Cabrerawalsh5453

A simple interpretation of our findings in transformed billiards, the “fictitious force,” allows us to extend our prediction to other classes of curved surfaces. This powerful analogy between two a priori unrelated systems not only brings forward an approach to control the degree of chaos, but also provides potentialities for further studies and applications in various fields, such as billiards design, optical fibers, or laser microcavities.SignificanceThe presence of RNA chemical modifications has long been known, but their precise molecular consequences remain unknown. 2'-O-methylation is an abundant modification that exists in RNA in all domains of life. Ribosomal RNA (rRNA) represents a functionally important RNA that is heavily modified by 2'-O-methylations. Although abundant at functionally important regions of the rRNA, the contribution of 2'-O-methylations to ribosome activities is unknown. By establishing a method to disturb rRNA 2'-O-methylation patterns, we show that rRNA 2'-O-methylations affect the function and fidelity of the ribosome and change the balance between different ribosome conformational states. Our work links 2'-O-methylation to ribosome dynamics and defines a set of critical rRNA 2'-O-methylations required for ribosome biogenesis and others that are dispensable.SignificanceMany bad decisions and their devastating consequences could be avoided if people used optimal decision strategies. Here, we introduce a principled computational approach to improving human decision making. learn more The basic idea is to give people feedback on how they reach their decisions. We develop a method that leverages artificial intelligence to generate this feedback in such a way that people quickly discover the best possible decision strategies. Our empirical findings suggest that a principled computational approach leads to improvements in decision-making competence that transfer to more difficult decisions in more complex environments. In the long run, this line of work might lead to apps that teach people clever strategies for decision making, reasoning, goal setting, planning, and goal achievement.Deep learning (DL) has had unprecedented success and is now entering scientific computing with full force. However, current DL methods typically suffer from instability, even when universal approximation properties guarantee the existence of stable neural networks (NNs). We address this paradox by demonstrating basic well-conditioned problems in scientific computing where one can prove the existence of NNs with great approximation qualities; however, there does not exist any algorithm, even randomized, that can train (or compute) such a NN. For any positive integers K>2 and L, there are cases where simultaneously 1) no randomized training algorithm can compute a NN correct to K digits with probability greater than 1/2; 2) there exists a deterministic training algorithm that computes a NN with K –1 correct digits, but any such (even randomized) algorithm needs arbitrarily many training data; and 3) there exists a deterministic training algorithm that computes a NN with K –2 correct digits using no more than L training samples. These results imply a classification theory describing conditions under which (stable) NNs with a given accuracy can be computed by an algorithm. We begin this theory by establishing sufficient conditions for the existence of algorithms that compute stable NNs in inverse problems. We introduce fast iterative restarted networks (FIRENETs), which we both prove and numerically verify are stable. Moreover, we prove that only O(|log (ϵ)|) layers are needed for an ϵ-accurate solution to the inverse problem.Cytokinesis is the final step of cell division during which a contractile ring forms a furrow that partitions the cytoplasm in two. How furrow ingression is spatiotemporally regulated and how it is adapted to complex cellular environments and developmental transitions remain poorly understood. Here, we examine furrow ingression dynamics in the context of the early mouse embryo and find that cell size is a powerful determinant of furrow ingression speed during reductive cell divisions. In addition, the emergence of cell polarity and the assembly of the apical domain in outer cells locally inhibits the recruitment of cytokinesis components and thereby negatively regulates furrow ingression specifically on one side of the furrow. We show that this biasing of cytokinesis is not dependent upon cell–cell adhesion or shape but rather is cell intrinsic and is caused by a paucity of cytokinetic machinery in the apical domain. The results thus reveal that in the mouse embryo cell polarity directly regulates the recruitment of cytokinetic machinery in a cell-autonomous manner and that subcellular organization can instigate differential force generation and constriction speed in different zones of the cytokinetic furrow.Multiple modes of asexual reproduction are observed among microbial organisms in natural populations. These modes are not only subject to evolution, but may drive evolutionary competition directly through their impact on population growth rates. The most prominent transition between two such modes is the one from unicellularity to multicellularity. We present a model of the evolution of reproduction modes, where a parent organism fragments into smaller parts. While the size of an organism at fragmentation, the number of offspring, and their sizes may vary a lot, the combined mass of fragments is limited by the mass of the parent organism. We found that mass conservation can fundamentally limit the number of possible reproduction modes. This has important direct implications for microbial life For unicellular species, the interplay between cell shape and kinetics of the cell growth implies that the largest and the smallest possible cells should be rod shaped rather than spherical. For primitive multicellular species, these considerations can explain why rosette cell colonies evolved a mechanistically complex binary split reproduction. Finally, we show that the loss of organism mass during sporulation can explain the macroscopic sizes of the formally unicellular microorganism Myxomycetes plasmodium. Our findings demonstrate that a number of seemingly unconnected phenomena observed in unrelated species may be different manifestations of the same underlying process.Hydrophobic interactions have long been established as essential for stabilizing struc-tured proteins as well as drivers of aggregation, but the impact of hydrophobicity on thefunctional significance of sequence variants has rarely been considered in a genome-wide context. Here we test the role of hydrophobicity on functional impact across70,000 disease- and non–disease-associated single-nucleotide polymorphisms (SNPs),using enrichment of disease association as an indicator of functionality. We find thatfunctional impact is uncorrelated with hydrophobicity of the SNP itself and only weaklycorrelated with the average local hydrophobicity, but is strongly correlated with boththe size and minimum hydrophobicity of the contiguously hydrophobic sequence (or“blob”) that contains the SNP. Disease association is found to vary by more than sixfoldas a function of contiguous hydrophobicity parameters, suggesting utility as a prior foridentifying causal variation. We further find signatures of differential selective constrainton hydrophobic blobs and that SNPs splitting a long hydrophobic blob or joiningtwo short hydrophobic blobs are particularly likely to be disease associated. Trends arepreserved for both aggregating and nonaggregating proteins, indicating that the role ofcontiguous hydrophobicity extends well beyond aggregation risk.Control over symmetry breaking in three-dimensional electromagnetic systems offers a pathway to tailoring their optical activity. We introduce fractured Pancharatnam–Berry-phase metasurface systems, in which a full-waveplate geometric phase metasurface is fractured into two half-waveplate-based metasurfaces and actively configured using shear displacement. Local relative rotations between stacked half-nanowaveplates within the metasurface system are transduced by shear displacement, leading to dynamic modulation of their collective geometric phase properties. We apply this concept to pairs of periodic Pancharatnam–Berry-phase metasurfaces and experimentally show that these systems support arbitrary and reconfigurable broadband circular birefringence response. High-speed circular birefringence modulation is demonstrated with modest shearing speeds, indicating the potential for these concepts to dynamically control polarization states with fast temporal responses. We anticipate that fractured geometric phase metasurface systems will serve as a nanophotonic platform that leverages systems-level symmetry breaking to enable active electromagnetic wave control.SignificanceOur results demonstrate the existence of early cellular pathways and network alterations in oligodendrocytes in the alpha-synucleinopathies Parkinson's disease and multiple system atrophy. They further reveal the involvement of an immune component triggered by alpha-synuclein protein, as well as a connection between (epi)genetic changes and immune reactivity in multiple system atrophy. The knowledge generated in this study could be used to devise novel therapeutic approaches to treat synucleinopathies.The sympathetic nervous system exhibits patterns of action potential (AP) discharge in human muscle sympathetic nerve activity that suggest coding strategies express reflex specificity. This study explored the interactive effects of baroreceptor unloading using lower body negative pressure (LBNP) and volitional end-expiratory apnea (APN) on sympathetic postganglionic neuronal discharge patterns inferred from the firing patterns of differently sized sympathetic AP clusters. Seven individuals were studied using multiunit microneurography (fibular) and a continuous wavelet approach to quantify AP discharge probability, recruitment, and latency during APN performed under ambient conditions, -10, and -40 mmHg LBNP. Compared with the ambient condition, LBNP increased AP discharge rate at -10 and -40 mmHg and recruited larger previously silent sympathetic neurons at -40 mmHg. Compared with spontaneous breathing, APN increased AP discharge when performed during the ambient condition (Δ351 ± 132 AP/min), -10 mmHg (Δ42te-, population-, and temporal-coding strategies. When performing end-expiratory apnea (APN) during graded baroreflex unloading via lower body negative pressure (LBNP), we found 1) augmented sympathetic axonal firing probability, 2) recruitment of larger and previously silent sympathetic postganglionic neurons at ambient and -10 mmHg, but not -40 mmHg LBNP, and 3) APN reduced axonal discharge latency similarly across all conditions, independent of the level of baroreflex unloading.Aim To evaluate the effectiveness of tele-ophthalmology (TO) versus face-to-face screening for diabetic retinopathy (DR) in diabetes care centers (DCC) across India. Methods This is an observational, multicenter, retrospective, cross-sectional study of DR screening in individuals with diabetes performed across 35 branches of a chain of DCC in 20 cities in India over 1 year. In 30 DCC, DR screening was performed by TO, where retinal images obtained using Fundus on Phone camera were uploaded through the telemedicine network for centralized DR grading by eight retina specialists. In five DCC, DR screening was performed by fundus examination (FE) by the same retina specialists. The rate of detection of sight-threatening DR (STDR) (defined as the presence of proliferative DR and/or diabetic macular edema) through the two modes was compared. Results A total of 58,612 individuals were screened for DR from January 1, 2018 to December 31, 2018 25,316 by TO and 33,296 by FE. The mean age and mean duration of diabetes of the individuals with diabetes screened by TO was 55.