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Researchers have uncovered a surprising culprit behind sleep loss in Alzheimer’s disease: the brain’s own immune cells。 In mice with amyloid plaques, overactive microglia triggered inflammation that kept the brain from getting enough deep, restorative sleep。 Temporarily removing most of these cells restored more than two hours of sleep per day, eve

Dying Sun-like stars may not fade away quietly。 As blobs of gas erupt unevenly from their swollen surfaces, each burst gives the star a tiny push in the opposite direction。 Thousands of these random kicks could eventually break apart distant stellar pairs or, in rare cases, drive two stars into a violent collision

From powerful air movers and whisper-quiet pedestal models to options that double as misters, lamps, and air purifiers, these are the fans that impressed us most

A new review highlights exciting progress in atomically thin quantum materials where light and magnetism work together in ways never before possible。 In these materials, light-generated excitons can interact directly with magnetic behavior, creating opportunities to control magnetic states using light alone。 Scientists believe this could pave the w

Troops received an email informing them that they were rapidly depleting their AI tokens

The company said earlier this year it expected to spend as much as $190bn on AI investments

Originally published as Lindblom, C.E. (1959). The science of muddling through, Public Administration Review, 19(2): 79-88. Reprinted with kind permission. For a critical analysis of this issue's Classic Paper The Science of 'Muddling' by Charles E. Lindblom, please refer to Ronald J. Scott, Jr.'s article The Science of Muddling Through Revisited on pages 5-18. SUPPOSE an administrator is given responsibility for formulating policy with respect to inflation. He might start by trying to list all related values in order of importance, e.g., full employment, reasonable business profit, protection of small savings, prevention of a stock market crash. Then all possible policy outcomes could be rated as more or less efficient in attaining a maximum of these values. This would of course require a prodigious inquiry into values held by members of society and an equally prodigious set of calculations on how much of each value is equal to how much of each other value. He could then proceed to outline all possible policy alternatives. In a third step, he would undertake systematic comparison of his multitude of alternatives to determine which attains the greatest amount of values. In comparing policies, he would take advantage of any theory available that generalized about classes of policies. In considering inflation, for example, he would compare all policies in the light of the theory of prices. Since no alternatives are beyond his investigation, he would consider strict central control and the abolition of all prices and markets on the one hand and elimination of all public controls with reliance completely on the free market on the other, both in the light of whatever theoretical generalizations he could find on such hypothetical economies. Finally, he would try to make the choice that would in fact maximize his values. An alternative line of attack would be to set as his principal objective, either explicitly or without conscious thought, the relatively simple goal of keeping prices level. This objective might be compromised or complicated by only a few other goals, such as full employment. He would in fact disregard most other social values as beyond his present interest, and he would for the moment not even attempt to rank the few values that he regarded as immediately relevant. Were he pressed, he would quickly admit that he was ignoring many related values and many possible important consequences of his policies. As a second step, he would outline those relatively few policy alternatives that occurred to him. He would then compare them. In comparing his limited number of alternatives, most of them familiar from past controversies, he would not ordinarily find a body of theory precise enough to carry him through a comparison of their respective consequences. Instead he would rely heavily on the record of past experience with small policy steps to predict the consequences of similar steps extended into the future. Moreover, he would find that the policy alternatives combined objectives or values in different ways. For example, one policy might offer price level stability at the cost of some risk of unemployment; another might offer less price stability but also less risk of unemployment. Hence, the next step in his approach-the final selection- would combine into one the choice among values and the choice among instruments for reaching values. It would not, as in the first method of policymaking, approximate a more mechanical process of choosing the means that best satisfied goals that were previously clarified and ranked. Because practitioners of the second approach expect to achieve their goals only partially, they would expect to repeat endlessly the sequence just described, as conditions and aspirations changed and as accuracy of prediction improved. By Root or by Branch For complex problems, the first of these two approaches is of course impossible. …

BACKGROUND: Sepsis represents a substantial health care burden, and there is limited epidemiologic information about the demography of sepsis or about the temporal changes in its incidence and outcome. We investigated the epidemiology of sepsis in the United States, with specific examination of race and sex, causative organisms, the disposition of patients, and the incidence and outcome. METHODS: We analyzed the occurrence of sepsis from 1979 through 2000 using a nationally representative sample of all nonfederal acute care hospitals in the United States. Data on new cases were obtained from hospital discharge records coded according to the International Classification of Diseases, Ninth Revision, Clinical Modification. RESULTS: Review of discharge data on approximately 750 million hospitalizations in the United States over the 22-year period identified 10,319,418 cases of sepsis. Sepsis was more common among men than among women (mean annual relative risk, 1.28 [95 percent confidence interval, 1.24 to 1.32]) and among nonwhite persons than among white persons (mean annual relative risk, 1.90 [95 percent confidence interval, 1.81 to 2.00]). Between 1979 and 2000, there was an annualized increase in the incidence of sepsis of 8.7 percent, from about 164,000 cases (82.7 per 100,000 population) to nearly 660,000 cases (240.4 per 100,000 population). The rate of sepsis due to fungal organisms increased by 207 percent, with gram-positive bacteria becoming the predominant pathogens after 1987. The total in-hospital mortality rate fell from 27.8 percent during the period from 1979 through 1984 to 17.9 percent during the period from 1995 through 2000, yet the total number of deaths continued to increase. Mortality was highest among black men. Organ failure contributed cumulatively to mortality, with temporal improvements in survival among patients with fewer than three failing organs. The average length of the hospital stay decreased, and the rate of discharge to nonacute care medical facilities increased. CONCLUSIONS: The incidence of sepsis and the number of sepsis-related deaths are increasing, although the overall mortality rate among patients with sepsis is declining. There are also disparities among races and between men and women in the incidence of sepsis. Gram-positive bacteria and fungal organisms are increasingly common causes of sepsis.

Because it lacks a lymphatic circulation, the brain must clear extracellular proteins by an alternative mechanism. The cerebrospinal fluid (CSF) functions as a sink for brain extracellular solutes, but it is not clear how solutes from the brain interstitium move from the parenchyma to the CSF. We demonstrate that a substantial portion of subarachnoid CSF cycles through the brain interstitial space. On the basis of in vivo two-photon imaging of small fluorescent tracers, we showed that CSF enters the parenchyma along paravascular spaces that surround penetrating arteries and that brain interstitial fluid is cleared along paravenous drainage pathways. Animals lacking the water channel aquaporin-4 (AQP4) in astrocytes exhibit slowed CSF influx through this system and a ~70% reduction in interstitial solute clearance, suggesting that the bulk fluid flow between these anatomical influx and efflux routes is supported by astrocytic water transport. Fluorescent-tagged amyloid β, a peptide thought to be pathogenic in Alzheimer's disease, was transported along this route, and deletion of the Aqp4 gene suppressed the clearance of soluble amyloid β, suggesting that this pathway may remove amyloid β from the central nervous system. Clearance through paravenous flow may also regulate extracellular levels of proteins involved with neurodegenerative conditions, its impairment perhaps contributing to the mis-accumulation of soluble proteins.

GROMACS is one of the most widely used open-source and free software codes in chemistry, used primarily for dynamical simulations of biomolecules. It provides a rich set of calculation types, preparation and analysis tools. Several advanced techniques for free-energy calculations are supported. In version 5, it reaches new performance heights, through several new and enhanced parallelization algorithms. These work on every level; SIMD registers inside cores, multithreading, heterogeneous CPU–GPU acceleration, state-of-the-art 3D domain decomposition, and ensemble-level parallelization through built-in replica exchange and the separate Copernicus framework. The latest best-in-class compressed trajectory storage format is supported.

Signaling through the Ror2 receptor tyrosine kinase promotes invadopodia formation for tumor invasion. Here, we identify intraflagellar transport 20 (IFT20) as a new target of this signaling in tumors that lack primary cilia, and find that IFT20 mediates the ability of Ror2 signaling to induce the invasiveness of these tumors. We also find that IFT20 regulates the nucleation of Golgi-derived microtubules by affecting the GM130-AKAP450 complex, which promotes Golgi ribbon formation in achieving polarized secretion for cell migration and invasion. Furthermore, IFT20 promotes the efficiency of transport through the Golgi complex. These findings shed new insights into how Ror2 signaling promotes tumor invasiveness, and also advance the understanding of how Golgi structure and transport can be regulated.

The finite mixture (FM) model is the most commonly used model for statistical segmentation of brain magnetic resonance (MR) images because of its simple mathematical form and the piecewise constant nature of ideal brain MR images. However, being a histogram-based model, the FM has an intrinsic limitation--no spatial information is taken into account. This causes the FM model to work only on well-defined images with low levels of noise; unfortunately, this is often not the the case due to artifacts such as partial volume effect and bias field distortion. Under these conditions, FM model-based methods produce unreliable results. In this paper, we propose a novel hidden Markov random field (HMRF) model, which is a stochastic process generated by a MRF whose state sequence cannot be observed directly but which can be indirectly estimated through observations. Mathematically, it can be shown that the FM model is a degenerate version of the HMRF model. The advantage of the HMRF model derives from the way in which the spatial information is encoded through the mutual influences of neighboring sites. Although MRF modeling has been employed in MR image segmentation by other researchers, most reported methods are limited to using MRF as a general prior in an FM model-based approach. To fit the HMRF model, an EM algorithm is used. We show that by incorporating both the HMRF model and the EM algorithm into a HMRF-EM framework, an accurate and robust segmentation can be achieved. More importantly, the HMRF-EM framework can easily be combined with other techniques. As an example, we show how the bias field correction algorithm of Guillemaud and Brady (1997) can be incorporated into this framework to achieve a three-dimensional fully automated approach for brain MR image segmentation.