Measuring a New Stress Domain: Validation of the Couple-Level Minority Stress Scale

Existing social stress frameworks largely conceive of stress as emanating from individual experience. Recent theory and research concerning minority stress have focused on same-sex couples' experiences of both eventful and chronic stressors associated with being in a stigmatized relationship, including having ongoing or episodic fears of discrimination, and experiencing actual acts of discrimination. Such couple-level minority stressors represent a novel domain of social stress affecting minority populations that is only beginning to become a focus in empirical investigations testing minority stress theory. This article presents the results of psychometric analyses of dyadic data from 106 same-sex couples from across the U.S., introducing the Couple-Level Minority Stress (CLMS) scale featuring eight new couple-level minority stress factors: (1) Couple-Level Stigma; (2) Couple-Level Discrimination; (3) Seeking Safety as a Couple; (4) Perceived Unequal Relationship Recognition; (5) Couple-Level Visibility; (6) Managing Stereotypes about Same-Sex Couples; (7) Lack of Integration with Families of Origin; and (8) Lack of Social Support for Couples. The CLMS demonstrated a clear factor structure with satisfactory model-data fit and subscale reliabilities. The CLMS also exhibited validity as a correlate of one indicator of relationship quality (relationship satisfaction) and three indicators of mental health (nonspecific psychological distress, depressive symptomatology, and problematic drinking) when controlling for individual-level minority stressors and has great potential to extend and enrich minority stress research, particularly studies that deepen understandings of longstanding health inequities based on sexual orientation

Atrial fibrillation-related cardiomyopathy: a case report

Sustained chronic tachyarrhythmias often cause a deterioration of cardiac function known as tachycardia-induced cardiomyopathy or tachycardiomyopathy

Quantification challenges for atom probe tomography of hydrogen and deuterium in zircaloy-4

Analysis and understanding of the role of hydrogen in metals is a significant challenge for the future of materials science, and this is a clear objective of recent work in the atom probe tomography (APT) community. Isotopic marking by deuteration has often been proposed as the preferred route to enable quantification of hydrogen by APT. Zircaloy-4 was charged electrochemically with hydrogen and deuterium under the same conditions to form large hydrides and deuterides. Our results from a Zr hydride and a Zr deuteride highlight the challenges associated with accurate quantification of hydrogen and deuterium, in particular associated with the overlap of peaks at a low mass-to-charge ratio and of hydrogen/deuterium containing molecular ions. We discuss possible ways to ensure that appropriate information is extracted from APT analysis of hydrogen in zirconium alloy systems that are important for nuclear power applications

Robustness Verification of Support Vector Machines

We study the problem of formally verifying the robustness to adversarial examples of support vector machines (SVMs), a major machine learning model for classification and regression tasks. Following a recent stream of works on formal robustness verification of (deep) neural networks, our approach relies on a sound abstract version of a given SVM classifier to be used for checking its robustness. This methodology is parametric on a given numerical abstraction of real values and, analogously to the case of neural networks, needs neither abstract least upper bounds nor widening operators on this abstraction. The standard interval domain provides a simple instantiation of our abstraction technique, which is enhanced with the domain of reduced affine forms, which is an efficient abstraction of the zonotope abstract domain. This robustness verification technique has been fully implemented and experimentally evaluated on SVMs based on linear and nonlinear (polynomial and radial basis function) kernels, which have been trained on the popular MNIST dataset of images and on the recent and more challenging Fashion-MNIST dataset. The experimental results of our prototype SVM robustness verifier appear to be encouraging: this automated verification is fast, scalable and shows significantly high percentages of provable robustness on the test set of MNIST, in particular compared to the analogous provable robustness of neural networks

A metabolite-derived protein modification integrates glycolysis with KEAP1-NRF2 signalling.

Mechanisms that integrate the metabolic state of a cell with regulatory pathways are necessary to maintain cellular homeostasis. Endogenous, intrinsically reactive metabolites can form functional, covalent modifications on proteins without the aid of enzymes1,2, and regulate cellular functions such as metabolism3-5 and transcription6. An important 'sensor' protein that captures specific metabolic information and transforms it into an appropriate response is KEAP1, which contains reactive cysteine residues that collectively act as an electrophile sensor tuned to respond to reactive species resulting from endogenous and xenobiotic molecules. Covalent modification of KEAP1 results in reduced ubiquitination and the accumulation of NRF27,8, which then initiates the transcription of cytoprotective genes at antioxidant-response element loci. Here we identify a small-molecule inhibitor of the glycolytic enzyme PGK1, and reveal a direct link between glycolysis and NRF2 signalling. Inhibition of PGK1 results in accumulation of the reactive metabolite methylglyoxal, which selectively modifies KEAP1 to form a methylimidazole crosslink between proximal cysteine and arginine residues (MICA). This posttranslational modification results in the dimerization of KEAP1, the accumulation of NRF2 and activation of the NRF2 transcriptional program. These results demonstrate the existence of direct inter-pathway communication between glycolysis and the KEAP1-NRF2 transcriptional axis, provide insight into the metabolic regulation of the cellular stress response, and suggest a therapeutic strategy for controlling the cytoprotective antioxidant response in several human diseases

Modeling magnetic nanopolymer flow with induction and nanoparticle solid volume fraction effects : solar magnetic nanopolymer fabrication simulation

A mathematical model is presented for the nonlinear steady, forced convection, hydromagnetic flow of electro-conductive magnetic nano-polymer with magnetic induction effects included. The transformed two-parameter, non-dimensional governing partial differential equations for mass, momentum, magnetic induction and heat conservation are solved with the local non-similarity method (LNM) subject to appropriate boundary conditions. Keller’s implicit finite difference “box” method (KBM) is used to validate solutions. Computations for four different nanoparticles and three different base fluids are included. Silver nanoparticles in combination with various base fluids enhance temperatures and induced magnetic field and accelerate the flow. An elevation in magnetic body force number decelerates the flow whereas an increase in magnetic Prandtl number elevates the magnetic induction. Furthermore, increasing nanoparticle solid volume fraction is found to substantially boost temperatures. Applications of the study arise in advanced magnetic solar nano-materials (fluids) processing technologies

Voxel-wise comparisons of cellular microstructure and diffusion-MRI in mouse hippocampus using 3D Bridging of Optically-clear histology with Neuroimaging Data (3D-BOND)

A key challenge in medical imaging is determining a precise correspondence between image properties and tissue microstructure. This comparison is hindered by disparate scales and resolutions between medical imaging and histology. We present a new technique, 3D Bridging of Optically-clear histology with Neuroimaging Data (3D-BOND), for registering medical images with 3D histology to overcome these limitations. Ex vivo 120 × 120 × 200 μm resolution diffusion-MRI (dMRI) data was acquired at 7 T from adult C57Bl/6 mouse hippocampus. Tissue was then optically cleared using CLARITY and stained with cellular markers and confocal microscopy used to produce high-resolution images of the 3D-tissue microstructure. For each sample, a dense array of hippocampal landmarks was used to drive registration between upsampled dMRI data and the corresponding confocal images. The cell population in each MRI voxel was determined within hippocampal subregions and compared to MRI-derived metrics. 3D-BOND provided robust voxel-wise, cellular correlates of dMRI data. CA1 pyramidal and dentate gyrus granular layers had significantly different mean diffusivity (p > 0.001), which was related to microstructural features. Overall, mean and radial diffusivity correlated with cell and axon density and fractional anisotropy with astrocyte density, while apparent fibre density correlated negatively with axon density. Astrocytes, axons and blood vessels correlated to tensor orientation

Decitabine impact on the endocytosis regulator RhoA, the folate carriers RFC1 and FOLR1, and the glucose transporter GLUT4 in human tumors.

BackgroundIn 31 solid tumor patients treated with the demethylating agent decitabine, we performed tumor biopsies before and after the first cycle of decitabine and used immunohistochemistry (IHC) to assess whether decitabine increased expression of various membrane transporters. Resistance to chemotherapy may arise due to promoter methylation/downregulation of expression of transporters required for drug uptake, and decitabine can reverse resistance in vitro. The endocytosis regulator RhoA, the folate carriers FOLR1 and RFC1, and the glucose transporter GLUT4 were assessed.ResultsPre-decitabine RhoA was higher in patients who had received their last therapy >3 months previously than in patients with more recent prior therapy (P = 0.02), and varied inversely with global DNA methylation as assessed by LINE1 methylation (r = -0.58, P = 0.006). Tumor RhoA scores increased with decitabine (P = 0.03), and RFC1 also increased in patients with pre-decitabine scores ≤150 (P = 0.004). Change in LINE1 methylation with decitabine did not correlate significantly with change in IHC scores for any transporter assessed. We also assessed methylation of the RFC1 gene (alias SLC19A1). SLC19A1 methylation correlated with tumor LINE1 methylation (r = 0.45, P = 0.02). There was a small (statistically insignificant) decrease in SLC19A1 methylation with decitabine, and there was a trend towards change in SLC19A1 methylation with decitabine correlating with change in LINE1 methylation (r = 0.47, P <0.15). While SLC19A1 methylation did not correlate with RFC1 scores, there was a trend towards an inverse correlation between change in SLC19A1 methylation and change in RFC1 expression (r = -0.45, P = 0.19).ConclusionsIn conclusion, after decitabine administration, there was increased expression of some (but not other) transporters that may play a role in chemotherapy uptake. Larger patient numbers will be needed to define the extent to which this increased expression is associated with changes in DNA methylation

Parity-Violating Electron Scattering from 4He and the Strange Electric Form Factor of the Nucleon

We have measured the parity-violating electroweak asymmetry in the elastic scattering of polarized electrons from ^4He at an average scattering angle = 5.7 degrees and a four-momentum transfer Q^2 = 0.091 GeV^2. From these data, for the first time, the strange electric form factor of the nucleon G^s_E can be isolated. The measured asymmetry of A_PV = (6.72 +/- 0.84 (stat) +/- 0.21 (syst) parts per million yields a value of G^s_E = -0.038 +/- 0.042 (stat) +/- 0.010 (syst), consistent with zero

Chronic, low-dose rotenone reproduces Lewy neurites found in early stages of Parkinson's disease, reduces mitochondrial movement and slowly kills differentiated SH-SY5Y neural cells

<p>Abstract</p> <p>Background</p> <p>Parkinson's disease, the most common adult neurodegenerative movement disorder, demonstrates a brain-wide pathology that begins pre-clinically with alpha-synuclein aggregates ("Lewy neurites") in processes of gut enteric and vagal motor neurons. Rostral progression into substantia nigra with death of dopamine neurons produces the motor impairment phenotype that yields a clinical diagnosis. The vast majority of Parkinson's disease occurs sporadically, and current models of sporadic Parkinson's disease (sPD) can utilize directly infused or systemic neurotoxins.</p> <p>Results</p> <p>We developed a differentiation protocol for human SH-SY5Y neuroblastoma that yielded non-dividing dopaminergic neural cells with long processes that we then exposed to 50 nM rotenone, a complex I inhibitor used in Parkinson's disease models. After 21 days of rotenone, ~60% of cells died. Their processes retracted and accumulated ASYN-(+) and UB-(+) aggregates that blocked organelle transport. Mitochondrial movement velocities were reduced by 8 days of rotenone and continued to decline over time. No cytoplasmic inclusions resembling Lewy bodies were observed. Gene microarray analyses showed that the majority of genes were under-expressed. qPCR analyses of 11 mtDNA-encoded and 10 nDNA-encoded mitochondrial electron transport chain RNAs' relative expressions revealed small increases in mtDNA-encoded genes and lesser regulation of nDNA-encoded ETC genes.</p> <p>Conclusion</p> <p>Subacute rotenone treatment of differentiated SH-SY5Y neuroblastoma cells causes process retraction and partial death over several weeks, slowed mitochondrial movement in processes and appears to reproduce the Lewy neuritic changes of early Parkinson's disease pathology but does not cause Lewy body inclusions. The overall pattern of transcriptional regulation is gene under-expression with minimal regulation of ETC genes in spite of rotenone's being a complex I toxin. This rotenone-SH-SY5Y model in a differentiated human neural cell mimics changes of early Parkinson's disease and may be useful for screening therapeutics for neuroprotection in that disease stage.</p