemic cerebrovascular disease, the vasomotor adjustment was impaired in such a manner that the relations among Ht, CBF, and oxygen delivery were different from those in healthy subjects. Further, an "optimal hematocrit" for brain oxygenation was also discussed.