1,484 research outputs found
Nodal dynamics, not degree distributions, determine the structural controllability of complex networks
Structural controllability has been proposed as an analytical framework for
making predictions regarding the control of complex networks across myriad
disciplines in the physical and life sciences (Liu et al.,
Nature:473(7346):167-173, 2011). Although the integration of control theory and
network analysis is important, we argue that the application of the structural
controllability framework to most if not all real-world networks leads to the
conclusion that a single control input, applied to the power dominating set
(PDS), is all that is needed for structural controllability. This result is
consistent with the well-known fact that controllability and its dual
observability are generic properties of systems. We argue that more important
than issues of structural controllability are the questions of whether a system
is almost uncontrollable, whether it is almost unobservable, and whether it
possesses almost pole-zero cancellations.Comment: 1 Figures, 6 page
The genetic contribution of the NO system at the glutamatergic post-synapse to schizophrenia : further evidence and meta-analysis
NO is a pleiotropic signaling molecule and has an important role in cognition and emotion. In the brain, NO is produced by neuronal nitric oxide synthase (NOS-I, encoded by NOS1) coupled to the NMDA receptor via PDZ. interactions; this protein-protein interaction is disrupted upon binding of NOS1 adapter protein (encoded by NOS1AP) to NOS-I. As both NOS1 and NOS1AP were associated with schizophrenia, we here investigated these genes in greater detail by genotyping new samples and conducting a meta-analysis of our own and published data. In doing so, we confirmed association of both genes with schizophrenia and found evidence for their interaction in increasing risk towards disease. Our strongest finding was the NOS1 promoter SNP rs41279104, yielding an odds ratio of 1.29 in the meta-analysis. As findings from heterologous cell systems have suggested that the risk allele decreases gene expression, we studied the effect of the variant on NOS1 expression in human post-mortem brain samples and found that the risk allele significantly decreases expression of NOS1 in the prefrontal cortex. Bioinformatic analyses suggest that this might be due the replacement of six transcription factor binding sites by two new binding sites as a consequence of proxy SNPs. Taken together, our data argue that genetic variance in NOS1 resulting in lower prefrontal brain expression of this gene contributes to schizophrenia liability, and that NOS1 interacts with NOS1AP in doing so. The NOS1-NOS1AP PDZ interface may thus well constitute a novel target for small molecules in at least some forms of schizophrenia. PostprintPeer reviewe
Understanding students’ motivation towards proactive career behaviours through goal-setting theory and the job demands–resources model
The graduate labour market is highly competitive but little is known about why students vary in their development of employability. This study contributes to the literature by applying goal-setting theory and the job demands–resources model to investigate how motivational processes influence students’ proactive career behaviours. We tested four hypotheses using structural equation modelling and moderation/mediation analysis using a nested model approach; 432 undergraduates from 21 UK universities participated in this cross-sectional study. The results showed that students higher in mastery approach had greater perceived employability mediated by two proactive career behaviours (skill development and network building). Students’ career goal commitment was associated with all four proactive career behaviours (career planning, skill development, career consultation and network building). Students’ academic and employment workloads did not negatively impact their proactive career behaviours. University tutors and career services should therefore encourage students to set challenging career goals that reflect mastery approach
Albumin-coupled methotrexate (MTX-HSA) is a new anti-arthritic drug which acts synergistically to MTX
Objective. To evaluate the anti-arthritic effects of the new inflammation-targeted drug MTX-HSA and to investigate whether peripheral blood mononuclear cells (PBMC) are potential target cells for albumin-mediated drug delivery. Methods. The murine model of collagen-induced arthritis (CIA) was used to measure the anti-arthritic effect of MTX, MTX-HSA or a combination of both (n = 30 to 35 per group). In addition, the uptake of fluorescence-labelled albumin (AFLc-HSA) in PBMC of 14 patients with RA was measured by fluorescence-activated cell sorting (FACS). Results. In equivalent doses of 7.5 mg/kg intravenously (IV) twice a week, MTX-HSA is significantly (P<0.02) superior to MTX in inhibiting the development of CIA and reducing the joint count as well as the number of affected paws. When given in lower doses as combination therapy, both drugs act synergistically (P<0.03). A mean of 96, 72 and 64% of the CD14-, CD16- and CD20-positive cells from peripheral blood of rheumatoid arthritis (RA) patients showed an uptake of albumin after incubation with AFLc-HSA in vitro. This finding was not significantly different in comparison to healthy controls. In contrast, the number of CD3-positive cells taking up albumin is increased significantly in RA patients in comparison to controls (26.3 ± 12.9% s.d. vs 11.6 ± 7.3% s.d.; P = 0.005). Conclusion. The data show that the effectiveness of MTX-HSA in CIA is superior to MTX and that both drugs act synergistically. In addition, albumin appears to be taken up by peripheral blood cells, suggesting that they might be one of the potential target cells of this novel anti-arthritic treatment approac
Epitaxial growth and anisotropy of La(O,F)FeAs thin films deposited by Pulsed Laser Deposition
LaFeAsO1-xFx thin films were deposited successfully on (001)-oriented LaAlO3
and MgO substrates from stoichiometric LaFeAsO1-xFx polycrystalline targets
with fluorine concentrations up to x = 0.25 by PLD. Room temperature deposition
and post annealing of the films yield nearly phase pure films with a pronounced
c-axis texture and a strong biaxial in-plane orientation. Transport
measurements show metallic resistance and onset of superconductivity at 11 K.
Hc2(T) was determined by resistive measurements and yield Hc2 values of 3 T at
3.6 K for B||c and 6 T at 6.4 K for B||ab.Comment: 11 pages, 5 figure
Shift towards pro-inflammatory intestinal bacteria aggravates acute murine colitis via Toll-like receptors 2 and 4.
BACKGROUND: Gut bacteria trigger colitis in animal models and are suspected to aggravate inflammatory bowel diseases. We have recently reported that Escherichia coli accumulates in murine ileitis and exacerbates small intestinal inflammation via Toll-like receptor (TLR) signaling. METHODOLOGY AND PRINCIPAL FINDINGS: Because knowledge on shifts in the intestinal microflora during colitis is limited, we performed a global survey of the colon flora of C57BL/10 wild-type (wt), TLR2(-/-), TLR4(-/-), and TLR2/4(-/-) mice treated for seven days with 3.5% dextrane-sulfate-sodium (DSS). As compared to wt animals, TLR2(-/-), TLR4(-/-), and TLR2/4(-/-) mice displayed reduced macroscopic signs of acute colitis and the amelioration of inflammation was associated with reduced IFN-gamma levels in mesenteric lymph nodes, lower amounts of neutrophils, and less FOXP3-positive T-cells in the colon in situ. During acute colitis E. coli increased in wt and TLR-deficient mice (P&lt;0.05), but the final numbers reached were significantly lower in TLR2(-/-), TLR4(-/-) and TLR2/4(-/-) animals, as compared to wt controls (P&lt;0.01). Concentrations of Bacteroides/ Prevotella spp., and enterococci did not increase during colitis, but their numbers were significantly reduced in the colon of DSS-treated TLR2/4(-/-) animals (P&lt;0.01). Numbers of lactobacilli and clostridia remained unaffected by colitis, irrespective of the TLR-genotype of mice. Culture-independent molecular analyses confirmed the microflora shifts towards enterobacteria during colitis and showed that the gut flora composition was similar in both, healthy wt and TLR-deficient animals. CONCLUSIONS AND SIGNIFICANCE: DSS-induced colitis is characterized by a shift in the intestinal microflora towards pro-inflammatory Gram-negative bacteria. Bacterial products exacerbate acute inflammation via TLR2- and TLR4-signaling and direct the recruitment of neutrophils and regulatory T-cells to intestinal sites. E. coli may serve as a biomarker for colitis severity and DSS-induced barrier damage seems to be a valuable model to further identify bacterial factors involved in maintaining intestinal homeostasis and to test therapeutic interventions based upon anti-TLR strategies
Eureka and beyond: mining's impact on African urbanisation
This collection brings separate literatures on mining and urbanisation together at a time when both artisanal and large-scale mining are expanding in many African economies. While much has been written about contestation over land and mineral rights, the impact of mining on settlement, notably its catalytic and fluctuating effects on migration and urban growth, has been largely ignored. African nation-states’ urbanisation trends have shown considerable variation over the past half century. The current surge in ‘new’ mining countries and the slow-down in ‘old’ mining countries are generating some remarkable settlement patterns and welfare outcomes. Presently, the African continent is a laboratory of national mining experiences. This special issue on African mining and urbanisation encompasses a wide cross-section of country case studies: beginning with the historical experiences of mining in Southern Africa (South Africa, Zambia, Zimbabwe), followed by more recent mineralizing trends in comparatively new mineral-producing countries (Tanzania) and an established West African gold producer (Ghana), before turning to the influence of conflict minerals (Angola, the Democratic Republic of Congo and Sierra Leone)
Role of tax knowledge and skills: What are the graduate skills required by small to medium accounting firms
Smallandmediumaccounting(SMA)firmscanaccountforapproximately40percentofgraduaterecruitmentinAustralia.DoesthecontextofobtainingemploymentwithaSMAfirm require graduates to have certain knowledge and skills?This article reportsthefindings of a study into the technical and generic skills required by graduatescommencing employment within an Australian SMA firm. The findings suggest thattogether with financial statement and reporting, tax knowledge is highly valued forgraduatestoaSMAfirm.Intermsoftax,thisalsoincludestheabilitytousetaxsoftware.Also,thegenericskillsofcommunication,teamworkandethicsarehighlyregarded.Thisraises the question as to whether current university degrees are providing adequatetechnicalandgenericskilldevelopmentforthosegraduatesseekingemploymentwithaSMAfirm
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