Iran’s nuclear ambitions under the shah and ayatollahs

During the 1970s, under the last shah, Iran’s nuclear program seemed to be gearing up so that nation could gain the option of declaring weapons capability if deemed necessary and at a point when the international community could no longer forestall it. So re-examining activities during the Pahlavi dynasty and using them as a context for the Islamic Republic’s more recent actions casts light upon motivations for pursuing weaponization and intransigence in reaching accommodation with the West after the rise of the ayatollahs, despite differences between the two Iranian regimes

The development of a cislunar space infrastructure

The primary objective of this Advanced Mission Design Program is to define the general characteristics and phased evolution of a near-Earth space infrastructure. The envisioned foundation includes a permanently manned, self-sustaining base on the lunar surface, a space station at the Libration Point between earth and the moon (L1), and a transportation system that anchors these elements to the Low Earth Orbit (LEO) station. The implementation of this conceptual design was carried out with the idea that the infrastructure is an important step in a larger plan to expand man's capabilities in space science and technology. Such expansion depends on low cost, reliable, and frequent access to space for those who wish to use the multiple benefits of this environment. The presence of a cislunar space infrastructure would greatly facilitate the staging of future planetary missions, as well as the full exploration of the lunar potential for science and industry. The rationale for, and a proposed detailed scenario in support of, the cislunar space infrastructure are discussed

Mediators of Interpersonal Psychotherapy for Depressed Adolescents On Outcomes in Latinos: The Role of Peer and Family Interpersonal Functioning

Peer and family interpersonal functioning were examined as mediators of the impact of Interpersonal Psychotherapy for Depressed Adolescents (IPT-A; Mufson, Dorta, Moreau, & Weissman, 2004) on depression and suicidal ideation among Latino youth. Only youth self-identifying as Latino (n = 50) were included in the analyses. The majority were female (86%) with a mean age of 14.58 (SD = 1.91). The current sample was drawn from the intent to treat sample of a clinical trial examining the effectiveness of IPT-A as compared with treatment as usual (TAU; Mufson, Dorta, Wickramaratne et al., 2004). Youth were randomly assigned to receive IPT-A or TAU delivered by school-based mental health clinicians. Assessments, completed at baseline and at Weeks 4, 8, and 12 (or at early termination), included self-report measures of depression and interpersonal functioning as well as clinician-Administered measures of depression. Multilevel modeling indicated that IPT-A led to greater improvement in interpersonal functioning with family and peers. Improved family and peer interpersonal functioning emerged as significant partial mediators of the relationship between IPT-A and depression. Only improved family interpersonal functioning emerged as a significant partial mediator of the relationship between IPT-A and suicidal ideation. However, this indirect effect was small, suggesting that most of the benefit of IPT-A for suicidal ideation appears to proceed through a pathway other than family interpersonal functioning. These results suggest that the impact of IPT-A on depressive symptoms is partially mediated by family and peer interpersonal functioning and contributes to our understanding of the mechanisms of IPT-A

A characterization of Gaucher iPS-derived astrocytes: Potential implications for Parkinson\u27s disease

While astrocytes, the most abundant cells found in the brain, have many diverse functions, their role in the lysosomal storage disorder Gaucher disease (GD) has not been explored. GD, resulting from the inherited deficiency of the enzyme glucocerebrosidase and subsequent accumulation of glucosylceramide and its acylated derivative glucosylsphingosine, has both non-neuronopathic (GD1) and neuronopathic forms (GD2 and 3). Furthermore, mutations in GBA1, the gene mutated in GD, are an important risk factor for Parkinson\u27s disease (PD). To elucidate the role of astrocytes in the disease pathogenesis, we generated iAstrocytes from induced pluripotent stem cells made from fibroblasts taken from controls and patients with GD1, with and without PD. We also made iAstrocytes from an infant with GD2, the most severe and progressive form, manifesting in infancy. Gaucher iAstrocytes appropriately showed deficient glucocerebrosidase activity and levels and substrate accumulation. These cells exhibited varying degrees of astrogliosis, Glial Fibrillary Acidic Protein (GFAP) up-regulation and cellular proliferation, depending on the level of residual glucocerebrosidase activity. Glutamte uptake assays demonstrated that the cells were functionally active, although the glutamine transporter EEAT2 was upregulated and EEAT1 downregulated in the GD2 samples. GD2 iAstrocytes were morphologically different, with severe cytoskeletal hypertrophy, overlapping of astrocyte processes, pronounced up-regulation of GFAP and S100β, and significant astrocyte proliferation, recapitulating the neuropathology observed in patients with GD2. Although astrocytes do not express α-synuclein, when the iAstrocytes were co-cultured with dopaminergic neurons generated from the same iPSC lines, excessive α-synuclein released from neurons was endocytosed by astrocytes, translocating into lysosomes. Levels of aggregated α-synuclein increased significantly when cells were treated with monomeric or fibrillar α-synuclein. GD1-PD and GD2 iAstrocytes also exhibited impaired Cathepsin D activity, leading to further α-synuclein accumulation. Cytokine and chemokine profiling of the iAstrocytes demonstrated an inflammatory response. Thus, in patients with GBA1-associated parkinsonism, astrocytes appear to play a role in α-synuclein accumulation and processing, contributing to neuroinflammation

PASI: A novel pathway method to identify delicate group effects

Pathway analysis is a common approach in diverse biomedical studies, yet the currently-available pathway tools do not typically support the increasingly popular personalized analyses. Another weakness of the currently-available pathway methods is their inability to handle challenging data with only modest group-based effects compared to natural individual variation. In an effort to address these issues, this study presents a novel pathway method PASI (Pathway Analysis for Sample-level Information) and demonstrates its performance on complex diseases with different levels of group-based differences in gene expression. PASI is freely available as an R package

Plasma diagnostic in eruptive prominences from SDO/AIA observations at 304 {\AA}

Context. Theoretical calculations have shown that when solar prominences move away from the surface of the Sun, their radiative output is affected via the Doppler dimming or brightening effects. Aims. In this paper we ask whether observational signatures of the changes in the radiative output of eruptive prominences can be found in EUV (extreme ultraviolet) observations of the first resonance line of ionised helium at 304 {\AA}. We also investigate whether these observations can be used to perform a diagnostic of the plasma of the eruptive prominence. Methods. We first look for suitable events in the SDO/AIA database. The variation of intensity of arbitrarily selected features in the 304 channel is studied as a function of velocity in the plane of the sky. These results are then compared with new non-LTE radiative transfer calculations of the intensity of the He II 304 resonance line. Results. We find that observations of intensities in various parts of the four eruptive prominences studied here are sometimes consistent with the Doppler dimming effect on the He II 304 {\AA} line. However, in some cases, one observes an increase in intensity in the 304 channel with velocity, in contradiction to what is expected from the Doppler dimming effect alone. The use of the non-LTE models allows us to explain the different behaviour of the intensity by changes in the plasma parameters inside the prominence, in particular the column mass of the plasma and its temperature. Conclusions. The non-LTE models used here are more realistic than what was used in previous calculations. They are able to reproduce qualitatively the range of observations from SDO/AIA analysed in this study. Thanks to non-LTE modelling, we can infer the plasma parameters in eruptive prominences from SDO/AIA observations at 304 {\AA}.Comment: 7 pages, 8 figures. Movies available at http://www.astro.gla.ac.uk/users/labrosse/aa17801

5-Fluorouracil-induced cardiotoxicity mimicking myocardial infarction: a case report

BACKGROUND: Severe cardiotoxicity is a documented, but very unusual side-effect of intravenous 5-fluorouracil therapy. The mechanism producing cardiotoxicity is poorly understood. CASE PRESENTATION: A case of 5-fluorouracil-induced cardiotoxicity, possibly due to coronary artery spasm, and mimicking acute anterolateral myocardial infarction is presented and discussed. Electrocardiographs highlighting the severity of the presentation are included in the report along with coronary angiograms demonstrating the absence of significant coronary atherosclerosis. CONCLUSION: Severe 5-fluorouracil-induced cardiotoxicity is rare, but can be severe and may mimic acute myocardial infarction, leading to diagnostic and therapeutic dilemmas. Readministration of 5-fluorouracil is not advised following an episode of cardiotoxicity

Synthetic nuclear diagnostics for inferring plasma properties of inertial confinement fusion implosions

A suite of synthetic nuclear diagnostics has been developed to post-process radiation hydrodynamics simulations performed with the code Chimera. These provide experimental observables based on simulated capsule properties and are used to assess alternative experimental and data analysis techniques. These diagnostics include neutron spectroscopy, primary and scattered neutron imaging, neutron activation, γ-ray time histories and carbon γ-ray imaging. Novel features of the neutron spectrum have been analysed to infer plasma parameters. The nT and nD backscatter edges have been shown to provide a shell velocity measurement. Areal density asymmetries created by low mode perturbations have been inferred from the slope of the downscatter spectrum down to 10 MeV. Neutron activation diagnostics showed significant aliasing of high mode areal density asymmetries when observing a capsule implosion with 3D multimode perturbations applied. Carbon γ-ray imaging could be used to image the ablator at a high convergence ratio. Time histories of both the fusion and carbon γ signals showed a greater time difference between peak intensities for the perturbed case when compared to a symmetric simulation

Exposure to environmental contaminants is associated with altered hepatic lipid metabolism in non-alcoholic fatty liver disease

Background & aims: Recent experimental models and epidemiological studies suggest that specific environmental contaminants (ECs) contribute to the initiation and pathology of nonalcoholic fatty liver disease (NAFLD). However, the underlying mechanisms linking EC exposure with NAFLD remain poorly understood and there is no data on their impact on the human liver metabolome. Herein, we hypothesized that exposure to ECs, particularly perfluorinated alkyl substances (PFAS), impacts liver metabolism, specifically bile acid metabolism. Methods: In a well-characterized human NAFLD cohort of 105 individuals, we investigated the effects of EC exposure on liver metabolism. We characterized the liver (via biopsy) and circulating metabolomes using 4 mass spectrometry-based analytical platforms, and measured PFAS and other ECs in serum. We subsequently compared these results with an exposure study in a PPARa-humanized mouse model. Results: PFAS exposure appears associated with perturbation of key hepatic metabolic pathways previously found altered in NAFLD, particularly those related to bile acid and lipid metabolism. We identified stronger associations between the liver metabolome, chemical exposure and NAFLD-associated clinical variables (liver fat content, HOMA-IR), in females than males. Specifically, we observed PFAS-associated upregulation of bile acids, triacylglycerols and ceramides, and association between chemical exposure and dysregulated glucose metabolism in females. The murine exposure study further corroborated our findings, vis-a-vis a sex-specific association between PFAS exposure and NAFLD-associated lipid changes. Conclusions: Females may be more sensitive to the harmful impacts of PFAS. Lipid-related changes subsequent to PFAS exposure may be secondary to the interplay between PFAS and bile acid metabolism. Lay summary: There is increasing evidence that specific environmental contaminants, such as perfluorinated alkyl substances (PFAS), contribute to the progression of non-alcoholic fatty liver disease (NAFLD). However, it is poorly understood how these chemicals impact human liver metabolism. Here we show that human exposure to PFAS impacts metabolic processes associated with NAFLD, and that the effect is different in females and males. (C) 2021 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver.Peer reviewe