Laboratory Development

This research was sponsored by the National Science Foundation Grant NSF PHY 87-1440

Enhanced groundwater flow on and below Vera Rubin ridge, the Murray Formation, Gale Crater: Evidence from thermochemical modeling

NASAs Mars Science Laboratory Curiosity rover has been exploring Vera Rubin ridge (VRR), part of the Murray formation in Gale crater, Mars, between sol 1809 and 2302. Evidence for Fe-oxides and phyllosilicates in mineralogical and geochemical data for this region was returned by Curiosity [1-5]. We applied thermochemical modeling to con-strain the formation conditions of the phyllosilicate-hematite assemblage identified on and below VRR. Average alteration compositions for the Murray formation on and below VRR were derived using CheMin and APXS data. These compositions were reacted with Gale Portage Water (GPW) between 25100 C and for 10% and 50% Fe3+/Fetot of the host rock [6]. Here we summarize models run at 50 C and 10% Fe3+/Fetot for alteration compositions derived from Murray host rock compositions

The meaning in grandiose delusions: measure development and cohort studies in clinical psychosis and non-clinical general population groups in the UK and Ireland

Background The content of grandiose delusions—inaccurate beliefs that one has special powers, wealth, mission, or identity—is likely to be highly meaningful. The meaning, for example providing a sense of purpose, could prove to be a key factor in the delusion taking hold. We aimed to empirically define and develop measures of the experience of meaning in grandiose delusions and the sources of this meaning, and to test whether severity of grandiosity in clinical and non-clinical populations is associated with level of meaning. Methods We did a cross-sectional self-report questionnaire study in two cohorts: non-clinical participants aged 18 years and older, with UK or Irish nationality or residence; and patients with affective or non-affective psychosis diagnoses, aged 16 years and older, and accessing secondary care mental health services in 39 National Health Service providers in England and Wales. Participants with high grandiosity completed two large item pools: one assessing the experience of meaning in grandiose delusions (Grandiosity Meaning Measure [termed gram]) and one assessing the sources of meaning (Grandiosity Meaning Measure–Sources [termed grams]). The Grandiosity Meaning Measure and Grandiosity Meaning Measure–Sources were developed using exploratory factor analysis and confirmatory factor analysis. Structural equation modelling was used to test the associations of meaning with the severity of grandiosity. The primary outcome measure for grandiosity was the Specific Psychotic Experiences Questionnaire (grandiosity subscale) and associations were tested with the Grandiosity Meaning Measure and the Grandiosity Meaning Measure–Sources. Findings From Aug 30, 2019, to Nov 21, 2020, 13 323 non-clinical participants were enrolled. 2821 (21%) were men and 10 134 (76%) were women, 11 974 (90%) were White, and the mean age was 39·5 years (SD 18·6 [range 18–93]). From March 22, 2021, to March 3, 2022, 798 patients with psychosis were enrolled. 475 (60%) were men and 313 (39%) were women, 614 (77%) were White, and the mean age was 43·4 years (SD 13·8 [range 16–81]). The experience of meaning in relation to grandiose delusions had three components: coherence, purpose, and significance. The sources of meaning had seven components: positive social perceptions, spirituality, overcoming adversity, confidence in self among others, greater good, supporting loved ones, and happiness. The measurement of meaning was invariant across clinical and non-clinical populations. In the clinical population, each person typically endorsed multiple meanings and sources of meaning for the grandiose delusion. Meaning in grandiose delusions was strongly associated with severity of grandiosity, explaining 53·5% of variance, and with grandiose delusion conviction explaining 27·4% of variance. Grandiosity was especially associated with sense of purpose, and grandiose delusion conviction with coherence. Similar findings were found for the non-clinical population. Interpretation Meaning is inherently tied to grandiose delusions. This study provides a framework for research and clinical practice to understand the different types of meaning of grandiosity. The framework is likely to have clinical use in psychological therapy to help guide patients to find sources of equivalent meaning from other areas of their lives and thereby reduce the extent to which the grandiose delusion is needed

Laboratory Development

This research was sponsored by the National Science Foundation Grant NSF PHY 87-1440

A one-shot deviation principle for stability in matching problems

This paper considers marriage problems, roommate problems with nonempty core, and college admissions problems with responsive preferences. All stochastically stable matchings are shown to be contained in the set of matchings which are most robust to one-shot deviation

Metabolic reprogramming of macrophages: Glucose transporter 1 (GLUT1)-mediated glucose metabolism drives a proinflammatory phenotype

Glucose is a critical component in the proinflammatory response of macrophages (MΦs). However, the contribution of glucose transporters (GLUTs) and the mechanisms regulating subsequent glucose metabolism in the inflammatory response are not well understood. Because MΦs contribute to obesity-induced inflammation, it is important to understand how substrate metabolism may alter inflammatory function. We report that GLUT1 (SLC2A1) is the primary rate-limiting glucose transporter on proinflammatory-polarized MΦs. Furthermore, in high fat diet-fed rodents, MΦs in crown-like structures and inflammatory loci in adipose and liver, respectively, stain positively for GLUT1. We hypothesized that metabolic reprogramming via increased glucose availability could modulate the MΦ inflammatory response. To increase glucose uptake, we stably overexpressed the GLUT1 transporter in RAW264.7 MΦs (GLUT1-OE MΦs). Cellular bioenergetics analysis, metabolomics, and radiotracer studies demonstrated that GLUT1 overexpression resulted in elevated glucose uptake and metabolism, increased pentose phosphate pathway intermediates, with a complimentary reduction in cellular oxygen consumption rates. Gene expression and proteome profiling analysis revealed that GLUT1-OE MΦs demonstrated a hyperinflammatory state characterized by elevated secretion of inflammatory mediators and that this effect could be blunted by pharmacologic inhibition of glycolysis. Finally, reactive oxygen species production and evidence of oxidative stress were significantly enhanced in GLUT1-OEMΦs; antioxidant treatment blunted the expression of inflammatory mediators such as PAI-1 (plasminogen activator inhibitor 1), suggesting that glucose-mediated oxidative stress was driving the proinflammatory response. Our results indicate that increased utilization of glucose induced a ROS-driven proinflammatory phenotype in MΦs, which may play an integral role in the promotion of obesity-associated insulin resistance

No major flaws in "Identification of individuals by trait prediction using whole-genome sequencing data"

In a recently published PNAS article, we studied the identifiability of genomic samples using machine learning methods [Lippert et al., 2017]. In a response, Erlich [2017] argued that our work contained major flaws. The main technical critique of Erlich [2017] builds on a simulation experiment that shows that our proposed algorithm, which uses only a genomic sample for identification, performed no better than a strategy that uses demographic variables. Below, we show why this comparison is misleading and provide a detailed discussion of the key critical points in our analyses that have been brought up in Erlich [2017] and in the media. Further, not only faces may be derived from DNA, but a wide range of phenotypes and demographic variables. In this light, the main contribution of Lippert et al. [2017] is an algorithm that identifies genomes of individuals by combining multiple DNA-based predictive models for a myriad of traits

Shadowing in Inelastic Scattering of Muons on Carbon, Calcium and Lead at Low XBj

Nuclear shadowing is observed in the per-nucleon cross-sections of positive muons on carbon, calcium and lead as compared to deuterium. The data were taken by Fermilab experiment E665 using inelastically scattered muons of mean incident momentum 470 GeV/c. Cross-section ratios are presented in the kinematic region 0.0001 < XBj <0.56 and 0.1 < Q**2 < 80 GeVc. The data are consistent with no significant nu or Q**2 dependence at fixed XBj. As XBj decreases, the size of the shadowing effect, as well as its A dependence, are found to approach the corresponding measurements in photoproduction.Comment: 22 pages, incl. 6 figures, to be published in Z. Phys.

Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC) for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants: 2016 Update

Personalised Therapeutic

Deep exclusive π+\pi^+ electroproduction off the proton at CLAS

The exclusive electroproduction of $\pi^+$ above the resonance region was studied using the $\rm{CEBAF}$ Large Acceptance Spectrometer ($\rm{CLAS}$) at Jefferson Laboratory by scattering a 6 GeV continuous electron beam off a hydrogen target. The large acceptance and good resolution of $\rm{CLAS}$, together with the high luminosity, allowed us to measure the cross section for the $\gamma^* p \to n \pi^+$ process in 140 ($Q^2$, $x_B$, $t$) bins: $0.16<x_B<0.58$, 1.6 GeV$^2<$$Q^2$$<4.5$ GeV$^2$ and 0.1 GeV$^2<$$-t$$<5.3$ GeV$^2$. For most bins, the statistical accuracy is on the order of a few percent. Differential cross sections are compared to two theoretical models, based either on hadronic (Regge phenomenology) or on partonic (handbag diagram) degrees of freedom. Both can describe the gross features of the data reasonably well, but differ strongly in their ingredients. If the handbag approach can be validated in this kinematical region, our data contain the interesting potential to experimentally access transversity Generalized Parton Distributions.Comment: 18pages, 21figures,2table