Broadening of the Derivative Discontinuity in Density Functional Theory

We clarify an important aspect of density functional theories, the broadening of the derivative discontinuity (DD) in a quantum system, with fluctuating particle number. Our focus is on a correlated model system, the single level quantum dot in the regime of the Coulomb blockade. We find that the DD-broadening is controlled by the small parameter $\Gamma/U$, where $\Gamma$ is the level broadening due to contacting and $U$ is a measure of the charging energy. Our analysis suggests, that Kondoesque fluctuations have a tendency to increase the DD-broadening, in our model by a factor of two.Comment: 4 pages, 2 figure

Bound States in Time-Dependent Quantum Transport: Oscillations and Memory Effects in Current and Density

The presence of bound states in a nanoscale electronic system attached to two biased, macroscopic electrodes is shown to give rise to persistent, non-decaying, localized current oscillations which can be much larger than the steady part of the current. The amplitude of these oscillations depends on the entire history of the applied potential. The bound-state contribution to the {\em static} density is history-dependent as well. Moreover, the time-dependent formulation leads to a natural definition of the bound-state occupations out of equilibrium.Comment: 4 pages, 3 figure

Highly Conducting pi-Conjugated Molecular Junctions Covalently Bonded to Gold Electrodes

We measure electronic conductance through single conjugated molecules bonded to Au metal electrodes with direct Au-C covalent bonds using the scanning tunneling microscope based break-junction technique. We start with molecules terminated with trimethyltin end groups that cleave off in situ resulting in formation of a direct covalent sigma bond between the carbon backbone and the gold metal electrodes. The molecular carbon backbone used in this study consist of a conjugated pi-system that has one terminal methylene group on each end, which bonds to the electrodes, achieving large electronic coupling of the electrodes to the pi-system. The junctions formed with the prototypical example of 1,4-dimethylenebenzene show a conductance approaching one conductance quantum (G0 = 2e2/h). Junctions formed with methylene terminated oligophenyls with two to four phenyl units show a hundred-fold increase in conductance compared with junctions formed with amine-linked oligophenyls. The conduction mechanism for these longer oligophenyls is tunneling as they exhibit an exponential dependence of conductance with oligomer length. In addition, density functional theory based calculations for the Au-xylylene-Au junction show near-resonant transmission with a cross-over to tunneling for the longer oligomers.Comment: Accepted to the Journal of the American Chemical Society as a Communication

Additive Anti-Tumor Effects of Lovastatin and Everolimus In Vitro through Simultaneous Inhibition of Signaling Pathways

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedThis work was supported by a research grant from the Ludwig-Maximilians University of Munich (Förderprogramm für Forschung und Lehre [FöFoLe], grant number 865/829)

Fatigue, reduced sleep quality and restless legs syndrome in Charcot-Marie-Tooth disease: a web-based survey

To investigate the prevalence of fatigue, daytime sleepiness, reduced sleep quality, and restless legs syndrome (RLS) in a large cohort of patients with Charcot-Marie-Tooth disease (CMT) and their impact on health-related quality of life (HRQoL). Participants of a web-based survey answered the Epworth Sleepiness Scale, the Pittsburgh Sleep Quality Index, the Multidimensional Fatigue Inventory, and, if the diagnostic criteria of RLS were met, the International RLS Severity Scale. Diagnosis of RLS was affirmed in screen-positive patients by means of a standardized telephone interview. HRQoL was assessed by using the SF-36 questionnaire. Age- and sex-matched control subjects were recruited from waiting relatives of surgical outpatients. 227 adult self-reported CMT patients answered the above questionnaires, 42.9% were male, and 57.1% were female. Age ranged from 18 to 78 years. Compared to controls (n = 234), CMT patients reported significantly higher fatigue, a higher extent and prevalence of daytime sleepiness and worse sleep quality. Prevalence of RLS was 18.1% in CMT patients and 5.6% in controls (p = 0.001). RLS severity was correlated with worse sleep quality and reduced HRQoL. Women with CMT were affected more often and more severely by RLS than male patients. With regard to fatigue, sleep quality, daytime sleepiness, RLS prevalence, RLS severity, and HRQoL, we did not find significant differences between genetically distinct subtypes of CMT. HRQoL is reduced in CMT patients which may be due to fatigue, sleep-related symptoms, and RLS in particular. Since causative treatment for CMT is not available, sleep-related symptoms should be recognized and treated in order to improve quality of life

A Q-methodology study of flare help-seeking behaviours and different experiences of daily life in rheumatoid arthritis

© 2014 Lin et al.; licensee BioMed Central Ltd. Background: Previous studies have not addressed rheumatoid arthritis (RA) patients' help-seeking behaviours for RA flares, and only one small qualitative study has addressed how patients experience daily life on current treatment regimes. Thus, this study aims to identify clusters of opinion related to RA patients' experiences of daily life on current treatments, and their help-seeking behaviours for RA flares. Methods: Using Q-methodology (a methodology using qualitative and quantitative methods to sort people according to subjective experience), two separate studies were conducted with the same sample of RA patients (mean age 55, 73% female). Thirty participants sorted 39 statements about daily life (Q-study 1) and 29 participants separately sorted 23 statements about flare help-seeking (Q-study 2). Data were examined using Q-factor analysis. Results: Daily life with RA (Q-study 1): Three factors relating to the experience of living with RA were extracted and explained. Patients belonging to Factor A (mean age 62, 86% female) use effective self-management techniques to control the daily impact of RA. Those in Factor B (mean age 55, 75% male) struggle to self-manage and cope. Whilst patients in Factor C (mean age 42, 100% female) prioritise life responsibilities over their RA, reporting less impact. Flare help-seeking (Q-study 2): Two factors explaining the experience of flare help-seeking (unrelated to the factors from Q-study 1) were extracted and explained. Factor X (68.8% on biologics) reported seeking help quickly, believing the medical team is there to help. Factor Y (0% on biologics) delay help-seeking, concerned about wasting the rheumatologist's time, believing they should manage alone. All participants agreed they sought help due to intense pain and persistent, unmanageable symptoms. Conclusions: Patients with different characteristics appear to manage RA life in different ways and men may struggle more than women. Whilst all patients are prompted to seek help by persistent, unmanageable symptoms, some delay help-seeking. Further research is needed to quantify the severity of daily symptoms, the level of symptoms needed for patients to define themselves as in flare and to understand the support needs of RA men

Knowledge transfer & exchange through social networks: building foundations for a community of practice within tobacco control

BACKGROUND: Health services and population health innovations advance when knowledge transfer and exchange (KTE) occurs among researchers, practitioners, policy-makers and consumers using high-quality evidence. However, few KTE models have been evaluated in practice. Communities of practice (CoP) – voluntary, self-organizing, and focused groups of individuals and organizations – may provide one option. This paper outlines an approach to lay the foundation for a CoP within the area of Web-assisted tobacco interventions (WATI). The objectives of the study were to provide a data-driven foundation to inform decisions about organizing a CoP within the geographically diverse, multi-disciplinary WATI group using evaluation and social network methodologies. METHODS: A single-group design was employed using a survey of expectations, knowledge, and interpersonal WATI-related relationships administered prior to a meeting of the WATI group followed by a 3-week post-meeting Web survey to assess short-term impact on learning and networking outcomes. RESULTS: Twenty-three of 27 WATI attendees (85%) from diverse disciplinary and practice backgrounds completed the baseline survey, with 21 (91%) of those participants completing the three-week follow-up. Participants had modest expectations of the meeting at baseline. A social network map produced from the data illustrated a centralized, yet sparse network comprising of interdisciplinary teams with little trans-sectoral collaboration. Three-week follow-up survey results showed that participants had made new network connections and had actively engaged in KTE activities with WATI members outside their original network. CONCLUSION: Data illustrating both the shape and size of the WATI network as well as member's interests and commitment to KTE, when shared and used to frame action steps, can positively influence the motivation to collaborate and create communities of practice. Guiding KTE planning through blending data and theory can create more informed transdisciplinary and trans-sectoral collaboration environments

Association between lifestyle factors and headache

Modification of lifestyle habits is a key preventive strategy for many diseases. The role of lifestyle for the onset of headache in general and for specific headache types, such as migraine and tension-type headache (TTH), has been discussed for many years. Most results, however, were inconsistent and data on the association between lifestyle factors and probable headache forms are completely lacking. We evaluated the cross-sectional association between different lifestyle factors and headache subtypes using data from three different German cohorts. Information was assessed by standardized face-to-face interviews. Lifestyle factors included alcohol consumption, smoking status, physical activity and body mass index. According to the 2004 diagnostic criteria, we distinguished the following headache types: migraine, TTH and their probable forms. Regional variations of lifestyle factors were observed. In the age- and gender-adjusted logistic regression models, none of the lifestyle factors was statistically significant associated with migraine, TTH, and their probable headache forms. In addition, we found no association between headache subtypes and the health index representing the sum of individual lifestyle factors. The lifestyle factors such as alcohol consumption, smoking, physical activity and overweight seem to be unrelated to migraine and TTH prevalence. For a judgement on their role in the onset of new or first attacks of migraine or TTH (incident cases), prospective cohort studies are required

Essential Roles of BCCIP in Mouse Embryonic Development and Structural Stability of Chromosomes

BCCIP is a BRCA2- and CDKN1A(p21)-interacting protein that has been implicated in the maintenance of genomic integrity. To understand the in vivo functions of BCCIP, we generated a conditional BCCIP knockdown transgenic mouse model using Cre-LoxP mediated RNA interference. The BCCIP knockdown embryos displayed impaired cellular proliferation and apoptosis at day E7.5. Consistent with these results, the in vitro proliferation of blastocysts and mouse embryonic fibroblasts (MEFs) of BCCIP knockdown mice were impaired considerably. The BCCIP deficient mouse embryos die before E11.5 day. Deletion of the p53 gene could not rescue the embryonic lethality due to BCCIP deficiency, but partially rescues the growth delay of mouse embryonic fibroblasts in vitro. To further understand the cause of development and proliferation defects in BCCIP-deficient mice, MEFs were subjected to chromosome stability analysis. The BCCIP-deficient MEFs displayed significant spontaneous chromosome structural alterations associated with replication stress, including a 3.5-fold induction of chromatid breaks. Remarkably, the BCCIP-deficient MEFs had a ∼20-fold increase in sister chromatid union (SCU), yet the induction of sister chromatid exchanges (SCE) was modestly at 1.5 fold. SCU is a unique type of chromatid aberration that may give rise to chromatin bridges between daughter nuclei in anaphase. In addition, the BCCIP-deficient MEFs have reduced repair of irradiation-induced DNA damage and reductions of Rad51 protein and nuclear foci. Our data suggest a unique function of BCCIP, not only in repair of DNA damage, but also in resolving stalled replication forks and prevention of replication stress. In addition, BCCIP deficiency causes excessive spontaneous chromatin bridges via the formation of SCU, which can subsequently impair chromosome segregations in mitosis and cell division

Sterol Intermediates of Cholesterol Biosynthesis Inhibit Hair Growth and Trigger an Innate Immune Response in Cicatricial Alopecia

Primary cicatricial alopecia (PCA) is a group of inflammatory hair disorders that cause scarring and permanent hair loss. Previous studies have implicated PPARγ, a transcription factor that integrates lipogenic and inflammatory signals, in the pathogenesis of PCA. However, it is unknown what triggers the inflammatory response in these disorders, whether the inflammation is a primary or secondary event in disease pathogenesis, and whether the inflammatory reaction reflects an autoimmune process. In this paper, we show that the cholesterol biosynthetic pathway is impaired in the skin and hair follicles of PCA patients. Treatment of hair follicle cells with BM15766, a cholesterol biosynthesis inhibitor, or 7-dehydrocholesterol (7-DHC), a sterol precursor, stimulates the expression of pro-inflammatory chemokine genes. Painting of mouse skin with 7-DHC or BM15766 inhibits hair growth, causes follicular plugging and induces the infiltration of inflammatory cells into the interfollicular dermis. Our results demonstrate that cholesterologenic changes within hair follicle cells trigger an innate immune response that is associated with the induction of toll-like receptor (TLR) and interferon (IFN) gene expression, and the recruitment of macrophages that surround the hair follicles and initiate their destruction. These findings reveal a previously unsuspected role for cholesterol precursors in PCA pathogenesis and identify a novel link between sterols and inflammation that may prove transformative in the diagnosis and treatment of these disorders