Deadly Secrecy: The Erosion of Public Information Under Private Justice

Published in cooperation with the American Bar Association Section of Dispute Resolutio

Comparison of the DNA Association Kinetics of the Lacy Repressor Tetramet, Its Dimeric Mutant LacI(Adi), and the Native Dimeric Gal Repressor

The rates of association of the tetrameric Lacy repressor (LacI), dimeric LacI(adi) (a deletion mutant of LacI), and the native dimeric Gal repressor (GalR) to DNA restriction fragments containing a single specific site were investigated using a quench-flow DNase I \u27foot-printing\u27 technique. The dimeric proteins, LacI(adi) and GalR, and tetrameric LacI possess one and two DNA binding sites, respectively. The nanomolar protein concentrations used in these studies ensured that the state of oligomerization of each protein was predominantly either dimeric or tetrameric, respectively. The bimolecular association rate constants (k(a)) determined for the LacI tetramer exceed those of the dimeric proteins. The values of k(a) obtained for LacI, LacI(adi), and GalR display different dependences on [KCl]. For LacI(adi) and GalR, they diminish as [KCl] increases from 25 mM to 200 mM, approaching rates predicted for three-dimensional diffusion. In contrast, the k(a) values determined for the tetrameric LacI remain constant up to 300 mM [KCl], the highest salt concentration that could be investigated by quench- flow footprinting. The enhanced rate of association of the tetramer relative to the dimeric proteins can be modeled by enhanced \u27sliding\u27 (Berg, O. G., Winter, R. B., and von Hippel, P. H. (1981) Biochemistry 20, 6929-6948) of the LacI tetramer relative to the LaeI(adi) dimer or a combination of enhanced sliding and the superimposition of \u27direct transfer\u27 mediated by the bidentate DNA interactions of the tetramer

Neurogenesis in an adult avian song nucleus is reduced by decreasing caspase-mediated apoptosis

Neuron death and replacement are fundamental components of brain plasticity. Much remains unknown, however, about the mechanistic interaction between neuron death and neurogenesis in adult vertebrates. In seasonally breeding adult male white-crowned sparrows, the song system nucleus HVC loses ∼26% of its neurons via caspase-dependent apoptosis within 4 d after a transition to nonbreeding physiological conditions. To determine whether neuronal death is necessary for the recruitment of new neurons, we infused caspase inhibitors into HVC in vivo and suppressed neurodegeneration for at least 20 d after the transition to nonbreeding conditions. The blockade of HVC neuron death reduced the number and density of new neurons recruited to the ipsilateral HVC by 48 and 29%, respectively, compared with contralateral HVC. Our results are the first to show that reducing neuronal death in the adult brain decreases the recruitment of new neurons

Treated Hypothyroidism Is Associated with Cerebrovascular Disease but Not Alzheimer\u27s Disease Pathology in Older Adults

Thyroid hormone (TH) disease is common among older adults and is associated with cognitive impairment. However, pathologic correlates are not well understood. We studied pathologic and clinical factors associated with hypothyroidism, the most common form of TH disease, in research subjects seen annually for clinical evaluations at U.S. Alzheimer’s Disease Centers. Thyroid disease and treatment status were assessed during clinician interviews. Among autopsied subjects, there were 555 participants with treated hypothyroidism and 2,146 with no known thyroid disease; hypothyroidism was associated with severe atherosclerosis (OR=1.35 95% CI: 1.02, 1.79) but not Alzheimer’s disease (AD) pathologies (amyloid plaques or neurofibrillary tangles). Among participants that did not come to autopsy (4,598 with treated hypothyroidism and 20,045 without known TH disease), hypercholesterolemia and cerebrovascular disease (stroke and transient ischemic attack) were associated with hypothyroidism, complementing findings in the smaller autopsy sample. This is the first large-scale evaluation of neuropathologic concomitants of hypothyroidism in aged individuals. Clinical hypothyroidism was prevalent (~25% of individuals studied) and was associated with cerebrovascular disease but not AD-type neuropathology

Improving the predictions of ML-corrected climate models with novelty detection

While previous works have shown that machine learning (ML) can improve the prediction accuracy of coarse-grid climate models, these ML-augmented methods are more vulnerable to irregular inputs than the traditional physics-based models they rely on. Because ML-predicted corrections feed back into the climate model's base physics, the ML-corrected model regularly produces out of sample data, which can cause model instability and frequent crashes. This work shows that adding semi-supervised novelty detection to identify out-of-sample data and disable the ML-correction accordingly stabilizes simulations and sharply improves the quality of predictions. We design an augmented climate model with a one-class support vector machine (OCSVM) novelty detector that provides better temperature and precipitation forecasts in a year-long simulation than either a baseline (no-ML) or a standard ML-corrected run. By improving the accuracy of coarse-grid climate models, this work helps make accurate climate models accessible to researchers without massive computational resources.Comment: Appearing at Tackling Climate Change with Machine Learning Workshop at NeurIPS 202