Cluster analysis and display of genome-wide expression patterns

A system of cluster analysis for genome-wide expression data from DNA microarray hybridization is described that uses standard statistical algorithms to arrange genes according to similarity in pattern of gene expression. The output is displayed graphically, conveying the clustering and the underlying expression data simultaneously in a form intuitive for biologists. We have found in the budding yeast Saccharomyces cerevisiae that clustering gene expression data groups together efficiently genes of known similar function, and we find a similar tendency in human data. Thus patterns seen in genome-wide expression experiments can be interpreted as indications of the status of cellular processes. Also, coexpression of genes of known function with poorly characterized or novel genes may provide a simple means of gaining leads to the functions of many genes for which information is not available currently.     

Improved outcome after severe head injury with a new therapy based on principles for brain volume regulation and preserved microcirculation

OBJECTIVE: To assess the new "Lund therapy" of posttraumatic brain edema, based on principles for brain-volume regulation and improved microcirculation. DESIGN: A prospective, nonrandomized outcome study over a 5-yr period on severely head-injured patients with increased intracranial pressure, comparing the results with a historical control group with the same selection criteria for patients who were treated according to conventional principles. SETTING: General intensive care unit of a university hospital. PATIENTS: Fifty-three consecutive head-injured patients with a Glasgow Coma Score of <8, and with increased intracranial pressure (>25 mm Hg), despite conventional treatment. INTERVENTIONS: Interstitial fluid resorption was obtained by lowering intracapillary hydrostatic pressure, by preserving normal colloid osmotic pressure, and by maintaining a normovolemic (normal albumin/serum and hemoglobin/serum), not overtransfused patient. Intracapillary pressure was reduced by the combination of precapillary vasoconstriction (low-dose thiopental, dihydroergotamine) and reduction of mean arterial pressure, the latter attained with a beta1-antagonist (metoprolol 0.2 to 0.3 mg/kg/24 hrs iv) and an alpha2-agonist (clonidine 0.4 to 0.8 microg/kg x 4 to 6 iv). Clonidine, in combination with normovolemia, also improves microcirculation by reducing catecholamines in plasma. Intracranial blood volume was reduced by arterial (low-dose thiopental sodium and dihydroergotamine) and large-vein (dihydroergotamine) vasoconstriction. The start dose of dihydroergotamine (maximum 0.9 microg/kg/hr) was successively reduced toward discontinuation within 4 to 5 days. MEASUREMENTS AND MAIN RESULTS: There were 8% of patients who died and the neurologic conditions of 13% remained severely damaged, compared with 47% and 11%, respectively, for the control group. CONCLUSIONS: The low mortality compared with previous outcome studies strongly indicates that this therapy improves outcome for severe head injuries. However, a randomized, controlled study is needed to reach general acceptance of this new therapy.     

Gene transfer to the central nervous system by transplantation of cerebral endothelial cells

I recorded the electric organ discharges (EODs) of 331 immature Brachyhypopomus pinnicaudatus 6-88 mm long. Larvae produced head-positive pulses 1.3 ms long at 7 mm (6 days) and added a second, small head-negative phase at 12 mm. Both phases shortened duration and increased amplitude during growth. Relative to the whole EOD, the negative phase increased duration until 22 mm and amplitude until 37 mm. Fish above 37 mm produced a "symmetric" EOD like that of adult females. I stained cleared fish with Sudan black, or fluorescently labeled serial sections with anti-desmin (electric organ) or anti-myosin (muscle). From day 6 onward, a single electric organ was found at the ventral margin of the hypaxial muscle. Electrocytes were initially cylindrical, overlapping, and stalk-less, but later shortened along the rostrocaudal axis, separated into rows, and formed caudal stalks. This differentiation started in the posterior electric organ in 12-mm fish and was complete in the anterior region of fish with "symmetric" EODs. The lack of a distinct "larval" electric organ in this pulse-type species weakens the hypothesis that all gymnotiforms develop both a temporary (larval) and a permanent (adult) electric organ.     

When the severely ill elderly patient refuses food. Ethical reasoning among nurses

Forty registered nurses (RNs) regarded as "good and experienced" in either cancer or dementia care, were asked about their decision to feed or not feed a severely ill elderly woman (a hypothetical case). In order to compare ethical reasoning in the two groups of nurses and to illuminate what it means to RNs to face a situation where the patients can/cannot decide for themselves, a phenomenological hermeneutic approach was used for the analysis. Both groups saw themselves as the advocate for their patients but in different ways. The RNs who talked about a mentally alert patient emphasized that they encouraged their patient to speak up for herself, while the RNs who talked about a severely demented patient emphasized that they tried very hard to interpret their patient's vague and unclear communicative cues and to act as her advocate, especially in relation to physicians. Transcending experiences of dying relatives and patients as well as role models helped them to achieve their ambition of putting themselves in the patient's shoes in order to respect and understand her or his wish and/or what was best for them. The majority of RNs strongly rejected active euthanasia.     

美国电池市场小考

通过对1994年1—5月间美国从世界各地进口各种一次电池、二次电池总贸易额的分析,结合近年来对美国日本电池工业发展动向的观察,本文试图阐明中国电池出口美国应努力的目标。     

Crystal structure of dUTPase from equine infectious anaemia virus; active site metal binding in a substrate analogue complex

The X-ray structures of dUTPase from equine infectious anaemia virus (EIAV) in unliganded and complexed forms have been determined to 1.9 and 2.0 A resolution, respectively. The structures were solved by molecular replacement using Escherichia coli dUTPase as search model. The exploitation of a relatively novel refinement approach for the initial model, combining maximum likelihood refinement with stereochemically unrestrained updating of the model, proved to be of crucial importance and should be of general relevance.EIAV dUTPase is a homotrimer where each subunit folds into a twisted antiparallel beta-barrel with the N and C-terminal portions interacting with adjacent subunits. The C-terminal 14 and 17 amino acid residues are disordered in the crystal structure of the unliganded and complexed enzyme, respectively. Interactions along the 3-fold axis include a water-containing volume (size 207 A3) which has no contact with bulk solvent. It has earlier been shown that a divalent metal ion is essential for catalysis. For the first time, a putative binding site for such a metal ion, in this case Sr2+, is established. The positions of the inhibitor (the non-hydrolysable substrate analogue dUDP) and the metal ion in the complex are consistent with the location of the active centre established for trimeric dUTPase structures, in which subunit interfaces form three surface clefts lined with evolutionary conserved residues. However, a detailed comparison of the active sites of the EIAV and E. coli enzymes reveals some structural differences. The viral enzyme undergoes a small conformational change in the uracil-binding beta-hairpin structure upon dUDP binding not observed in the other known dUTPase structures.