OED Word of the Day: microfinance, n. The provision of loans and other financial services to low-income individuals and communities for the creation of small businesses…

“Even after weeks of staying home, my kids are just not interested in all the stuff we have. Let’s be honest. If a toy isn’t getting any action amid this distraction-free, stuck-at-home living, chances are it’s never getting touched again.” Liz Russell figures out what really engages and changes kids during the quarantine, and will […]

At Let Grow, a wise mom named Kate Sundquist admits that while her kids were already good at playing, they certainly weren’t good at filling hours and hours of free time, playing by themselves. (Read the piece here.) So she her and boys created a schedule. “While these routines might seem restrictive or even the […]

“The most difficult part was persuading our children that they had the freedom to make anything they wanted,” writes mom Anam Ahmed at Let Grow. (Click here!) …Like most kids, my children live prescheduled lives (at least they did in “the time before”). At school, someone tells them when to play outside and when to […]

“When I was 17, I was in a serious accident and had to be home for months. Looking out at our boring backyard, I daydreamed a plan for my life. It became a blueprint.” So writes Holly Korbey in a lovely piece at Let Grow. There are different kinds of daydreaming, of course, and some don’t […]

Parents, kids: Fear not the silica gel pack. Sure it says DO NOT EAT and THROW AWAY. But you should only follow one of those rules.    Instead, save the packs and use them a whole lot of ways: Place them on the car dashboard by the windshield to keep it from fogging up.   […]

1.8 million people in the United States drive heavy trucks for a living and are at risk of losing their jobs when trucks become autonomous. That number is from the BLS category heavy and tractor-trailer trucking with 1.8 million employees. A separate category Delivery Truck Drivers and Driver/Sales Workers has 1.3 million workers. The heavy duty truckers are more at risk than the local delivery drivers because it is easier to automate long haul driving on interstates than to automate driving on more complex (cross traffic, pedestrians, parked cars, etc) local roads. Plus, delivery drivers have to run up to houses and businesses to make most deliveries. Building robots to do that work will take longer. Railroad operation is easier...

The incentive to automate will be enormous for $15 per hour minimum wage. Of America’s nearly 16 million retail workers, the biggest group — 4.6 million — are salespeople. Their average wage is $10.47 an hour. After that, the country has another 3.4 million cashiers, and their average wage is $9.28 an hour. Only a quarter of salespeople earn more than $14 — and only 10 percent earn more than $19. The figures are worse for cashiers. But in the race to automate there will be a clear winner: Amazon. Why: Amazon can automate more easily than can physical stores. It is analogous to why long haul trucking can be automated before taxis: Just as highways are simpler places than...

Nitrozac had to undergo an emergency endodontic procedure, *ouch*, so she is off for a few days to let her recover. We'll be back with a new smile soon, in the meantime, here's one of our fave retros...

On accorde "The World of Art Award" (WAA) aux artistes, aux galeries et aux musées qui poursuivent les "meilleures pratiques" dans l'art et la culture. Cette concurrence cherche à attirer dies artistes, galeries, les musées qui redéfinissent des normes de l'excellence d'art. Ceux qui défie des trends et des tendances existantes dans l'art et la culture.

A little old lady walks into Bank of America and asks to open a savings account. The new accounts receptionist first thinks this is strange, probably because everyone is leaving them for credit unions now. At any rate, the accounts person asks her how much she wanted to deposit to open the account, and the […]

The post Getting Bank of America By The Balls appeared first on Funny & Jokes.

It’s not everyday we regurgitate a few old (and new!) chemistry jokes. How often do we tell them? Periodically. We told one the other day, but there was no reaction. Hahaha! Wait? How come nobody else is laughing? Ehem… well, anyways, here are a few more: When I first heard oxygen and magnesium got together […]

The post Top 20 Chemistry Jokes of Some Time appeared first on Funny & Jokes.

The post Blue Marlin: One of the Greatest Game Fish of all Time appeared first on Ocean Blue Fishing Adventures.

Hearing loss caused by the death of sensory hair cells of the inner ear is an unfortunate side effect for many patients treated with aminoglycoside antibiotics or platinum-containing chemotherapy agents. In animal models, induction of heat shock confers substantial otoprotection against aminoglycoside- and cisplatin-induced hair cell death. In this issue of the JCI, Breglio et al. demonstrate that inner ear tissue released exosomes carrying heat shock protein 70 (HSP70) in response to heat stress. HSP70 acted by a paracrine mechanism that engaged the Toll-like receptor 4 (TLR4) on hair cells to protect them from death. Exosomes and the HSP70/TLR4 pathway could thus provide treatment targets for the protection of hair cells from chemically induced death or from other insults, such as noise.

Levodopa-induced dyskinesia (LID) poses a significant health care challenge for Parkinson’s disease (PD) patients. Amantadine is currently the only drug proven to alleviate LID. Although its efficacy in treating LID is widely assumed to be mediated by blockade of N-methyl-D-aspartate (NMDA) glutamate receptors, our experiments demonstrate that at therapeutically relevant concentrations, amantadine preferentially blocks inward-rectifying K+ channel type 2 (Kir2) channels in striatal spiny projection neurons (SPNs) — not NMDA receptors. In so doing, amantadine enhances dendritic integration of excitatory synaptic potentials in SPNs and enhances — not antagonizes — the induction of long-term potentiation (LTP) at excitatory, axospinous synapses. Taken together, our studies suggest that the alleviation of LID in PD patients is mediated by diminishing the disparity in the excitability of direct- and indirect-pathway SPNs in the on state, rather than by disrupting LTP induction. This insight points to a pharmacological approach that could be used to effectively ameliorate LID and improve the quality of life for PD patients.

Tumor-associated peptide–human leukocyte antigen complexes (pHLAs) represent the largest pool of cell surface–expressed cancer-specific epitopes, making them attractive targets for cancer therapies. Soluble bispecific molecules that incorporate an anti-CD3 effector function are being developed to redirect T cells against these targets using 2 different approaches. The first achieves pHLA recognition via affinity-enhanced versions of natural TCRs (e.g., immune-mobilizing monoclonal T cell receptors against cancer [ImmTAC] molecules), whereas the second harnesses an antibody-based format (TCR-mimic antibodies). For both classes of reagent, target specificity is vital, considering the vast universe of potential pHLA molecules that can be presented on healthy cells. Here, we made use of structural, biochemical, and computational approaches to investigate the molecular rules underpinning the reactivity patterns of pHLA-targeting bispecifics. We demonstrate that affinity-enhanced TCRs engage pHLA using a comparatively broad and balanced energetic footprint, with interactions distributed over several HLA and peptide side chains. As ImmTAC molecules, these TCRs also retained a greater degree of pHLA selectivity, with less off-target activity in cellular assays. Conversely, TCR-mimic antibodies tended to exhibit binding modes focused more toward hot spots on the HLA surface and exhibited a greater degree of crossreactivity. Our findings extend our understanding of the basic principles that underpin pHLA selectivity and exemplify a number of molecular approaches that can be used to probe the specificity of pHLA-targeting molecules, aiding the development of future reagents.

BACKGROUND Neurofibroma/schwannoma hybrid nerve sheath tumors (N/S HNSTs) are neoplasms associated with larger nerves that occur sporadically and in the context of schwannomatosis or neurofibromatosis type 2 or 1. Clinical management of N/S HNSTs is challenging, especially for large tumors, and established systemic treatments are lacking.METHODS We used next-generation sequencing and array-based DNA methylation profiling to determine the clinically actionable genomic and epigenomic landscapes of N/S HNSTs.RESULTS Whole-exome sequencing within a precision oncology program identified an activating mutation (p.Asp769Tyr) in the catalytic domain of the ERBB2 receptor tyrosine kinase in a patient with schwannomatosis-associated N/S HNST, and targeted treatment with the small-molecule ERBB inhibitor lapatinib led to prolonged clinical benefit and a lasting radiographic and metabolic response. Analysis of a multicenter validation cohort revealed recurrent ERBB2 mutations (p.Leu755Ser, p.Asp769Tyr, p.Val777Leu) in N/S HNSTs occurring in patients who met diagnostic criteria for sporadic schwannomatosis (3 of 7 patients), but not in N/S HNSTs arising in the context of neurofibromatosis (6 patients) or outside a tumor syndrome (1 patient), and showed that ERBB2-mutant N/S HNSTs cluster in a distinct subgroup of peripheral nerve sheath tumors based on genome-wide DNA methylation patterns.CONCLUSION These findings uncover a key biological feature of N/S HNSTs that may have important diagnostic and therapeutic implications.FUNDING This work was supported by grant H021 from DKFZ-HIPO, the University Cancer Center Frankfurt, and the Frankfurt Research Funding Clinician Scientist Program.

BACKGROUND Since December 2019, an outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, and is now becoming a global threat. We aimed to delineate and compare the immunological features of severe and moderate COVID-19.METHODS In this retrospective study, the clinical and immunological characteristics of 21 patients (17 male and 4 female) with COVID-19 were analyzed. These patients were classified as severe (11 cases) and moderate (10 cases) according to the guidelines released by the National Health Commission of China.RESULTS The median age of severe and moderate cases was 61.0 and 52.0 years, respectively. Common clinical manifestations included fever, cough, and fatigue. Compared with moderate cases, severe cases more frequently had dyspnea, lymphopenia, and hypoalbuminemia, with higher levels of alanine aminotransferase, lactate dehydrogenase, C-reactive protein, ferritin, and D-dimer as well as markedly higher levels of IL-2R, IL-6, IL-10, and TNF-α. Absolute numbers of T lymphocytes, CD4+ T cells, and CD8+ T cells decreased in nearly all the patients, and were markedly lower in severe cases (294.0, 177.5, and 89.0 × 106/L, respectively) than moderate cases (640.5, 381.5, and 254.0 × 106/L, respectively). The expression of IFN-γ by CD4+ T cells tended to be lower in severe cases (14.1%) than in moderate cases (22.8%).CONCLUSION The SARS-CoV-2 infection may affect primarily T lymphocytes, particularly CD4+ and CD8+ T cells, resulting in a decrease in numbers as well as IFN-γ production by CD4+ T cells. These potential immunological markers may be of importance because of their correlation with disease severity in COVID-19.TRIAL REGISTRATION This is a retrospective observational study without a trial registration number.FUNDING This work is funded by grants from Tongji Hospital for the Pilot Scheme Project, and partly supported by the Chinese National Thirteenth Five Years Project in Science and Technology for Infectious Disease (2017ZX10202201).

BACKGROUND Preclinical experiments have shown that donor blood cells, modified in vitro by an alkylating agent (modified immune cells [MICs]), induced long-term specific immunosuppression against the allogeneic donor.METHODS In this phase I trial, patients received either 1.5 × 106 MICs per kg BW on day –2 (n = 3, group A), or 1.5 × 108 MICs per kg BW on day –2 (n = 3, group B) or day –7 (n = 4, group C) before living donor kidney transplantation in addition to post-transplantation immunosuppression. The primary outcome measure was the frequency of adverse events (AEs) until day 30 (study phase) with follow-up out to day 360.RESULTS MIC infusions were extremely well tolerated. During the study phase, 10 treated patients experienced a total of 69 AEs that were unlikely to be related or not related to MIC infusion. No donor-specific human leukocyte antigen Abs or rejection episodes were noted, even though the patients received up to 1.3 × 1010 donor mononuclear cells before transplantation. Group C patients with low immunosuppression during follow-up showed no in vitro reactivity against stimulatory donor blood cells on day 360, whereas reactivity against third-party cells was still preserved. Frequencies of CD19+CD24hiCD38hi transitional B lymphocytes (Bregs) increased from a median of 6% before MIC infusion to 20% on day 180, which was 19- and 68-fold higher, respectively, than in 2 independent cohorts of transplanted controls. The majority of Bregs produced the immunosuppressive cytokine IL-10. MIC-treated patients showed the Immune Tolerance Network operational tolerance signature.CONCLUSION MIC administration was safe and could be a future tool for the targeted induction of tolerogenic Bregs.TRIAL REGISTRATION EudraCT number: 2014-002086-30; ClinicalTrials.gov identifier: NCT02560220FUNDING Federal Ministry for Economic Affairs and Technology, Berlin, Germany, and TolerogenixX GmbH, Heidelberg, Germany.

Regenerative pain medicine, which seeks to harness the body’s own reparative capacity, is rapidly emerging as a field within pain medicine and orthopedics. It is increasingly appreciated that common analgesic mechanisms for these treatments depend on neuroimmune modulation. In this Review, we discuss recent progress in mechanistic understanding of nociceptive sensitization in chronic pain with a focus on neuroimmune modulation. We also examine the spectrum of regenerative outcomes, including preclinical and clinical outcomes. We further distinguish the analgesic mechanisms of regenerative therapies from those of cellular replacement, creating a conceptual and mechanistic framework to evaluate future research on regenerative medicine.

The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. Although gene-environment interactions have been implicated in the etiology of several disorders, the impact of paternal and/or maternal metabolic syndrome on the clinical phenotypes of offspring and the underlying genetic and epigenetic contributors of NAFLD have not been fully explored. To this end, we used the liver-specific insulin receptor knockout (LIRKO) mouse, a unique nondietary model manifesting 3 hallmarks that confer high risk for the development of NAFLD: hyperglycemia, insulin resistance, and dyslipidemia. We report that parental metabolic syndrome epigenetically reprograms members of the TGF-β family, including neuronal regeneration–related protein (NREP) and growth differentiation factor 15 (GDF15). NREP and GDF15 modulate the expression of several genes involved in the regulation of hepatic lipid metabolism. In particular, NREP downregulation increases the protein abundance of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and ATP-citrate lyase (ACLY) in a TGF-β receptor/PI3K/protein kinase B–dependent manner, to regulate hepatic acetyl-CoA and cholesterol synthesis. Reduced hepatic expression of NREP in patients with NAFLD and substantial correlations between low serum NREP levels and the presence of steatosis and nonalcoholic steatohepatitis highlight the clinical translational relevance of our findings in the context of recent preclinical trials implicating ACLY in NAFLD progression.

Fibroblasts are key effector cells in tissue remodeling. They remain persistently activated in fibrotic diseases, resulting in progressive deposition of extracellular matrix. Although fibroblast activation may be initiated by external factors, prolonged activation can induce an “autonomous,” self-maintaining profibrotic phenotype in fibroblasts. Accumulating evidence suggests that epigenetic alterations play a central role in establishing this persistently activated pathologic phenotype of fibroblasts. We demonstrated that in fibrotic skin of patients with systemic sclerosis (SSc), a prototypical idiopathic fibrotic disease, TGF-β induced the expression of DNA methyltransferase 3A (DNMT3A) and DNMT1 in fibroblasts in a SMAD-dependent manner to silence the expression of suppressor of cytokine signaling 3 (SOCS3) by promoter hypermethylation. Downregulation of SOCS3 facilitated activation of STAT3 to promote fibroblast-to-myofibroblast transition, collagen release, and fibrosis in vitro and in vivo. Reestablishment of the epigenetic control of STAT3 signaling by genetic or pharmacological inactivation of DNMT3A reversed the activated phenotype of SSc fibroblasts in tissue culture, inhibited TGF-β–dependent fibroblast activation, and ameliorated experimental fibrosis in murine models. These findings identify a pathway of epigenetic imprinting of fibroblasts in fibrotic disease with translational implications for the development of targeted therapies in fibrotic diseases.

Facioscapulohumeral muscular dystrophy (FSHD) is caused by loss of repression of the DUX4 gene; however, the DUX4 protein is rare and difficult to detect in human muscle biopsies, and pathological mechanisms are obscure. FSHD is also a chronic disease that progresses slowly over decades. We used the sporadic, low-level, muscle-specific expression of DUX4 enabled by the iDUX4pA-HSA mouse to develop a chronic long-term muscle disease model. After 6 months of extremely low sporadic DUX4 expression, dystrophic muscle presented hallmarks of FSHD histopathology, including muscle degeneration, capillary loss, fibrosis, and atrophy. We investigated the transcriptional profile of whole muscle as well as endothelial cells and fibroadiopogenic progenitors (FAPs). Strikingly, differential gene expression profiles of both whole muscle and, to a lesser extent, FAPs, showed significant overlap with transcriptional profiles of MRI-guided human FSHD muscle biopsies. These results demonstrate a pathophysiological similarity between disease in muscles of iDUX4pA-HSA mice and humans with FSHD, solidifying the value of chronic rare DUX4 expression in mice for modeling pathological mechanisms in FSHD and highlighting the importance FAPs in this disease.

Seizures often herald the clinical appearance of gliomas or appear at later stages. Dissecting their precise evolution and cellular pathogenesis in brain malignancies could inform the development of staged therapies for these highly pharmaco-resistant epilepsies. Studies in immunodeficient xenograft models have identified local interneuron loss and excess glial glutamate release as chief contributors to network disinhibition, but how hyperexcitability in the peritumoral microenvironment evolves in an immunocompetent brain is unclear. We generated gliomas in WT mice via in utero deletion of key tumor suppressor genes and serially monitored cortical epileptogenesis during tumor infiltration with in vivo electrophysiology and GCAMP7 calcium imaging, revealing a reproducible progression from hyperexcitability to convulsive seizures. Long before seizures, coincident with loss of inhibitory cells and their protective scaffolding, gain of glial glutamate antiporter xCT expression, and reactive astrocytosis, we detected local Iba1+ microglial inflammation that intensified and later extended far beyond tumor boundaries. Hitherto unrecognized episodes of cortical spreading depolarization that arose frequently from the peritumoral region may provide a mechanism for transient neurological deficits. Early blockade of glial xCT activity inhibited later seizures, and genomic reduction of host brain excitability by deleting MapT suppressed molecular markers of epileptogenesis and seizures. Our studies confirmed xenograft tumor–driven pathobiology and revealed early and late components of tumor-related epileptogenesis in a genetically tractable, immunocompetent mouse model of glioma, allowing the complex dissection of tumor versus host pathogenic seizure mechanisms.

Hypoxia-inducible factor (HIF) is strikingly upregulated in many types of cancer, and there is great interest in applying inhibitors of HIF as anticancer therapeutics. The most advanced of these are small molecules that target the HIF-2 isoform through binding the PAS-B domain of HIF-2α. These molecules are undergoing clinical trials with promising results in renal and other cancers where HIF-2 is considered to be driving growth. Nevertheless, a central question remains as to whether such inhibitors affect physiological responses to hypoxia at relevant doses. Here, we show that pharmacological HIF-2α inhibition with PT2385, at doses similar to those reported to inhibit tumor growth, rapidly impaired ventilatory responses to hypoxia, abrogating both ventilatory acclimatization and carotid body cell proliferative responses to sustained hypoxia. Mice carrying a HIF-2α PAS-B S305M mutation that disrupts PT2385 binding, but not dimerization with HIF-1β, did not respond to PT2385, indicating that these effects are on-target. Furthermore, the finding of a hypomorphic ventilatory phenotype in untreated HIF-2α S305M mutant mice suggests a function for the HIF-2α PAS-B domain beyond heterodimerization with HIF-1β. Although PT2385 was well tolerated, the findings indicate the need for caution in patients who are dependent on hypoxic ventilatory drive.

Increased microvascular permeability to plasma proteins and neutrophil emigration are hallmarks of innate immunity and key features of numerous inflammatory disorders. Although neutrophils can promote microvascular leakage, the impact of vascular permeability on neutrophil trafficking is unknown. Here, through the application of confocal intravital microscopy, we report that vascular permeability–enhancing stimuli caused a significant frequency of neutrophil reverse transendothelial cell migration (rTEM). Furthermore, mice with a selective defect in microvascular permeability enhancement (VEC-Y685F-ki) showed reduced incidence of neutrophil rTEM. Mechanistically, elevated vascular leakage promoted movement of interstitial chemokines into the bloodstream, a response that supported abluminal-to-luminal neutrophil TEM. Through development of an in vivo cell labeling method we provide direct evidence for the systemic dissemination of rTEM neutrophils, and showed them to exhibit an activated phenotype and be capable of trafficking to the lungs where their presence was aligned with regions of vascular injury. Collectively, we demonstrate that increased microvascular leakage reverses the localization of directional cues across venular walls, thus causing neutrophils engaged in diapedesis to reenter the systemic circulation. This cascade of events offers a mechanism to explain how local tissue inflammation and vascular permeability can induce downstream pathological effects in remote organs, most notably in the lungs.

Brown and beige adipose tissues contain thermogenic fat cells that can be activated by β3-adrenergic receptor agonists. In rodents, such drugs both diminish obesity and improve glucose homeostasis. In this issue of the JCI, O’Mara et al. and Finlin and Memetimin et al. report that chronic administration of the approved β3 agonist mirabegron to human subjects was without effect on body weight or fat mass, but improved several measures of glucose homeostasis. Though the mechanisms mediating these metabolic effects are uncertain, the data suggest that β3 agonists could have therapeutic utility in disorders of glucose homeostasis.

I’ve been to Forks and La Push, where the Twilight book series takes place, but I’ve never been to the actual filming locations from the movies! That’s because while the director wanted to film in Forks, when he came to scout the town he realized there was just not enough infrastructure to support an entire film crew– there were literally not enough places to house and feed all of the people who would be working on the movie, and there was no other large town within driving distance! (Yeah, Forks is really far out there) Enter Halloweento— I mean, St. Helens, Oregon! St. Helens stands in for most of Forks in the movies, and a few places in nearby Portland, Oregon make up most of the rest. I ended up nearby by complete accident, as it was only when I picked up a brochure at Halloweentown that I learned that Bella’s house was just on the other side of town! LUCKY!!!  So, we took a short break to drive over to the locations that were still standing, and made a special detour to Portland because how could we leave the Cullen house behind?! I WANTED TO GO INSIDE SO BADLY! It is a real house with real people that live there, and although they encouraged taking photos from outside (according both to a brochure from City Hall and a sign in front of the house), the inside was off-limits. Honestly, it’s not Bella that I particularly love. I didn’t care for her portrayal by Kristen Stewart (sorry!), or her melancholy, passive attitude in the book. Actually, I didn’t care for Edward, either. It was the idea of a love so strong that forces of  nature were pulling you together. It’s the idea of fitting together so perfectly that you can’t do anything without the other that I am a complete sucker for! I said it on my old Livejournal years ago, but Twilight is just a big Mary Sue anyway, so I like to imagine myself as Bella, with a gorgeous (female) Edward out there waiting for me. ???? Like I said, it’s the love, not the characters themselves. I’ll fight you on this (just kidding). ???? Here is where Edward rescued Bella from some catcallers, complete with the mural that the movie crew painted (!) on the building. And the theater that they drove past, that you can’t really see well in the movie but hey, it was on the map!! This is Jilly’s, which supplied all of the dresses in the shop when Bella went to pick out something with her friends for prom. Oddly enough, they had this sign outside but no actual merchandise inside. Go figure. ???? This place, which is a private house now, was the bookstore where Bella went to find out more information about the Quileute myths. And then, though we only had a little bit of time, we drove over to Portland and checked out Edward’s house. I have to say…. THIS HOUSE WAS GORGEOUS. Whew! I would LOVE to live there. LOVE LOVE LOVE! I would also have loved a tour, but it is a private residence, and therefore we kept our distance. Mmm, but it sure is gorgeous! Twilight brings back a lot of memories for me, and it’s special because I grew up (mostly) in Washington. It’s also not the only book series to claim that there are werewolves living amongst the local residents. The town that I spent most of my childhood in also has a series revolving around it! I’m planning to take a trip over there to see my old friends and photograph all of the wolfy places of interest, so I’ll post about it then! Love ya, and see ya tomorrow!

Platform: Javascript/HTML5 — Bearing the fruit of thoughtful craftsmanship, Rudowski Brothers gifts us with The Trader of Stories - Chapter 2. After spending nearly a Blossoming in the human city of Bark, Little Willow's life seems fairly ordered. She works as a waitress... Tagged as: adventure, bigoldtreethatdreams, browser, free, game, html5, linux, mac, mobile, mrudowski, narrative, pointandclick, traderofstories

iFixit hasn't yet done a full teardown of the new Magic Keyboard designed for the new iPad Pro models, but the repair site today partnered with x-ray company Creative Electron to create Magic Keyboard x-rays that give us a view of just what's inside.


The Magic Keyboard uses scissor switch keys instead of butterfly keys, which have now been effectively eliminated from Apple's product lineup. The scissor switch mechanism is clearly visible in the x-ray view, and iFixit calls it the simplest mechanism in the accessory, but the biggest improvement compared to the Smart Keyboard.

Below the keyboard, there are metal plates that iFixit believes are for reinforcing the keyboard's body against bending, and the trackpad is a new design that's different from MacBook trackpads.

There appear to be multiple buttons under the trackpad to capture presses, while the MacBook Trackpads have no buttons and simulate presses with haptic feedback.


There are at least two spring loaded hinge designs at the folding point, featuring both a small coil and a larger coil, plus there are two cables for connecting the Smart Connector to the keyboard for power and data transfer.

Lots and lots of magnets are visible in the x-ray, with the magnets used to hold the Magic Keyboard on the ‌iPad Pro‌. There's a whole ring of tiny magnets around the camera cutout, which iFixit said was a "lot of little polarized bits" to line up, space out, and configure with the ‌iPad Pro‌ components.

According to iFixit, there's more going on in the Magic Keyboard than there is in many laptops, which could explain its price point. Apple charges $299 for the 11-inch Magic Keyboard and $349 for the 12.9-inch version.

Microsoft plans to add trackpad and mouse support to its Word, Excel, and PowerPoint apps for iPad by the fall, according to TechCrunch and The Verge.

iPadOS 13.4 introduced trackpad and mouse support on all iPad models released in the past four to five years. Keyboards with trackpads include Apple's Magic Keyboard and Brydge's Pro+ for the iPad Pro and Logitech's Combo for the 10.2-inch iPad and the 10.5-inch iPad Air.

When using a trackpad, the cursor displays as a circle on the screen, popping up only when you have a finger on the trackpad. The circle then morphs into various other shapes when hovering over app icons, text fields, or other on-screen elements.

Woot is ending the week with a refurbished sale on the 15-inch MacBook Pro, available in multiple storage sizes and colors. The sale starts with the 256GB SSD model (16GB RAM, Intel Core i7) for $1,579.99.

Note: MacRumors is an affiliate partner with Woot. When you click a link and make a purchase, we may receive a small payment, which helps us keep the site running.

For more storage, the 512GB SSD model (16GB RAM, Intel Core i9) is on sale for $1,849.99. Woot's refurbished sales are offering more than $800 in savings when compared to the original prices of these notebooks, which began at $2,399.00 when they launched in May 2019.

Similar to previous Woot sales, each MacBook Pro comes with a One Year Limited Woot Warranty. Each device has been refurbished and is ensured to be in full working condition. When shipped, they are packaged in a generic white box.

You can find even more discounts on new MacBooks by visiting our Best Deals guide for MacBook Pro and MacBook Air. In this guide we track the steepest discounts for the newest MacBook models every week, so be sure to bookmark it and check back often if you're shopping for a new Apple notebook.

Rick May, best known to furries and non-furries alike as the voice of Peppy Hare in the English version of the game Star Fox 64 passed away April 13, 2020 due to COVID-19. May was born September 21, 1940 (with the full name of Richard J. May), meaning he would have turned 80 later this year. May had also recently suffered a stroke in February, making him even more vulnerable to the disease caused by the novel coronavirus.

May will forever be known as the man who originally uttered the memetic line "Do a barrel roll! (Z or R twice.)" in Star Fox 64, explaining to players how to perform what is technically an aileron roll in order to deflect enemy attacks. May also played the villain of Star Fox 64, Andross. Outside of furry video games, May is probably best known for voicing the Soldier of Team Fortress 2; furries might also recognize his voice behind the villainous Dr. M from the third Sly Cooper game. In addition to voice work for video games, May has had a long history of working both on and for the stage as both a director and actor, beginning with USO shows while stationed in Japan. His part in a Renton, Washington production of Cotton Patch Gospel featured a combination of his voice and stage work, as he used different voices to portray 21 characters in what was reportedly his favorite stage role.

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The Voyages of Cinrak the Dapper is a collection of seven short stories written by A. J. Fitzwater centred around Cinrak, a lesbian, capybara pirate. It has a couple of strong elements as well as several weak points. I struggled with my thoughts as I read it and, in the end, I would say that, overall, I found it frustrating.

I will start this review briefly talking about politics. It might seem like an unusual starting point but the introduction makes clear that the book is political and it touches on several hot button issues.

Come for handsome, huggable Cinrak in a dapper three-piece, stay for her becoming a house-ship Mother to an enormous found family, the ethical polyamory, trans boy chinchilla, genderqueer rat mentor, fairy, and whale, drag queen mer, democratic monarchy, socialist pirates, and strong unionization.

What I do like about the way politics is handled in this book, is that it is not set up as a conflict between opposing ideologies; the book presents its favoured way of seeing the world and just leaves it as that. Even the religious character (and there is a fascinating take on religion inside) is played off sympathetically. However, by taking the stances it does, the book is also going to be, though it has no regrets about it, alienating for certain readers. If you can not tolerate a heavy emphasis on, and I quote, LGBTQIA characters, then this book is definitely not for you and you may as well stop here. On the other hand, if that’s what you crave, it may be exactly what you want and you should read further.

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While the pandemic has been chipping away at the furry convention scene, other furs have stepped forward to try and give those in the community events to look forward to over the now dormant weekends. This had started with a group of Furnal Equinox members creating a digital replacement for their late March convention called Keep Calm and Carry Con - Furnal Isolation. More have started to spring up this spring.

They can have internet dealers dens, streaming dance competitions, and other staples that conventions are known for. Accessible from the safety of your own home.

Below is a comprehensive list of conventions. Last updated May 2nd, 2020 12:18 ET.

Please feel free to place any not listed here in the comments below and we will look into adding it if it appears legitimate.

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On the Young Turks, Cenk Uygur quotes passages from Bob Woodward's book, "The Price of Politics", quoting statements made by President Obama proving that he intends to cut entitlements like social security, medicare, and medicaid. Continue reading →

Glenn Greenwald predicts over the next four years that "it's all going to get much worse", with President Obama shifting politically more to the right while the Democratic base continues to support him. Continue reading →

Thinking of using TurboTax to file your tax returns? Think again. The Minnesota Department of Revenue advises against using Intuit software to file tax returns! It found unacceptable errors in Intuit tax software, including TurboTax, ProSeries, Lacerte, and Intuit online. Continue reading →

Have you ever noticed that the Internal Revenue Service's regulations often are illogical? Does anyone at the IRS think through its regulations? Continue reading →