Chomsky, Noam -- Political and social views.

Detroit, Mich. : G.S. Davis, 1887.

Resurrecting an old idea about assessing school quality could allow schools to examine a broad range of data on performance and practices and lead to improvement.

MY mother was known for her pizza but they were never round, not when we were growing up anyway. She would pull them from the ancient coal-fired cast iron range in the living room on long blackened oblong trays, the dough she had spent the day making puffed and undulating but always thin and super chewy.

DRAKE - DARK LANE DEMO TAPES

FACE it – we are going nowhere. Even if we had a particular place to venture the regulations would not permit. For the foreseeable we shall have to contract out our travelling to others. On the upside, no airport hassle. On the downside, no giant Toblerone.

Proposed changes to the massive trove of civil rights data the U.S. Department of Education collects from every public school in the country has drawn organized praise from advocates concerned about anti-Semitism in schools.

A new mandate under the Every Student Succeeds Act requires a top-to-bottom look at how such districts deploy their money, staff, and the time used to support improvement.

Critics argue that pediatric research without the potential for clinical benefit treats children as mere means to benefit others. Yet, there are no data to assess whether adolescents who participate in research, or their parents, agree with this view.

Respondents felt that by participating in research the adolescents were making important contributions to help others, and the adolescents felt proud to be doing so. These findings support the view that nonbeneficial pediatric research involves a type of charitable activity. (Read the full article)

Adolescents show mixed opinions over gender equality in recent survey.

As editor Wilhelm Crous puts it, "We haven't seen this movie before."

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lies behind the ongoing outbreak of coronavirus disease 2019 (COVID-19). There is a growing understanding of SARS-CoV-2 in the virology, epidemiology and clinical management strategies. However, no anti-SARS-CoV-2 drug or vaccine has been officially approved due to the absence of adequate evidence. Scientists are racing towards the development of treatment for COVID-19. Recent studies have revealed many attractive threptic options, even if some of them remain to be further confirmed in rigorous preclinical models and clinical trials. In this minireview, we aim to summarize the updated potential approaches against SARS-CoV-2. We emphasize that further efforts are warranted to develop the safest and most effective approach.

Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI) are associated with substantial morbidity and mortality. Monotherapy with first-line antimicrobials such as vancomycin (VAN; glycopeptide) and daptomycin (DAP; lipopeptide) are inadequate in some cases due to reduced antibiotic susceptibilities or therapeutic failure. In recent years, β-lactam antibiotics have emerged as a potential option for combination therapy with VAN/DAP that may meet an unmet therapeutic need for MRSA BSI. Ceftaroline (CPT), the only commercially available β-lactam in the United States with intrinsic in vitro activity against MRSA, has been increasingly studied in the setting of VAN and DAP failures. Novel combinations of first-line agents (VAN and DAP) with β-lactams have been the subject of many recent investigations due to in vitro findings such as the "see-saw effect", where β-lactam susceptibility may be improved in the presence of decreased glycopeptide and lipopeptide susceptibility. The combination of CPT and DAP, in particular, has become the focus of many scientific evaluations, due to intrinsic anti-MRSA activities and potent in vitro synergistic activity against various MRSA strains. This article reviews the available literature describing these innovative therapeutic approaches for MRSA BSI, focusing on preclinical and clinical studies, and evaluates the potential benefits and limitations of each strategy.

Methicillin-resistant Staphylococcus aureus (MRSA) has grown to become a major burden on healthcare systems. The cumulation of limited therapeutic options and worsened patient outcomes with persistent MRSA bacteremia has driven research in optimizing its initial management. The guidelines published by the Infectious Disease of America currently recommend combination therapy for refractory MRSA bacteremia, but the utility of combining antibiotics from the start of therapy is under investigation. The alternative strategy of early use of a β-lactam antibiotics in combination with vancomycin upon initial MRSA bacteremia detection has shown promise. While this concept has gained international attention, providers should give this strategy serious consideration prior to implementation. The objective of this review is to examine retrospective and prospective evidence for early combination with vancomycin and β-lactam antibiotics, as well as explore potential consequences of combination therapy.

Thaddeus Lorenz, senior in information science and technology, wasn’t always sure what his academic path would be. After starting at Penn State in the Division of Undergraduate Studies, he took some classes centered on one of his passions: coding. Then, he decided to make it more than just a passion.

ViewSonic's Elite XG270QG gaming monitor delivers everything that 1440p gamers could want, and a bunch more. It's a premium panel that, despite the price, still packs tremendous value for serious high-speed play.

Members of the Scottish Parliament’s Justice Committee have launched a call for views on the Scottish Government’s plans to update hate crime laws.

The Scottish Parliament’s Covid-19 Committee, which will be tasked with considering any changes to lockdown legislation, has launched a consultation to gather views about moving out of the current lockdown phase.

Another new monitor and another win for ViewSonic, the Elite XG270 shares much of its DNA with the Editors' Choice XG270QG, and helps to move the entire category of gaming displays forward with screaming speeds and beautiful picture quality.

UEFA's ground-breaking weekly vlog Press Play has now had over three million views on the Together #WePlayStrong Youtube channel.

Other important issues, such as the propagation of renewables, flexibility in coal supply and enforcement of contracts for attracting private investment in the sector were also discussed in the meeting.

IPC China President Phil Carmichael shares his insights, as well as those of some of his colleagues, into the current state of the general economy in China.

Check here each week to keep up with the latest from John MacArthur's pulpit at Grace Community Church.

By Rebecca Strating HONOLULU (24 April 2020)—Many argue that China’s increasingly aggressive posture in the South China Sea is an attempt to unilaterally alter the US-led regional order, which includes an emphasis on freedom of navigation. In response, the US has stressed the importance of support from “like-minded” states—including Japan and South Korea—in defending freedom of navigation in the South China Sea and elsewhere. This characterization, however, disguises important differences in attitudes and behavior that could hinder joint efforts to push back against China.

This is a summary only. Click the title for the full article, or visit www.EastWestCenter.org/Research-Wire for more.

Opposition leader Adrian Delia meets PBS top officials

The Singapore government is reviewing the sale and slaughter of live animals at wet markets, Dr Amy Khor, Senior Minister of State for the Environment and Water Resources, said on Tuesday. The relevant agencies are doing so while taking into consideration international benchmarking and scientific evidence, she added.Her comments were in response to a parliamentary question from MP for Nee Soon Group Representation Constituency Louis Ng. He asked whether her ministry would consider banning the…

A serial litigant known for taking the Hong Kong government to court faces being declared bankrupt after the justice department filed a petition against him.Retired civil servant Kwok Cheuk-kin, dubbed the “king of judicial reviews” by the media, has been filing applications with the High Court since 2006, often challenging the legality of government policies and decisions.But many of his attempts ended in failure, and despite being ordered to bear the government’s legal costs in such…

LAHORE: Chief Minister Sardar Usman Buzdar chaired a meeting at his office here Friday which reviewed anti-coronavirus steps and future roadmap of phase-wise easing of lockdown. It expressed concern over increase in the number of coronavirus cases in Lahore and decided to devise a separate policy...

Paris and the Netherlands are lending their respective parts of Air France-KLM up to 11 bln euros. The tricky bailout exposes the frailty of the 2004 merger. Ed Cropley reveals how other operators, including Germany’s Lufthansa and Britain’s IAG, could fly into similar problems.

The coronavirus has helped make Big Tech too big to fail. Before the pandemic, political pressure in D.C. and Brussels was mounting on Silicon Valley giants like Facebook. Gina Chon explains how their size has been an asset in a crisis, which will mute arguments to break them up.

North Korea’s portly dictator has dropped out of sight. Concern is rampant: Is he sick with coronavirus? In a coma? Dead? Whatever his condition, Pete Sweeney discusses the country’s succession problem and its implications for the region.

Goldman Sachs shareholders gave lukewarm approval for CEO David Solomon’s $27.5 mln package. It’s similar to what his peers get, and most of it doesn’t come for at least a year. Still, in a time of economic crisis, eight-digit rewards attract extra scrutiny, John Foley suggests.

Shares in Europe’s top banks have plunged as investors fret about a surge in bad debts. Yet most lenders’ capital buffers can absorb a spike three times as bad as the 2009 average. As Liam Proud explains, that makes taxpayer bailouts and widespread equity hikes unlikely.

U.S. billionaire John Malone may merge his Virgin Media broadband outfit with mobile operator O2. A joint venture could see Spain’s Telefonica, O2’s indebted parent, pocketing over 4 billion pounds. Ed Cropley explains how this might mean a lonelier future for rival Vodafone.

Could President Trump refuse to pay back the $1.1 trln the U.S. owes to China? While markets would hate the idea, it’s theoretically possible thanks to broad powers designed for times of emergency. John Foley explains how this dangerous weapon could be used if push came to shove.

Kingsoft Cloud will debut on Nasdaq, testing appetite for Chinese shares a month after the Luckin Coffee scandal. Data demand is booming in China amid Covid-19, and Kingsoft is a strong rival to market leader Alibaba. Robyn Mak explains why New York might like this listing.

U.S. cable firms are in for pain even after the pandemic starts to fade. Sports rights to air football games and other matchups are expected to soar and so will monthly bills. Jennifer Saba explains why non-sports lovers will choose Netflix and Disney+ and ditch their cable.

Like diseases in the past, the pandemic will change intimacy patterns. Covid-19 will make it harder for lovers to swipe right on platforms like $22 bln Match Group’s Tinder with peace of mind. But more engagement, if fewer hookups, may benefit the model, argues Dasha Afanasieva.

U.S. cable firms are in for pain even after the pandemic starts to fade. Sports rights to air football games and other matchups are expected to soar and so will monthly bills. Jennifer Saba explains why non-sports lovers will choose Netflix and Disney+ and ditch their cable.

Title: Take Online Reviews of Plastic Surgeons With a Grain of Salt
Category: Health News
Created: 4/27/2018 12:00:00 AM
Last Editorial Review: 4/30/2018 12:00:00 AM

Lipid rafts regulate the initiation of cellular metabolic and signaling pathways by organizing the pathway components in ordered microdomains on the cell surface. Cellular responses regulated by lipid rafts range from physiological to pathological, and the success of a therapeutic approach targeting "pathological" lipid rafts depends on the ability of a remedial agent to recognize them and disrupt pathological lipid rafts without affecting normal raft-dependent cellular functions. In this article, concluding the Thematic Review Series on Biology of Lipid Rafts, we review current experimental therapies targeting pathological lipid rafts, including examples of inflammarafts and clusters of apoptotic signaling molecule-enriched rafts. The corrective approaches include regulation of cholesterol and sphingolipid metabolism and membrane trafficking by using HDL and its mimetics, LXR agonists, ABCA1 overexpression, and cyclodextrins, as well as a more targeted intervention with apoA-I binding protein. Among others, we highlight the design of antagonists that target inflammatory receptors only in their activated form of homo- or heterodimers, when receptor dimerization occurs in pathological lipid rafts. Other therapies aim to promote raft-dependent physiological functions, such as augmenting caveolae-dependent tissue repair. The overview of this highly dynamic field will provide readers with a view on the emerging concept of targeting lipid rafts as a therapeutic strategy.

Cellular membranes are not homogenous mixtures of proteins; rather, they are segregated into microdomains on the basis of preferential association between specific lipids and proteins. These microdomains, called lipid rafts, are well known for their role in receptor signaling on the plasma membrane (PM) and are essential to such cellular functions as signal transduction and spatial organization of the PM. A number of disease states, including atherosclerosis and other cardiovascular disorders, may be caused by dysfunctional maintenance of lipid rafts. Lipid rafts do not occur only in the PM but also have been found in intracellular membranes and extracellular vesicles (EVs). Here, we focus on discussing newly discovered functions of lipid rafts and microdomains in intracellular membranes, including lipid and protein trafficking from the ER, Golgi bodies, and endosomes to the PM, and we examine lipid raft involvement in the production and composition of EVs. Because lipid rafts are small and transient, visualization remains challenging. Future work with advanced techniques will continue to expand our knowledge about the roles of lipid rafts in cellular functioning.

Lipid rafts are highly ordered regions of the plasma membrane that are enriched in cholesterol and sphingolipids and play important roles in many cells. In hematopoietic stem and progenitor cells (HSPCs), lipid rafts house receptors critical for normal hematopoiesis. Lipid rafts also can bind and sequester kinases that induce negative feedback pathways to limit proliferative cytokine receptor cycling back to the cell membrane. Modulation of lipid rafts occurs through an array of mechanisms, with optimal cholesterol efflux one of the major regulators. As such, cholesterol homeostasis also regulates hematopoiesis. Increased lipid raft content, which occurs in response to changes in cholesterol efflux in the membrane, can result in prolonged receptor occupancy in the cell membrane and enhanced signaling. In addition, certain diseases, like diabetes, may contribute to lipid raft formation and affect cholesterol retention in rafts. In this review, we explore the role of lipid raft-related mechanisms in hematopoiesis and CVD (specifically, atherosclerosis) and discuss how defective cholesterol efflux pathways in HSPCs contribute to expansion of lipid rafts, thereby promoting myelopoiesis and thrombopoiesis. We also discuss the utility of cholesterol acceptors in contributing to lipid raft regulation and disruption, and highlight the potential to manipulate these pathways for therapeutic gain in CVD as well as other disorders with aberrant hematopoiesis.

Activation of microglia and astrocytes secondary to inflammatory processes contributes to the development and perpetuation of pain with a neuropathic phenotype. This pain state presents as a chronic debilitating condition and affects a large population of patients with conditions like rheumatoid arthritis and diabetes, or after surgery, trauma, or chemotherapy. Here, we review the regulation of lipid rafts in glial cells and the role they play as a key component of neuroinflammatory sensitization of central pain signaling pathways. In this context, we introduce the concept of an inflammaraft (i-raft), enlarged lipid rafts harboring activated receptors and adaptor molecules and serving as an organizing platform to initiate inflammatory signaling and the cellular response. Characteristics of the inflammaraft include increased relative abundance of lipid rafts in inflammatory cells, increased content of cholesterol per raft, and increased levels of inflammatory receptors, such as toll-like receptor (TLR)4, adaptor molecules, ion channels, and enzymes in lipid rafts. This inflammaraft motif serves an important role in the membrane assembly of protein complexes, for example, TLR4 dimerization. Operating within this framework, we demonstrate the involvement of inflammatory receptors, redox molecules, and ion channels in the inflammaraft formation and the regulation of cholesterol and sphingolipid metabolism in the inflammaraft maintenance and disruption. Strategies for targeting inflammarafts, without affecting the integrity of lipid rafts in noninflammatory cells, may lead to developing novel therapies for neuropathic pain states and other neuroinflammatory conditions.

Lipid rafts are small, dynamic membrane areas characterized by the clustering of selected membrane lipids as the result of the spontaneous separation of glycolipids, sphingolipids, and cholesterol in a liquid-ordered phase. The exact dynamics underlying phase separation of membrane lipids in the complex biological membranes are still not fully understood. Nevertheless, alterations in the membrane lipid composition affect the lateral organization of molecules belonging to lipid rafts. Neural lipid rafts are found in brain cells, including neurons, astrocytes, and microglia, and are characterized by a high enrichment of specific lipids depending on the cell type. These lipid rafts seem to organize and determine the function of multiprotein complexes involved in several aspects of signal transduction, thus regulating the homeostasis of the brain. The progressive decline of brain performance along with physiological aging is at least in part associated with alterations in the composition and structure of neural lipid rafts. In addition, neurodegenerative conditions, such as lysosomal storage disorders, multiple sclerosis, and Parkinson’s, Huntington’s, and Alzheimer’s diseases, are frequently characterized by dysregulated lipid metabolism, which in turn affects the structure of lipid rafts. Several events underlying the pathogenesis of these diseases appear to depend on the altered composition of lipid rafts. Thus, the structure and function of lipid rafts play a central role in the pathogenesis of many common neurodegenerative diseases.

Cholesterol/sphingolipid-rich membrane domains, known as lipid rafts or membrane rafts, play a critical role in the compartmentalization of signaling pathways. Physical segregation of proteins in lipid rafts may modulate the accessibility of proteins to regulatory or effector molecules. Thus, lipid rafts serve as sorting platforms and hubs for signal transduction proteins. Cancer cells contain higher levels of intracellular cholesterol and lipid rafts than their normal non-tumorigenic counterparts. Many signal transduction processes involved in cancer development (insulin-like growth factor system and phosphatidylinositol 3-kinase-AKT) and metastasis [cluster of differentiation (CD)44] are dependent on or modulated by lipid rafts. Additional proteins playing an important role in several malignant cancers (e.g., transmembrane glycoprotein mucin 1) are also being detected in association with lipid rafts, suggesting a major role of lipid rafts in tumor progression. Conversely, lipid rafts also serve as scaffolds for the recruitment and clustering of Fas/CD95 death receptors and downstream signaling molecules leading to cell death-promoting raft platforms. The partition of death receptors and downstream signaling molecules in aggregated lipid rafts has led to the formation of the so-called cluster of apoptotic signaling molecule-enriched rafts, or CASMER, which leads to apoptosis amplification and can be pharmacologically modulated. These death-promoting rafts can be viewed as a linchpin from which apoptotic signals are launched. In this review, we discuss the involvement of lipid rafts in major signaling processes in cancer cells, including cell survival, cell death, and metastasis, and we consider the potential of lipid raft modulation as a promising target in cancer therapy.

Lipid rafts, solid regions of the plasma membrane enriched in cholesterol and glycosphingolipids, are essential parts of a cell. Functionally, lipid rafts present a platform that facilitates interaction of cells with the outside world. However, the unique properties of lipid rafts required to fulfill this function at the same time make them susceptible to exploitation by pathogens. Many steps of pathogen interaction with host cells, and sometimes all steps within the entire lifecycle of various pathogens, rely on host lipid rafts. Such steps as binding of pathogens to the host cells, invasion of intracellular parasites into the cell, the intracellular dwelling of parasites, microbial assembly and exit from the host cell, and microbe transfer from one cell to another all involve lipid rafts. Interaction also includes modification of lipid rafts in host cells, inflicted by pathogens from both inside and outside the cell, through contact or remotely, to advance pathogen replication, to utilize cellular resources, and/or to mitigate immune response. Here, we provide a systematic overview of how and why pathogens interact with and exploit host lipid rafts, as well as the consequences of this interaction for the host, locally and systemically, and for the microbe. We also raise the possibility of modulation of lipid rafts as a therapeutic approach against a variety of infectious agents.