Discriminative learning of Bayesian networks via factorized conditional log-likelihood

We propose an efficient and parameter-free scoring criterion, the factorized conditional log-likelihood (ˆfCLL), for learning Bayesian network classifiers. The proposed score is an approximation of the conditional log-likelihood criterion. The approximation is devised in order to guarantee decomposability over the network structure, as well as efficient estimation of the optimal parameters, achieving the same time and space complexity as the traditional log-likelihood scoring criterion. The resulting criterion has an information-theoretic interpretation based on interaction information, which exhibits its discriminative nature. To evaluate the performance of the proposed criterion, we present an empirical comparison with state-of-the-art classifiers. Results on a large suite of benchmark data sets from the UCI repository show that ˆfCLL-trained classifiers achieve at least as good accuracy as the best compared classifiers, using significantly less computational resources.Peer reviewe

Hubble flow variance and the cosmic rest frame

We characterize the radial and angular variance of the Hubble flow in the COMPOSITE sample of 4534 galaxies, on scales in which much of the flow is in the nonlinear regime. With no cosmological assumptions other than the existence of a suitably averaged linear Hubble law, we find with decisive Bayesian evidence (ln B >> 5) that the Hubble constant averaged in independent spherical radial shells is closer to its asymptotic value when referred to the rest frame of the Local Group, rather than the standard rest frame of the Cosmic Microwave Background. An exception occurs for radial shells in the range 40/h-60/h Mpc. Angular averages reveal a dipole structure in the Hubble flow, whose amplitude changes markedly over the range 32/h-62/h Mpc. Whereas the LG frame dipole is initially constant and then decreases significantly, the CMB frame dipole initially decreases but then increases. The map of angular Hubble flow variation in the LG rest frame is found to coincide with that of the residual CMB temperature dipole, with correlation coefficient -0.92. These results are difficult to reconcile with the standard kinematic interpretation of the motion of the Local Group in response to the clustering dipole, but are consistent with a foreground non-kinematic anisotropy in the distance-redshift relation of 0.5% on scales up to 65/h Mpc. Effectively, the differential expansion of space produced by nearby nonlinear structures of local voids and denser walls and filaments cannot be reduced to a local boost. This hypothesis suggests a reinterpretation of bulk flows, which may potentially impact on calibration of supernovae distances, anomalies associated with large angles in the CMB anisotropy spectrum, and the dark flow inferred from the kinematic Sunyaev-Zel'dovich effect. It is consistent with recent studies that find evidence for a non-kinematic dipole in the distribution of distant radio sources.Comment: 37 pages, 9 tables, 13 figures; v2 adds extensive new analysis (including additional subsections, tables, figures); v3 adds a Monte Carlo analysis (with additional table, figure) which further tightens the statistical robustness of the dipole results; v4 adds further clarifications, small corrections, references and discussion of Planck satellite results; v5 typos fixed, matches published versio

Does antibacterial treatment for urinary tract infection contribute to the risk of breast cancer?

Low lignan status has been reported to be related to an elevated risk of breast cancer. Since lignan status is reduced by antibacterial medications, it is plausible to hypothesize that repeated use of antibiotics may also be a risk factor for breast cancer. History of treatment for urinary tract infection was studied for its prediction of breast cancer among 9461 Finnish women 19–89 years of age and initially cancer-free. During a follow-up in 1973–1991, a total of 157 breast cancer cases were diagnosed. Women reporting previous or present medication for urinary tract infection at baseline showed an elevated breast cancer risk in comparison with other women. The age-adjusted relative risk was 1.34 (95% confidence interval (CI) = 0.98–1.83). The association was concentrated to women under 50 years of age. The relative risk for these women was 1.74 (95% CI 1.13–2.68), whereas it was 0.97 (95% CI 0.59–1.58) for older women. The relative risk in the younger age-group was 1.47 (95% CI 0.73–2.97) during the first 10 years of follow-up, and 1.93 (95% CI 1.11–3.37) for follow-up times longer than 10 years. These data suggest that premenopausal women using long-term medication for urinary tract infections show a possible elevated risk of future breast cancer. The results are, however, still inconclusive and the hypothesis needs to be tested by other studies. © 2000 Cancer ResearchCampaig

Plasma etch characteristics of aluminum nitride mask layers grown by low-temperature plasma enhanced atomic layer deposition in SF6 based plasmas

The plasmaetch characteristics of aluminum nitride(AlN)deposited by low-temperature, 200 °C, plasma enhanced atomic layer deposition (PEALD) was investigated for reactive ion etch (RIE) and inductively coupled plasma-reactive ion etch (ICP-RIE) systems using various mixtures of SF6 and O2 under different etch conditions. During RIE, the film exhibits good mask properties with etch rates below 10r nm/min. For ICP-RIE processes, the film exhibits exceptionally low etch rates in the subnanometer region with lower platen power. The AlN film’s removal occurred through physical mechanisms; consequently, rf power and chamber pressure were the most significant parameters in PEALD AlN film removal because the film was inert to the SF+x and O+ chemistries. The etch experiments showed the film to be a resilient masking material. This makes it an attractive candidate for use as an etch mask in demanding SF6 based plasmaetch applications, such as through-wafer etching, or when oxide films are not suitable.Peer reviewe

Escherichia coli–expressed near full length HIV-1 envelope glycoprotein is a highly sensitive and specific diagnostic antigen

Background: The Human Immunodeficiency Virus type 1 (HIV-1) envelope glycoprotein gp160, useful in detecting anti-HIV-1 antibodies, is difficult to express in heterologous hosts. The major hurdles are its signal sequence, strong hydrophobic regions and heavy glycosylation. While it has not been possible to express full length recombinant (r)-gp160 in E. coli, it can be expressed in insect and mammalian cells, but at relatively higher cost. In this work, we report E. coli-based over-expression of r-gp160 variant and evaluate its performance in diagnostic immunoassays for the detection of anti-HIV-1 antibodies. Methods: A deletion variant of r-gp160 lacking hydrophobic regions of the parent full length molecule was expressed in E. coli and purified to near homogeneity using single-step Ni (II)-affinity chromatography. Biotinylated and europium (III) chelate-labeled versions of this antigen were used to set up one- and two-step time-resolved fluorometric double antigen sandwich assays. The performance of these assays was evaluated against a collection of well-characterized human sera (n = 131), that included an in-house panel and four commercially procured panels. Results: In-frame deletion of three hydrophobic regions, spanning amino acid residues 1–43, 519–538 and 676–706, of full length HIV-1 gp160 resulted in its expression in E. coli. Both the one- and two-step assays manifested high sensitivity unambiguously identifying 75/77 and 77/77 HIV-1 positive sera, respectively. Both assays also identified all 52 HIV-seronegative sera correctly. Between the two assays, the mean signal-to-cutoff value of the two-step assay was an order of magnitude greater than that of the one-step assay. Both assays were highly specific manifesting no cross-reactivity towards antibodies specific to other viruses like hepatitis B, C and human T cell leukemia viruses. Conclusions: This study has demonstrated the expression of r-gp160 variant in E. coli, by deletion of hydrophobic regions, and its purification in reasonable yields. This underscores the potential for cost saving in antigen production. Evaluation of this antigen in a double antigen sandwich two-step assay showed it to be a highly sensitive and specific HIV-1 diagnostic reagent. The amenability of this assay to the one-step format suggests its potential utility in developing a rapid point-of-care HIV-1 diagnostic test

Siderophores as an iron source for picocyanobacteria in deep chlorophyll maximum layers of the oligotrophic ocean

Prochlorococcus and Synechococcus are the most abundant photosynthesizing organisms in the oceans. Gene content variation among picocyanobacterial populations in separate ocean basins often mirrors the selective pressures imposed by the region's distinct biogeochemistry. By pairing genomic datasets with trace metal concentrations from across the global ocean, we show that the genomic capacity for siderophore-mediated iron uptake is widespread in Synechococcus and low-light adapted Prochlorococcus populations from deep chlorophyll maximum layers of iron-depleted regions of the oligotrophic Pacific and S. Atlantic oceans: Prochlorococcus siderophore consumers were absent in the N. Atlantic ocean (higher new iron flux) but constituted up to half of all Prochlorococcus genomes from metagenomes in the N. Pacific (lower new iron flux). Picocyanobacterial siderophore consumers, like many other bacteria with this trait, also lack siderophore biosynthesis genes indicating that they scavenge exogenous siderophores from seawater. Statistical modeling suggests that the capacity for siderophore uptake is endemic to remote ocean regions where atmospheric iron fluxes are the smallest, especially at deep chlorophyll maximum and primary nitrite maximum layers. We argue that abundant siderophore consumers at these two common oceanographic features could be a symptom of wider community iron stress, consistent with prior hypotheses. Our results provide a clear example of iron as a selective force driving the evolution of marine picocyanobacteria

Use of prescription benzodiazepines and related drugs in family caregivers : a nation-wide register-based study

Peer reviewe

Stapled truncated orexin peptides as orexin receptor agonists

The peptides orexin-A and -B, the endogenous agonists of the orexin receptors, have similar 19-amino-acid C-termini which retain full maximum response as truncated peptides with only marginally reduced potency, while further N-terminal truncations successively reduce the activity. The peptides have been suggested to bind in an α‐helical conformation, and truncation beyond a certain critical length is likely to disrupt the overall helical structure. In this study, we set out to stabilize the α‐helical conformation of orexin‐A15–33 via peptide stapling at four different sites. At a suggested hinge region, we varied the length of the cross-linker as well as replaced the staple with two α-aminoisobutyric acid residues. Modifications close to the peptide C‐terminus, which is crucial for activity, were not allowed. However, central and N‐terminal modifications yielded bioactive peptides, albeit with decreased potencies. This provides evidence that the orexin receptors can accommodate and be activated by α-helical peptides. The decrease in potency is likely linked to a stabilization of suboptimal peptide conformation or blocking of peptide backbone–receptor interactions at the hinge region by the helical stabilization or the modified amino acids.Peer reviewe

A prospective seroepidemiological study of human herpesvirus-8 infection and the risk of multiple myeloma

Presence of the Human Herpesvirus 8 (HHV8) genome has been reported in the bone marrow of multiple myeloma (MM) patients. So far, serological studies of HHV8 and MM have been inconsistent but have not included prospective epidemiological studies. We evaluated whether HHV8 infection is associated with increased risk for MM in a prospective population-based study of 39 000 Finnish subjects who donated serum samples in the period 1968–72. Serum samples from 47 subjects who developed MM during a 23-year follow-up and 224 age, area of residence and sex-matched subjects who remained healthy over a similar follow-up period were evaluated for HHV8 antibodies at enrolment, as assayed both with an immunofluorescence assay (IFA) for lytic and latent HHV8 antigens and by Western blot (WB) with three recombinant HHV8 proteins (ORFs 65, 73 and K8.1A). HHV8 seropositivity for at least one HHV8 protein on WB was found in 7% of the Finnish population and was not associated with the risk of developing MM (Relative Risk (RR) = 0.89, Confidence Interval (CI): 0.25–3.25). HHV8 seropositivity for lytic and latent antigens in the IFA was found in 16% and 0.4% of the Finnish population and tended to associate with risk of MM (RR = 2.02, CI: 0.94–4.33 and RR = 10.00, CI: 0.91–110.29, respectively). In conclusion, no statistically significant evidence for an association between HHV8 infection and the risk of future MM was found. © 2001 Cancer Research Campaign http://www.bjcancer.co