Least angle and ℓ1\ell_1 penalized regression: A review

Least Angle Regression is a promising technique for variable selection applications, offering a nice alternative to stepwise regression. It provides an explanation for the similar behavior of LASSO ($\ell_1$-penalized regression) and forward stagewise regression, and provides a fast implementation of both. The idea has caught on rapidly, and sparked a great deal of research interest. In this paper, we give an overview of Least Angle Regression and the current state of related research.Comment: Published in at http://dx.doi.org/10.1214/08-SS035 the Statistics Surveys (http://www.i-journals.org/ss/) by the Institute of Mathematical Statistics (http://www.imstat.org

A transcriptional analysis of carotenoid, chlorophyll and plastidial isoprenoid biosynthesis genes during development and osmotic stress responses in Arabidopsis thaliana

<p>Abstract</p> <p>Background</p> <p>The carotenoids are pure isoprenoids that are essential components of the photosynthetic apparatus and are coordinately synthesized with chlorophylls in chloroplasts. However, little is known about the mechanisms that regulate carotenoid biosynthesis or the mechanisms that coordinate this synthesis with that of chlorophylls and other plastidial synthesized isoprenoid-derived compounds, including quinones, gibberellic acid and abscisic acid. Here, a comprehensive transcriptional analysis of individual carotenoid and isoprenoid-related biosynthesis pathway genes was performed in order to elucidate the role of transcriptional regulation in the coordinated synthesis of these compounds and to identify regulatory components that may mediate this process in <it>Arabidopsis thaliana</it>.</p> <p>Results</p> <p>A global microarray expression correlation analysis revealed that the phytoene synthase gene, which encodes the first dedicated and rate-limiting enzyme of carotenogenesis, is highly co-expressed with many photosynthesis-related genes including many isoprenoid-related biosynthesis pathway genes. Chemical and mutant analysis revealed that induction of the co-expressed genes following germination was dependent on gibberellic acid and brassinosteroids (BR) but was inhibited by abscisic acid (ABA). Mutant analyses further revealed that expression of many of the genes is suppressed in dark grown plants by Phytochrome Interacting transcription Factors (PIFs) and activated by photoactivated phytochromes, which in turn degrade PIFs and mediate a coordinated induction of the genes. The promoters of <it>PSY </it>and the co-expressed genes were found to contain an enrichment in putative BR-auxin response elements and G-boxes, which bind PIFs, further supporting a role for BRs and PIFs in regulating expression of the genes. In osmotically stressed root tissue, transcription of Calvin cycle, methylerythritol 4-phosphate pathway and carotenoid biosynthesis genes is induced and uncoupled from that of chlorophyll biosynthesis genes in a manner that is consistent with the increased synthesis of carotenoid precursors for ABA biosynthesis. In all tissues examined, induction of β-carotene hydroxylase transcript levels are linked to an increased demand for ABA.</p> <p>Conclusions</p> <p>This analysis provides compelling evidence to suggest that coordinated transcriptional regulation of isoprenoid-related biosynthesis pathway genes plays a major role in coordinating the synthesis of functionally related chloroplast localized isoprenoid-derived compounds.</p

General Relativistic Magnetohydrodynamic Simulations of the Hard State as a Magnetically-Dominated Accretion Flow

(Abridged) We present one of the first physically-motivated two-dimensional general relativistic magnetohydrodynamic (GRMHD) numerical simulations of a radiatively-cooled black-hole accretion disk. The fiducial simulation combines a total-energy-conserving formulation with a radiative cooling function, which includes bremsstrahlung, synchrotron, and Compton effects. By comparison with other simulations we show that in optically thin advection-dominated accretion flows, radiative cooling can significantly affect the structure, without necessarily leading to an optically thick, geometrically thin accretion disk. We further compare the results of our radiatively-cooled simulation to the predictions of a previously developed analytic model for such flows. For the very low stress parameter and accretion rate found in our simulated disk, we closely match a state called the "transition" solution between an outer advection-dominated accretion flow and what would be a magnetically-dominated accretion flow (MDAF) in the interior. The qualitative and quantitative agreement between the numerical and analytic models is quite good, with only a few well-understood exceptions. According to the analytic model then, at significantly higher stress or accretion, we would expect a full MDAF to form. The collection of simulations in this work also provide important data for interpreting other numerical results in the literature, as they span the most common treatments of thermodynamics, including simulations evolving: 1) the internal energy only; 2) the internal energy plus an explicit cooling function; 3) the total energy without cooling; and 4) total energy including cooling. We find that the total energy formulation is a necessary prerequisite for proper treatment of radiative cooling in MRI accretion flows.Comment: 13 pages, 7 figures, submitted to Ap

Treatment of intracranial neoplasia in dogs using higher doses: A randomized controlled trial comparing a boosted to a conventional radiation protocol

Background: Local progression of intracranial tumors can be the consequence of insufficient radiation dose delivered. Dose increases in the brain must be made carefully so as not to risk debilitating adverse effects such as radiation necrosis. Hypothesis: A new protocol with 10 × 4 Gy + 11% physical dose increase limited to the macroscopic tumor volume results in a clinically better outcome compared to a 10 × 4 Gy protocol. Animals: Fifty-seven client-owned dogs with primary intracranial neoplasia. Methods: Randomized controlled trial. Twenty-eight dogs were assigned to the control protocol (10 × 4 Gy) and 29 to the simultaneous integrated boost (SIB) protocol with 4.45 Gy dose increase. Treatment groups were compared for outcome and signs of toxicity. Results: Mild, transient acute or early-delayed adverse radiation effects were observed in 5 dogs. Severe late adverse effects were not seen. Between the protocols, no significant differences were found for outcome (intention-to-treat analysis): overall time to progression (TTP) was 708 days (95% confidence interval (95% CI) [545,872]), in the control group it was 828 days (95% CI [401,1256]), and in the SIB group 627 days (95% CI [282,973]; P = .07). Median overall survival (OS) was 684 days (95% CI [516,853]), in the control group it was 724 days (95% CI [623,826]), and in the SIB group 557 days (95% CI [95,1020]; P = .47). None of the tested variables was prognostic in terms of outcome. Conclusion and clinical importance: The dose escalation used with an 11% physical dose increase did not result in better outcome

Co-expression and promoter content analyses assign a role in biotic and abiotic stress responses to plant natriuretic peptides

<p>Abstract</p> <p>Background</p> <p>Plant natriuretic peptides (PNPs) are a class of systemically mobile molecules distantly related to expansins. While several physiological responses to PNPs have been reported, their biological role has remained elusive. Here we use a combination of expression correlation analysis, meta-analysis of gene expression profiles in response to specific stimuli and in selected mutants, and promoter content analysis to infer the biological role of the <it>Arabidopsis thaliana </it>PNP, AtPNP-A.</p> <p>Results</p> <p>A gene ontology analysis of <it>AtPNP-A </it>and the 25 most expression correlated genes revealed a significant over representation of genes annotated as part of the systemic acquired resistance (SAR) pathway. Transcription of these genes is strongly induced in response to salicylic acid (SA) and its functional synthetic analogue benzothiadiazole S-methylester (BTH), a number of biotic and abiotic stresses including many SA-mediated SAR-inducing conditions, as well as in the constitutive SAR expressing mutants <it>cpr5 </it>and <it>mpk4 </it>which have elevated SA levels. Furthermore, the expression of <it>AtPNP-A </it>was determined to be significantly correlated with the SAR annotated transcription factor, <it>WRKY 70</it>, and the promoters of <it>AtPNP-A </it>and the correlated genes contain an enrichment in the core WRKY binding W-box <it>cis</it>-elements. In constitutively expressing <it>WRKY 70 </it>lines the expression of <it>AtPNP-A </it>and the correlated genes, including the SAR marker genes, <it>PR-2 </it>and <it>PR-5</it>, were determined to be strongly induced.</p> <p>Conclusion</p> <p>The co-expression analyses, both in wild type and mutants, provides compelling evidence that suggests <it>AtPNP-A </it>may function as a component of plant defence responses and SAR in particular. The presented evidence also suggests that the expression of <it>AtPNP-A </it>is controlled by WRKY transcription factors and WRKY 70 in particular. <it>AtPNP-A </it>shares many characteristics with PR proteins in that its transcription is strongly induced in response to pathogen challenges, it contains an N-terminal signalling peptide and is secreted into the extracellular space and along with PR-1, PR-2 and PR-5 proteins it has been isolated from the Arabidopsis apoplast. Based on these findings we suggest that <it>AtPNP-A </it>could be classified as a newly identified PR protein.</p

Harman and Lorandos’ False Critique of Meier et al.’s Family Court Study

Jennifer Harman and Demosthenes Lorandos purport to have identified numerous methodological flaws in our 2019 study of family court outcomes in cases involving abuse and alienation allegations (“FCO study”; Meier et al., 2019). At least half of the supposed flaws they itemized relate to one claim - that they were unable to access our methods and data. They treat the claimed lack of public access as evidence that our study is unreliable, while speculating about other potential flaws. Yet we note - and they acknowledge - that most of the methodological information they sought was in fact available before publication of their article. This article responds to and refutes Harman and Lorandos’ exaggerated and unfounded condemnation of our study. In addition to pointing out that the claimed lack of information would not be a methodological flaw even if true, we explain that their other criticisms are speculative, incorrect, or insignificant. We appreciate this opportunity to clarify that the important findings of the FCO study are valid and should be taken seriously by the courts and those interested in the fairness and safety of custody decisions when there are allegations of abuse and alienation

Child Custody Outcomes in Cases Involving Parental Alienation and Abuse Allegations

Arguably the most troubling aspect of justice system response to intimate partner violence is custody courts\u27 failure to protect children when mothers allege the father is abusive. Family courts\u27 errors in assessing adult and child abuse, and punitive responses to abuse allegations, have been widely documented. A significant contributor to these errors is the pseudo-scientific theory of parental alienation (PA). Originally termed parental alienation syndrome (PAS), the theory suggests that when mothers allege that a child is not safe with the father, they are doing so illegitimately, to alienate the child from the father. PA labeling often results in dismissal of women\u27s and children\u27s reports of abuse, and sometimes trumps even expert child abuse evaluations. PAS was explicitly based on negative stereotypes of mothers and has been widely discredited. The term parental alienation – while treated as distinct - is still widely used in ways that are virtually identical to PAS. Nonetheless, because PA is nominally gender neutral (and not called a scientific syndrome), it continues to have substantial credibility in court. The first goal of this project was to ascertain whether empirical evidence indicates that parental alienation is, like PAS, gender-biased in practice and outcome. Second, the study sought to explore outcomes in custody/abuse litigation by gender and by differing types of abuse. Analysis of over 2000 court opinions confirms that courts are skeptical of mothers’ claims of abuse by fathers; this skepticism is greatest when mothers claim child abuse. The findings also confirm that fathers’ cross-claims of parental alienation increase (virtually doubling) courts’ rejection of mothers’ abuse claims, and mothers’ losses of custody to the father accused of abuse. In comparing court responses when fathers accuse mothers of abuse, a significant gender difference is identified. Finally, the findings indicate that where Guardians Ad Litem or custody evaluators are appointed, unfavorable outcomes for mothers and gender differences are increased. The study relies solely on electronically available published opinions in child custody cases. It has produced an invaluable database identifying 10 years of published cases involving alienation, abuse and custody, while coding parties’ claims and defenses, outcomes, and other key factors by gender and parental status

The trouble with Harman and Lorandos’s attempted refutation of the Meier et al. Family court study

Harman and Lorandos assert that they have produced a study analyzing custody cases involving alienation allegations, which “disconfirms” the findings from our study of family court out- comes in cases involving abuse and alienation. In addition to pointing out the authors’ misrepresentation and mis-reporting of some of their findings, this Response details a series of profound flaws in their study’s design, dataset construction and variable coding, interpretations and analytic approach, as well as a series of statistical errors. The statistical analyses demonstrate that Harman and Lorandos’s five findings of a gender bias in favor of fathers are not supported by their data; the only statistically significant findings that persist after re-analysis of the correct data are consistent with the Meier et al. study. These pervasive design and methodological errors undermine both the appearance and assertion of rigor in their approach; these problems and the foundational differences in their dataset from our own disqualify their study from serving as any kind of credible test or disconfirmation of our study