On Resource-bounded versions of the van Lambalgen theorem

The van Lambalgen theorem is a surprising result in algorithmic information theory concerning the symmetry of relative randomness. It establishes that for any pair of infinite sequences $A$ and $B$, $B$ is Martin-L\"of random and $A$ is Martin-L\"of random relative to $B$ if and only if the interleaved sequence $A \uplus B$ is Martin-L\"of random. This implies that $A$ is relative random to $B$ if and only if $B$ is random relative to $A$ \cite{vanLambalgen}, \cite{Nies09}, \cite{HirschfeldtBook}. This paper studies the validity of this phenomenon for different notions of time-bounded relative randomness. We prove the classical van Lambalgen theorem using martingales and Kolmogorov compressibility. We establish the failure of relative randomness in these settings, for both time-bounded martingales and time-bounded Kolmogorov complexity. We adapt our classical proofs when applicable to the time-bounded setting, and construct counterexamples when they fail. The mode of failure of the theorem may depend on the notion of time-bounded randomness

A P-type ATPase importer that discriminates between essential and toxic transition metals

Transition metals, although being essential cofactors in many physiological processes, are toxic at elevated concentrations. Among the membrane-embedded transport proteins that maintain appropriate intracellular levels of transition metals are ATP-driven pumps belonging to the P-type ATPase superfamily. These metal transporters may be differentiated according to their substrate specificities, where the majority of pumps can extrude either silver and copper or zinc, cadmium, and lead. In the present report, we have established the substrate specificities of nine previously uncharacterized prokaryotic transition-metal P-type ATPases. We find that all of the newly identified exporters indeed fall into one of the two above-mentioned categories. In addition to these exporters, one importer, Pseudomonas aeruginosa Q9I147, was also identified. This protein, designated HmtA (heavy metal transporter A), exhibited a different substrate recognition profile from the exporters. In vivo metal susceptibility assays, intracellular metal measurements, and transport experiments all suggest that HmtA mediates the uptake of copper and zinc but not of silver, mercury, or cadmium. The substrate selectivity of this importer ensures the high-affinity uptake of essential metals, while avoiding intracellular contamination by their toxic counterparts

Identification of the Transcriptional Regulator NcrB in the Nickel Resistance Determinant of Leptospirillum ferriphilum UBK03

The nickel resistance determinant ncrABCY was identified in Leptospirillum ferriphilum UBK03. Within this operon, ncrA and ncrC encode two membrane proteins that form an efflux system, and ncrB encodes NcrB, which belongs to an uncharacterized family (DUF156) of proteins. How this determinant is regulated remains unknown. Our data indicate that expression of the nickel resistance determinant is induced by nickel. The promoter of ncrA, designated pncrA, was cloned into the promoter probe vector pPR9TT, and co-transformed with either a wild-type or mutant nickel resistance determinant. The results revealed that ncrB encoded a transcriptional regulator that could regulate the expression of ncrA, ncrB, and ncrC. A GC-rich inverted repeat sequence was identified in the promoter pncrA. Electrophoretic mobility shift assays (EMSAs) and footprinting assays showed that purified NcrB could specifically bind to the inverted repeat sequence of pncrA in vitro; this was confirmed by bacterial one-hybrid analysis. Moreover, this binding was inhibited in the presence of nickel ions. Thus, we classified NcrB as a transcriptional regulator that recognizes the inverted repeat sequence binding motif to regulate the expression of the key nickel resistance gene, ncrA

Effect evaluation of a two-year complex intervention to reduce loneliness in non-institutionalised elderly Dutch people

Background: Public health policy calls for intervention programmes to reduce loneliness in the ageing population. So far, numerous loneliness interventions have been developed, with effectiveness demonstrated for few of these interventions. The loneliness intervention described in this manuscript distinguishes itself from others by including multiple intervention components and targeting individuals and their environment. Intervention components included a mass media campaign, information meetings, psychosocial group courses, social activities organised by neighbours, and training of intermediaries. The aim of this manuscript is to study the effects of this integrated approach on initial and long-term outcomes. Methods: A quasi-experimental pre-test post-test intervention study was conducted among non-institutionalised elderly people aged 65 years and over to evaluate the effectiveness of the intervention by comparing the intervention community and the control community. Data on outputs, initial and long-term outcomes, and the overall goal were collected by self-administered questionnaires. Data of 858 elderly people were available for the analyses. To assess the effect linear regression analyses with adjustments for age, gender, church attendance, and mental health were used. In addition, the process evaluation provided information about the reach of the intervention components. Results: After two years, 39% of the elderly people were familiar with the intervention programme. The intervention group scored more favourably than the control group on three subscales of the initial outcome, motivation (-4.4%, 95% CI-8.3-0.7), perceived social support (-8.2%, 95% CI-13.6-2.4), and subjective norm (-11.5%, 95% CI-17.4-5.4). However, no overall effects were observed for the long-term outcome, social support, and overall goal, loneliness. Conclusions: Two years after its initiation the reach of the intervention programme was modest. Though no effect of the complex intervention was found on social support and loneliness, more favourable scores on loneliness literacy subscales were induced

Isomeric excitation energy for 99^{99}Inm^{m} from mass spectrometry reveals constant trend next to doubly magic 100^{100}Sn

The excitation energy of the 1/2$^-$ isomer in $^{99}$In at ${N=50}$ is measured to be 671(37) keV and the mass uncertainty of the 9/2$^+$ ground state is significantly reduced using the ISOLTRAP mass spectrometer at ISOLDE/CERN. The measurements exploit a major improvement in the resolution of the multi-reflection time-of-flight mass spectrometer. The results reveal an intriguing constancy of the $1/2^-$ isomer excitation energies in neutron-deficient indium that persists down to the $N = 50$ shell closure, even when all neutrons are removed from the valence shell. This trend is used to test large-scale shell model, \textit{ab initio}, and density functional theory calculations. The models have difficulties describing both the isomer excitation energies and ground-state electromagnetic moments along the indium chain.Comment: 13 pages, 4 figure

Cesium, iodine and tritium in NW Pacific waters - a comparison of the Fukushima impact with global fallout

Radionuclide impact of the Fukushima Dai-ichi nuclear power plant accident on the distribution of radionuclides in seawater of the NW Pacific Ocean is compared with global fallout from atmospheric tests of nuclear weapons. Surface and water column samples collected during the <i>Ka'imikai-o-Kanaloa</i> (<i>KOK</i>) international expedition carried out in June 2011 were analyzed for ¹³⁴Cs, ¹³⁷Cs, ¹²⁹I and ³H. The ¹³⁷Cs, ¹²⁹I and ³H levels in surface seawater offshore Fukushima varied between 0.002–3.5 Bq L⁻¹, 0.01–0.8 μBq L⁻¹, and 0.05–0.15 Bq L⁻¹, respectively. At the sampling site about 40 km from the coast, where all three radionuclides were analyzed, the Fukushima impact on the levels of these three radionuclides represents an increase above the global fallout background by factors of about 1000, 50 and 3, respectively. The water column data indicate that the transport of Fukushima-derived radionuclides downward to the depth of 300 m has already occurred. The observed ¹³⁷Cs levels in surface waters and in the water column are compared with predictions obtained from the ocean general circulation model, which indicates that the Kuroshio Current acts as a southern boundary for the transport of the radionuclides, which have been transported from the Fukushima coast eastward in the NW Pacific Ocean. The ¹³⁷Cs inventory in the water column is estimated to be about 2.2 PBq, what can be regarded as a lower limit of the direct liquid discharges into the sea as the seawater sampling was carried out only in the area from 34 to 37° N, and from 142 to 147° E. About 4.6 GBq of ¹²⁹I was deposited in the NW Pacific Ocean, and 2.4–7 GBq of ¹²⁹I was directly discharged as liquid wastes into the sea offshore Fukushima. The total amount of ³H released and deposited over the NW Pacific Ocean was estimated to be 0.1–0.5 PBq. These estimations depend, however, on the evaluation of the total ¹³⁷Cs activities released as liquid wastes directly into the sea, which should improve when more data are available. Due to a suitable residence time in the ocean, Fukushima-derived radionuclides will provide useful tracers for isotope oceanography studies on the transport of water masses during the next decades in the NW Pacific Ocean

Chronic non-specific low back pain - sub-groups or a single mechanism?

Copyright 2008 Wand and O'Connell; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Low back pain is a substantial health problem and has subsequently attracted a considerable amount of research. Clinical trials evaluating the efficacy of a variety of interventions for chronic non-specific low back pain indicate limited effectiveness for most commonly applied interventions and approaches. Discussion: Many clinicians challenge the results of clinical trials as they feel that this lack of effectiveness is at odds with their clinical experience of managing patients with back pain. A common explanation for this discrepancy is the perceived heterogeneity of patients with chronic non-specific low back pain. It is felt that the effects of treatment may be diluted by the application of a single intervention to a complex, heterogeneous group with diverse treatment needs. This argument presupposes that current treatment is effective when applied to the correct patient. An alternative perspective is that the clinical trials are correct and current treatments have limited efficacy. Preoccupation with sub-grouping may stifle engagement with this view and it is important that the sub-grouping paradigm is closely examined. This paper argues that there are numerous problems with the sub-grouping approach and that it may not be an important reason for the disappointing results of clinical trials. We propose instead that current treatment may be ineffective because it has been misdirected. Recent evidence that demonstrates changes within the brain in chronic low back pain sufferers raises the possibility that persistent back pain may be a problem of cortical reorganisation and degeneration. This perspective offers interesting insights into the chronic low back pain experience and suggests alternative models of intervention. Summary: The disappointing results of clinical research are commonly explained by the failure of researchers to adequately attend to sub-grouping of the chronic non-specific low back pain population. Alternatively, current approaches may be ineffective and clinicians and researchers may need to radically rethink the nature of the problem and how it should best be managed

Search for CP violation in D+→K−K+π+D^{+} \to K^{-}K^{+}\pi^{+} decays

A model-independent search for direct CP violation in the Cabibbo suppressed decay $D^+ \to K^- K^+\pi^+$ in a sample of approximately 370,000 decays is carried out. The data were collected by the LHCb experiment in 2010 and correspond to an integrated luminosity of 35 pb$^{-1}$. The normalized Dalitz plot distributions for $D^+$ and $D^-$ are compared using four different binning schemes that are sensitive to different manifestations of CP violation. No evidence for CP asymmetry is found.Comment: 13 pages, 8 figures, submitted to Phys. Rev.

Proton Pump Inhibitors Inhibit Metformin Uptake by Organic Cation Transporters (OCTs)

Metformin, an oral insulin-sensitizing drug, is actively transported into cells by organic cation transporters (OCT) 1, 2, and 3 (encoded by SLC22A1, SLC22A2, or SLC22A3), which are tissue specifically expressed at significant levels in various organs such as liver, muscle, and kidney. Because metformin does not undergo hepatic metabolism, drug-drug interaction by inhibition of OCT transporters may be important. So far, comprehensive data on the interaction of proton pump inhibitors (PPIs) with OCTs are missing although PPIs are frequently used in metformin-treated patients. Using in silico modeling and computational analyses, we derived pharmacophore models indicating that PPIs (i.e. omeprazole, pantoprazole, lansoprazole, rabeprazole, and tenatoprazole) are potent OCT inhibitors. We then established stably transfected cell lines expressing the human uptake transporters OCT1, OCT2, or OCT3 and tested whether these PPIs inhibit OCT-mediated metformin uptake in vitro. All tested PPIs significantly inhibited metformin uptake by OCT1, OCT2, and OCT3 in a concentration-dependent manner. Half-maximal inhibitory concentration values (IC50) were in the low micromolar range (3–36 µM) and thereby in the range of IC50 values of other potent OCT drug inhibitors. Finally, we tested whether the PPIs are also transported by OCTs, but did not identify PPIs as OCT substrates. In conclusion, PPIs are potent inhibitors of the OCT-mediated metformin transport in vitro. Further studies are needed to elucidate the clinical relevance of this drug-drug interaction with potential consequences on metformin disposition and/or efficacy

First observation of Bs -> D_{s2}^{*+} X mu nu decays

Using data collected with the LHCb detector in proton-proton collisions at a centre-of-mass energy of 7 TeV, the semileptonic decays Bs -> Ds+ X mu nu and Bs -> D0 K+ X mu nu are detected. Two structures are observed in the D0 K+ mass spectrum at masses consistent with the known D^+_{s1}(2536) and $D^{*+}_{s2}(2573) mesons. The measured branching fractions relative to the total Bs semileptonic rate are B(Bs -> D_{s2}^{*+} X mu nu)/B(Bs -> X mu nu)= (3.3\pm 1.0\pm 0.4)%, and B(Bs -> D_{s1}^+ X munu)/B(Bs -> X mu nu)= (5.4\pm 1.2\pm 0.5)%, where the first uncertainty is statistical and the second is systematic. This is the first observation of the D_{s2}^{*+} state in Bs decays; we also measure its mass and width.Comment: 8 pages 2 figures. Published in Physics Letters