The effects of aneuploidy on gene expression in a dosage series of maize chromosome arm 1L /

Aneuploidy is a class of genetic conditions involving an unbalanced number of chromosomes. The most familiar human aneuploid condition is trisomy 21, called Down syndrome. Aneuploid conditions necessarily involve a change in the dosage of those genes which are located on the varied chromosome. However, the dosage level of a gene does not automatically correspond to the amount of RNA or protein that will be produced in vivo. Based on previously published studies, the impact of chromosome dosage changes on the transcription of single genes may be direct, inverse, or anywhere in between; and genes may be impacted anywhere in the genome, not just on the varied chromosome. Using a maize model system, a dosage series of plants was produced in which sibling plants are identical, except for the copy number of chromosome arm 1L. These plants were grown until 45 days postgermination, at which point leaf tissue was collected for RNA extraction. This dosage series included 5 dosage levels for comparison: diploid, trisomic, tetrasomic, haploid, and disomic haploid. A second dosage series was grown up to day 55, and included diploid, monosomic, and trisomic. Using RNA sequencing, expression levels for all genes were determined. The results were analyzed in aggregate, allowing for a view of effects on the level of the whole transcriptome. Results suggest that dosage of genes on the varied chromosome region has some correlation with expression of those genes, though the change compared to a diploid is often partial. Inverse relationships between chromosome dosage and RNA expression of genes elsewhere in the genome are seen to occur. Both direct and inverse reactions were amplified by increased levels of genomic imbalance. The kinetics of interacting proteins and other cellular components, as described in the gene balance hypothesis, may be the mechanism leading to these responses. Using the same methods of analysis, similar phenomena were observed in aneuploid/euploid comparisons in other organisms. Partial dosage compensation and inverse effects were observed in published datasets from aneuploid yeast and mouse. A set of trisomics in Arabidopsis displayed the same effects, though to a different extent in different trisomies. Using a published database of transcription factors, the responses of genes to dosage changes of their regulators was analyzed. A number of cascade effects were observed, in which inverse relationships of transcription factor dosage and target gene expression occurred sequentially, disrupting normal regulation of several genes in a network by changing the dosage of a single component.Dr. James Birchler, Dissertation Supervisor.|Includes vita.Includes bibliographical references (pages 88-90)

Online detection and sorting of extracellularly recorded action potentials in human medial temporal lobe recordings, in vivo

Understanding the function of complex cortical circuits requires the simultaneous recording of action potentials from many neurons in awake and behaving animals. Practically, this can be achieved by extracellularly recording from multiple brain sites using single wire electrodes. However, in densely packed neural structures such as the human hippocampus, a single electrode can record the activity of multiple neurons. Thus, analytic techniques that differentiate action potentials of different neurons are required. Offline spike sorting approaches are currently used to detect and sort action potentials after finishing the experiment. Because the opportunities to record from the human brain are relatively rare, it is desirable to analyze large numbers of simultaneous recordings quickly using online sorting and detection algorithms. In this way, the experiment can be optimized for the particular response properties of the recorded neurons. Here we present and evaluate a method that is capable of detecting and sorting extracellular single-wire recordings in realtime. We demonstrate the utility of the method by applying it to an extensive data set we acquired from chronically-implanted depth electrodes in the hippocampus of human epilepsy patients. This dataset is particularly challenging because it was recorded in a noisy clinical environment. This method will allow the development of closed-loop experiments, which immediately adapt the experimental stimuli and/or tasks to the neural response observed.Comment: 9 figures, 2 tables. Journal of Neuroscience Methods 2006 (in press). Journal of Neuroscience Methods, 2006 (in press

Science and Ideology in Economic, Political, and Social Thought

This paper has two sources: One is my own research in three broad areas: business cycles, economic measurement and social choice. In all of these fields I attempted to apply the basic precepts of the scientific method as it is understood in the natural sciences. I found that my effort at using natural science methods in economics was met with little understanding and often considerable hostility. I found economics to be driven less by common sense and empirical evidence, then by various ideologies that exhibited either a political or a methodological bias, or both. This brings me to the second source: Several books have appeared recently that describe in historical terms the ideological forces that have shaped either the direct areas in which I worked, or a broader background. These books taught me that the ideological forces in the social sciences are even stronger than I imagined on the basis of my own experiences. The scientific method is the antipode to ideology. I feel that the scientific work that I have done on specific, long standing and fundamental problems in economics and political science have given me additional insights into the destructive role of ideology beyond the history of thought orientation of the works I will be discussing

Systematic Review and Meta-Analysis: An Empirical Approach to Defining Treatment Response and Remission in Pediatric Obsessive-Compulsive Disorder

©. This manuscript version is made available under the CC-BY-NC 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the, Submitted, version of a Published Work that appeared in final form in Journal of the American Academy of Child and Adolescent Psychiatry. To access the final edited and published work see: https://doi.org/10.1016/j.jaac.2021.05.027Objective: A lack of universal definitions for response and remission in pediatric obsessive- compulsive disorder (OCD) has hampered the comparability of results across trials. To address this problem, we conducted an individual participant data diagnostic test accuracy meta-analysis to evaluate the discriminative ability of the Children’s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) in determining response and remission. We also aimed to generate empirically derived cutoffs on the CY-BOCS for these outcomes. Method: A systematic review of PubMed, PsycINFO, Embase and CENTRAL identified 5,401 references, 42 randomized controlled clinical trials (RCTs) were considered eligible and 21 provided data for inclusion (N 1,234). A score ≤ 2 in the Clinical Global Impressions Improvement and Severity scales were chosen to define response and remission, respectively. A two-stage random-effects meta-analysis model was established. The area under the curve (AUC) and the Youden Index were computed to indicate the discriminative ability of the CY-BOCS and to guide for the optimal cutoff, respectively. Results: The CY-BOCS had sufficient discriminative ability to determine response (AUC 0.89) and remission (AUC 0.92). The optimal cutoff for response was a ≥ 35% reduction from baseline to posttreatment (sensitivity [95% CI] 83.9 [83.7, 84.1]; specificity [95% CI] 81.7 [81.5, 81.9]). The optimal cutoff for remission was a posttreatment raw score ≤ 12 (sensitivity [95% CI] 82.0 [81.8, 82.2]; specificity [95% CI] 84.6 [84.4, 84.8]). Conclusion: Meta-analysis identified empirically optimal cutoffs on the CY-BOCS to determine response and remission in pediatric OCD RCTs. Systematic adoption of standardized operational definitions for response and remission will improve comparability across trials for pediatric OCD

Measurement of the Forward-Backward Asymmetry in the B -> K(*) mu+ mu- Decay and First Observation of the Bs -> phi mu+ mu- Decay

We reconstruct the rare decays $B^+ \to K^+\mu^+\mu^-$, $B^0 \to K^{*}(892)^0\mu^+\mu^-$, and $B^0_s \to \phi(1020)\mu^+\mu^-$ in a data sample corresponding to $4.4 {\rm fb^{-1}}$ collected in $p\bar{p}$ collisions at $\sqrt{s}=1.96 {\rm TeV}$ by the CDF II detector at the Fermilab Tevatron Collider. Using $121 \pm 16$ $B^+ \to K^+\mu^+\mu^-$ and $101 \pm 12$ $B^0 \to K^{*0}\mu^+\mu^-$ decays we report the branching ratios. In addition, we report the measurement of the differential branching ratio and the muon forward-backward asymmetry in the $B^+$ and $B^0$ decay modes, and the $K^{*0}$ longitudinal polarization in the $B^0$ decay mode with respect to the squared dimuon mass. These are consistent with the theoretical prediction from the standard model, and most recent determinations from other experiments and of comparable accuracy. We also report the first observation of the $B^0_s \to \phi\mu^+\mu^- decay and measure its branching ratio${\mathcal{B}}(B^0_s \to \phi\mu^+\mu^-) = [1.44 \pm 0.33 \pm 0.46] \times 10^{-6}$using$27 \pm 6$signal events. This is currently the most rare$B^0_s$ decay observed.Comment: 7 pages, 2 figures, 3 tables. Submitted to Phys. Rev. Let

Search for a New Heavy Gauge Boson Wprime with Electron + missing ET Event Signature in ppbar collisions at sqrt(s)=1.96 TeV

We present a search for a new heavy charged vector boson $W^\prime$ decaying to an electron-neutrino pair in $p\bar{p}$ collisions at a center-of-mass energy of 1.96\unit{TeV}. The data were collected with the CDF II detector and correspond to an integrated luminosity of 5.3\unit{fb}^{-1}. No significant excess above the standard model expectation is observed and we set upper limits on $\sigma\cdot{\cal B}(W^\prime\to e\nu)$. Assuming standard model couplings to fermions and the neutrino from the $W^\prime$ boson decay to be light, we exclude a $W^\prime$ boson with mass less than 1.12\unit{TeV/}c^2 at the 95\unit{%} confidence level.Comment: 7 pages, 2 figures Submitted to PR

Measurements of the properties of Lambda_c(2595), Lambda_c(2625), Sigma_c(2455), and Sigma_c(2520) baryons

We report measurements of the resonance properties of Lambda_c(2595)+ and Lambda_c(2625)+ baryons in their decays to Lambda_c+ pi+ pi- as well as Sigma_c(2455)++,0 and Sigma_c(2520)++,0 baryons in their decays to Lambda_c+ pi+/- final states. These measurements are performed using data corresponding to 5.2/fb of integrated luminosity from ppbar collisions at sqrt(s) = 1.96 TeV, collected with the CDF II detector at the Fermilab Tevatron. Exploiting the largest available charmed baryon sample, we measure masses and decay widths with uncertainties comparable to the world averages for Sigma_c states, and significantly smaller uncertainties than the world averages for excited Lambda_c+ states.Comment: added one reference and one table, changed order of figures, 17 pages, 15 figure

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV