oscon: RT @oreillyanimals Vote Instant Wild's Digital Eyes & Ears for Wildlife Protection to win Google Global Impact Award http://t.co/BM3qufX1PF

Teacher question: When working with state educational standards are the expectations for the student to be able to accomplish each of the standards with grade level text. Some of us believe that if a fourth-grade student can determine the main idea in a second-grade text that the student has mastered that standard. Please help us settle this argument. Shanahan's response:

Teacher question: When working with state educational standards are the expectations for the student to be able to accomplish each of the standards with grade level text. Some of us believe that if a fourth-grade student can determine the main idea in a second-grade text that the student has mastered that standard. Please help us settle this argument. Shanahan's response:

Instant Reaction: September Jobs Report

Instant reaction: NAR’s Lawrence Yun on Case-Shiller

Here are the latest developments in the coronavirus crisis.

Here is the latest news from around the world.

velocityconf: If you don't understand your ppl, you don't understand #Ops http://t.co/DQTBLJlWza New #velocityconf interview w/ @katemats

velocityconf: RT @oreillyanimals Vote Instant Wild's Digital Eyes & Ears for Wildlife Protection to win Google Global Impact Award http://t.co/Z0EetiQshZ

Rather than waiting for offices to reopen, REALTOR® associations are conducting timely, safe, and efficient ethics hearings through Zoom.

From the virtual 2020 REALTORS® Legislative Meetings, April 27-May 15

After a month-long hiatus, additional instant offer firms are stepping back in to purchase homes, using contact-free processes.

Istanbul Turkey

The Amateur Traveler talks to Friedel from TravellingTwo.com about their continuing bike tour around the world. Friedel was on previously talking about travel to Iran and has come back to talk about the Central Asian countries of Turkmenistan, Uzbekistan, Kazakhstan, and Kyrgyzstan. This region of the world offers adventure travelers deserts, tea houses, camels, wild horses, yurts, tea houses, spectacular mountains, friendly locals and fermented mares milk.

The Amateur Traveler talks to Mike about his recent trip to Kazakhstan.  He explored this large area on a backpacker's budget.  Kazakhstan is the 9th biggest country in the world. "In the very West end of the country you have old mosques. In the new capital Astana you have futuristic buildings."

The Amateur Traveler talks to Michael Soncina again about his trip to Tajikistan in Central Asia. Tajikistan is smack dab between Pakistan, Afghanistan, Uzbekistan and Kyrgyzstan. Unlike the other countries Tajikistan is mostly mountainous. A lot of its influences, history and culture is influenced by Persia while its neighbors have more Mongolian or nomadic influences.

Hear about travel to Kyrgyzstan as the Amateur Traveler talks to Eric Anderson about the central asian country where he has been serving as a Peace Corp volunteer.

Eric admits that he might not have been able to find Kyrgyzstan on a map before being sent to this beautiful mountainous country just west of China...

Hear about travel to Uzbekistan as the Amateur Traveler talks to Latish Sharma about his travels on the Silk Road to ancient cities including Samarkand.

Hear about travel to Istanbul, Turkey as the Amateur Traveler talks to Christopher Mitchel from travelingmitch.com about the city where he lived for 3 years.

Hear about travel to Istanbul, Turkey as the Amateur Traveler talks to Christopher Mitchell from travelingmitch.com about the city where he lived for 3 years.

Hear about travel to Northern Pakistan and the  Karakoram Highway as the Amateur Traveler talks to David Harden from travelwornsatchel.com about his road trip in this remote and beautiful country.

At a cost of $7.5 million a patient, they were 16 very expensive field hospitals. Yet, according to NPR, those hospitals are now “stand[ing] down.” You probably remember them from headlines early in the pandemic: makeshift medical centers being assembled at breakneck speed by companies contracted by the Army Corps of Engineers in anticipation of…

The post After Treating Barely Any Patients for a Massive $7.5 Million Each, 16 Emergency COVID Hospitals Are Standing Down appeared first on The Western Journal.

The health expert who helped shaped Britain’s lockdown policies in response to the coronavirus has resigned after admitting he broke his own rules by having his married lover visit him at his home. Professor Neil Ferguson, 51, of Imperial College in London was a prominent member of the Scientific Advisory Group for Emergencies. The Telegraph…

The post Scientist Behind Social Distancing Breaks Own Rules To Cheat with Married Woman, Resigns appeared first on The Western Journal.

It’s not good for people to be alone. Quarantining has been difficult for many people who have gotten used to socializing daily, and because of that, some have found ways to follow the rules but feel a little less isolated. Some neighborhoods have decided to be social while maintaining the suggested distance apart, whether that’s…

The post ‘The Voice’ Contestant Alexa Cappelli Treats Neighbors to Weekly Performance in Her Cul-de-Sac appeared first on The Western Journal.

A man is in custody following a six-hour standoff in eastern Prince Edward Island that started when police responded to a domestic dispute that quickly escalated when officers learned the suspect could be armed.

The Defense Department's Inspector General has opened an investigation into whether U.S. troops were discouraged from reporting the rape and sexual abuse of children by their Afghan allies.

The emergence of ISIS in Afghanistan has introduced a new level of brutality to the conflict, beyond what has been practiced by the Taliban.

Najibullah Quraishi has covered the war in Afghanistan for more than a decade, but embedding with ISIS fighters who've recently emerged there "was the most risky and dangerous job ever I've done in my life," he says.

It appears ISIS-allied fighters are gaining a foothold in Afghanistan, but just how similar are they to the group's branches in Iraq and Syria?

The coronavirus pandemic has many of us nostalgic for a simpler time — maybe when we were teenagers and/or watching our favorite early oughts sitcoms. 

Actress Cobie Smulders seems to be feeling that itch, and sensed we are too. The former How I Met Your Mother actress decided to recreate her character Robin Scherbatsky's hit song from the series, "Let's Go to The Mall."

For those who need a refresher, "Let's Go to The Mall" was released during Robin's short career as a pop star (under the name Robin Sparkles) in her homeland of Canada. While it has all the flair of an '80s banger — jelly bracelets, worshipping the mall — it was released in the '90s because apparently that's when '80s culture reached Canada.  Read more...

Prime Minister Justin Trudeau says Canada will not pay the full price for medical masks that do not live up to medical standards.

Instant Reaction: Unemployment, May 8, 2020

Christmas is not an official holiday in Japan, nor a widely observed religious holiday, but it is celebrated nonetheless in its own unique way. Here's some data that highlights Christmas in Japan.

School bus drivers in the Upper Grand District School Board are transporting school work instead of students.

Prostate cancer (PCa) cells heavily rely on an active androgen receptor (AR) pathway for their survival. Enzalutamide (MDV3100) is a second-generation antiandrogenic drug that was approved by the Food and Drug Administration in 2012 to treat patients with castration-resistant prostate cancer (CRPC). However, emergence of resistance against this drug is inevitable, and it has been a major challenge to develop interventions that help manage enzalutamide-resistant CRPC. Erythropoietin-producing human hepatocellular (Eph) receptors are targeted by ephrin protein ligands and have a broad range of functions. Increasing evidence indicates that this signaling pathway plays an important role in tumorigenesis. Overexpression of EPH receptor B4 (EPHB4) has been observed in multiple types of cancer, being closely associated with proliferation, invasion, and metastasis of tumors. Here, using RNA-Seq analyses of clinical and preclinical samples, along with several biochemical and molecular methods, we report that enzalutamide-resistant PCa requires an active EPHB4 pathway that supports drug resistance of this tumor type. Using a small kinase inhibitor and RNAi-based gene silencing to disrupt EPHB4 activity, we found that these disruptions re-sensitize enzalutamide-resistant PCa to the drug both in vitro and in vivo. Mechanistically, we found that EPHB4 stimulates the AR by inducing proto-oncogene c-Myc (c-Myc) expression. Taken together, these results provide critical insight into the mechanism of enzalutamide resistance in PCa, potentially offering a therapeutic avenue for enhancing the efficacy of enzalutamide to better manage this common malignancy.

The rapid emergence and dissemination of methicillin-resistant Staphylococcus aureus (MRSA) strains poses a major threat to public health. MRSA possesses an arsenal of secreted host-damaging virulence factors that mediate pathogenicity and blunt immune defenses. Panton–Valentine leukocidin (PVL) and α-toxin are exotoxins that create lytic pores in the host cell membrane. They are recognized as being important for the development of invasive MRSA infections and are thus potential targets for antivirulence therapies. Here, we report the high-resolution X-ray crystal structures of both PVL and α-toxin in their soluble, monomeric, and oligomeric membrane-inserted pore states in complex with n-tetradecylphosphocholine (C14PC). The structures revealed two evolutionarily conserved phosphatidylcholine-binding mechanisms and their roles in modulating host cell attachment, oligomer assembly, and membrane perforation. Moreover, we demonstrate that the soluble C14PC compound protects primary human immune cells in vitro against cytolysis by PVL and α-toxin and hence may serve as the basis for the development of an antivirulence agent for managing MRSA infections.

Research Event

Event participants

David Roberts, Assistant Professor and School of Security Studies Lead for Regional Security and Development, King's College London
Kristian Coates Ulrichsen, Associate Fellow, Middle East and North Africa Programme, Chatham House
Chair: Sanam Vakil, Deputy Director and Senior Research Fellow, Middle East and North Africa Programme, Chatham House

Research Event

Event participants

Tim Jinks, Head of Drug-Resistant Infections Programme, Wellcome
Jim O’Neill, Chair, Review on Antimicrobial Resistance; Chair, Chatham House
Haileyesus Getahun, Director of Global Coordination and Partnership on Antimicrobial Resistance, World Health Organization 
Juan Lubroth, Chief Veterinary Officer, Food and Agriculture Organization (Videolink)
Jyoti Joshi, Head, South Asia, Center for Disease Dynamics, Economics & Policy
Estelle Mbadiwe, Coordinator-Nigeria, Global Antibiotic Resistance Partnership
Charles Clift, Senior Consulting Fellow, Chatham House; Report Author

Treatment of patients with chronic lymphocytic leukemia (CLL) with inhibitors of Bruton's tyrosine kinase (BTK), such as ibrutinib, is limited by primary or secondary resistance to this drug. Examinations of CLL patients with late relapses while on ibrutinib, which inhibits BTK's catalytic activity, revealed several mutations in BTK, most frequently resulting in the C481S substitution, and disclosed many mutations in PLCG2, encoding phospholipase C-γ2 (PLCγ2). The PLCγ2 variants typically do not exhibit constitutive activity in cell-free systems, leading to the suggestion that in intact cells they are hypersensitive to Rac family small GTPases or to the upstream kinases spleen-associated tyrosine kinase (SYK) and Lck/Yes-related novel tyrosine kinase (LYN). The sensitivity of the PLCγ2 variants to BTK itself has remained unknown. Here, using genetically-modified DT40 B lymphocytes, along with various biochemical assays, including analysis of PLCγ2-mediated inositol phosphate formation, inositol phospholipid assessments, fluorescence recovery after photobleaching (FRAP) static laser microscopy, and determination of intracellular calcium ([Ca2+]i), we show that various CLL-specific PLCγ2 variants such as PLCγ2S707Y are hyper-responsive to activated BTK, even in the absence of BTK's catalytic activity and independently of enhanced PLCγ2 phospholipid substrate supply. At high levels of B-cell receptor (BCR) activation, which may occur in individual CLL patients, catalytically-inactive BTK restored the ability of the BCR to mediate increases in [Ca2+]i. Because catalytically-inactive BTK is insensitive to active-site BTK inhibitors, the mechanism involving the noncatalytic BTK uncovered here may contribute to preexisting reduced sensitivity or even primary resistance of CLL to these drugs.

6 November 2019 , Volume 96, Number 1

The first issue of International Affairs in 2020 explores the geopolitics of the 'Indo-Pacific' region.

Research Event

Event participants

David Roberts, Assistant Professor and School of Security Studies Lead for Regional Security and Development, King's College London
Kristian Coates Ulrichsen, Associate Fellow, Middle East and North Africa Programme, Chatham House
Chair: Sanam Vakil, Deputy Director and Senior Research Fellow, Middle East and North Africa Programme, Chatham House

Research Event

Event participants

Erlan Idrissov, Minister of Foreign Affairs, Kazakhstan