Adult attachment style across individuals and role-relationships: Avoidance is relationship-specific, but anxiety shows greater generalizability

A generalisability study examined the hypotheses that avoidant attachment, reflecting the representation of others, should be more relationship-specific (vary across relationships more than across individuals), while attachment anxiety, reflecting self-representation, should be more generalisable across a person’s relationships. College students responded to 6-item questionnaire measures of these variables for 5 relationships (mother, father, best same-gender friend, romantic partner or best opposite-gender friend, other close person), on 3 (N = 120) or 2 (N = 77) occasions separated by a few weeks. Results supported the hypotheses, with the person variance component being larger than the relationship-specific component for anxiety, and the opposite happening for avoidance. Anxiety therefore seems not to be as relationship-specific as previous research suggested. Possible reasons for discrepancies between the current and previous studies are discussed

Iκbα gene transfer is cytotoxic to squamous-cell lung cancer cells and sensitizes them to tumor necrosis factor-α-mediated cell death

Current paradigms in cancer therapy suggest that activation of nuclear factor-κB (NF-κB) by a variety of stimuli, including some cytoreductive agents, may inhibit apoptosis. Thus, inhibiting NF-κB activation may sensitize cells to anticancer therapy, thereby providing a more effective treatment for certain cancers. E-1-deleted adenoviral (Ad) vectors encoding a "superrepressor" form of the NF-κB inhibitor IκBα (AdIκBαSR) or β-galactosidase (AdLacZ) were tested alone and in combination with tumor necrosis factor-α (TNF-α) in lung cancer cells for sensitization of the cells to death. Following transduction with AdIκBαSR, lung cancer cells expressed IκBαSR in a dose-dependent manner. Probing nuclear extracts of lung cancer cells with NF-κB-sequence-specific oligonucleotides indicated that there was a minimal amount of NF-κB in the nucleus at baseline and an expected and dramatic increase in nuclear NF-κB following exposure of cells to TNF-α. Control E-1-deleted AdLacZ did not promote NF-κB activation. Importantly, AdIκBαSR-mediated gene transfer resulted in the complete block of nuclear translocation of NF-κB by specific binding of its p65/relA component with transgenic IκBαSR. At the cellular level, transduction with AdIκBαSR resulted in increased cytotoxicity in lung cancer cells as opposed to transduction with equivalent doses of AdLacZ. In addition, whereas the parental cells were resistant to TNF-α-mediated cytotoxicity, IκBαSR-transduced cells could be sensitized to TNF-α. Consequently, AdIκBαSR transduction followed by exposure to TNF-α uniformly resulted in the death of non-small-cell lung cancer cells. These data suggest that novel approaches incorporating IκBα gene therapy may have a role in the treatment of lung cancer

The development of executive function and language skills in the early school years

Background: The developmental relationships between executive functions (EF) and early language skills are unclear. This study explores the longitudinal relationships between children's early EF and language skills in a sample of children with a wide range of language abilities including children at risk of dyslexia. In addition, we investigated whether these skills independently predict children's attention/behaviour skills. Method: Data are presented from 243 children at four time points. Children were selected for being at risk of reading difficulties either because of a family history of dyslexia (FR; N = 90) or because of concerns regarding their language development (LI; N = 79) or as typically developing controls (TD; N = 74). The children completed tasks to assess their executive function and language skills at ages 4, 5 and 6 years. At 6 (T4) and 7 years (T5) parents and teachers rated the children's attention/behaviour skills. Results: There was a strong concurrent relationship between language and EF at each assessment. Longitudinal analyses indicated a considerable degree of stability in children's language and EF skills: the influence of language on later EF skills (and vice versa) was weak and not significant in the current sample. Children's EF, but not language, skills at T3 predicted attention/behaviour ratings at T4/T5. Conclusions: There is a strong concurrent association between language and EF skills during the preschool and early school years, when children with language impairment show persistent EF deficits. Latent variables measuring language and EF show high longitudinal stability with little evidence of significant or strong reciprocal influences between these constructs. EF, but not language, skills predict later ratings of children's attention and behaviour

Early phonological and sociocognitive skills as predictors of later language and social communication outcomes

Background:  Previous studies of outcome for children with early language delay have focused on measures of early language as predictors of language outcome. This study investigates whether very early processing skills (VEPS) known to underpin language development will be better predictors of specific language and social communication outcomes than measures of language itself. Method:  Participants were 163 children referred to clinical services with concerns about language at 2;6–3;6 years and followed up at 4–5 years. Novel assessments of phonological and sociocognitive processing were administered at Time 1 (T1), together with a standardised test of receptive and expressive language, and parental report of expressive vocabulary. The language test was re-administered at Time 2 (T2), together with assessments of morphosyntax and parental reports of social communication. Results:  Intercorrelations at and between T1 and T2 were high, and dissociations were rare. Ordinal regressions were run, entering predictors singly and simultaneously. With the exception of the phonological task, every early measure on its own was significantly predictive of most outcomes, and receptive language was the strongest all-round predictor. Results of simultaneous entry, controlling for the effect of other predictors, showed that early language was the strongest predictor of general language outcome, but early phonology was the strongest predictor of a measure of morphosyntax, and early sociocognition the strongest predictor of social communication. Conclusions:  Language measures which draw on a wide range of skills were the strongest overall predictors of general language outcomes. However, our VEPS measures were stronger predictors of specific outcomes. The clinical and theoretical implications of these findings are discussed

Physical model for the gating mechanism of ionic channels

We propose a physical model for the gating mechanism of ionic channels. First, we investigate the fluctuation-mediated interactions between two proteins imbedded in a cellular membrane and find that the interaction depends on their orientational configuration as well as the distance between them. The orientational dependence of interactions arises from the fact that the noncircular cross-sectional shapes of individual proteins constrain fluctuations of the membrane differently according to their orientational configuration. Then, we apply these interactions to ionic channels composed of four, five, and six proteins. As the gating stimulus creates the changes in the structural shape of proteins composing ionic channels, the orientational configuration of the ionic channels changes due to the free energy minimization, and ionic channels are open or closed according to the conformation thereof.open3

Negative Energy and Angular Momentum Modes of Thin Accretion Disks

This work derives the linearized equations of motion, the Lagrangian density, the Hamiltonian density, and the canonical angular momentum density for general perturbations [$\propto \exp(im\phi)$ with $m=0,\pm 1,..$] of a geometrically thin self-gravitating, homentropic fluid disk including the pressure. The theory is applied to ``eccentric,'' $m=\pm 1$ perturbations of a geometrically thin Keplerian disk. We find $m=1$ modes at low frequencies relative to the Keplerian frequency. Further, it shown that these modes can have negative energy and negative angular momentum. The radial propagation of these low frequency $m=1$ modes can transport angular momentum away from the inner region of a disk and thus increase the rate of mass accretion. Depending on the radial boundary conditions there can be discrete low-frequency, negative-energy, $m=1$ modes.Comment: 24 pages, 8 figure

HI in the Outskirts of Nearby Galaxies

The HI in disk galaxies frequently extends beyond the optical image, and can trace the dark matter there. I briefly highlight the history of high spatial resolution HI imaging, the contribution it made to the dark matter problem, and the current tension between several dynamical methods to break the disk-halo degeneracy. I then turn to the flaring problem, which could in principle probe the shape of the dark halo. Instead, however, a lot of attention is now devoted to understanding the role of gas accretion via galactic fountains. The current $\rm \Lambda$ cold dark matter theory has problems on galactic scales, such as the core-cusp problem, which can be addressed with HI observations of dwarf galaxies. For a similar range in rotation velocities, galaxies of type Sd have thin disks, while those of type Im are much thicker. After a few comments on modified Newtonian dynamics and on irregular galaxies, I close with statistics on the HI extent of galaxies.Comment: 38 pages, 17 figures, invited review, book chapter in "Outskirts of Galaxies", Eds. J. H. Knapen, J. C. Lee and A. Gil de Paz, Astrophysics and Space Science Library, Springer, in pres

Low-dose thiamine supplementation of lactating Cambodian mothers improves human milk thiamine concentrations: a randomized controlled trial

Background Infantile beriberi-related mortality is still common in South and Southeast Asia. Interventions to increase maternal thiamine intakes, and thus human milk thiamine, are warranted; however, the required dose remains unknown. Objectives We sought to estimate the dose at which additional maternal intake of oral thiamine no longer meaningfully increased milk thiamine concentrations in infants at 24 wk postpartum, and to investigate the impact of 4 thiamine supplementation doses on milk and blood thiamine status biomarkers. Methods In this double-blind, 4-parallel arm randomized controlled dose-response trial, healthy mothers were recruited in Kampong Thom, Cambodia. At 2 wk postpartum, women were randomly assigned to consume 1 capsule, containing 0, 1.2 (estimated average requirement), 2.4, or 10 mg of thiamine daily from 2 through 24 weeks postpartum. Human milk total thiamine concentrations were measured using HPLC. An Emax curve was plotted, which was estimated using a nonlinear least squares model in an intention-to-treat analysis. Linear mixed-effects models were used to test for differences between treatment groups. Maternal and infant blood thiamine biomarkers were also assessed. Results In total, each of 335 women was randomly assigned to1 of the following thiamine-dose groups: placebo (n = 83), 1.2 mg (n = 86), 2.4 mg (n = 81), and 10 mg (n = 85). The estimated dose required to reach 90% of the maximum average total thiamine concentration in human milk (191 µg/L) is 2.35 (95% CI: 0.58, 7.01) mg/d. The mean ± SD milk thiamine concentrations were significantly higher in all intervention groups (183 ± 91, 190 ± 105, and 206 ± 89 µg/L for 1.2, 2.4, and 10 mg, respectively) compared with the placebo group (153 ± 85 µg/L; P < 0.0001) and did not significantly differ from each other. Conclusions A supplemental thiamine dose of 2.35 mg/d was required to achieve a milk total thiamine concentration of 191 µg/L. However, 1.2 mg/d for 22 wk was sufficient to increase milk thiamine concentrations to similar levels achieved by higher supplementation doses (2.4 and 10 mg/d), and comparable to those of healthy mothers in regions without beriberi. This trial was registered at clinicaltrials.gov as NCT03616288.Jelisa Gallant, Kathleen Chan, Tim J Green, Frank T Wieringa, Shalem Leemaqz, Rem Ngik ... et al