A Map of the Universe

We have produced a new conformal map of the universe illustrating recent discoveries, ranging from Kuiper belt objects in the Solar system, to the galaxies and quasars from the Sloan Digital Sky Survey. This map projection, based on the logarithm map of the complex plane, preserves shapes locally, and yet is able to display the entire range of astronomical scales from the Earth's neighborhood to the cosmic microwave background. The conformal nature of the projection, preserving shapes locally, may be of particular use for analyzing large scale structure. Prominent in the map is a Sloan Great Wall of galaxies 1.37 billion light years long, 80% longer than the Great Wall discovered by Geller and Huchra and therefore the largest observed structure in the universe.Comment: Figure 8, and additional material accessible on the web at: http://www.astro.princeton.edu/~mjuric/universe

Psychosocial Correlates of Gender-Based Violence Among HIV-Infected and HIV-Uninfected Women in Three US Cities

Gender-based violence (GBV) is common among women with and at risk for HIV, yet little is known about the GBV associated psychological factors that could be modifiable through behavioral interventions. The current study examined the associations between some of these psychological factors (i.e., hopelessness, consideration of future consequences, self esteem), mental health symptoms, substance abuse, and GBV among a sample of 736 HIV-infected and sociodemographically similar uninfected participants in the Women\u27s Interagency HIV Study (WIHS). Results indicated high rates of lifetime GBV among the sample (58%), as well as high rates of childhood sexual abuse (CSA) (22.2%). HIV-infected women were more likely to be hopeless and to experience lower consideration of future consequences as compared to uninfected women. Multivariable analysis indicated that current non-injection drug use and a history of injection drug use were the main correlates of GBV and CSA, even when other psychosocial variables were included in analytic models. Being born outside of the US reduced the likelihood of GBV and CSA. Future research directions and intervention implications are discussed

Low energy polarization sensitivity of the Gas Pixel Detector

An X-ray photoelectric polarimeter based on the Gas Pixel Detector has been proposed to be included in many upcoming space missions to fill the gap of about 30 years from the first (and to date only) positive measurement of polarized X-ray emission from an astrophysical source. The estimated sensitivity of the current prototype peaks at an energy of about 3 keV, but the lack of readily available polarized sources in this energy range has prevented the measurement of detector polarimetric performances. In this paper we present the measurement of the Gas Pixel Detector polarimetric sensitivity at energies of a few keV and the new, light, compact and transportable polarized source that was devised and built to this aim. Polarized photons are produced, from unpolarized radiation generated with an X-ray tube, by means of Bragg diffraction at nearly 45 degrees. The employment of mosaic graphite and flat aluminum crystals allow the production of nearly completely polarized photons at 2.6, 3.7 and 5.2 keV from the diffraction of unpolarized continuum or line emission. The measured modulation factor of the Gas Pixel Detector at these energies is in good agreement with the estimates derived from a Monte Carlo software, which was up to now employed for driving the development of the instrument and for estimating its low energy sensitivity. In this paper we present the excellent polarimetric performance of the Gas Pixel Detector at energies where the peak sensitivity is expected. These measurements not only support our previous claims of high sensitivity but confirm the feasibility of astrophysical X-ray photoelectric polarimetry.Comment: 15 pages, 12 figures. Accepted for publication in NIM

Targeting tumour re-wiring by triple blockade of mTORC1, epidermal growth factor, and oestrogen receptor signalling pathways in endocrine-resistant breast cancer

Background Endocrine therapies are the mainstay of treatment for oestrogen receptor (ER)-positive (ER+) breast cancer (BC). However, resistance remains problematic largely due to enhanced cross-talk between ER and growth factor pathways, circumventing the need for steroid hormones. Previously, we reported the anti-proliferative effect of everolimus (RAD001-mTORC1 inhibitor) with endocrine therapy in resistance models; however, potential routes of escape from treatment via ERBB2/3 signalling were observed. We hypothesised that combined targeting of three cellular nodes (ER, ERBB, and mTORC1) may provide enhanced long-term clinical utility. Methods A panel of ER+ BC cell lines adapted to long-term oestrogen deprivation (LTED) and expressing ESR1wt or ESR1Y537S, modelling acquired resistance to an aromatase-inhibitor (AI), were treated in vitro with a combination of RAD001 and neratinib (pan-ERBB inhibitor) in the presence or absence of oestradiol (E2), tamoxifen (4-OHT), or fulvestrant (ICI182780). End points included proliferation, cell signalling, cell cycle, and effect on ER-mediated transactivation. An in-vivo model of AI resistance was treated with monotherapies and combinations to assess the efficacy in delaying tumour progression. RNA-seq analysis was performed to identify changes in global gene expression as a result of the indicated therapies. Results Here, we show RAD001 and neratinib (pan-ERBB inhibitor) caused a concentration-dependent decrease in proliferation, irrespective of the ESR1 mutation status. The combination of either agent with endocrine therapy further reduced proliferation but the maximum effect was observed with a triple combination of RAD001, neratinib, and endocrine therapy. In the absence of oestrogen, RAD001 caused a reduction in ER-mediated transcription in the majority of the cell lines, which associated with a decrease in recruitment of ER to an oestrogen-response element on the TFF1 promoter. Contrastingly, neratinib increased both ER-mediated transactivation and ER recruitment, an effect reduced by the addition of RAD001. In-vivo analysis of an LTED model showed the triple combination of RAD001, neratinib, and fulvestrant was most effective at reducing tumour volume. Gene set enrichment analysis revealed that the addition of neratinib negated the epidermal growth factor (EGF)/EGF receptor feedback loops associated with RAD001. Conclusions Our data support the combination of therapies targeting ERBB2/3 and mTORC1 signalling, together with fulvestrant, in patients who relapse on endocrine therapy and retain a functional ER

Emergence of dissipative structures in current-carrying superconducting wires

We discuss the emergence of a spontaneous temperature and critical current spatial modulation in current-carrying high temperature superconducting wire. The modulation of the critical current along the wire on a scale of 3 - 10 mm forces a fraction of the transport current to crisscross the resistive interface between the superconducting film and normal metal stabilizer attached to it. This generates additional heat that allows such a structure to be self sustainable. Stability and the conditions for experimental observation of this phenomenon are also discussed.Comment: To be published in Phys. Rev. E (in section Chaos and Pattern Formation

Tau Oligomer–Containing Synapse Elimination by Microglia and Astrocytes in Alzheimer Disease

Importance: Factors associated with synapse loss beyond amyloid-β plaques and neurofibrillary tangles may more closely correlate with the emergence of cognitive deficits in Alzheimer disease (AD) and be relevant for early therapeutic intervention. // Objective: To investigate whether accumulation of tau oligomers in synapses is associated with excessive synapse elimination by microglia or astrocytes and with cognitive outcomes (dementia vs no dementia [hereinafter termed resilient]) of individuals with equal burdens of AD neuropathologic changes at autopsy. // Design, Setting, and Participants: This cross-sectional postmortem study included 40 human brains from the Massachusetts Alzheimer Disease Research Center Brain Bank with Braak III to IV stages of tau pathology but divergent antemortem cognition (dementia vs resilient) and cognitively normal controls with negligible AD neuropathologic changes. The visual cortex, a region without tau tangle deposition at Braak III to IV stages, was assessed after expansion microscopy to analyze spatial relationships of synapses with microglia and astrocytes. Participants were matched for age, sex, and apolipoprotein E status. Evidence of Lewy bodies, TDP-43 aggregates, or other lesions different from AD neuropathology were exclusion criteria. Tissue was collected from July 1998 to November 2020, and analyses were conducted from February 1, 2022, through May 31, 2023. // Main Outcomes and Measures: Amyloid-β plaques, tau neuropil thread burden, synapse density, tau oligomers in synapses, and internalization of tau oligomer–tagged synapses by microglia and astrocytes were quantitated. Analyses were performed using 1-way analysis of variance for parametric variables and the Kruskal-Wallis test for nonparametric variables; between-group differences were evaluated with Holm-Šídák tests. // Results: Of 40 included participants (mean [SD] age at death, 88 [8] years; 21 [52%] male), 19 had early-stage dementia with Braak stages III to IV, 13 had resilient brains with similar Braak stages III to IV, and 8 had no dementia (Braak stages 0-II). Brains with dementia but not resilient brains had substantial loss of presynaptic (43%), postsynaptic (33%), and colocalized mature synaptic elements (38%) compared with controls and significantly higher percentages of mature synapses internalized by IBA1-positive microglia (mean [SD], 13.3% [3.9%] in dementia vs 2.6% [1.9%] in resilient vs 0.9% [0.5%] in control; P < .001) and by GFAP-positive astrocytes (mean [SD], 17.2% [10.9%] in dementia vs 3.7% [4.0%] in resilient vs 2.7% [1.8%] in control; P = .001). In brains with dementia but not in resilient brains, tau oligomers more often colocalized with synapses, and the proportions of tau oligomer–containing synapses inside microglia (mean [SD] for presynapses, mean [SD], 7.4% [1.8%] in dementia vs 5.1% [1.9%] resilient vs 3.7% [0.8%] control; P = .006; and for postsynapses 11.6% [3.6%] dementia vs 6.8% [1.3%] resilient vs 7.4% [2.5%] control; P = .001) and astrocytes (mean [SD] for presynapses, 7.0% [2.1%] dementia vs 4.3% [2.2%] resilient vs 4.0% [0.7%] control; P = .001; and for postsynapses, 7.9% [2.2%] dementia vs 5.3% [1.8%] resilient vs 3.0% [1.5%] control; P < .001) were significantly increased compared with controls. Those changes in brains with dementia occurred in the absence of tau tangle deposition in visual cortex. // Conclusion and Relevance: The findings from this cross-sectional study suggest that microglia and astrocytes may excessively engulf synapses in brains of individuals with dementia and that the abnormal presence of tau oligomers in synapses may serve as signals for increased glial-mediated synapse elimination and early loss of brain function in AD

Observational Constraints on the Modified Gravity Model (MOG) Proposed by Moffat: Using the Magellanic System

A simple model for the dynamics of the Magellanic Stream (MS), in the framework of modified gravity models is investigated. We assume that the galaxy is made up of baryonic matter out of context of dark matter scenario. The model we used here is named Modified Gravity (MOG) proposed by Moffat (2005). In order to examine the compatibility of the overall properties of the MS under the MOG theory, the observational radial velocity profile of the MS is compared with the numerical results using the $\chi^2$ fit method. In order to obtain the best model parameters, a maximum likelihood analysis is performed. We also compare the results of this model with the Cold Dark Matter (CDM) halo model and the other alternative gravity model that proposed by Bekenstein (2004), so called TeVeS. We show that by selecting the appropriate values for the free parameters, the MOG theory seems to be plausible to explain the dynamics of the MS as well as the CDM and the TeVeS models.Comment: 14 pages, 3 Figures, accepted in Int. J. Theor. Phy