Possible X-ray diagnostic for jet/disk dominance in Type 1 AGN

Using Rossi X-ray Timing Explorer Seyfert 1 and 1.2 data spanning 9 years, we study correlations between X-ray spectral features. The sample consists of 350 time-resolved spectra from 12 Seyfert 1 and 1.2 galaxies. Each spectrum is fitted to a model with an intrinsic powerlaw X-ray spectrum produced close to the central black hole that is reprocessed and absorbed by material around the black hole. To test the robustness of our results, we performed Monte Carlo simulations of the spectral sample. We find a complex relationship between the iron line equivalent width (EW) and the underlying power law index (Gamma). The data reveal a correlation between Gamma and EW which turns over at Gamma <~ 2, but finds a weak anti-correlation for steeper photon indices. We propose that this relationship is driven by dilution of a disk spectrum (which includes the narrow iron line) by a beamed jet component and, hence, could be used as a diagnostic of jet-dominance. In addition, our sample shows a strong correlation between the reflection fraction (R) and Gamma, but we find that it is likely the result of modeling degeneracies. We also see the X-ray Baldwin effect (an anti-correlation between the 2-10 keV X-ray luminosity and EW) for the sample as a whole, but not for the individual galaxies and galaxy types.Comment: Accepted for publication in ApJ, 14 page

Using a product's sustainability space as a design exploration tool

Sustainable design is often practiced and assessed through the consideration of three essential areas: economic sustainability, environmental sustainability, and social sustainability. For even the simplest of products, the complexities of these three areas and their tradeoffs cause decision-making transparency to be lost in most practical situations. The existing field of multiobjective optimization offers a natural framework to define and explore a given design space. In this paper, a method for defining a product’s sustainability space (defined by economic, environmental, and social sustainability objectives) is outlined and used to explore the tradeoffs within the space, thus offering both the design team and the decision makers a means of better understanding the sustainability tradeoffs. This paper concludes that sustainable product development can indeed benefit from tradeoff characterization using multiobjective optimization techniques – even when using only basic models of sustainability. Interestingly, the unique characteristics of the three essential sustainable development areas lead to an alternative view of some traditional multiobjective optimization concepts, such as weak-Pareto optimality. The sustainable redesign of a machine to drill boreholes for water wells is presented as a practical example for method demonstration and discussion

Capacitative Calcium Entry Deficits and Elevated Luminal Calcium Content in Mutant Presenilin-1 Knockin Mice

Dysregulation of calcium signaling has been causally implicated in brain aging and Alzheimer's disease. Mutations in the presenilin genes (PS1, PS2), the leading cause of autosomal dominant familial Alzheimer's disease (FAD), cause highly specific alterations in intracellular calcium signaling pathways that may contribute to the neurodegenerative and pathological lesions of the disease. To elucidate the cellular mechanisms underlying these disturbances, we studied calcium signaling in fibroblasts isolated from mutant PS1 knockin mice. Mutant PS1 knockin cells exhibited a marked potentiation in the amplitude of calcium transients evoked by agonist stimulation. These cells also showed significant impairments in capacitative calcium entry (CCE, also known as store-operated calcium entry), an important cellular signaling pathway wherein depletion of intracellular calcium stores triggers influx of extracellular calcium into the cytosol. Notably, deficits in CCE were evident after agonist stimulation, but not if intracellular calcium stores were completely depleted with thapsigargin. Treatment with ionomycin and thapsigargin revealed that calcium levels within the ER were significantly increased in mutant PS1 knockin cells. Collectively, our findings suggest that the overfilling of calcium stores represents the fundamental cellular defect underlying the alterations in calcium signaling conferred by presenilin mutations

Efficient propagation of error through system models for functions common in engineering

System modeling can help designers make and verify design decisions early in the design process if the model&apos;s accuracy can be determined. The formula typically used to analytically propagate error is based on a first-order Taylor series expansion. Consequently, this formula can be wrong by one or more orders of magnitude for nonlinear systems. Clearly, adding higher-order terms increases the accuracy of the approximation but it also requires higher computational cost. This paper shows that truncation error can be reduced and accuracy increased without additional computational cost by applying a predictable correction factor to lower-order approximations. The efficiency of this method is demonstrated in the kinematic model of a flapping wing. While Taylor series error propagation is typically applicable only to closedform equations, the procedure followed in this paper may be used with other types of models, provided that model outputs can be determined from model inputs, derivatives can be calculated, and truncation error is predictable

Chiral Multiplets of Heavy-Light Mesons

The recent discovery of a narrow resonance in D_s+pi^0 by the BABAR collaboration is consistent with the interpretation of a heavy J^P(0+,1+) spin multiplet. This system is the parity partner of the groundstate (0-,1-) multiplet, which we argue is required in the implementation of SU(3)_L x SU(3)_R chiral symmetry in heavy-light meson systems. The (0+,1+)->(0-,1-)+pi transition couplings satisfy a Goldberger-Treiman relation, g_pi = Delta(M)/f_pi, where Delta(M) is the mass gap. The BABAR resonance fits the 0+ state, with a kinematically blocked principal decay mode to D+K. The allowed D_s+pi, D_s+2pi and electromagnetic transitions are computed from the full chiral theory and found to be suppressed, consistent with the narrowness of the state. This state establishes the chiral mass difference for all such heavy-quark chiral multiplets, and precise predictions exist for the analogous B_s and strange doubly-heavy baryon states.Comment: 10 pages; minor editorial revisions; recomputed M1 transitio

Recombinant T-Cell Receptor Ligand (RTL) for Treatment of Multiple Sclerosis: A Double-Blind, Placebo-Controlled, Phase 1, Dose-Escalation Study

Background. Recombinant T-cell receptor ligand 1000 (RTL1000) is a single-chain protein construct containing the outer two domains of HLA-DR2 linked to myelin-oligodendrocyte-glycoprotein- (MOG-) 35–55 peptide. Analogues of RTL1000 induce T-cell tolerance, reverse clinical and histological disease, and promote repair in experimental autoimmune encephalomyelitis (EAE) in DR2 transgenic, C57BL/6, and SJL/J mice. Objective. Determining the maximum tolerated dose, safety, and tolerability of RTL1000 in multiple sclerosis (MS) subjects. Methods. This was a multicenter, Phase I dose-escalation study in HLA-DR2+ MS subjects. Consecutive cohorts received RTL1000 doses of 2, 6, 20, 60, 200, and 100 mg, respectively. Subjects within each cohort randomly received a single intravenous infusion of RTL1000 or placebo at a 4 : 2 ratio. Safety monitoring included clinical, laboratory, and brain magnetic resonance imaging (MRI) evaluations. Results. Thirty-four subjects completed the protocol. All subjects tolerated the 2–60 mg doses of RTL1000. Doses ≥100 mg caused hypotension and diarrhea in 3 of 4 subjects, leading to discontinuation of further enrollment. Conclusions. The maximum tolerated dose of RTL1000 in MS subjects is 60 mg, comparable to effective RTL doses in EAE. RTL1000 is a novel approach for MS treatment that may induce immunoregulation without immunosuppression and promote neural repair

Language and social/emotional problems identified at a universal developmental assessment at 30 months

Non peer reviewedPublisher PD

Circumcision of Male Children for Reduction of Future Risk for HIV: Acceptability among HIV Serodiscordant Couples in Kampala, Uganda

The ultimate success of medical male circumcision for HIV prevention may depend on targeting male infants and children as well as adults, in order to maximally reduce new HIV infections into the future.We conducted a cross-sectional study among heterosexual HIV serodiscordant couples (a population at high risk for HIV transmission) attending a research clinic in Kampala, Uganda on perceptions and attitudes about medical circumcision for male children for HIV prevention. Correlates of willingness to circumcise male children were assessed using generalized estimating equations methods.318 HIV serodiscordant couples were interviewed, 51.3% in which the female partner was HIV uninfected. Most couples were married and cohabiting, and almost 50% had at least one uncircumcised male child of ≤18 years of age. Overall, 90.2% of male partners and 94.6% of female partners expressed interest in medical circumcision for their male children for reduction of future risk for HIV infection, including 79.9% of men and 87.6% of women who had an uncircumcised male child. Among both men and women, those who were knowledgeable that circumcision reduces men's risk for HIV (adjusted prevalence ratio [APR] 1.34 and 1.14) and those who had discussed the HIV prevention effects of medical circumcision with their partner (APR 1.08 and 1.07) were significantly (p≤0.05) more likely to be interested in male child circumcision for HIV prevention. Among men, those who were circumcised (APR 1.09, p = 0.004) and those who were HIV seropositive (APR 1.09, p = 0.03) were also more likely to be interested in child circumcision for HIV prevention.A high proportion of men and women in Ugandan heterosexual HIV serodiscordant partnerships were willing to have their male children circumcised for eventual HIV prevention benefits. Engaging both parents may increase interest in medical male circumcision for HIV prevention

Identification and Validation of Novel Cerebrospinal Fluid Biomarkers for Staging Early Alzheimer's Disease

Ideally, disease modifying therapies for Alzheimer disease (AD) will be applied during the 'preclinical' stage (pathology present with cognition intact) before severe neuronal damage occurs, or upon recognizing very mild cognitive impairment. Developing and judiciously administering such therapies will require biomarker panels to identify early AD pathology, classify disease stage, monitor pathological progression, and predict cognitive decline. To discover such biomarkers, we measured AD-associated changes in the cerebrospinal fluid (CSF) proteome.CSF samples from individuals with mild AD (Clinical Dementia Rating [CDR] 1) (n = 24) and cognitively normal controls (CDR 0) (n = 24) were subjected to two-dimensional difference-in-gel electrophoresis. Within 119 differentially-abundant gel features, mass spectrometry (LC-MS/MS) identified 47 proteins. For validation, eleven proteins were re-evaluated by enzyme-linked immunosorbent assays (ELISA). Six of these assays (NrCAM, YKL-40, chromogranin A, carnosinase I, transthyretin, cystatin C) distinguished CDR 1 and CDR 0 groups and were subsequently applied (with tau, p-tau181 and Aβ42 ELISAs) to a larger independent cohort (n = 292) that included individuals with very mild dementia (CDR 0.5). Receiver-operating characteristic curve analyses using stepwise logistic regression yielded optimal biomarker combinations to distinguish CDR 0 from CDR>0 (tau, YKL-40, NrCAM) and CDR 1 from CDR<1 (tau, chromogranin A, carnosinase I) with areas under the curve of 0.90 (0.85-0.94 95% confidence interval [CI]) and 0.88 (0.81-0.94 CI), respectively.Four novel CSF biomarkers for AD (NrCAM, YKL-40, chromogranin A, carnosinase I) can improve the diagnostic accuracy of Aβ42 and tau. Together, these six markers describe six clinicopathological stages from cognitive normalcy to mild dementia, including stages defined by increased risk of cognitive decline. Such a panel might improve clinical trial efficiency by guiding subject enrollment and monitoring disease progression. Further studies will be required to validate this panel and evaluate its potential for distinguishing AD from other dementing conditions