Estimation of high-dimensional low-rank matrices

Suppose that we observe entries or, more generally, linear combinations of entries of an unknown $m\times T$-matrix $A$ corrupted by noise. We are particularly interested in the high-dimensional setting where the number $mT$ of unknown entries can be much larger than the sample size $N$. Motivated by several applications, we consider estimation of matrix $A$ under the assumption that it has small rank. This can be viewed as dimension reduction or sparsity assumption. In order to shrink toward a low-rank representation, we investigate penalized least squares estimators with a Schatten-$p$ quasi-norm penalty term, $p\leq1$. We study these estimators under two possible assumptions---a modified version of the restricted isometry condition and a uniform bound on the ratio "empirical norm induced by the sampling operator/Frobenius norm." The main results are stated as nonasymptotic upper bounds on the prediction risk and on the Schatten-$q$ risk of the estimators, where $q\in[p,2]$. The rates that we obtain for the prediction risk are of the form $rm/N$ (for $m=T$), up to logarithmic factors, where $r$ is the rank of $A$. The particular examples of multi-task learning and matrix completion are worked out in detail. The proofs are based on tools from the theory of empirical processes. As a by-product, we derive bounds for the $k$th entropy numbers of the quasi-convex Schatten class embeddings $S_p^M\hookrightarrow S_2^M$, $p<1$, which are of independent interest.Comment: Published in at http://dx.doi.org/10.1214/10-AOS860 the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org

The Effect of Lockdowns on the Status of Women in the World

Coronavirus disease (COVID-19) is an infectious respiratory illness that causes moderate to severe symptoms that can be fatal to older people or those with other underlying health concerns. Considered a global pandemic, this disease spreads rapidly across the world, calling for a need for the implementation of lockdowns. This study examines the effects of lockdowns on joblessness among women, controlling for household conditions, namely, perceived household responsibility, hours allotted for household chores, and safety at home. Data for lockdowns were sourced from Google’s Community Mobility reports, whereas joblessness among women and household conditions were sourced from Facebook’s Survey on Gender Equality at Home. The findings suggest that lockdowns positively and significantly affect joblessness among women and that household conditions (hours allotted for household chores and safety at home) also have the same effect, except for perceived household responsibility. The implications of these results are discussed in detail throughout the study

Nuclear Factor-κB-Independent Anti-Inflammatory Action of Salicylate in Human Endothelial Cells

In contrast to aspirin, salicylate, its active metabolite, possesses profound anti-inflammatory properties without blocking cyclooxygenase. Inhibition of the transcription factor nuclear factor-κB (NF-κB) has been discussed to play a role in the anti-inflammatory profile of salicylate. However, NF-κB-independent effects of salicylate have been assumed but have up to now been poorly investigated. Therefore, the aim of the present study was to investigate NF-κB-independent anti-inflammatory mechanisms of salicylate in human umbilical vein endothelial cells using interleukin-4 (IL-4) as NF-κB-independent proinflammatory stimulus and P-selectin as inflammatory read-out parameter. Using quantitative real-time reverse transcriptionpolymerase chain reaction, we found that salicylate decreases IL-4-induced P-selectin expression. As judged by Western blot analysis, salicylate increased endothelial heme oxygenase-1 (HO-1) protein levels. Using both the HO-1 inhibitor tin(II) protoporphyrin IX and HO-1 antisense oligonucleotides, we causally linked the induction of HO-1 to the decrease of P-selectin. Moreover, we were interested in the signaling mechanisms leading to the up-regulation of HO-1 by salicylate. c-Jun NH2-terminal kinase (JNK) was found to be activated by salicylate, and we could causally link this activation to the induction of HO-1 by using the JNK inhibitor 1,9-pyrazoloanthrone. By applying activator protein-1 (AP-1) decoys, it was shown that the transcription factor AP-1 is crucially involved in the up-regulation of HO-1 downstream of JNK. In summary, our study introduces HO-1 as novel NF-κB-independent anti-inflammatory target of salicylate in human endothelial cells. Moreover, we elucidated the JNK/AP-1 pathway as crucial for the induction of HO-1 by salicylate

Aneuploidy triggers a TFEB-mediated lysosomal stress response

Aneuploidy, defined as an alteration in chromosome number that is not a multiple of the haploid complement, severely affects cellular physiology. Changes in chromosome number lead to imbalances in cellular protein composition, thus disrupting cellular processes and causing proteins to misfold and aggregate. We recently reported that in mammalian cells protein aggregates are readily encapsulated within autophagosomes but are not degraded by lysosomes. This leads to a lysosomal stress response in which the transcription factor TFEB induces expression of factors needed for macroautophagy-mediated protein degradation. Our studies uncover lysosomal degradation defects as a feature of the aneuploid state, and a role for the transcription factor TFEB in the response thereto. Keywords: aneuploidy; autophagy; cancer; proteotoxicity; TFE

Fluorine in silicate glasses: A multinuclear nuclear magnetic resonance study

Anhydrous nepheline, jadeite, and albite glasses doped with F as well as hydrous F-containing haplogranitic glasses were investigated using 19F combined rotation and multiple-pulse spectroscopy; 19F → 29Si cross-polarization/magic angle spinning (MAS); and high-power 19F decoupled 29Si, 23Na, and 27Al MAS nuclear magnetic resonance methods. Fluorine preferentially coordinates with Al to form octahedral AlF63− complexes in all glasses studied. In addition, F anions bridging two Al cations, units containing octahedral Al coordinated by both O and F, or tetrahedral Al-F complexes might be present. The presence of Si-F bonds cannot be entirely ruled out but appears unlikely on the basis of the 19F → 29Si CP/MAS spectra. There is no evidence for any significant coordination of F with alkalis in the glasses studied. 23Na spectra are identical for the samples and their F-free equivalents and the spectra do not change upon decoupling of 19F. The speciation of F in the hydrous and anhydrous glasses appears to be very similar. Over the range of F contents studied ( up to 5 wt.% ), there seems to be hardly any dependence of F speciation on the concentration of F in the samples. The spectroscopic results explain the decrease of the viscosity of silicate melts with increasing F content by removal of Al from bridging AlO4-units due to complexing with F, which causes depolymerization of the melt. The same mechanism can account for the shift of the eutectic point in the haplogranite system to more feldspar-rich compositions with increasing F content, and for the peraluminous composition of most F-rich granites. Liquid immiscibility in F-rich granitic melts might be caused by formation of (Na,K)3AlF6 units in the melt with little or no interaction with the silicate component. The presence of F in granitic melts might increase the solubility of high field strength cations by making nonbridging O atoms available which form complexes with these cations

Gamete Formation Resets the Aging Clock in Yeast

Gametogenesis is a process whereby a germ cell differentiates into haploid gametes. We found that, in budding yeast, replicatively aged cells remove age-induced cellular damage during gametogenesis. Importantly, gametes of aged cells have the same replicative potential as those derived from young cells, indicating that life span resets during gametogenesis. Here, we explore the potential mechanisms responsible for gametogenesis-induced rejuvenation and discuss putative analogous mechanisms in higher eukaryotes.National Institutes of Health (U.S.) (grant GM62207

Short- and long-term effects of chromosome mis-segregation and aneuploidy

Dividing cells that experience chromosome mis-segregation generate aneuploid daughter cells, which contain an incorrect number of chromosomes. Although aneuploidy interferes with the proliferation of untransformed cells, it is also, paradoxically, a hallmark of cancer, a disease defined by increased proliferative potential. These contradictory effects are also observed in mouse models of chromosome instability (CIN). CIN can inhibit and promote tumorigenesis. Recent work has provided insights into the cellular consequences of CIN and aneuploidy. Chromosome mis-segregation per se can alter the genome in many more ways than just causing the gain or loss of chromosomes. The short- and long-term effects of aneuploidy are caused by gene-specific effects and a stereotypic aneuploidy stress response. Importantly, these recent findings provide insights into the role of aneuploidy in tumorigenesis.National Institutes of Health (U.S.) (Grant GM56800

Gametogenesis Eliminates Age-Induced Cellular Damage and Resets Life Span in Yeast

Eukaryotic organisms age, yet detrimental age-associated traits are not passed on to progeny. How life span is reset from one generation to the next is not known. We show that in budding yeast resetting of life span occurs during gametogenesis. Gametes (spores) generated by aged cells show the same replicative potential as gametes generated by young cells. Age-associated damage is no longer detectable in mature gametes. Furthermore, transient induction of a transcription factor essential for later stages of gametogenesis extends the replicative life span of aged cells. Our results indicate that gamete formation brings about rejuvenation by eliminating age-induced cellular damage.National Institutes of Health (U.S.) (Grant GM62207

DRG-targeted helper-dependent adenoviruses mediate selective gene delivery for therapeutic rescue of sensory neuronopathies in mice

Dorsal root ganglion (DRG) neuron dysfunction occurs in a variety of sensory neuronopathies for which there are currently no satisfactory treatments. Here we describe the development of a strategy to target therapeutic genes to DRG neurons for the treatment of these disorders. We genetically modified an adenovirus (Ad) to generate a helper virus (HV) that was detargeted for native adenoviral tropism and contained DRG homing peptides in the adenoviral capsid fiber protein; we used this HV to generate DRG-targeted helper-dependent Ad (HDAd). In mice, intrathecal injection of this HDAd produced a 100-fold higher transduction of DRG neurons and a markedly attenuated inflammatory response compared with unmodified HDAd. We also injected HDAd encoding the β subunit of β-hexosaminidase (Hexb) into Hexb-deficient mice, a model of the neuronopathy Sandhoff disease. Delivery of the DRG-targeted HDAd reinstated neuron-specific Hexb production, reversed gangliosidosis, and ameliorated peripheral sensory dysfunction. The development of DRG neuron–targeted HDAd with proven efficacy in a preclinical model may have implications for the treatment of sensory neuronopathies of diverse etiologies