The effects of spacecraft environments on some hydrolytic enzyme patterns in bacteria

The effects of space flight on the production and characteristics of proteolytic enzymes are studied for a number of bacterial species isolated from crew members and spacecraft. Enzymatic make-up and cultural characteristics of bacteria isolated from spacecraft crew members are determined. The organism Aeromonas proteolytica and the proteolytic enzymes which it produces are used as models for future spacecraft experiments

Preregistration house officers in general practice: review of evidence

OBJECTIVES: To examine the strengths and weaknesses of the national and local schemes for preregistration house officers to spend four months in general practice, to identify any added value from such placements, and to examine the impact on career choices. DESIGN: Review of all studies that reported on placements of preregistration house officers in general practice. SETTING: 19 accounts of preregistration house officers’ experience in general practice, ranging from single case reports to a national evaluation study, in a variety of locations in Scotland and England. PARTICIPANTS: Views of 180 preregistration house officers, 45 general practitioner trainers, and 105 consultant trainers. MAIN OUTCOME MEASURES: Main findings or themes weighted according to number of studies reporting them and weighted for sample size. RESULTS: The studies were unanimous about the educational benefits of the placements. The additional learning included communication skills, social and psychological factors in illness, patient centred consultations, broadening of knowledge base, and dealing with uncertainty about diagnosis and referral. CONCLUSIONS: Despite the reported benefits and recommendations of the scheme, it is not expanding. General practitioner trainers reported additional supervision that was unremunerated. The reforms of the senior house officer grade may resolve this problem by offering the placements to senior house officers, who require less supervision

Vital prognosis after hospitalization for COPD: A study of a random population sample

AbstractStudy aim: To examine survival after admission due to chronic obstructive pulmonary disease (COPD) in a population sample over a time span of 15 years.Design: Linkage between a prospective population cohort and register information on hospitalization and mortality.Setting: The Copenhagen City Heart Study (CCHS).Participants: A total of 267 men and 220 women who had participated in the CCHS and who were hospitalized with a discharge diagnosis of COPD (ICD-8 491-2).Main results: The crude 5-yr survival rate after a COPD admission was 45% (37% for men and 52% for women). Mortality risk increased with age and with decreasing forced expiratory volume in 1 s (FEV1)% predicted; for subjects with an FEV1 ≤40% at the CCHS survey, 5-yr survival after subsequent hospitalization was only 28%. Smoking and presence of chronic mucus hypersecretion at the examination in CCHS were not strongly associated with prognosis. Survival after admission due to COPD did not change significantly over time.Conclusion: Compared to previous studies of COPD patients, the present study indicates that prognosis after hospital admission remains virtually unchanged over the last decades. FEV1 is still the strongest predictor of survival in this patient group

Measurement of the parity violating 6S-7S transition amplitude in cesium achieved within 2 \times 10^{-13} atomic-unit accuracy by stimulated-emission detection

We exploit the process of asymmetry amplification by stimulated emission which provides an original method for parity violation (PV) measurements in a highly forbidden atomic transition. The method involves measurements of a chiral, transient, optical gain of a cesium vapor on the 7S-6P_{3/2} transition, probed after it is excited by an intense, linearly polarized, collinear laser, tuned to resonance for one hyperfine line of the forbidden 6S-7S transition in a longitudinal electric field. We report here a 3.5 fold increase, of the one-second-measurement sensitivity, and subsequent reduction by a factor of 3.5 of the statistical accuracy compared with our previous result [J. Gu\'ena et al., Phys. Rev. Lett. 90, 143001 (2003)]. Decisive improvements to the set-up include an increased repetition rate, better extinction of the probe beam at the end of the probe pulse and, for the first time to our knowledge, the following: a polarization-tilt magnifier, quasi-suppression of beam reflections at the cell windows, and a Cs cell with electrically conductive windows. We also present real-time tests of systematic effects, consistency checks on the data, as well as a 1% accurate measurement of the electric field seen by the atoms, from atomic signals. PV measurements performed in seven different vapor cells agree within the statistical error. Our present result is compatible with the more precise Boulder result within our present relative statistical accuracy of 2.6%, corresponding to a 2 \times 10^{-13} atomic-unit uncertainty in E_1^{pv}. Theoretical motivations for further measurements are emphasized and we give a brief overview of a recent proposal that would allow the uncertainty to be reduced to the 0.1% level by creating conditions where asymmetry amplification is much greater.Comment: Article 21 pages, 6 figures, 3 tables Typos, addition of few comments and little more data (1 week) leading to a slight reduction of the error bar Accepted for publication in Phys.Rev.

The Buckland Park air shower array

The new Buckland Park Air Shower Array has been producing analyzed shower data since July 1984. The array is described and some preliminary performance figures are presented

Improving the economic value of photographic screening for optical coherence tomography-detectable macular oedema : a prospective, multicentre, UK study

Peer reviewedPublisher PD

Large Differences in Small RNA Composition Between Human Biofluids.

Extracellular microRNAs (miRNAs) and other small RNAs are implicated in cellular communication and may be useful as disease biomarkers. We systematically compared small RNAs in 12 human biofluid types using RNA sequencing (RNA-seq). miRNAs and tRNA-derived RNAs (tDRs) accounted for the majority of mapped reads in all biofluids, but the ratio of miRNA to tDR reads varied from 72 in plasma to 0.004 in bile. miRNA levels were highly correlated across all biofluids, but levels of some miRNAs differed markedly between biofluids. tDR populations differed extensively between biofluids. Y RNA fragments were seen in all biofluids and accounted for >10% of reads in blood plasma, serum, and cerebrospinal fluid (CSF). Reads mapping exclusively to Piwi-interacting RNAs (piRNAs) were very rare, except in seminal plasma. These results demonstrate extensive differences in small RNAs between human biofluids and provide a useful resource for investigating extracellular RNA biology and developing biomarkers

Cerebellum-based Adaptation for Fine Haptic Control over the Space of Uncertain Surfaces

This work aims to augment the capacities for haptic perception in the iCub robot to generate a controller for surface exploration. The main task involves moving the hand over an irregular surface with uncertain slope, by concurrently regulating the pressure of the contact. Providing this ability will enable the autonomous extraction of important haptic features, such as texture and shape. We propose a hand controller whose operational space is defined over the surface of contact. The surface is estimated using a robust probabilistic estimator, which is then used for path planning. The motor commands are generated using a feedback controller, taking advantage of the kinematic information available by proprioception. Finally, the effectiveness of this controller is extended using a cerebellar-like adapter that generates reliable pressure tracking over the finger and results in a trajectory with less vulnerability to perturbations. The results of this work are consistent with insights about the role of the cerebellum on haptic perception in humans

Characterization of VPS34-IN1, a selective inhibitor of Vps34, reveals that the phosphatidylinositol 3-phosphate-binding SGK3 protein kinase is a downstream target of class III phosphoinositide 3-kinase

The Vps34 (vacuolar protein sorting 34) class III PI3K (phosphoinositide 3-kinase) phosphorylates PtdIns (phosphatidylinositol) at endosomal membranes to generate PtdIns(3)P that regulates membrane trafficking processes via its ability to recruit a subset of proteins possessing PtdIns(3)P-binding PX (phox homology) and FYVE domains. In the present study, we describe a highly selective and potent inhibitor of Vps34, termed VPS34-IN1, that inhibits Vps34 with 25 nM ICin vitro, but does not significantly inhibit the activity of 340 protein kinases or 25 lipid kinases tested that include all isoforms of class I as well as class II PI3Ks. Administration of VPS34-IN1 to cells induces a rapid dose-dependent dispersal of a specific PtdIns(3)P-binding probe from endosome membranes, within 1 min, without affecting the ability of class I PI3K to regulate Akt. Moreover, we explored whether SGK3 (serum- and glucocorticoid-regulated kinase-3), the only protein kinase known to interact specifically with PtdIns(3)P via its N-terminal PX domain, might be controlled by Vps34. Mutations disrupting PtdIns(3)P binding ablated SGK3 kinase activity by suppressing phosphorylation of the T-loop [PDK1 (phosphoinositide-dependent kinase 1) site] and hydrophobic motif (mammalian target of rapamycin site) residues. VPS34-IN1 induced a rapid ~50-60% loss of SGK3 phosphorylation within 1 min. VPS34-IN1 did not inhibit activity of the SGK2 isoform that does not possess a PtdIns(3)P-binding PX domain. Furthermore, class I PI3K inhibitors (GDC-0941 and BKM120) that do not inhibit Vps34 suppressed SGK3 activity by ~40%. Combining VPS34-IN1 and GDC-0941 reduced SGK3 activity ~80-90%. These data suggest SGK3 phosphorylation and hence activity is controlled by two pools of PtdIns(3)P. The first is produced through phosphorylation of PtdIns by Vps34 at the endosome. The second is due to the conversion of class I PI3K product, PtdIns(3,4,5)P3 into PtdIns(3)P, via the sequential actions of the PtdIns 5-phosphatases [SHIP1/2 (Src homology 2-domain-containing inositol phosphatase 1/2)] and PtdIns 4-phosphatase [INPP4B (inositol polyphosphate 4-phosphatase type II)]. VPS34-IN1 will be a useful probe to delineate physiological roles of the Vps34. Monitoring SGK3 phosphorylation and activity could be employed as a biomarker of Vps34 activity, in an analogous manner by which Akt is used to probe cellular class I PI3K activity. Combining class I (GDC-0941) and class III (VPS34-IN1) PI3K inhibitors could be used as a strategy to better analyse the roles and regulation of the elusive class II PI3K