One-year-old company NovaMed has inked a deal with Hong Kong-based DHB Global that will see the start-up medical consultancy transitioning to a producer of healthcare personal protective equipment, or PPE. Under the deal finalised earlier this...

Opposition spokesman on tourism, Dr Wykeham McNeill, is calling for an investigation into allegations that some employers of tourism workers have not been turning over income tax deductions to government.  The situation has resulted in...

Hi everyone, Maybe we aren’t *completely* dead. Stay tuned.

Компания Xiaomi осенью прошлого года выпустила смартфон Mi Note 10, но обновление Android 10 добралось до аппарата только сейчас.

Аналитики из Canalys опубликовали рейтинг 10 самых продаваемых смартфонов на глобальном рынке в первом квартале 2020 года.

Экспедиционная группа из Китая поднялась на гору Эверест и решила там же протестировать в экстремальных условиях камеры смартфонов.

Смартфон появился на сайте Google Play Console, благодаря чему стали известны его некоторые характеристики и дизайн.

In between topics to rant about, I thought I would tell you a little bit more about what it's like to be a biotech scientist. I've been in many different sized biotechs and even between them, the culture can vary quite a bit. Therefore, I'll try and describe it in general terms to give you an overview of the life of an industry scientist in research and development (R&D). Of course, some people wi; (read more)

Source: Suzy - Discipline: BioTech

For those of you who follow the tweets of @DivaBiotech, you are already familiar with the varied interests and activities of outgoing world traveler and international marketing guru in the area of genomics, Ruby Gadelrab. Ruby is one of my favorite tweeps, keeping me up to date on the personal genomics scene and the latest biotech science news. I asked Ruby to guest post; (read more)

Source: Suzy - Discipline: BioTech

I began a series of posts that explained how products are born, that is, how they go from a concept or idea to a product on the shelf waiting to be bought. So far we've discussed what R&D does and what marketing does to make sure that a product has the greatest possibility for success. Well there is another person on this team who plays a critical role in the product development ; (read more)

Source: Suzy - Discipline: BioTech

“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 […]

These “cards” are really an excuse for kids to interview their moms and shower them with the ultimate gifts: attention to mom’s quirky uniqueness, gratitude, and offers of help! Here you go — click here! (Mother’s Day is SUNDAY!)

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...

Uber also made a deal with Volvo to cooperate on self-driving cars. Self-driving cars are an existential threat to Uber if Uber doesn't develop them first. Suppose Ford makes self-driving cars viable a few years before does and rolls them out in many cities. Uber gets wiped out by Ford's ability to charge less for a ride. Uber's big competitive advantage from a large set of recruited drivers could vanish as fast as sufficiently safe autonomous vehicles can get manufactured. Sufficiently safe: that's the challenge. But autonomous vehicle makers who limit themselves to some urban markets can lower the bar for their initial roll-out by just excluding any streets and corners that are too tricky to handle. They'll lose some...

Already we've hit the $1000 genome and faster and cheaper DNA sequencing is on the way. DNA sequencing is going through a speed-up and cost-cutting rate that is similar to that which computer processors have been going through for decades. While the doubling rate of computer power has slowed quite a bit the rate of decrease in DNA sequencing costs has kept up the pace and, in fact, the rate of decline in DNA sequencing costs suddenly accelerated at the end of 2007 has been going down pretty sharply ever since. The cost decline seemed to halt during 2014 only to plunge in 2015. So why should you care? Really cheap massive amounts of DNA sequencing of cancerous cells will...

Contes de fées aux enfants - Frédéric la grenouille et Elias l'éléphant.

Cadeau de Noël pour vous :
Clic ici - et je vous guiderai au père noël.

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A man walks in a bar with his pet monkey. He sits down and orders a drink, meanwhile the monkey is running around all over the place and jumps up on a pool table. He grabs the 8 ball, shoves it into his mouth and swallows it hole. “Holy crap!” says the bartender, completely livid. […]

The post The Not So Stupid Monkey appeared first on Funny & Jokes.

Date: May 1, 2020

As COVID-19 continues to impact communities around the world, people and families everywhere are spending more time at home. In light of this, we’re launching a throwback Doodle series looking back at some of our popular interactive Google Doodle games!

Stay and play at home with today’s featured throwback: 

Our 2018 Doodle game celebrating Garden Gnomes!
 

 

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Help stop the spread of COVID-19 by following these steps.  
 

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Learn more here about the latest ways we’re responding, and how our products can help people stay connected during this time.

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The post Team Spotlight: Getting to Know Ocean Blue’s James Stamatis appeared first on Ocean Blue Fishing Adventures.

The post Reel Review: What’s New with the Shimano Stella SW 2020? appeared first on Ocean Blue Fishing Adventures.

Although CEACAM1 (CC1) glycoprotein resides at the interface of immune liver injury and metabolic homeostasis, its role in orthotopic liver transplantation (OLT) remains elusive. We aimed to determine whether/how CEACAM1 signaling may affect hepatic ischemia-reperfusion injury (IRI) and OLT outcomes. In the mouse, donor liver CC1 null mutation augmented IRI-OLT (CC1-KO→WT) by enhancing ROS expression and HMGB1 translocation during cold storage, data supported by in vitro studies where hepatic flush from CC1-deficient livers enhanced macrophage activation in bone marrow–derived macrophage cultures. Although hepatic CC1 deficiency augmented cold stress–triggered ASK1/p-p38 upregulation, adjunctive ASK1 inhibition alleviated IRI and improved OLT survival by suppressing p-p38 upregulation, ROS induction, and HMGB1 translocation (CC1-KO→WT), whereas ASK1 silencing (siRNA) promoted cytoprotection in cold-stressed and damage-prone CC1-deficient hepatocyte cultures. Consistent with mouse data, CEACAM1 expression in 60 human donor liver biopsies correlated negatively with activation of the ASK1/p-p38 axis, whereas low CC1 levels associated with increased ROS and HMGB1 translocation, enhanced innate and adaptive immune responses, and inferior early OLT function. Notably, reduced donor liver CEACAM1 expression was identified as one of the independent predictors for early allograft dysfunction (EAD) in human OLT patients. Thus, as a checkpoint regulator of IR stress and sterile inflammation, CEACAM1 may be considered as a denominator of donor hepatic tissue quality, and a target for therapeutic modulation in OLT recipients.

Whether mutations in cancer driver genes directly affect cancer immune phenotype and T cell immunity remains a standing question. ARID1A is a core member of the polymorphic BRG/BRM-associated factor chromatin remodeling complex. ARID1A mutations occur in human cancers and drive cancer development. Here, we studied the molecular, cellular, and clinical impact of ARID1A aberrations on cancer immunity. We demonstrated that ARID1A aberrations resulted in limited chromatin accessibility to IFN-responsive genes, impaired IFN gene expression, anemic T cell tumor infiltration, poor tumor immunity, and shortened host survival in many human cancer histologies and in murine cancer models. Impaired IFN signaling was associated with poor immunotherapy response. Mechanistically, ARID1A interacted with EZH2 via its carboxyl terminal and antagonized EZH2-mediated IFN responsiveness. Thus, the interaction between ARID1A and EZH2 defines cancer IFN responsiveness and immune evasion. Our work indicates that cancer epigenetic driver mutations can shape cancer immune phenotype and immunotherapy.

Organ shortage continues to limit the lives of patients who require liver transplantation. While extending criteria for liver organs provides a needed resource, tissue damage from prolonged ischemic injury can result in early allograft dysfunction and consequent rejection. In this issue of the JCI, Nakamura et al. used a mouse transplantation model with prolonged ex vivo cold storage to explore liver graft protection. The authors found that liver grafts with absent carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) exhibited increased ischemia-reperfusion injury inflammation and decreased function in wild-type recipients. The authors went on to correlate CEACAM1 levels with postreperfusion damage in human liver transplant recipients. Notably, this study identified a potential biomarker for liver transplant donor graft quality.

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.

Familial dysautonomia (FD) is the most prevalent form of hereditary sensory and autonomic neuropathy (HSAN). In FD, a germline mutation in the Elp1 gene leads to Elp1 protein decrease that causes sympathetic neuron death and sympathetic nervous system dysfunction (dysautonomia). Elp1 is best known as a scaffolding protein within the nuclear hetero-hexameric transcriptional Elongator protein complex, but how it functions in sympathetic neuron survival is very poorly understood. Here, we identified a cytoplasmic function for Elp1 in sympathetic neurons that was essential for retrograde nerve growth factor (NGF) signaling and neuron target tissue innervation and survival. Elp1 was found to bind to internalized TrkA receptors in an NGF-dependent manner, where it was essential for maintaining TrkA receptor phosphorylation (activation) by regulating PTPN6 (Shp1) phosphatase activity within the signaling complex. In the absence of Elp1, Shp1 was hyperactivated, leading to premature TrkA receptor dephosphorylation, which resulted in retrograde signaling failure and neuron death. Inhibiting Shp1 phosphatase activity in the absence of Elp1 rescued NGF-dependent retrograde signaling, and in an animal model of FD it rescued abnormal sympathetic target tissue innervation. These results suggest that regulation of retrograde NGF signaling in sympathetic neurons by Elp1 may explain sympathetic neuron loss and physiologic dysautonomia in patients with FD.

An in-depth understanding of immune escape mechanisms in cancer is likely to lead to innovative advances in immunotherapeutic strategies. However, much remains unknown regarding these mechanisms and how they impact immunotherapy resistance. Using several preclinical tumor models as well as clinical specimens, we identified a mechanism whereby CD8+ T cell activation in response to programmed cell death 1 (PD-1) blockade induced a programmed death ligand 1/NOD-, LRR-, and pyrin domain–containing protein 3 (PD-L1/NLRP3) inflammasome signaling cascade that ultimately led to the recruitment of granulocytic myeloid-derived suppressor cells (PMN-MDSCs) into tumor tissues, thereby dampening the resulting antitumor immune response. The genetic and pharmacologic inhibition of NLRP3 suppressed PMN-MDSC tumor infiltration and significantly augmented the efficacy of anti–PD-1 antibody immunotherapy. This pathway therefore represents a tumor-intrinsic mechanism of adaptive resistance to anti–PD-1 checkpoint inhibitor immunotherapy and is a promising target for future translational research.

BACKGROUND The anti–programmed cell death 1 (anti–PD-1) antibody pembrolizumab is clinically active against non–small cell lung cancer (NSCLC). In addition to T cells, human natural killer (NK) cells, reported to have the potential to prolong the survival of patients with advanced NSCLC, also express PD-1. This study aimed to investigate the safety and efficacy of pembrolizumab plus allogeneic NK cells in patients with previously treated advanced NSCLC.METHODS In total, 109 enrolled patients with a programmed death ligand 1 (PD-L1) tumor proportion score (TPS) of 1% or higher were randomly allocated to group A (n = 55 patients given pembrolizumab plus NK cells) or group B (n = 54 patients given pembrolizumab alone). The patients received i.v. pembrolizumab (10 mg/kg) once every 3 weeks and continued treatment until the occurrence of tumor progression or unacceptable toxicity. The patients in group A continuously received 2 cycles of NK cell therapy as 1 course of treatment.RESULTS In our study, patients in group A had longer survival than did patients in group B (median overall survival [OS]: 15.5 months vs. 13.3 months; median progression-free survival [PFS]: 6.5 months vs. 4.3 months; P < 0.05). In group A patients with a TPS of 50% or higher, the median OS and PFS was significantly longer. Moreover, the patients in group A treated with multiple courses of NK cell infusion had better OS (18.5 months) than did those who received a single course of NK cell infusion (13.5 months).CONCLUSIONS Pembrolizumab plus NK cell therapy yielded improved survival benefits in patients with previously treated PD-L1+ advanced NSCLC.TRIAL REGISTRATION ClinicalTrials.gov NCT02843204.FUNDING This work was supported by grants from the National Natural Science Foundation of China (NSFC) – Guangdong Joint Foundation of China (no. U1601225); the NSFC (no. 81671965); the Guangdong Provincial Key Laboratory Construction Project of China (no. 2017B030314034); and the Key Scientific and Technological Program of Guangzhou City (no. 201607020016).

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).

Lymph node stromal cells (LNSCs) regulate immunity through constructing lymphocyte niches. LNSC-produced laminin α5 (Lama5) regulates CD4+ T cells but the underlying mechanisms of its functions are poorly understood. Here we show that depleting Lama5 in LNSCs resulted in decreased Lama5 protein in the LN cortical ridge (CR) and around high endothelial venules (HEVs). Lama5 depletion affected LN structure with increased HEVs, upregulated chemokines, and cell adhesion molecules, and led to greater numbers of Tregs in the T cell zone. Mouse and human T cell transendothelial migration and T cell entry into LNs were suppressed by Lama5 through the receptors α6 integrin and α-dystroglycan. During immune responses and allograft transplantation, depleting Lama5 promoted antigen-specific CD4+ T cell entry into the CR through HEVs, suppressed T cell activation, and altered T cell differentiation to suppressive regulatory phenotypes. Enhanced allograft acceptance resulted from depleting Lama5 or blockade of T cell Lama5 receptors. Lama5 and Lama4/Lama5 ratios in allografts were associated with the rejection severity. Overall, our results demonstrated that stromal Lama5 regulated immune responses through altering LN structures and T cell behaviors. This study delineated a stromal Lama5–T cell receptor axis that can be targeted for immune tolerance modulation.

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.

Facioscapulohumeral muscular dystrophy (FSHD) results from expression of the full-length double homeobox 4 (DUX4-FL) retrogene in skeletal muscle. However, even in cases of severe FSHD the presence of DUX4 is barely detectable. In this issue of the JCI, Bosnakovski et al. used an inducible, muscle-specific human DUX4 to reproduce the low-level, sporadic DUX4 expression of human FSHD muscle as well the myopathology seen in human FSHD disease. Notably, dysregulated fibroadipogenic progenitors accumulated in affected muscles, thus providing a mechanism for the replacement of muscle by fibrosis and fat.

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.

BACKGROUND Glucose-6-phosphate dehydrogenase (G6PD) deficiency decreases the ability of red blood cells (RBCs) to withstand oxidative stress. Refrigerated storage of RBCs induces oxidative stress. We hypothesized that G6PD-deficient donor RBCs would have inferior storage quality for transfusion as compared with G6PD-normal RBCs.METHODS Male volunteers were screened for G6PD deficiency; 27 control and 10 G6PD-deficient volunteers each donated 1 RBC unit. After 42 days of refrigerated storage, autologous 51-chromium 24-hour posttransfusion RBC recovery (PTR) studies were performed. Metabolomics analyses of these RBC units were also performed.RESULTS The mean 24-hour PTR for G6PD-deficient subjects was 78.5% ± 8.4% (mean ± SD), which was significantly lower than that for G6PD-normal RBCs (85.3% ± 3.2%; P = 0.0009). None of the G6PD-normal volunteers (0/27) and 3 G6PD-deficient volunteers (3/10) had PTR results below 75%, a key FDA acceptability criterion for stored donor RBCs. As expected, fresh G6PD-deficient RBCs demonstrated defects in the oxidative phase of the pentose phosphate pathway. During refrigerated storage, G6PD-deficient RBCs demonstrated increased glycolysis, impaired glutathione homeostasis, and increased purine oxidation, as compared with G6PD-normal RBCs. In addition, there were significant correlations between PTR and specific metabolites in these pathways.CONCLUSION Based on current FDA criteria, RBCs from G6PD-deficient donors would not meet the requirements for storage quality. Metabolomics assessment identified markers of PTR and G6PD deficiency (e.g., pyruvate/lactate ratios), along with potential compensatory pathways that could be leveraged to ameliorate the metabolic needs of G6PD-deficient RBCs.TRIAL REGISTRATION ClinicalTrials.gov NCT04081272.FUNDING The Harold Amos Medical Faculty Development Program, Robert Wood Johnson Foundation grant 71590, the National Blood Foundation, NIH grant UL1 TR000040, the Webb-Waring Early Career Award 2017 by the Boettcher Foundation, and National Heart, Lung, and Blood Institute grants R01HL14644 and R01HL148151.

Prenatal alcohol exposure (PAE) affects at least 10% of newborns globally and leads to the development of fetal alcohol spectrum disorders (FASDs). Despite its high incidence, there is no consensus on the implications of PAE on metabolic disease risk in adults. Here, we describe a cohort of adults with FASDs that had an increased incidence of metabolic abnormalities, including type 2 diabetes, low HDL, high triglycerides, and female-specific overweight and obesity. Using a zebrafish model for PAE, we performed population studies to elucidate the metabolic disease seen in the clinical cohort. Embryonic alcohol exposure (EAE) in male zebrafish increased the propensity for diet-induced obesity and fasting hyperglycemia in adulthood. We identified several consequences of EAE that may contribute to these phenotypes, including a reduction in adult locomotor activity, alterations in visceral adipose tissue and hepatic development, and persistent diet-responsive transcriptional changes. Taken together, our findings define metabolic vulnerabilities due to EAE and provide evidence that behavioral changes and primary organ dysfunction contribute to resultant metabolic abnormalities.

☆ To see all of the parts in this series, click here ☆ Although it seemed as if my little fangirl heart couldn’t have taken any more, the day after the Nagayan Fanclub event, I went to see the Hyoutei myu for the first time. Just in case you’re reading this and going Huh? What’s a Hyoutei myu??, I can summarize by saying that it’s one in a series of musicals based on The Prince of Tennis. Yes, the manga that I ended up working on a few years later. ???? I was such a fangirl! Before I copy/paste my report on that musical, I want to say that the reason that I’m making this public again (they’re long gone now, and a lot of it was written privately) is because I want to show how much of a “silly,” squealing fangirl I was. I went from fan to insider purely because, later on, I took crazy-sounding chances and worked hard. And I sincerely believe that you, whomever you are, can do the same! By the way, all of this is eventually becoming fodder for an online comic that I’ve been formulating for a long time! No release date, though. I’m still working on Denkiki, this blog, my Youtube channel, and a few other things. And trying to put a new life together for myself. ???? In the meantime, let’s get to it! My friends and I ready for our dreams to come true, and our dreams were to see the Prince of Tennis musical! August 11, 2005 Tenimyu ~ Imperial Match Hyoutei!! This is the most detailed report on a musical that I’ve ever written. I’m going to do my best from now on to do the same each time!! (I did, for years) As Seigaku said, ♪♪DO YOUR BEST DO YOUR BEST!! DO YOUR BEST DO YOUR BEST!!♪♪ So far I’ve went to the opening performance of Hyoutei musical last night and to the second performance, which was tonight. ^^ I waited to write my report until seeing it a second time because I took very detailed notes the second time and added things and clarified things that the other people had seen afterwards! We had a tenimyu conference. =D (a tradition afterwards!!) It was a solid conclusion that cast improved a lot between the first and second performances. I can’t wait to see the last Tokyo performance, this Sunday. My bet is that they’re going to be VERY solid before then!! Oh wow. Deliciousness on a stick!! My overall feelings can be summed up in the chant that Hyoutei led, *clap clap* “Katsu no wa – Hyoutei! Makeru no Sei-gaku!!” 勝つのは氷帝！負けるの青学！！ (‘The winner will be Hyoutei! The loser will be Seigaku!’) Well, let’s start at what happened today before the musical!! Being hungry and having little other choice in the area for food, we went to the convenience store down the block from the musical… first off, I stopped and stared at this guy who was about to cross the road– who looked a lot like Ishibashi! But I couldn’t tell for sure because he’s changed his hair recently according to his picture set. He stared back at me, but it might have been because I was a tall red-headed foreigner wearing a Hyoutei jersey and a short black skirt.. ? LOL I don’t know if it was him, but I think that it was! He turned and looked back, and I think that he recognized me? I think.. maybe.. hmm..! He definitely recognized me yesterday, but that story is at the end of this report~ In the convenience store, while we are browsing the food sections, who do I notice has walked up alongside our aisle, but quite a few of the cast members! From what I remember, it was Yuu (Tezuka), Aiba (Fuji), Adachi (Kikumaru), Konishi (Kawamura), and Araki (Inui). Araki was wearing a cute hat so it took a minute to recognize him, and while most of the boys wandered along next to me without trouble in the aisle that I was in, Adachi stayed well away by the magazines. He was wearing a mask– which likely means that he has a cold!! Poor boy!! I only talked to Yuu– because I feel most comfortable talking to Yuu out of that group… ^^;; err, sorta. I (stupidly) shouted too loudly, “Yuu!!” when he came into my aisle, and of course he couldn’t ignore something like that. ^^;;; I feel a little bad, because I think that he gave me one of those, ‘why are you talking to me?’ looks. It’s not normal for a fan to actually talk to an actor here if they see them. I said, “hisashiburi!!’ (“It’s been a while!”) thinking that it’s been a while since I talked to him at all, to which he replied, “kino mita….” (“I saw you yesterday”)… Oh yeah…….. he’d obviously seen me at demachi yesterday (more later), and I felt kind of stupid and like I’d been really fannish, so I smiled and left him to do his things with the other boys. It wasn’t until later that I realized that I should have wished him good luck. Ah well, next time!! Itte yosh~! I probably acted way too familar, since we aren’t friends or anything, but it’s the way that I’ve always been with anyone that I’m fond of, friends or acquaintences. So it naturally carries off to them, without me even thinking of it. ^^; Ah well… in any case, I wish them all good luck for the future and rest of the performances!! On to the myu itself! (again! lol) Tenimyu ~ Imperial Match Hyoutei!! KENN special guest star. For both of these performances and for tomororw’s two shows also, KENN (Yuuta) is the special St. Rudolph guest star!! After that is Shiozawa for the next 3 days and Shinoda for the last day. I have tickets to shows with both of them (Thu and Sat for Shio, Sun of course for Shino), so I’m going to note the differences in separate posts. ^^ I can’t wait to see the differences!! ^____________________________^ This is my favorite~ I think that this is the best of all of the musicals. Hands down. Hyoutei was…. droolworthy. Hyoutei rocked the world, and they didn’t even show up for a little while. I’ll start at the beginning~ Tenimyu tenimyu tenimyu tenimyu tenimyu yaaay! <—— (me) First, as in all of the musicals, the curtain wa down andthere were suddenly the sounds of sneakers hitting the pavement. Cue the excitement level to rise and everyone to quiet down suddenly. The lights went down, and the curtain raised silently. A spotlight appeared off to the side, and onto the stage walks Sengoku (Wada) from the right, who does a short introduction. “Welcome,” etc. From the other side, lit with another spotlight, Yuuta (Kenn) made his entrance. They noticed each other and started to walk towards the center, but Yuuta suddenly stops as his cell phone goes off — with his ringer being Ore wa ore no namae de!! XDXDXD Wada starts to interrupt him, but his own phone goes off — with his ringer being Oretachi Jimi-su from bukimyu!! ROFLOL!! So hilarious!! They both managed to get off the phones shortly and walk over to each other, and began to argue — Sengoku asks Yuuta ‘So, who is the coolest player?’ Kenn begins right in saying that his buchou is the coolest, just look at him! And up above them on the screen appears a rather dorky shot of Akazawa and Kaneda from an earlier musical! Yuuta was embarrassed, saying, ‘ack!! I didn’t mean to put both of them up there!!’ Sengoku corrected him, saying, ‘My team is really cool’ — ‘Hey, who put that there?!’ Up on the screen had appeared a shot from Bukimyu of the Jimis mid-dance! Definitely NOT cool! XDXDXD In the end, they couldn’t decide who was the coolest, because music started up behind them…. Cue them to run off of stage and the second curtain to raise~ Starting with Fuji, all of Seigaku minus Ryoma took their places among the strong opening beats of the new Seigaku fight song, ♪Do Your Best! They did a long typical number for the kind of song- with lots of group singing and solos, the whole team going all out on their dancing just as they’d done for Bukimyu. Then they gathered in the center and Ryoma (Yanagi) was raised above! The crowd went noticeably more silent, this was the first time that Yanagi would be performing Ryoma on his own again!! How recovered WAS he? Yanagi didn’t move too much during this song, but he did do a bit of posing, and tried his very very best at singing. He still can’t sing well, but he’s obviously working on it. Hard. (So basically, he sounded terrible, but much better than he had at graduation myu!) Throughout the musical, Yanagi did very little dancing, and mostly posing. When he walked, he mostly walked without a limp, but there were a few times when it was noticeable, especially in the second performance. He could mostly manage it though, but he could not manage any kind of turns, as he stumbled slightly pretty much every time he tried. ;__;  Ganbarou Yanagi!! He’s improved a LOT!! Though there’s still a long road ahead, I think, he really seems to be trying hard. Everyone talked about it afterward and felt the same, very very respectful of what he must have to face and what he’s going through. What a strong boy~~ After Do Your Best, the lyrics consisting mostly of the team outlining their strengths and how they would try their hardest, Seigaku exited the stage and it all went dark. When the curtain raised again, the ichinen trio were sitting at desks on the left side of the stage, puzzling over the answers to their english test. Horio kept copying Kachiro, who shouted at him for it, and when they noticed us, they started in on another hilarious song, led by Horio, and beginning with english!! Horio belted out, “Hello, good day, how are you?” while Kachiro and Katsuo start chiming in. Kachiro seems to think that Horio is copying too much, so he stands up on the desk for his next refrain, and very very slashily (to me), Horio offers him a hand down. Then…….. they start a tap dance across stage that somehow incorporates the lyrics “A B C D”!! XDXD They have their usual display of awesome and hilarious dancing and suddenly rush off stage in the middle of the test when they realize that they’re about to miss the tennis team’s ranking tournament!! Most of Seigaku’s ranking matches are glossed over quickly, with the actors coming in and out quickly, pretending to hit a few balls or so. They give special attention to Ryoma vs. Oishi, after which Ryoma is congratulated for becoming a regular again. Next is the most important match, however. Inui vs. Momo and Inui vs. Tezuka. They do both matches at once, by having Inui stand on the right in the background, and Momo on the left in the background, with Tezuka in the front center (like a triangle). There is scary data-like music playing in the background (hard to describe.. it sounds like data). Inui is hitting balls and every other time that he hits a ball either Tezuka or Momo hits it. He finishes the Momo match first, and lo and behold ~ he beats Momo, who is no longer a regular because of it. Momo can’t believe it and stalks off stage. Then the Inu-Tez match is stopped, and the stage is resituated for a proper viewing of the rest of the match. The entire team is talking about how scary data tennis is, and I agree after seeing that. Inui is powerful in the musical! On to the real InuTez match. Inui tells Tezuka that he can break him with data tennis, because data doesn’t lie. In fact, after he counters Tezuka’s zero-shiki drop shot with data, he...

This isn’t in the photos, but it’s foggy and cold this morning in western Washington. It’s the weirdest summer I’ve ever experienced — foggy, frigid mornings, cool days, and then freezing nights! It’s not very pleasant for a desert creature like myself, but it’s quite nice to sit inside and write in my blog a least. I have to say, it sure is weird, though. It’s August and I wear a sweater or sweatshirt most of the time and then I’m still cold! ^^; There are a few sunny days here and there, though. I get out on those days, into the wilderness and bright blue beyond. Sometimes, I just drive and drive in my still-unnamed yellow bug, and other times I find something that not a lot of people know about. This is about one of them. ^^ I love to wander, to find all of the nooks and crannies of wherever I happen to be. Tourist sites? Well, they’re usually cool and I want to see them, but it’s the little, hidden things off the beaten trail that really get my soul revving. So, Johns River (no apostrophe, it was named back when apostrophes weren’t used on maps) was one of those things. I found out about it by googling and googling, thinking that someone, somewhere, must have written about something other than the two really traveled trails in Grays Harbor. I mean, this area is the gateway to the wild peninsula of Washington, where according to Stephanie Meyer and Patricia Briggs, vampires and werewolves run wild. I also loooooooove mountain meadows. Johns river is not in the mountains, so I suppose that it mostly qualifies as grassland surrounded by trees? It’s just a little concrete path, and it’s not even a mile (0.6 miles one way) long, but with the river on one side and a huge expanse of pasture to the other side, it took my breath away.   Just look at this. Elk supposedly graze around here a lot, and I didn’t see any since I went during midday, but I bet it’s really a sight at sunset. It’s not far, so I will definitely have to come back. Can’t you just imagine little river sprites lounging on the bank, cleaning themselves? And little fairies flitting through the air? I bet this is a really magical place at sunset.   The little shack in the distance is off the trail. It’s supposedly for hunters (YUCK) and photographers. It would make a wonderful place to watch the sprites from. This shack is at the very end of the trail, and the same thing. It’s boring inside. I didn’t see any geldings, but I saw a few mosquitoes and a spider. If you’re lucky enough to have a horse that loves to take you along on its adventures, you can continue. I was wearing shorts, so I didn’t go, because ticks! But I will come back. Yes, I will come back. :3 Road to nowhere. Ignore the buildings. They’re only there for magical curse removal. Here’s a panorama of wildness. I’m feeling really magical today, can’t you tell? I think it’s because I have Daniel Waples playing in the background, and it’s all foggy outside. That reminds me that I want a handpan so badly. I need to find a handpan that I can afford soooooo badly, because I think it’s a music that speaks to my inner essence. Does anyone know what these gorgeous purple flowers are? They’re not lavender. The River People watch over this creek. Be careful to please them. It’s me. Sometimes I wear bright colors, sometimes I wear pastels. I don’t think that a magical being has to stick to  neutrals. (That hand thing is a shaka, a very cool gesture that I learned during my time in Hawaii that means “hang loose.” I like to think that it also means that you should be yourself and follow your instincts.) I think that I’ll go research handpans again. I should write down how much they cost so that I can be sure to stock my Airstream with one when I get it. ???? Here’s to the future! Excelsior! (Is that a good “to infinity, and beyond!!” kind of quote? If not, what should I use instead? I feel like “banzai!” is overused) Oh, and I’ve been arting on my Tumblr lately. I’ve been writing a serial ficiton that is mysterious connected to my soon-to-come comic, Denkiki on my other tumblr. Go check them out!  I’m going to start using my mailing list soon, too, to keep people updated, so stay tuned and I’ll post the link soon! Or make it a popup, I’m not sure. But I want to offer something cool for when people sign up. ???? Chaoness!

It’s release day for my new MM romance! My last release was Christmas 2018, so I’m very excited to finally have a new book for you. When I was in Australia earlier this year, I got hooked on Bondi Rescue, and this (completely fictional!) romance between a trainee and an older, very closeted lifeguard was born. […]

We're still waiting to hear news about Apple Card's performance relative to the major card issuers, but that hasn't stopped Samsung from announcing plans to launch an "innovative" debit card as part of a new mobile-first money management platform the company has been developing over the last year.


Announced on Thursday in a blog post by Samsung Pay vice-president Sang Ahn, the forthcoming debit card is in partnership with finance company SoFi and will be backed by a cash management account.

"In 2020, Samsung Pay will be expanding our service from being a rewarding way to shop and pay, to also being a rewarding way to manage money," writes Ahn. "Over the past year we have been busy developing a mobile-first money management platform. Our vision is to help consumers better manage their money so that they can achieve their dreams and goals. Now more than ever, mobile financial services and money management tools will play an even bigger role in our daily lives while also opening up new possibilities."

The debit card is scheduled to launch this summer. Other than that, Samsung hasn't offered any details on how it will work, but expect it to integrate with Samsung's existing mobile payment system.

Launched in August 2019, ‌Apple Card‌ is a credit card linked to Apple Pay and built into the Wallet app on iPhone. Apple partnered with Goldman Sachs to launch the card, and in October the investment bank hailed it as "the most successful credit-card launch ever." Nine months later, neither Apple nor Goldman Sachs has offered any concrete details on its performance.

During the global health crisis, Apple has introduced an ‌Apple Card‌ Assistance Program that allows ‌‌Apple Card‌‌ holders to skip their March and April payments without incurring interest charges for that billing cycle. For more details on how the card works, check out our comprehensive Apple Card guide.
This article, "Samsung Announces 'Innovative' Debit Card Launching this Summer" first appeared on MacRumors.com

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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.

This article, "Deals: Refurbished 15-Inch MacBook Pro Notebooks on Sale at Woot From $1,580 ($800+ Off)" first appeared on MacRumors.com

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Apple has been selling audio accessories since December 2016 when the original AirPods launched. We now have the ‌AirPods‌ 2 and the AirPods Pro, and Apple is planning to add to its lineup with new over-ear Apple-branded headphones.

Apple already sells over-ear headphones under its Beats brand, but as with the ‌AirPods‌, Apple is also working on headphones that will be Apple branded rather than Beats branded. These headphones are said to be aimed at the high-end market.

Design

The headphones will feature an all-new design, and while we don't know a lot about it, we do know some details shared by Bloomberg.

Apple is said to be working on two versions of the high-end over-ear headphones, including a premium version with leather-like fabrics and a fitness-focused model that uses lighter, breathable materials with small perforations for better airflow.

Prototypes of the headphones have been described as having a retro-like look with over-ear cups that swivel along with a headband connected with thin metal arms.

Apple is planning to attach the ear pads and the head padding to the headphone's frame magnetically, allowing users to swap different colors and variants in and out for customization purposes.

An icon representing the headphones was found in the code in a leaked version of iOS 14, but little detail can be gleaned from the imagery.

Rumored Features

According to Apple analyst Ming-Chi Kuo, Apple's over-ear headphones will feature Active Noise Cancellation, a high-end feature baked into the Beats Studio 3 headphones, Solo Pro headphones, and the ‌AirPods Pro‌.

Active Noise Cancellation is designed to cut down on ambient noise so you can focus on what you're listening to. If it mimics ANC on the ‌AirPods Pro‌, there will be a transparency mode that will enable noise cancelling features, but with an option to continue to hear what's going on around you.

Sound quality is expected to be better than the sound quality of the ‌AirPods‌.

Pricing

Apple could price the new headphones at around $350.

Launch Date

Current rumors indicate the headphones will launch at some point in 2020, though a specific date has not yet been nailed down. Mass production on the headphones is scheduled to begin in mid-2020, which perhaps suggests a fall 2020 launch.

There were rumors indicating that Apple initially planned to launch the headphones at some point in 2019, but that did not happen.

Over-Ear Headphones Rumor History

• Mass Production on Apple's High-End Headphones Rumored to Start in Mid-2020


• Apple to Unveil High-End Over-Ear Wireless Headphones With Magnetically Swappable Parts Later This Year


• Apple Reportedly Targeting WWDC for Over-Ear Headphones Launch, New 'AirPods X' Later in the Year


• Icon for Apple's Rumored Over-Ear Noise Canceling Headphones Discovered in Leaked iOS 14 Code


• Apple-Branded Over-Ear Headphones Said to Launch as Early as Second Half of 2019


• Apple's Upcoming Over-Ear Wireless Headphones to Target High-End Noise-Canceling Market


• KGI: Apple Developing High-End Over-Ear Headphones, Launching Late 2018 at the Earliest

Guide Feedback

Have a question about Apple's over-ear headphones, know of something we left out, or want to offer feedback? Send us an email here.
This article, "Apple's Work on High-End Over-Ear Headphones: Everything We Know" first appeared on MacRumors.com

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