Supernova SN 2011fe from an exploding carbon-oxygen white dwarf star.

Type Ia supernovae have been used empirically as 'standard candles' to demonstrate the acceleration of the expansion of the Universe even though fundamental details, such as the nature of their progenitor systems and how the stars explode, remain a mystery. There is consensus that a white dwarf star explodes after accreting matter in a binary system, but the secondary body could be anything from a main-sequence star to a red giant, or even another white dwarf. This uncertainty stems from the fact that no recent type Ia supernova has been discovered close enough to Earth to detect the stars before explosion. Here we report early observations of supernova SN 2011fe in the galaxy M101 at a distance from Earth of 6.4 megaparsecs. We find that the exploding star was probably a carbon-oxygen white dwarf, and from the lack of an early shock we conclude that the companion was probably a main-sequence star. Early spectroscopy shows high-velocity oxygen that slows rapidly, on a timescale of hours, and extensive mixing of newly synthesized intermediate-mass elements in the outermost layers of the supernova. A companion paper uses pre-explosion images to rule out luminous red giants and most helium stars as companions to the progenitor.

The properties of ribosomal proteins from a moderate halophile.

The ribosomes from the extreme halophile Halobacterium cutirubrum are unusual in that their ribosomal proteins are acidic rather than basic as is the case with almost all bacterial ribosomes (Bayley, S.T. (1966) J. Mol. Biol. 15, 420-427). To determine whether the ribosomes of a moderate halophile show similar properties the ribosomal proteins from an unidentified moderate halophile, which grows over a wide range of NaCl concentrations (0.04-4.3 M), were compared to those of Escherichia coli and H. cutirubrum. The proteins are slightly more acidic than those of E. coli but much less acidic than those from the extreme halophile as judged by their mobility on polyacrylamide gels and their amino acid composition. The electrophoretic profile on polyacrylamide gels of the ribosomal proteins from the moderate halophile is similar whether the cells are grown in 0.5 M or 4.25 M NaCl.

The N-terminal sequence of the ribosomal 'A' protein from two moderate halophiles, Vibrio costicola and an unidentified moderate (NRCC 11227).

The 'A' protein, equivalent to ribosomal protein EL7/L12 from Escherichia coli, has been isolated and purified from two moderate halophiles Vibrio costicola and NRCC 11227. The 'A' protein from V. costicola contained an N-terminal serine and separated into two forms on DEAE-cellulose and two-dimensional electrophoresis while the equivalent protein in NRCC 11227 contained an N-terminal alanine residue and was present in only one form. The amino acid composition and mobility on two-dimensional gels indicated these proteins were very similar to EL7/L12. The first 38 residues of the 'A' proteins were sequenced and compared to the equivalent protein from E. coli and the extreme halophile Halobacterium cutirubrum. The N-terminal region of the 'A' protein from both moderate halophiles showed substantial homology to EL 12 (75--80%) but no evidence of any homology to the equivalent protein from the extreme halophile. The ribosomal proteins equivalent to ES1A in E. coli were also isolated and their amino acid compositions determined.

Cefepine vs. ceftazidime treatment of pyelonephritis: a European, randomized, controlled study of 300 pediatric cases. European Society for Paediatric Infectious Diseases (ESPID) Pyelonephritis Study Group.

BACKGROUND: Cefepime has been used in clinical therapeutic trials for meningitis, serious infection and febrile neutropenia, comprising more than 800 pediatric patients. This agent has also been used in patients 12 years of age and older with uncomplicated and complicated urinary tract infections including pyelonephritis, but not in younger patients. In this study the safety and efficacy of cefepime were compared with those of ceftazidime for treatment of pyelonephritis in pediatric patients younger than 12 years of age. METHODS: Two hundred ninety-nine pediatric patients (ages 1 month to 12 years) with pyelonephritis (300 episodes) were enrolled in a randomized, open label, multicenter trial. Individual results were evaluated by a blinded committee of experts. Cefepime was compared with ceftazidime, both administered parenterally at 50 mg/kg every 8 h. Patients were to receive the assigned study drug until at least 48 h after becoming afebrile. The i.v. treatment was then to be continued or replaced by oral trimethoprimsulfamethoxazole for a maximum of 12 to 14 days. RESULTS: The predominant causative pathogens were Escherichia coli, 88%; Proteus spp., 6%; Pseudomonas aeruginosa, 2%; and Klebsiella spp., 2%. Bacteriologic eradication was achieved in 96 and 94% of cefepime and ceftazidime patients, respectively, at the end of i.v. study drug treatment and was maintained in 94 and 91%, respectively, at the end of total study therapy. After study therapy bacteriologic eradication was maintained after 4 to 6 weeks in 86% of cefepime cases and in 83% of ceftazidime cases. A satisfactory clinical response occurred in 98 and 96% of cefepime and ceftazidime patients, respectively, at the end of i.v. treatment and in 93% at the end of total study therapy in both treatment arms. Drug-related clinical adverse events occurred in 14 cefepime patients (91%) and in 10 ceftazidime patients (7%). CONCLUSIONS: Cefepime and ceftazidime are equally safe and efficacious treatment for pyelonephritis in pediatric patients.

Recognition of the colicin A N-terminal epitope 1C11 in vitro and in vivo in Escherichia coli by its cognate monoclonal antibody.

We demonstrate that the 1C10 monoclonal antibody (mAb) directed against the N-terminal domain of the colicin A recognizes a 13 residue-region (13Thr-Gly-Trp-Ser-Ser-Glu-Arg-Gly-Ser-Gly-Pro- Asp-Pro25). When this peptide is inserted into a protein in the amino-terminal or an internal position, the tagged protein is efficiently detected by the 1C11 mAb either by immunoblotting or immunoprecipitation. In vitro, the minimal structure required for detection using the pepscan system is 19Arg-Gly-Ser-Gly-Pro-Glu-Pro25, indicating that in vivo the proper exposure of the epitope requires additional residues. The construction of a versatile vector allowing overproduction of tagged proteins is described. Various applications of the 1C11 epitope are mentioned. This epitope did not alter the function of any of the proteins so far tested.

A cortical-spinal prosthesis for targeted limb movement in paralysed primate avatars.

Motor paralysis is among the most disabling aspects of injury to the central nervous system. Here we develop and test a target-based cortical-spinal neural prosthesis that employs neural activity recorded from premotor neurons to control limb movements in functionally paralysed primate avatars. Given the complexity by which muscle contractions are naturally controlled, we approach the problem of eliciting goal-directed limb movement in paralysed animals by focusing on the intended targets of movement rather than their intermediate trajectories. We then match this information in real-time with spinal cord and muscle stimulation parameters that produce free planar limb movements to those intended target locations. We demonstrate that both the decoded activities of premotor populations and their adaptive responses can be used, after brief training, to effectively direct an avatar's limb to distinct targets variably displayed on a screen. These findings advance the future possibility of reconstituting targeted limb movement in paralysed subjects.

A real-time brain-machine interface combining motor target and trajectory intent using an optimal feedback control design.

Real-time brain-machine interfaces (BMI) have focused on either estimating the continuous movement trajectory or target intent. However, natural movement often incorporates both. Additionally, BMIs can be modeled as a feedback control system in which the subject modulates the neural activity to move the prosthetic device towards a desired target while receiving real-time sensory feedback of the state of the movement. We develop a novel real-time BMI using an optimal feedback control design that jointly estimates the movement target and trajectory of monkeys in two stages. First, the target is decoded from neural spiking activity before movement initiation. Second, the trajectory is decoded by combining the decoded target with the peri-movement spiking activity using an optimal feedback control design. This design exploits a recursive Bayesian decoder that uses an optimal feedback control model of the sensorimotor system to take into account the intended target location and the sensory feedback in its trajectory estimation from spiking activity. The real-time BMI processes the spiking activity directly using point process modeling. We implement the BMI in experiments consisting of an instructed-delay center-out task in which monkeys are presented with a target location on the screen during a delay period and then have to move a cursor to it without touching the incorrect targets. We show that the two-stage BMI performs more accurately than either stage alone. Correct target prediction can compensate for inaccurate trajectory estimation and vice versa. The optimal feedback control design also results in trajectories that are smoother and have lower estimation error. The two-stage decoder also performs better than linear regression approaches in offline cross-validation analyses. Our results demonstrate the advantage of a BMI design that jointly estimates the target and trajectory of movement and more closely mimics the sensorimotor control system.

Neural population partitioning and a concurrent brain-machine interface for sequential motor function.

Although brain-machine interfaces (BMIs) have focused largely on performing single-targeted movements, many natural tasks involve planning a complete sequence of such movements before execution. For these tasks, a BMI that can concurrently decode the full planned sequence before its execution may also consider the higher-level goal of the task to reformulate and perform it more effectively. Using population-wide modeling, we discovered two distinct subpopulations of neurons in the rhesus monkey premotor cortex that allow two planned targets of a sequential movement to be simultaneously held in working memory without degradation. Such marked stability occurred because each subpopulation encoded either only currently held or only newly added target information irrespective of the exact sequence. On the basis of these findings, we developed a BMI that concurrently decodes a full motor sequence in advance of movement and can then accurately execute it as desired.

An unusually fast-evolving supernova.

Analyses of supernovae (SNe) have revealed two main types of progenitors: exploding white dwarfs and collapsing massive stars. Here we describe SN 2002bj, which stands out as different from any SN reported to date. Its light curve rose and declined very rapidly, yet reached a peak intrinsic brightness greater than -18 magnitude. A spectrum obtained 7 days after discovery shows the presence of helium and intermediate-mass elements, yet no clear hydrogen or iron-peak elements. The spectrum only barely resembles that of a type Ia SN, with added carbon and helium. Its properties suggest that SN 2002bj may be representative of a class of progenitors that previously has been only hypothesized: a helium detonation on a white dwarf, ejecting a small envelope of material. New surveys should find many such objects, despite their scarcity.

Personal development planning.

Since the introduction of general management into the NHS in 1985, greater emphasis has been placed on managing the service through clearly defined objectives. Jill Sandford and Christine Rollin describe Lifespan Healthcare's personal development plan for managers, and report on some of the benefits it has brought the organisation.

The 5-S RNA binding protein from yeast (Saccharomyces cerevisiae) ribosomes. Evolution of the eukaryotic 5-S RNA binding protein.

The ribonucleoprotein complex between 5-S RNA and its binding protein (5-S RNA . protein complex) of yeast ribosomes was released from 60-S subunits with 25 mM EDTA and the protein component was purified by chromatography on DEAE-cellulose. This protein, designated YL3 (Mr = 36000 on dodecylsulfate gels), was relatively insoluble in neutral solutions (pH 4--9) and migrated as one of four acidic 60-S subunit proteins when analyzed by the Kaltschmidt and Wittman two-dimensional gel system. Amino acid analyses indicated lower amounts of lysine and arginine than most ribosomal proteins. Sequence homology was observed in the N terminus of YL3, and two prokaryotic 5-S RNA binding proteins, EL18 from Escherichia coli and HL13 from Halobacterium cutirubrum: Ala1-Phe2-Gln3-Lys4-Asp5-Ala6-Lys7-Ser8-Ser9-Ala10-Tyr11-Ser12-Ser13-Arg14-Phe15-Gln16-Tyr17-Pro18-Phe19-Arg20-Arg21-Arg22-Arg23-Glu24-Gly25-Lys26-Thr27-Asp28-Tyr29-Tyr35; of particular interest was homology in the cluster of basic residues (18--23). Since the protein contained one methionine residue it could be split into two fragments, CN1 (Mr = 24700) and CN2 (Mr = 11300) by CNBr treatment; the larger fragment originated from the N terminus. The N-terminal amino acid sequence of CN2 shared a limited sequence homology with an internal portion of a second 5-S RNA binding protein from E. coli, EL5, and, based also on the molecular weights of the proteins and studies on the protein binding sites in 5-S RNAs, a model for the evolution of the eukaryotic 5-S RNA binding protein is suggested in which a fusion of the prokaryotic sequences may have occurred. Unlike the native 5-S RNA . protein complex, a variety of RNAs interacted with the smaller CN2 fragment to form homogeneous ribonucleoprotein complexes; the results suggest that the CN1 fragment may confer specificity on the natural 5-S RNA-protein interaction.

Sex differences result in increased morbidity from hyponatremia in female rats.

The development of symptomatic hyponatremia in otherwise healthy young women can result in death or permanent brain damage. The reasons for the increased female susceptibility to complications from hyponatremia are, however, unclear. To determine whether mechanisms that normally defend the brain against damage from hyponatremia are less effective in females than males, we studied both sodium transport in the brains of hyponatremic male and female rats and the effects of parenteral arginine vasopressin on brain high-energy phosphate metabolism and intracellular pH. Basal sodium uptake in synaptosomes prepared from whole brain of females (2.20 nmol/mg protein) and males (2.98 nmol/mg protein) was not statistically different. In contrast, veratridine-stimulated sodium uptake in female brain was 8.20 nmol/mg protein, which was 86% greater (P less than 0.001) than the 6.12 nmol/mg protein observed for male brain. Additionally, sodium uptake between 5 and 60 s was significantly (P less than 0.001) greater in females than males. These data suggest that the Na+-K+-adenosinetriphosphatase (ATPase) pump function in female rat brain synaptosomes is less effective than in males. To determine whether arginine vasopressin, a peptide hormone that promotes water retention by the kidney, had any effects on cerebral energy metabolism, we performed phosphorus-31 (31P) magnetic resonance spectroscopy (MRS) studies on the brain of normonatremic young adult male and female rats subjected to high (20 IU) peripheral doses of arginine vasopressin. We found decreased high-energy phosphate generation, elevated inorganic phosphate, and intracellular acidosis after arginine vasopressin administration in females but not males.(ABSTRACT TRUNCATED AT 250 WORDS)

Osmoregulation of vasopressin secretion and thirst during the estrous cycle of pigs.

The influence of the reproductive cycle on ingestive behaviors, osmotically induced fluid intake, and peripheral blood levels of several hormones involved in fluid electrolyte balance was investigated in young adult female pigs. Food, water, and salt intakes and plasma aldosterone levels were significantly lower during estrus compared with the luteal and follicular phases, whereas plasma sodium (PNa) was higher. Plasma renin activity and lysine vasopressin (LVP) levels did not vary with the cycle. Regression analyses of the relationship between plasma LVP and PNa in unanesthetized, unstressed animals infused for 2 h with intravenous 5% NaCl revealed no significant differences in terms of the osmotic threshold and sensitivity of LVP release at different stages of the reproductive cycle. In contrast, when osmotic loading was carried out with continuous access to water, the osmotic threshold for drinking was found to be significantly higher and the rate of drinking lower during estrus. The results indicate that in the adult female pig the stage of the reproductive cycle has an influence on ingestive behaviors and the osmoregulation of thirst. Osmoregulation of vasopressin secretion, on the other hand, appears to be independent of the estrous cycle in this species.

Nicardipine reduces ischemic brain injury. Magnetic resonance imaging/spectroscopy study in cats.

We investigated whether the calcium channel entry blocker nicardipine would reduce ischemic brain damage in barbiturate-anesthetized cats subjected to permanent unilateral occlusion of the middle cerebral artery. The evolution of cerebral injury was assessed in vivo in 24 cats by a combination of proton magnetic resonance imaging and phosphorus-31 magnetic resonance spectroscopy for 5 hours following occlusion. Immediately thereafter, the volume of histochemically ischemic brain tissue was determined planimetrically in triphenyl tetrazolium chloride-stained serial coronal sections. Nicardipine was initially administered as an intravenous bolus injection of 10 mg/kg/hr 15 minutes before or 15 minutes after occlusion, followed by continuous infusion at 8 mg/kg/hr for the 5 hours of the experiment. Compared with untreated controls, cats that received nicardipine before or after occlusion showed a significant reduction in the extent of edema in the ipsilateral cerebral cortex, internal capsule, and basal ganglia. The results of phosphorus-31 magnetic resonance spectroscopy studies suggest that nicardipine may protect against cerebral ischemic damage by an action on cellular metabolic processes that preserve high-energy phosphates during the ischemic period.

13C-NMR studies of Corynebacterium melassecola metabolic pathways.

Coryneform bacteria are widely used to produce amino acids, in particularly glutamic acid, by fermentation. To study the metabolic fate of glucose as the carbon source, we developed a method to analyze intracellular extracts by NMR and HPLC. The intracellular metabolites represent the metabolic state of the cells. Glutamic acid was the major metabolic intermediate found in the extracts and its 13C isotopic enrichment reflected that of pyruvic acid. Thus, it was possible to determine the respective contributions of the two major glucose catabolic pathways during the exponential growth phase; glycolysis (55%) and the pentose phosphate pathway (45%). Absolute glutamate 13C enrichments resulting from the incorporation of [1-13C]glucose were determined to quantify the contribution of several metabolic pathways such as anaplerotic pathways (61%; phosphoenolpyruvate carboxylase, pyruvate carboxylase, malic enzyme), a single turn (32%) or multiple turns of the Krebs cycle and the glyoxylate shunt, to oxaloacetate synthesis. A previously described model was adapted to C. melassecola for these calculations. The Krebs cycle was active, whereas the glyoxylate shunt was inactive in exponentially growing cells of C. melassecola with glucose as the sole carbon source. The contributions of anaplerotic enzymes and pyruvate dehydrogenase to replenishing the Krebs' cycle were determined to be 38% and 62%, respectively.

A fungal cellulase shows sequence homology with the active site of hen egg-white lysozyme.

The N-terminal amino acid sequence of an endo-beta-1,4-glucanase from the cellulase complex of the white-rot fungus Schizophyllum commune has been determined. The sequence from Glu-33 to Tyr-51 was homologous with the active site sequences of various hen egg-white type lysozymes, including lysozyme catalytic residues (Glu-35, Asp-52) and substrate binding residue Asn-44. The homology offers evidence for a lysozyme-type mechanism in enzymic hydrolysis of cellulose.

The 5S RNA binding protein from yeast (Saccharomyces cerevisiae) ribosomes. An RNA binding sequence in the carboxyl-terminal region.

The carboxyl-terminal half (CN2 fragment) of the yeast 5S RNA binding protein (YL3) retains an ability to form homogeneous ribonucleoprotein complexes with RNA although the N-terminal half (CN1) appears to confer specificity for the 5S RNA molecule [Nazar, R.N., Yaguchi, M., Willick, G.E., Rollin, C.F. and Roy, C. (1979) Eur. J. Biochem. 102, 573-582]. The nucleic acid binding site in this fragment was more clearly delineated by cleaving the CN2 fragment with a variety of enzymatic and chemical reagents and further examining the ability of the products to form RNA-peptide complexes. Hot acetic acid treatment produced a 47-residue subfragment (CN2-A1) which originated from the C terminus and continued to form stable ribonucleopeptide complexes. The amino acid sequence of this subfragment was determined to be: -Pro-Ala-Phe-Lys-Pro-Thr-Glu-Lys50-Phe-Thr-Lys-Glu-Gln-Tyr-Ala-Ala -Glu60-Ser-Ly s -Lys-Tyr-Arg-Gln-Thr-Lys-Leu-Ser70-Lys-Gln-Gln-Arg-Ala-Ala-Arg-Val -Ala-Ala80-Ly s -Ile-Ala-Ala-Leu-Ala-Gly-Gln-Gln-COOH, with 12 of the 16 basic residues in the CN2 fragment being present in this binding site. The amino acid sequence of the CN2-A1 fragment bears a limited homology in both amino acid and charge distribution with histone 2B from mammals and with one of the 5S RNA binding proteins (EL25) from Escherichia coli. The results suggest that many protein binding sites for nucleic acids may share common structural features and further support the notion that the single large eukaryotic 5S RNA protein may have evolved through a fusion of genes for the multiple 5S RNA binding proteins in prokaryotes.

Purification, properties, and N-terminal amino acid sequence of certain 50S ribosomal subunit proteins from the archaebacterium Halobacterium cutirubrum.

Sixteen ribosomal proteins (r-proteins) from the 50S ribosomal subunit of the archaebacterium Halobacterium cutirubrum have been purified and their amino acid composition and partial N-terminal amino acid sequence have been determined. These proteins as a group are much more acidic than the large subunit r-proteins from eubacteria or eukaryotes. Little sequence homology is evident between the 50S subunit archaebacterial r-proteins and the equivalent proteins from the eubacterium Escherichia coli.

Comparative efficacy and safety of cefprozil and amoxycillin/clavulanate in the treatment of acute otitis media in children.

Cefprozil is a new oral cephalosporin with activity against the most common pathogens isolated in acute otitis media. This randomized study enrolled 361 patients (mean age 29 months). Physical examination and culture via tympanocentesis were required less than 48 h before therapy. One hundred and ninety-one patients were evaluable for clinical efficacy; 99 received cefprozil (20 mg/kg/day bd) and 92 received amoxycillin/clavulanate (13.3 mg/kg/day tid). Duration of treatment was 7-9 days for 81 patients, 10 days for 105 patients and 11-16 days for five patients. The treatment groups were comparable with respect to demographics, severity of infection and number of previous episodes. Clinical evaluations of efficacy were based on physical examination including otoscopy within a 14 day period after therapy. Satisfactory clinical responses were achieved in 84% of cefprozil-treated patients and 87% of amoxycillin/clavulanate-treated patients. Pathogens most commonly isolated included Haemophilus influenzae (33%) and Streptococcus pneumoniae (22%). All 361 patients were evaluable for safety. Adverse clinical events were reported in 13% (24) of cefprozil-treated patients and 20% (36) of amoxycillin/clavulanate-treated patients. Cefprozil, administered twice a day, is comparable to a regimen of amoxycillin/clavulanate three times a day in the treatment of acute otitis media in children.

Comparison of the immune response elicited by a free peptide and a lipopeptide construct.

Among the synthetic peptides derived from the 28-kDa Schistosoma mansoni gluthatione-S-transferase (Sm28GST), the C-terminal peptide, comprising amino acid residues 190 to 211, represents a major T-cell epitope in both infected humans and Sm28GST-immunized mice. The aim of this study was to determine the nature of the immune response induced by the 190-211 peptide coupled to a fatty acid (lipopeptide construction) in comparison to the free form. We explored B- and T-cell responses elicited by these two peptidic constructions in three different mouse strains (BALB/c, CBA/N and C57B1/6). For all strains, the addition of a lipid chain to the 190-211 peptide greatly modified its immunogenicity. The lipopeptide, compared to the free form, induced a greatly reduced antibody response against the peptide, whereas the production of messenger for cytokines was greatly increased after immunization with the lipopeptide. Immunization with peptide led mainly to a Th1-type cytokine profile following antigenic restimulation in vitro, while lipopeptide, in general, induced a mixed profile, and that occurred most significantly with the production of messengers for the protective cytokines IFN-gamma and IL-2, even without antigenic restimulations. This modification of immunogenicity of a peptide by the addition of a lipid chain could be of value in the development of efficient peptide vaccines.