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Indicatori e risultati. Principi e linee guida per lo sviluppo di un sistema informativo utile alla programmazione e alla valutazione della politica linguistica a sostegno delle minoranze tradizionali nella Provincia Autonoma di Trento (cimbri, ladini e mòcheni)
Gazzola, M., Burckhardt, T. & Mereu, D., 9 Apr 2021, Trento: Provincia Autonoma di Trento. 104 p.
Individual Characteristics Associated with Active Travel in Low and High Income Groups in the UK
Lawlor, B. A., Hunter, J. A., Adlakha, D., Kee, F. & Tully, M., 1 Oct 2021, (E-pub ahead of print) In: International Journal of Environmental Research and Public Health. 18, 19, e10360.
Industrial Wastes Utilization a Biorefinery Prospective: Biotechnological Recycling and Reuse of Brewer's Solid Wastes with other food industry residues
Singh - Nee Nigam, P., 21 Nov 2021, p. 1.
Influence of Binder Float Length on the Out-of-Plane and Axial Impact Performance of 3D Woven Composites
Ralph, C., Dahale, M., Neale, G., Ramaswamy, K., McCarthy, M., Yoo, S., Toso, N., Kelly, J., Mc Garrigle, C., Archer, E., Harkin-Jones, E. & McIlhagger, AT., 1 Aug 2021, In: Composites Part A: Applied Science and Manufacturing. 147, 17 p., 106459.
Influence of pigments on crystallisation, shrinkage and mechanical properties of LDPE, HDPE and PP
Ullah, J. & Dixon, D., 2021, (E-pub ahead of print)
Influence of pigments on the crystallisation, shrinkage, and mechanical properties of LDPE
Ullah, J., Dixon, D., Harkin-Jones, E. & Magee, C., 2021, (Accepted/In press).
Information transparency and pricing strategy in the Scottish housing market
Lo, D., Liu, N., McCord, M. & Haran, M., 22 Mar 2021, (Accepted/In press) In: International Journal of Housing Markets and Analysis.
Inhibition of corrosion causing Pseudomonas aeruginosa using plasma-activated water
Asimakopoulou, E., Εkonomou, S. Ι., Papakonstantinou, P., Doran, O. & Stratakos, A. C., 30 Nov 2021, (E-pub ahead of print) In: Journal of Applied Microbiology.
Inhibitory Effects of Lipopeptides and Glycolipids on C. albicans–Staphylococcus spp. Dual-Species Biofilms
Ceresa, C., Rinaldi, M., Tessarolo, F., Maniglio, D., Fedeli, E., Tambone, E., Caciagli, P., Banat, I. M., Diaz De Rienzo, M. & Fracchia, L., 13 Jan 2021, In: Frontiers in Microbiology. 11, 19 p., 545654.
Initial observations on the implementation of a CPS in a rural hospital in Austria
Guntschnig, S., Burnett, K., Courtenay, A. & Scott, M., 14 Oct 2021, (E-pub ahead of print) Hospital Pharmacy Europe, 99, p. 8-13.
Initiation of Paediatric Advance Care Planning: Cross Sectional Survey of Health professionals reported behaviour
Carr, K., Hasson, F., McIlfatrick, S. J. & Downing, J., 6 Dec 2021, (E-pub ahead of print) In: Child: Care, Health and Development.
Injury patterns in U15 rugby players in Ulster Schools: A Rugby Injury Surveillance (RISUS) study
Archbold, G. P. R., Rankin, A., Webb, M., Davies, R., Nicholas, R., Eames, N., Wilson, R. K., Vincent, J., McKeever, D., Duddy, K., Matthews, M. & Bleakley, C. M., 7 Apr 2021, (E-pub ahead of print) In: Translational Sports Medicine.
In need of review: Developing Sensory Provision in Northern Ireland's Mainstream Primary classrooms
Beck, G. J., O'Connor‐Bones, U., Gracey, J., Kelly, G. & Walsh, G., 2 Jun 2021, (E-pub ahead of print) In: Journal of Research in Special Educational Needs.
Innovative Food Business Models for Sustainable and Resilient Economies
Furey, S., Tocco, B., Freeman, R., Jewitt, C., Reeder, N., Melville, K., Mould, E. & Connolly, A., 20 Apr 2021, 20 p. Ulster University.
Innovative Student Engagement Mechanisms During A Global Pandemic: Insights from an Post-Graduate Online Research Methods module
Cadden, T. & Joseph-Richard, P., 23 Jun 2021, p. 1. 6 p.
Inscribed stones mark the bounds
Wilson, P., 11 Feb 2021, 1 p. Coleraine
Insights and lessons learned from trialling a mental health chatbot in the wild
Potts, C., Bond, RR., Mulvenna, M., Ennis, E., Bickerdike, A., Coughlan, E., Broderick, T., Burns, C., McTear, M., Kuosmanen, L., Nieminen, H., Boyd, K., Cahill, B., Vakaloudis, A., Dhanapala, I., Vartiainen, A-K., Kostenius, C. & Malcolm, M., 15 Dec 2021, 2021 IEEE Symposium on Computers and Communications (ISCC). IEEE Xplore, p. 1-6 6 p.
Insights on Sustaining NGO Participation in Post Conflict Space: Seize Redefine Share Name
Ní Aoláin, F., Malagon, L. & O'Connell, R., Oct 2021
Instruction and Practice: – are these enough for effective teaching?
Booth, N., Keenan, M. & Dillenburger, K., 1 Apr 2021, (E-pub ahead of print) International Journal of Educational Research Open , 2, 2 34 p.
Insulinotropic and antidiabetic properties of Eucalyptus citriodora leaves and isolation of bioactive phytomolecules
Ansari, P., Flatt, PR., Harriott, P. & Abdel-Wahab, Y., 1 Aug 2021, In: JOURNAL OF PHARMACY AND PHARMACOLOGY. 73, 8, p. 1049-1061 13 p.
In support of reacquainting functional contextualism and interbehaviorism
Finn, M. & Barnes-holmes, D., 1 Jan 2021, In: Journal of Contextual Behavioral Science. 19, p. 1-5 5 p.
Integrated, not inserted: A pedagogic framework for embedding entrepreneurship education across disciplines
Cummins, D., Joseph-Richard, P. & Morgan, M., 2021, Innovation in Global Entrepreneurship Education: Teaching Entrepreneurship in Practice. Neck, H. & Liu, Y. (eds.). 1 ed. Glasgow: Edward Elgar Publishing, p. 32-51 19 p.
Integrated space–frequency–time domain feature extraction for MEG-based Alzheimer's disease classification
Yang, S., Sanchez Bornot, J., Fernandez, R., Deravi, F., Wong-Lin, K. & Prasad, G., 2 Nov 2021, In: Brain Informatics. 8, 11 p., 24 (2021).
Integrating cultural and natural heritage approaches to Marine Protected Areas in the MENA region
Crystal El Safadi , Sophie Tews, Georgia Andreou, Ortiz-Vazquez, R. & Lucy Blue , 31 Oct 2021, In: Marine Policy. 132, 104676.
Integration of Small-Scale Compressed Air Energy Storage with Wind Generation for Flexible Household Power Supply
Zhang, X., Qin, C., Xu, Y., Li, W., Zhou, X., Li, R., Huang, Y. & Chen, H., 31 May 2021, In: Journal of Energy Storage. 37, 102430, p. 1-9 9 p., 102430.
Intercultural Sensitivity: Exploring Cultural Similarities and Differences to Promote CFL Teaching/Learning: Selected Papers from the British Chinese Language Teaching Society The 2018 and 2019 International Conferences
Li, X., Jun 2021, New Theories, New Approaches and Methodologies, New Issues and New Strategies in the Pedagogy of Teaching Chinese as an International Language: Applied Chinese Language Studies X. Wang, W., Chen, L. & Xu, S. (eds.). First published in Great Britain: Sinolingua, Vol. Applied Chinese Language Studies X. p. 271-272
Internet of Things for Mental Health: Open Issues in Data Acquisition, Self-Organization, Service Level Agreement, and Identity Management
J. Gutierrez, L., Rabbani, K., Ajayi, O., Gebresilassie, S., Rafferty, J., A. Castro, L. & Banos, O., 1 Feb 2021, Internet of things for mental health: Open issues in data acquisition, self-organization, service level agreement, and identity management. Mexico: Elsevier, Vol. 18. p. 1-19 19 p. (International Journal of Environmental Research and Public Health).
Intravitreal injections: past trends and future projections within a UK tertiary hospital
Chopra, R., Preston, G., Keenan, T., Mulholland, P., Patel, P., Balaskas, K., Hamilton, R. & Keane, P. A., 25 Jun 2021, (E-pub ahead of print) In: Eye (London, England). 6 p.
Introducing ARINS-analysing and researching Ireland, North and South: Authoritative, independent and non-partisan analysis and research on constitutional, institutional and policy options for Ireland, north and south in a post-Brexit context
Doyle, J., Gormley-Heenan, C. & Griffin, P., 2021, In: Irish Studies in International Affairs. 32, 2, p. vii-xvii 11 p.
Introduction: Special Issue in Honour of J.D. Smele
Thatcher, I., 29 Dec 2021, (E-pub ahead of print) In: Revolutionary Russia. 34, 2, p. 157-160 4 p.
Introduction to Sensor Nanotechnology and Flexible Electronics
Aljabali, A. A. A., Dua, K., Pal, K. & Tambuwala, M. M., 1 Sep 2021, Sensors for Stretchable Electronics in Nanotechnology. CRC Press, p. 1-13 13 p.
Investigating centrality in PTSD symptoms across diagnostic systems using network analysis*
Hansen, M., Armour, C., McGlinchey, E., Ross, J., Ravn, S. L., Andersen, T. E., Lindekilde, N., Elmose, M., Karsberg, S. & Fried, E., 1 Feb 2021, In: European Journal of Psychotraumatology. 12, sup1, p. 1866412 1 p.
Investigating Gaze Behaviour of Children Diagnosed with Autism Spectrum Disorders in a Classroom Setting
Mc Parland, A., Gallagher, S. & Keenan, M., 15 Feb 2021, (E-pub ahead of print) In: Journal of Autism and Developmental Disorders. 16 p.
Investigating the healthiness of food products on promotion: market brands and own brands
Beacom, E., Hollywood, L. E., McLaughlin, C., Furey, S., Price, RK., McMahon-Beattie, U. & Burns, A., 26 Aug 2021, (E-pub ahead of print) In: British Food Journal. 0007-070X
Investigating the performance of a novel pH and cathepsin B sensitive, stimulus-responsive nanoparticle for optimised sonodynamic therapy in prostate cancer
Hadi, M. M., Nesbitt, H., Masood, H., Sciscione, F., Patel, S., Ramesh, B. S., Emberton, M., Callan, J., MacRobert, A., McHale, A. P. & Nomikou, N., 10 Jan 2021, In: Journal of Controlled Release. 329, p. 76-86 11 p.
Investigating the physical activity, health, wellbeing, social and environmental effects of a new urban greenway: a natural experiment (the PARC study)
Hunter, R. F., Adlakha, D., Cardwell, C., Cupples, M. E., Donnelly, M., Ellis, G., Gough, A., Hutchinson, G., Kearney, T., Longo, A., Prior, L., McAneney, H., Ferguson, S., Johnston, B., Stevenson, M., Kee, F. & Tully, M. A., 30 Oct 2021, (E-pub ahead of print) In: International Journal of Behavioral Nutrition and Physical Activity. 18, 1, 142.
Investigating the prevalence and predictors of food insecurity: a comparison of HFSSM and EU-SILC indicators
Beacom, E., McLaughlin, C., Furey, S., Hollywood, L. E. & Humphreys, P., 15 Oct 2021, (E-pub ahead of print) In: British Food Journal.
Investigation of heat transfer in wavy and dual wavy micro-channel heat sink using alumina nanoparticles
Khan, M. Z. U., Younis, M. Y., Akram, N., Akbar, B., Rajput, U. A., Bhutta, R. A., Uddin, E., Jamil, M. A., García Márquez, F. P. & Zahid, F. B., 1 Oct 2021, (E-pub ahead of print) In: Case Studies in Thermal Engineering. 28, 101515.
Investigation of the use of wearable data for cancer-specific mortality prediction in older adults
Kelly, D., Condell, J., Tedesco, S., Andrulli, M., Akerlund, M., Alamäki, A., Barton, J. & Nordstrom, A., 15 Jul 2021, (Accepted/In press) 43rd Annual International Conference of the IEEE Engineering in Medicine and Biology Society.
Invisible Belfast: Flat ontologies and remediation of the post-conflict city
Barrios-O'Neill, D. & Hook, A., 1 Feb 2021, In: Convergence. 27, 1, p. 212-228 17 p.
In Vitro and In Vivo Effects of Palmaria palmata Derived Peptides on Glucose Metabolism
Harnedy‐Rothwell, P. A., McLaughlin, C., Le Gouic, AV., Mullen, C., V, P., Allsopp, P. J., McSorley, E. M., Fitzgerald, RJ. & O'Harte, F., 29 Mar 2021, In: International Journal of Peptide Research and Therapeutics. 27, p. 1667–1676
In vitro Dissolution Profile at Different Biological pH Conditions of Hydroxychloroquine Sulfate Tablets Is Available for the Treatment of COVID-19
Dongala, T., Katari, N. K., Ettaboina, S. K., Krishnan, A., Tambuwala, M. M. & Dua, K., 14 Jan 2021, (E-pub ahead of print) In: Frontiers in Molecular Biosciences. 7, p. 613393 6 p., 613393.
Iodine status among school age children in the Republic of Seychelles
Monaghan, A., Mulhern, M. S., McSorley, E. M., Strain, JJ., Winter, T., van Wijngaarden, E., Myers, G., Shamlaye, C. & Yeates, A. J., 17 Aug 2021. 1 p.
IoT-based Activities of Daily Living for Abnormal Behaviour Detection: Privacy Issues and Potential Countermeasures
Mustafa, M., Konios, A. & Garcia-Constantino, M., 30 Sep 2021, In: IEEE Internet of Things Magazine. 4, 3, p. 90-95 6 p.
IoT-Based Applications in Healthcare Devices
Pradhan, B., Bhattacharyya, S. & Pal, K., 19 Mar 2021, (E-pub ahead of print) In: Journal of Healthcare Engineering. 2021, 18 p., 6632599.
IoT based monitoring of air quality and traffic using regression analysis
Martın-Baos, J. A., Rodriguez-Benitez, L., Garcıa-Rodenas, R. & Liu, J., 10 Dec 2021, (E-pub ahead of print) In: Applied Soft Computing Journal. p. 1-48 48 p., 108282.
IoT-Enabled Social Relationships Meet Artificial Social Intelligence
Dhelim, S., Ning, H., Farha, F., Chen, L., Atzori, L. & Daneshmand, M., 18 May 2021, (E-pub ahead of print) In: IEEE Internet of Things.
Ireland, 2021: a century of insurgency, terrorism and security challenges
Edwards, A. & McGrattan, C., 4 Jul 2021, In: Small Wars and Insurgencies. 32, 4-5, p. 587-597 11 p.
Ireland, Colonialism and the Unfinished Revolution
McVeigh, R. & Rolston, B., 12 Jul 2021, United Kingdom: Beyond the Pale Publications. 480 p.
Irish Ceramics. 2021. The very best of Irish Contemporary Ceramics. ISBN: 978-0-9567987-3-2
Moore, M. & Goode, J., 12 Sep 2021, In: Irish Ceramics. 1, 3, p. 78 78 p.


Lil Wayne's speech came after accepting the I Am Hip-Hop award at the BET Hip-Hop Awards on Tuesday night.
Lil Wayne's performance was cut short after a fight, and false-rumors of a gun caused audience members to run for the exits.
Lil Wayne's Tha Carter V is heading for a record-setting first week on the Billbaord Hot 100.
Lil Wayne is collaborating with Wikipedia and Advisory Board Crystals for the last run of Carter V merch.
Lil Wayne also told Elliott Wilson he hasn't listened to the Tha Carter V since its release.
Lil Wayne revealed details of Tha Carter V's creation during a Tidal interview.
Watch Lil Wayne perform "Dedicate" on The Tonight Show.
Lil Wayne performed Tha Carter V song "Dedicate" and was interviewed by Jimmy Fallon on The Tonight Show.


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This week in focus: R2P: from Promise to Practice
Dr. Alexander J. Bellamy of the Asia Pacific Centre for the Responsibility to Protect (APR2P) and an ICRtoP Steering Committee member, and former UN Special Adviser to the Secretary-General on the Responsibility to Protect, Dr. Edward C. Luck, have recently published a new book, entitled R2P: From Promise to Practice. Please find below an abstract from the authors, as well a full summary by the authors on our blog in which they discuss the book's motivations and findings.
R2P: From Promise to Practice
Alex J. Bellamy & Edward C. Luck
Following more than a decade of decline, the incidence of atrocity crimes is again rising. The tide of forcibly displaced populations is at the highest level since the end of the Second World War. We need to do far better at preventing such horrific crimes and at protecting vulnerable populations. That is the purpose of the Responsibility to Protect (R2P), a set of rules and principles that has advanced far more rapidly in debating halls than in national and international policies and actions. This book is about how to turn the promise of R2P into practice.
As scholars and practitioners, however, we felt that something was missing, that the literature has been incomplete. While the scholarly and analytical work on R2P as a normative innovation and political enterprise has been truly impressive, there has been far less attention to what R2P looks like in practice. Following a decade of normative development and maturation, R2P principles have now been tested in practice for a decade as well. The principles have reached a settled state, but their practice is still far down the learning curve. We believe, nevertheless, that there is now enough of a track record to begin to offer some rough assessments of what is or is not working.
History tells us that the journey from principle to practice is never quick or sure. It demands persistence as much as intellect, learning from mistakes as well as from successes, and never forgetting where we are going or why we undertook the journey in the first place. Stepping aside, giving up, looking for easier paths is not an option. Curbing atrocities is as difficult as it is compelling. But experience also shows that it can be done. Those are the core lessons from R2P's early years. They offer the promise of stronger institutions, deeper commitments, and better policy in the years ahead. R2P is just getting started.
Burma: UN expert: Myanmar government shows 'no real interest in building democracy' (UN Office of the High Commissioner for Human Rights)
Yanghee Lee, UN Human Rights Council Special Rapporteur on Myanmar, said "the government is demonstrating no real interest in establishing a functioning democracy" in the country, and calls for the referral of the situation to the International Criminal Court (ICC), given the inability of the government to fulfill its international obligations. From her findings, she concluded the Burmese government is not doing enough to achieve peace and reconciliation in the country, abide by international law, and ensure accountability. Though she acknowledged the positive steps taken to create an independent mechanism to investigate and collect information about the atrocities perpetrated, she believes more needs to be done. She urged the international community to continue working to ensure accountability and that the independent mechanism has all resources needed to be fully functioning.
Gaza/West Bank: Interview: How Palestinian Authorities Crush Dissent (Human Rights Watch; Middle East Monitor)
A recent report released by Human Rights Watch (HRW) found that the Palestinian Authority has been conducting the systematic, arbitrary arrests and torture of critics and opponents in the West Bank and Gaza Strip. Together with Hamas, who has de facto control inside the Gaza Strip, critics and opponents are detained regardless of nonviolent expression, according to the interviews conducted. HRW documented more than two dozen cases of detained persons for writing a critical article, or a Facebook post. In response, the Palestinian Ministry of Interior and National Security refuted the report, claiming it is inaccurate and ignores the reality in the Gaza Strip.
South Sudan: Violations and Abuses Against Civilians in Gbudue and Tambura States (Western Equatoria) (UN Office of the High Commissioner for Human Rights and UNMISS)
The UN Office of the High Commissioner for Human Rights (OHCHR) and UNMISS, the UN Peacekeeping Operation in South Sudan, released a report on the human rights situation in the western states. In addition to High Commissioner Bachelet noting the SPLA still has yet to return some abducted civilians, Human Rights Watch attests that government forces are finding different ways of harming civilians in spite of the recent peace agreement, calling it "the latest chapter in a long history of violence and impunity."
Cameroon: Cameroon's President Paul Biya wins seventh term
The Constitutional Council announced President Biya was re-elected as President earning over 70% of the vote.
CAR: Central African Republic: Special Criminal Court Gets Underway
The country's hybrid court is set to begin, presenting its investigative strategy to prosecute atrocity crimes that have taken place since January 2003.
India: JRL Urges UN to Play Role in Ending Crimes Against Humanity in Kashmir
Over increasing allegations of Crimes Against Humanity in Kashmir, the Joint Resistance Leadership (JRL) asked the UN Secretary-General to take action to end human rights abuses in the region.
Mali: UN Secretary-General Report - Situation in Mali
UN Secretary General issued a report highlighting the the deterioration of human rights and the continued breaches of international law, calling upon authorities to comply with their responsibility to ensure accountability.
Syria: Rebels continue attacks inside Idlib buffer zone
Militants proceed with attacks in Idlib, Syria, violating the ceasefire agreement. Russia administered humanitarian aid for civilians in areas previously controlled by armed groups.

redpajama_set_name: RedPajamaCommonCrawl


Do Teeth Whitening Formulas Help Whiten Teeth?
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...have any buckleback 1B mitts from the 1920's to 1930's for sale or trade? I know I should probably put this in the items wanted section but I wanted to keep it in the vintage discussion. I'm looking for a high quality mitt in excellent condition. I'd be willing to trade items I have for sale or pay money. The reason I'm looking for one is because I'd like to give it to my dad for Christmas and these types of gloves are his favorite. Thanks for your time.
Brett, You should email Don M. in Toledo. He and your dad are buds and Don has a nice collection. Let me know if you need his email address. Or just email me at mjkm90@earthlink.net. I sold a nice double buckle in August on ebay that he would have liked.
This is sort of a related question, but has to do more with VINTAGE items wanted and/or for sale. Can this topic be kept in this vintage section rather than the FOR SALE or Wanted section? It seems like most of the items in there are all new or newer and may not have an interest to those just interested in vintage stuff.
I second that Max. I rarely ever look in that section because I get a rash from all the doubleknit and plastic.
I too would rather see a seperate B/S/T for this forum. Maybe it could be kept at the top of the forum list.


White cubby shelf build a toy storage bin box with shelves free and. Stackable shelves garage utility sorter box storage bin rack. Toy storage shelves with baskets wooden toy storage bin shelving. Playroom storage bins toy wood cabinets bin furniture box shelves.


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How to create the best hybrid work environment
Andy Cheng
55% of employees want to work remotely at least three days a week.
Hybrid work businesses will need to take both offices and homes into account.
Here are several qualities of successful hybrid workplaces.
Hybrid work is no longer a myth. A PwC survey found that most companies are already moving toward a hybrid workspace, defined as one where many office employees rotate in and out of shared office spaces.
Google is the latest to join the fray. Citigroup announced that most of its employees are now considered hybrid and expected to work in the office at least three days a week. Ford said that 30,000 of its North American employees will work a flexible hybrid model where they are on-site for certain projects or meetings but otherwise work independently at home.
Unlimited meetings and team messaging built for hybrid work. And it's totally free.
And employers aren't the only ones leading the way. Employees have a big stake in the game. The same PwC survey found that 55% of employees want to work remotely at least three days a week post-pandemic.
With hybrid work on the horizon, let's look at some of the qualities of a great hybrid environment.
Rethinking the office
A hybrid approach means seriously reconsidering a company's workspace.
Ranjan Singh, executive VP of technology for the workplace tech firm Creston, told TechRepublic, "Offices will transition to collaborative spaces, where the focus is on team connection and collaboration, versus a place to come, do work at a desk, maybe attend a few meetings in a boardroom, and leave."
Huddle rooms—small meeting rooms for perhaps four to six employees fitted with audio and video conferencing equipment—are essential. They allow small groups of teammates to quickly gather to chat together or speak with a client on a video call.
You'll still need to provide areas where employees can focus. Consider flexible spaces like small, single-person workstations and focus rooms that workers can book as needed. Perhaps you set up flex desking, where desks don't belong to any one person since everyone isn't there every day and there's a reservation system for signing up for a desk in the morning. Or maybe it's first come, first served. With shared desks, employees won't be able to leave personal items out, so consider providing lockers.
Consider incorporating wayfinding into your office for people who aren't there regularly. Do this by creating an interactive, up-to-date floor plan of the office with rooms, desks, and technology labeled.
Rethinking home offices
The success of the hybrid workplace means making sure your workers are set up for success at home, too. When the pandemic hit, we started working at home unexpectedly and had to make do. Some people worked from the dining room table—are they still? Leaders can take a proactive approach to making sure employees work efficiently, comfortably, and ergonomically at home.
Inquire about their equipment. Do your employees have a dedicated desk and comfortable office chair? Do they have the right computer monitor, and is it at the right height? Do they need a second monitor? Is there a fast and reliable WiFi connection and sufficient lighting? What about a laptop, cell phone, router, printer, headphones, and webcam? Many companies provide a one-time or recurring monthly stipend for employees' home offices.
Ask about their everyday tools too. Do they have the right apps? Do those apps maximize their productivity? What other tools do your employees need to work from home? Regularly checking in on their needs ensures that they're fully equipped.
Anywhere workers
Fully remote workers should feel they are part of the office, too, no matter where they work from, and they should have the same considerations as hybrid workers. But you'll need to take different approaches to collaboration for those who work from anywhere.
Video conferencing is the remote worker's best friend. They'll need enterprise-grade software that lets them communicate and collaborate through audio and video, share screens, share files, live stream, record meetings, and more.
Ideally, their video conferencing is integrated with team messaging too. One where conversations can seamlessly move from message to video with a single click, and workers always know where to find the right context.
The future of hybrid work
These setups only scratch the surface of what makes for successful hybrid work environments. Businesses will have to consider other factors including company culture, leadership, compensation, and more. It's also important to note that since hybrid work was essentially unknown until COVID, these setups aren't tried and tested.
But despite the newness of it all, we know after a year of remote work that there's no turning back to the old normal. The sooner we embrace change, the sooner we can adapt to our new work lives.
Originally published May 20, 2021, updated Jun 01, 2021
Built for your hybrid workforce. Unlimited video meetings and team messaging all in one single platform.
The new role of CIOs in the post-pandemic world
The role of Chief Information Officers (CIOs) has changed hugely in the wake of the pandemic. Until now, the role of the CIO (and sometimes the CDO, Chief Digital Officer) was often focused more on technology than on business models. But times are changing, and the roles of technology leaders and business leaders are more ...
6 hybrid work questions that businesses should be asking
4 advantages of "no downloads required" video meetings
The 3 different types of hybrid work


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Q: CSS Sidebar overlapping with Navbar, unable to get the divs to stack I'm trying to get the sidebar to stack under the nav bar, however I can't get the sidebar to stop overlapping the upper section of the nav bar. The footer is fine for some reason. I would like the sidebar to nest under the navbar and sit to the left of the webpage. The configuration I am using is bootstrap 4 as linked in the header.

<!DOCTYPE html>

      <title><%= full_title(yield(:title)) %></title>
      <link rel="stylesheet" href="https://stackpath.bootstrapcdn.com/bootstrap/4.2.1/css/bootstrap.min.css" integrity="sha384-GJzZqFGwb1QTTN6wy59ffF1BuGJpLSa9DkKMp0DgiMDm4iYMj70gZWKYbI706tWS" crossorigin="anonymous">

         <%= yield %>

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A: You had the .sidenav set as top: 0; meaning that it was going to stick to the top at the 0px position. I removed that and heres the result:

<!DOCTYPE html>

      <title><%= full_title(yield(:title)) %></title>
      <link rel="stylesheet" href="https://stackpath.bootstrapcdn.com/bootstrap/4.2.1/css/bootstrap.min.css" integrity="sha384-GJzZqFGwb1QTTN6wy59ffF1BuGJpLSa9DkKMp0DgiMDm4iYMj70gZWKYbI706tWS" crossorigin="anonymous">

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redpajama_set_name: RedPajamaStackExchange


text:
Busch sweeps all 3 NASCAR Bristol races
BRISTOL, Tenn. (AP) -- Kyle Busch made NASCAR history Saturday night with an unprecedented sweep of three national races in one week, completing the trifecta with a victory in the Sprint Cup race at Bristol Motor Speedway.
Busch hoisted a broom in Victory Lane, where he made his third visit in four days. He also won the Nationwide race Friday night, and the Trucks race Wednesday night to become the first driver to complete the sweep since NASCAR expanded to three national series in 1995.
"I've been trying to do this since I got to NASCAR," said Busch, who has tried for a three-race sweep five times in his career.
"I love Bristol and I love winning. And to do it for the first time ever in NASCAR, to sweep the weekend, man, that's pretty awesome."
The Cup victory, his third of the season and third in the last four at Bristol, was drama-free after another round in his ongoing feud with Brad Keselowski.
Busch admitted to intentionally wrecking Keselowski late in the Nationwide race, and he celebrated that win by mockingly rubbing his eyes like a crying baby as the crowd showered him with boos. Keselowski vowed revenge over the public address system, to the delight of the Bristol crowd.
The barbs continued all the way up to the start of the Cup race. As Busch was booed in pre-race introductions, he sarcastically told the crowd, "Aw, you're so loving."
Keselowski was introduced moments later, taking the microphone and earning a thunderous cheer by saying, "I'm Brad Keselowski ... Kyle Busch is (a jerk)."
There was almost no chance of an on-track altercation, though, as the two hardly raced near each other for most of the night.
Keselowski did make it hard for Busch to pass him late in the race, when Keselowski was fighting not to go a lap down, but Busch made a clean move around him in his No. 18 Joe Gibbs Racing Toyota after several attempts.
"Great job," his team radioed after the pass.
"I know," Busch replied. "I have more class."
Crew chief Dave Rogers reiterated that after Busch completed the victory.
"Some wiseguys got introduced behind him, and he raced like a champion and handled it with class all day," Rogers said.
David Reutimann rallied from a bout with food poisoning to finish second in a Toyota for Michael Waltrip Racing, his first top-15 finish since winning at Chicago last month.
"I feel really, really good about the finish, but I'm not feeling so hot right now," Reutimann said after the race. "I'm ready to go to sleep at some point. Maybe now."
Jamie McMurray was third in a Chevrolet for Earnhardt-Ganassi Racing, a finish good enough to move him to 13th in the standings. He trails Clint Bowyer by 100 points for the 12th and final spot in the Chase for the Sprint Cup championship.
But McMurray said he's not focused on making the Chase field. There's two races to go in the "regular season."
"I'm really fortunate this year that we were able to win those two big races because if we don't make the Chase, it's not going to be devastating," said McMurray, winner of the Daytona 500 and the Brickyard 400.
Bowyer rallied from an early pit-road speeding penalty to finish fourth in a Chevrolet for Richard Childress Racing, and he moved a step closer to locking down the final spot in the Chase. Mark Martin, who started the night 35 points Bowyer in 13th place, finished 23rd and is now 14th in the standings, 101 points out.
Kasey Kahne was fifth in a Ford for Richard Petty Motorsports, and Ryan Newman was sixth in a Chevrolet for Stewart-Haas Racing.
Juan Pablo Montoya, McMurray's teammate, finished seventh despite damage to his car from contact that wrecked four-time defending series champion Jimmie Johnson. The pole-sitter, Johnson finished 35th.
Greg Biffle was eighth in a Ford for Roush-Fenway Racing, Penske Racing's Kurt Busch was the highest finishing Dodge, and RFR's Matt Kenseth rounded out the top 10.


Victoria Beckham has revealed why her husband David was excluded from his first fashion shows.
The Spice Girls star started her fashion label of the same name 10 years ago. And after gaining worldwide fame as part of one of the best brides, and as half of the sexiest couple, she was interested in concentrating on her clothes.
So he kept his famous family away from the catwalk while letting his designs speak.
"I just kept my head down, worked hard, and always did on the product and the client, rather than on myself as a celebrity," he told Refinery29.
And during his first shows for the Victoria Beckham brand, his family stayed away.
"A lot of seasons went by before it came out at the end of the show, and my family did not attend the first seasons," he explained.
"I really wanted it to be about clothes and nothing else."
This week, on top of the success of the 10th anniversary of its fashion brand at the London Fashion Week, Posh Spice took the movements to its after party.


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Imprint: Peng. Mod. Classics
Non-fiction prose
Advertisements for Myself
Formats & editions
An essential guide to the life and work of one of America's most controversial writers.
Advertisements for Myself is a comprehensive collection of the best of Norman Mailer's essays, stories, interviews and journalism from the Forties and Fifties, linked by anarchic and riotous autobiographical commentary. Laying bare the heart of a witty, belligerent and vigorous writer, this manifesto of Mailer's key beliefs contains pieces on his war experiences in the Philippines (the basis for his famous first novel The Naked and the Dead), tributes to fellow novelists William Styron, Saul Bellow, Truman Capote and Gore Vidal and magnificent polemics against pornography, advertising, drugs and politics. Also included is his notorious exposition of the phenomenon of the 'White Negro', the Beat Generation's existentialist hero whose life, like Mailer's, is 'an unchartered journey into the rebellious imperatives of the self'
Norman Mailer was born in New Jersey in January 1923 and after graduating from Harvard, served in the US army from 1944-1946. His first novel, The Naked and the Dead, was published to immediate critical acclaim in 1948 - and has been hailed as 'the best war novel to emerge from the United States' (Anthony Burgess).
He has subsequently published both fiction and non-fiction and his books include Barbary Shore (1951), Advertisements for Myself (1959), The Presidential Papers (1963), An American Dream (1964), Armies of the Night (1968), Ancient Evenings (1983), and Tough Guys Don't Dance (1983).
The Executioner's Song, first published in 1979, won the Pulitzer Prize in 1980 - an award which Mailer has won twice during his writing career.
Norman Mailer was born in 1923 and went to Harvard when he was sixteen. He majored in engineering, but it was while he was at university that he became interested in writing; he published his first story when he was eighteen. After graduating he served during the war in the Philippines with the Twelfth Armoured Cavalry regiment from Texas; those were the years that formed The Naked and the Dead (1948). His other books include Barbary Shore (1951), The Deer Park (1955), Advertisements for Myself (1959), Deaths for the Ladies, a volume of poetry (1962), The Presidential Papers (1963), An American Dream (1964), Why Are We in Vietnam? (1967), The Armies of the Night (1968), Miami and the Siege of Chicago (1968), A Fire on the Moon (1970), The Prisoner of Sex (1971), Marilyn (1973), Some Honourable Men (1976), Genius and Lust - A Journey Through the Writings of Henry Miller (1976), A Transit to Narcissus (1978), The Executioner's Song (1979) and Tough Guys Don't Dance (1983). The Deer Park has been adapted into a play and was successfully profuced off Broadway. He also directed four films.
In 1955 Norman Mailer co-founded the Village Voice, and he was the editor of Dissent from 1952 until 1963. For his part in demonstrations against the war in Vietnam he was gaoled in 1967. He was President of PEN (US chapter) from 1984 to 1986 and was winner of the National Book Award for Arts and Letters in 1969 and of the Pulitzer Prize twice, once in 1969 and again in 1980.
Norman Mailer was married six times and had nine children. He died in November 2007.
Also by Norman Mailer
Homer Homer, Homer
Conversations on Love
Natasha Lunn
Call Us What We Carry
Rosita Boland
Between the Covers
Jilly Cooper
The Cancer Journals
Solutions and Other Problems
Allie Brosh
Personal Writings
Mercies
Figures in a Landscape
Paul Theroux
Collected Nonfiction Volume 1
Kid Gloves: A Voyage Round My Father
Adam Mars-Jones


This must be the best broccoli soup ever! I´m not particulary fond of soups. But this soup! It blew my mind away! If you eat fish or shrimps you can add some fried instead of/ or together with the avocado cream.
Boil the broccoli until soft.
Take a hand mixer and blend until a smooth soup.
Then add the coconut milk and stir. Let boil for a minute.
Place all the ingredients in a small mixer and mix until smooth.
Serve the avocado cream in the soup.
This has become one of my favorite dish. It is so tasty and so easy to make. Invite your frineds for dinner with this one!
Fry onion and garlic in the oil until soft.
Add all the ingredients except coconut milk & beans.
Boil on low heat until the potatoes and celery are soft.
Add the rest of the ingredients and let boil for a couple of minutes.
It is thanks to my creativity and passion for cooking I have been able to stick to my healthy lifestyle with delicious food. Before I started with my food changes some years ago I loved cheese.
This Parmesan I use on my pasta and risotto and other food that normally has parmesan. And- it has a lot of iron and calcium too!
Download this recipe as pdf. Click on the recipe below!
As you may know I love Indian food. I have eaten pakoras but not for some years since I don´t eat eggs or gluten. But surprise, surprise! Pakoras doesn´t contain eggs or gluten! They use chickpea flour! All those years skipping pakoras for nothing. Anyhow, the other day I was craving for this and was digging in my recipes and I found this wonderful recipe. Not sure it is an original Indian pakora, but it´s tasty, so try it!
Mix the ingredients to the batter. If needed add some more milk. Heat a pan with oil.
Dip the slices of eggplants in the batter, covered in the batter.
Fry the eggplants until they are golden brown.
Place the fried eggplants on paper to get rid of some oil.


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Bluebird è un singolo della cantante statunitense Miranda Lambert, pubblicato il 9 dicembre 2019 come secondo estratto dal settimo album in studio Wildcard.

Descrizione
Il brano è stato scritto dalla stessa interprete con Luke Dick e Natalie Hemby e prodotto da Jay Joyce. È composto in chiave di Sol maggiore ed ha un tempo di 82 battiti per minuto.

Video musicale
Il video musicale del brano, diretto da Trey Fanjoy, è stato reso disponibile il 20 marzo 2020.

Tracce
 Download digitale (versione acustica)

 Download digitale (versione dal vivo)

Successo commerciale
Nella pubblicazione del 1º agosto 2020 Bluebird ha raggiunto la vetta della Country Airplay, classifica radiofonica statunitense redatta dalla rivista Billboard e dedicata al suddetto genere, grazie ad un'audience pari a 32,4 milioni di ascoltatori. È diventata così la sesta numero uno di Miranda Lambert e la prima da solista da Over You del 2012.

Classifiche

Classifiche settimanali

Classifiche di fine anno

Note

Collegamenti esterni

redpajama_set_name: RedPajamaWikipedia


The race to make public transportation safe is accelerating, especially and appropriately in congested airports, bus terminals and train stations where thousands of passengers congregate every day. Government and private establishments alike are driving more innovative and out-of-the-box solutions to prevent disasters from happening. Smart sensors, supercomputers and cutting-edge radar technology are among the forerunners of a new breed of security devices that can spot hostiles and identify concealed weapons before they strike.
Automation and artificial intelligence (AI) are being hailed as the cavalry where human agents, despite their best efforts, have failed. Random checking or spot checks done by police officers in city areas deemed vulnerable to crime or attack are still seen as a necessary evil at best, or a near-unconstitutional intrusion at worst.
An angry complaint by The Online Citizen, for example, points out that human security officers are still subject to the usual biases and prejudices that afflict our species. Profile descriptions dictate which type of individuals would be searched more than others. Yet a terrorist who does not match these profiles can be overlooked, especially if he or she has the right street smarts and emotional intelligence to lower the usual caution of the police.
More troubling is a Newsweek report that shows that many of America's jam-packed airports were susceptible to passenger smuggling of illegal items, from banned food products and contraband to explosives. Agents from the Department of Homeland Security (DHS) disguised themselves as civilians carrying these outlawed items and went through the usual checkpoints that use a combination of advanced X-rays and human inspection. Their colleagues working for the Transportation Security Administration (TSA), tasked to guard the airport against potentially dangerous elements, failed 67 of the 70 tests.
With standard safety and security measures exhibiting these levels of weakness, establishments with the capabilities are driving innovation of new devices and systems to improve the existing structures.
Some of these changes look more user-friendly to provide a deterrent and are designed to boost security and protect passengers. Security Sales & Integration names the biometric screening instituted by the Hartsfield-Jackson Atlanta International Airport. Passengers can choose to have their identities verified by a screening device that checks their fingerprints. Individual fingerprint screening is deemed more accurate than an airport security officer looking at a passenger's passport and his or her boarding pass.
On a far wider scale, the Montreal government is investing in artificial intelligence to conduct broader sweeps of the city streets, roads, buildings and other establishments. According to the CIO report, the AI will coordinate the images taken by various flying drones, satellites, planes and city vehicles, checking whether the city and its inhabitants are safe. Any disruptive or unusual activity can be immediately flagged. A gunman holding a bus and its schoolchildren hostage or a bomb-laden truck zigzagging through the streets can be neutralized. The AI will relay the information to pertinent departments which should take action, like the police.
As people's needs for security heightens, more innovative security solutions will come down the pipeline. Passengers, especially in the more vulnerable, crowded areas where bad people can easily hide, can breathe easier in the future.


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Wedding Videographer Refuses Refund, Horribly Mocks Client Whose Fiance Died in Car Crash | LATEST NEWS
By gossip febrero 25, 2021
"We hope you sob and cry all day for what would have been your wedding day. Sorry, not sorry."
A wedding videographer has sparked online fury after refusing to refund a client whose fiancee died, threatening a lawsuit, and openly mocking him during his time of grief.
In February, Alexis Wyatt, 22, died in a car crash in Colorado Springs, Colorado. Her fiance, Justin Montney, 24, attempted to get back the $1,800 deposit the couple had given to Copper Stallion Media to film their wedding on May 23.
The company refused, saying it was non-refundable, but Montney thought they could make an exception considering the special circumstances and the fact that "they didn't render any services," according to KRDO-TV.
Montney also claimed that Copper Stallion Media said they could extend his service to his next wedding, which Mortney said "was a very insensitive thing to tell me."
They deleted their page, but not before making complete asses of themselves 🙂
We can all agree fuck Copper Stallion Media. I don't know a single photographer with morals that would act like this. pic.twitter.com/6prfAWVj3q
— big anime tinnitus (@alyssughjo) May 23, 2020
@alyssughjo
Per CBS News, the company's since-deleted website read, "We replied and expressed our sympathy and explained to him that all of our wedding contracts are non-refundable.
"He kept emailing us trying to get a refund and we kept reiterating that the contract is non-refundable. We eventually stopped responding since the issue was moot."
After months of not hearing from the company, Montney and Wyatt's family left negative reviews on TheKnot and Yelp, which Montney says prompted Copper Stallion Media to threaten a lawsuit for defamation.
At this point, Montney decided to take his story public, reaching out to KRDO.
Wow. #CopperStallionMedia didn't bat an eye when immediately responding to my post. "It's not our fault she can't drive" pic.twitter.com/bYfmyxRZ1k
— Cate Carson (@catecarson) May 27, 2020
@catecarson
"At first I was just going to tell friends and family, but when he started to threaten Alexis's family with a lawsuit for basically their daughter dying, that's when I was like, 'OK, I'm going to start going to the people who spread the news," he told the news source.
Copper Stallion Media retaliated by redirecting its website and Yelp page to a new website JustinMontney.com, accusing Montney of creating a "smear campaign," according to ABC News7.
The website's content has mostly been removed, but, per the outlet, it stated, "He admits the contract was nonrefundable but says we should give the money back due to the circumstance. Life is a b–ch, Justin."
The website then reportedly said Montney's non-refundable deposit was used to register JustinMontney.com.
"He could have quietly filed a small claim to 'try' to recoup the non-refundable deposit. Instead, he chose the internet to shake us down," a statement read. "This website is registered with us for the next two years. Thanks to your non-refundable deposit, you support this website and domain. Welcome to the interwebs you stupid s–t."
The videographer company's retaliation didn't stop there.
'Make Whites Great Again' Photo is Not George Floyd Arrest Cop, But Professional Troll
On May 23, the day the couple were to be married, the company posted a photo of the pair with the caption, "Today would have been the day where we would have filmed Justin and Alexis' wedding. After what Justin pulled with the media stunt to try and shake us down for a refund we hope you sob and cry all day for what would have been your wedding day."
"We will NEVER refund Justin Montney even with the online threats and harassment," the website continued. "If we knew he was going to shake us down, we would have charged a higher deposit."
Twitter blew up criticizing the "heartless" actions of Copper Mountain Media.
"We can all agree f–k Copper Stallion Media. I don't know a single photographer with morals that would act like this."
In another awful twist, a Twitter user captured a since-deleted tweet by Copper Stallion Media which appeared to suggest Montney's smear campaign was responsible for the recent suicide of one of its employees, Allison Davis.
"We are in contact with local authorities to see what can be done in terms of criminal charges. We are also reaching out to legal counsel to see what legal action we can take to obtain a judgment for damages. No company should have to go through this…" the since-deleted tweet read.
However, other followers raised doubts about the timing of the death of Allison Davis, posting a tweet by the company in December 2018 announcing her death.
As for Montney, he appears to be unfazed by the threats.
"[The company's owner] is trying to stir up a ruckus and defame my name, but obviously he doesn't have any ground to stand on," Montney told Buzzfeed. "He kind of made his own smear campaign."
Got a story or a tip for us? Email TooFab editors at tips@toofab.com.
Woman Strips in Middle of Post Office to Use Underwear as Mask After Being Denied Service
Beirut's Nightlife Survived Civil War. Can It Withstand Pandemic?
Scout Willis Reveals Why Bruce Willis Is Quarantining With Demi Moore | LATEST NEWS


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by Minnesota Historical Society
Minnesota Historical Society
Internships at the Minnesota Historical Society
The Society offers a limited number of internships to advanced undergraduate and graduate students interested in arranging work experience for academic credit. Most internships at the Minnesota Historical Society are unpaid. Internships can be arranged in the following MHS departments and programs: archeology, collections, conservation, historic sites, museum education, oral history, publications, and reference services. […]
Legacy Research Fellowships
These awards support researchers engaged in Minnesota-related research that draws on the Gale Family Library resources and adds to the body of knowledge and interpretation of Minnesota's history. Fellows will work at the Gale Family Library and interact with MNHS staff.


Cancer cells show a broad spectrum of bioenergetic states, with some cells using aerobic glycolysis while others rely on oxidative phosphorylation as their main source of energy. In addition, there is mounting evidence that metabolic coupling occurs in aggressive tumors, between epithelial cancer cells and the stromal compartment, and between well-oxygenated and hypoxic compartments. We recently showed that oxidative stress in the tumor stroma, due to aerobic glycolysis and mitochondrial dysfunction, is important for cancer cell mutagenesis and tumor progression. More specifically , increased autophagy/mitophagy in the tumor stroma drives a form of parasitic epithelial-stromal metabolic coupling. These findings explain why it is effective to treat tumors with either inducers or inhibitors of autophagy, as both would disrupt this energetic coupling. We also discuss evidence that glutamine addiction in cancer cells produces ammonia via oxidative mitochondrial metabolism. Ammonia production in cancer cells, in turn, could then help maintain autophagy in the tumor stromal compartment. In this vicious cycle, the initial glutamine provided to cancer cells would be produced by autophagy in the tumor stroma. Thus, we believe that parasitic epithelial-stromal metabolic coupling has important implications for cancer diagnosis and therapy, for example, in designing novel metabolic imaging techniques and establishing new targeted therapies. In direct support of this notion, we identified a loss of stromal caveolin-1 as a marker of oxidative stress, hypoxia, and autophagy in the tumor microenvironment, explaining its powerful predictive value. Loss of stromal caveolin-1 in breast cancers is associated with early tumor recurrence, metastasis, and drug resistance, leading to poor clinical outcome.
The Warburg effect, also known as aerobic glycolysis, is defined as the propensity of cancer cells to take up high levels of glucose and to secrete lactate in the presence of oxygen. Warburg's original work indicated that while glucose uptake and lactate production are greatly elevated, a cancer cell's rate of mitochondrial respiration is similar to that of normal cells [1, 2]. He, however, described it as a 'respiratory impairment' due to the fact that, in cancer cells, mitochondrial respiration is smaller, relative to their glycolytic power, but not smaller relative to normal cells. He recognized that oxygen consumption is not diminished in tumor cells, but that respiration is disturbed because glycolysis persists in the presence of oxygen [1, 2]. Unfortunately, the perception of his original findings was simplified over the years, and most subsequent papers validated that cancer cells undergo aerobic glycolysis and produce lactate, but did not measure mitochondrial respiration, and just presumed decreased tricarboxylic acid (TCA) cycle activity and reduced oxidative phosphorylation [1, 2]. It is indeed well documented that, as a consequence of intra-tumoral hypoxia, the hypoxia-inducible factor (HIF)1α pathway is activated in many tumors cells, resulting in the direct up-regulation of lactate dehydrogenase (LDH) and increased glucose consumption. For updated reviews on the Warburg effect , the reader is encouraged to refer to the following papers [3, 4].
However, new findings compel us to reconsider the current model of cancer cell metabolism. First, not all tumors are associated with increased aerobic glycolysis, and in fact it is now clear that cancer cells utilize both glycolysis and oxidative phosphorylation to satisfy their metabolic needs. Experimental assessments of ATP production in cancer cells have demonstrated that oxidative pathways play a significant role in energy generation, and may be responsible for about 50 to 80% of the ATP generated [5–8]. Also, it should be considered that most studies were performed using isolated cancer cells, which may behave very differently from cancer cells in vivo, surrounded by their natural microenvironment  (see also Koukourakis and colleagues  for another viewpoint).
Second, several studies now clearly indicate that mitochondrial activity and oxidative phosphorylation support tumor growth. Loss-of-function mutations in the TCA cycle gene IDH1 (isocitrate dehydrogenase 1) are found in about 70% of gliomas, but, interestingly, correlate with a better prognosis and improved survival, suggesting that severely decreased activity in one of the TCA cycle enzymes does not favor tumor aggressiveness . The mitochondrial protein p32 was shown to maintain high levels of oxidative phosphorylation in human cancer cells and to sustain tumorigenicity in vivo . In addition, STAT3 is known to enhance tumor growth and to predict poor prognosis in human cancers . Interestingly, a pool of STAT3 localizes to the mitochondria, to sustain high levels of mitochondrial respiration  and to augment transformation by oncogenic Ras [15, 16]. Similarly, the mitochondrial transcription factor A (TFAM), which is required for mitochondrial DNA replication and oxidative phosphorylation, is also required for K-Ras-induced lung tumorigenesis . Finally, when constrained to use glycolysis by depletion of mitochondrial DNA, melanoma B16 cells (B16ρ0) and breast cancer T47D cells (T47Dρ0), show severe impairment of tumorigenicity in vivo [18, 19].
There is also evidence that pro-oncogenic molecules regulate mitochondrial function. Cyclin D1 inhibits mitochondrial function in breast cancer cells . Over-expression of cyclin D1 is observed in about 50% of invasive breast cancers and is associated with a good clinical outcome , indicating that inhibition of mitochondrial activity correlates with favorable prognosis. Importantly, it was shown that the oncogene c-Myc stimulates mitochondrial biogenesis, and enhances glutamine metabolism by regulating the expression of mitochondrial glutaminase, the first enzyme in the glutamine utilization pathway . Glutamine is an essential metabolic fuel that is converted to alpha-ketoglutarate and serves as a substrate for the TCA cycle or for glutathione synthesis, to promote energy production and cellular biosynthesis, and to protect against oxidative stress . Interestingly, pharmacological targeting of mitochondrial glutaminase inhibits cancer cell transforming activity, suggesting that glutamine metabolism and its role in fueling and replenishing the TCA cycle are required for neoplastic transformation  (for a recent review on glutamine cancer metabolism, see ).
It is increasingly apparent that the tumor microenvironment regulates neoplastic growth and progression. Activation of the stroma is a critical step required for tumor formation. Among the stromal players, cancer associated fibroblasts (CAFs) have recently taken center stage . CAFs are activated, contractile fibroblasts that display features of myo-fibroblasts, express muscle-specific actin, and show an increased ability to secrete and remodel the extracellular matrix [26, 27]. They are not just neutral spectators, but actively support malignant transformation  and metastasis , as compared to normal resting fibroblasts. For example, in a humanized mouse model of breast cancer, oncogenically driven human organoids develop tumors only if coinjected with immortalized fibroblasts and not with normal primary fibroblasts, suggesting that stromal activation is required for breast cancer formation .
Importantly, the tumor stroma dictates clinical out-come and constitutes a source of potential biomarkers . Expression profiling has identified a cancer-associated stromal signature that predicts good and poor clinical prognosis in breast cancer patients, independently of other factors [32–34].
We and others have recently shown that a loss of caveolin-1 (Cav-1) in the stromal compartment is a novel biomarker for predicting poor clinical outcome in all of the most common subtypes of human breast cancer, including the more lethal triple negative subtype [35, 36]. A loss of stromal Cav-1 predicts early tumor recurrence, lymph-node metastasis, tamoxifen-resistance, and poor survival. Overall, breast cancer patients with a loss of stromal Cav-1 show a 20% 5-year survival rate, compared to the 80% 5-year survival of patients with high stromal Cav-1 expression. In triple negative patients, the 5-year survival rate is 75.5% for high stromal Cav-1 versus 9.4% for absent stromal Cav-1 . A loss of stromal Cav-1 also predicts progression to invasive disease in ductal carcinoma in situ patients, suggesting that a loss of Cav-1 regulates tumor progression . Similarly, a loss of stromal Cav-1 is associated with advanced disease and metastasis, as well as a high Gleason score, in prostate cancer patients .
In order to mechanistically dissect how a loss of stromal Cav-1 induces a lethal microenvironment, we have employed Cav-1(-/-) null mice as a model system. Complementary studies were also performed with a coculture model of normal human fibroblasts and MCF7 breast cancer cells.
Unbiased proteomic and transcriptional analysis has shown that Cav-1(-/-) null bone-marrow-derived stromal cells display the up-regulation of both myo-fibroblast markers and glycolytic enzymes, clearly indicating that a loss of Cav-1 promotes myo-fibroblast conversion and induces aerobic glycolysis in stromal cells . Thus, stromal cells lacking Cav-1 undergo aerobic glycolysis and secrete energy-rich metabolites (such as lactate and pyruvate) that directly feed cancer cells and fuel mitochondrial respiration of adjacent cancer cells. We have termed this novel hypothesis the 'reverse Warburg effect '. This novel idea has now also been independently confirmed by Pol and colleagues , who demonstrated that genetic ablation of Cav-1 in murine fibroblasts is indeed sufficient to functionally induce the onset of aerobic glycolysis via mitochondrial dysfunction . Interestingly, immunohistochemistry on human breast cancers lacking stromal Cav-1 has demonstrated the over-expression of key glycolytic enzymes, such as PKM2 and LDH, in the fibroblastic tumor stroma .
In further support of this hypothesis, co-culture with cancer cells promotes Cav-1 down-regulation in adjacent fibroblasts. Importantly, when cultured under homotypic conditions, MCF7 cancer cells have a very low mitochondrial mass (the conventional Warburg effect ). However, co-culture with fibroblasts, which more closely mirrors the microenvironment of a naturally occurring tumor, promotes a very significant increase in mitochondrial mass in MCF7 cancer cells, suggesting that the Warburg effect might be an in vitro artifact . Importantly, lactate administration to homotypic MCF7 cancer cell cultures significantly increases mitochondrial mass, suggesting that lactate administration phenocopies the presence of reactive fibroblasts , by promoting mitochondrial biogenesis. These new data indicate that cancer cells and CAFs develop a 'symbiotic' or 'parasitic' relationship, with the vectorial and unilateral transfer of energy from glycolytic stromal cells to oxidative cancer cells (Figures 1 and 2).
The autophagic tumor stroma model of cancer metabolism. Cancer cells induce oxidative stress in adjacent cancer-associated fibroblasts (CAFs). This activates reactive oxygen species (ROS) production and autophagy. ROS production in CAFs, via the bystander effect, serves to induce random mutagenesis in epithelial cancer cells, leading to double-strand DNA breaks and aneuploidy. Cancer cells mount an anti-oxidant defense and up-regulate molecules that protect them against ROS and autophagy, preventing them from undergoing apoptosis. So, stromal fibroblasts conveniently feed and mutagenize cancer cells, while protecting them against death. See the text for more details. A+, autophagy positive; A-, autophagy negative; AR, autophagy resistant.
The reverse Warburg effect. (a) Via oxidative stress, cancer cells activate two major transcription factors in adjacent stromal fibroblasts (hypoxia-inducible factor (HIF)1α and NFκB). This leads to the onset of both autophagy and mitophagy, as well as aerobic glycolysis, which then produces recycled nutrients (such as lactate, ketones, and glutamine). These high-energy chemical building blocks can then be transferred and used as fuel in the tricarboxylic acid cycle (TCA) in adjacent cancer cells. The outcome is high ATP production in cancer cells, and protection against cell death. ROS, reactive oxygen species. (b) Homotypic cultures (upper panels) of MCF7 cells (right) and hTERT-fibroblasts (left) were immunostained with a mitochondrial membrane antibody (red). Note that mitochondrial mass is lower in mono-cultures of MCF7 cells compared to fibroblasts. However, co-culture of MCF7 cells with fibroblasts (lower panel) induces a dramatic increase in mitochondrial mass in the 'central MCF7 cell colony', outlined by the dotted white oval. In contrast, mitochondrial mass is decreased in co-cultured fibroblasts. Panel (b) was modified and reproduced with permission from [41, 78].
Clinically, high glucose uptake has been exploited to monitor tumor growth using position emission tomography (PET) scanning via radiolabeled 2-deoxy-glucose. However, we should acknowledge that PET avidity does not necessarily correlate with high aerobic glycolysis. For example, PET is not useful in clear cell renal carcinomas [42, 43], which are the tumor 'prototype' in which the Warburg effect should sustain tumor formation. About half of clear cell renal carcinomas are due to mutations in the Von Hippel-Lindau (VHL) gene [44, 45], leading to HIF1α constitutive activation and forced induction of aerobic glycolysis [46–48]. Conversely, little attention is paid to understanding which cell- type or compartments within a tumor are most PET avid. In fact, the clinical use of PET is well established in Hodgkin's lymphomas , which are composed of less than 10% tumor cells, the rest being stromal and inflammatory cells . Yet, Hodgkin's lymphomas are very PET avid tumors, suggesting that 2-deoxy-glucose uptake may be associated with the tumor stroma. That the fibrotic component may be glucose avid is further supported by the notion that PET is clinically used to assess the therapeutic response in gastrointestinal stromal tumors (GIST), which are a subset of tumors of mesenchymal origin. Finally, pilot clinical studies have shown that PET is useful for detection of various forms of fibrosis, including pulmonary fibrosis .
The reverse Warburg effect can also be described as 'metabolic coupling' between supporting glycolytic stromal cells and oxidative tumor cells. Metabolic cooperativity between adjacent cell-compartments is observed in several normal physiological settings. During folliculogenesis and early embryogenesis, oocytes are surrounded by supporting cumulus granulosa (CG) cells. Oocytes lack some crucial metabolic functions, such as the ability to utilize glucose, to produce cholesterol and to transport certain amino acids. Thus, oocytes control CG cell metabolism, promoting their glycolysis, cholesterol synthesis and amino acid uptake [52, 53]. Remarkably, both oocytes and zygotes can reach a two-cell stage only in the presence of pyruvate and oxaloacetate, but not using glucose [54, 55]. However, upon co-culture with CG cells, oocytes or zygotes can cleave to a two-cell stage also in the presence of glucose, clearly indicating that CG cells metabolize glucose and supply the oocyte with the glycolytic product pyruvate to permit maturation . In this regard, transcriptional profiling of CG cells and oocytes has revealed that key enzymes of the glycolytic pathway (aldolase A, enolase 1, LDHA, and PKM2) are very highly expressed in CG cells, but are undetectable in oocytes . These results indicate that granulosa cells support the development and maturation of oocytes and early embryos by providing them with essential nutrients, such as oxidative phosphorylation substrates (pyruvate and lactate ), amino acids , and cholesterol .
Metabolic coupling is also normally observed in the brain between astrocytes and neurons, and this is known as 'neuron-glia metabolic coupling' [60, 61]. In this regard, glycolytic astrocytes generate high levels of lactate to support mitochondrial oxidative phosphorylation in adjacent neurons. Consistent with this idea, LDH is preferentially expressed in astrocytes, and the mitochondrial enzyme pyruvate dehydrogenase is present selectively within the neurons [62, 63]. Also, in skeletal muscle it is well established that glycolytic fast-twitch muscle fibers produce lactate, which is then secreted via monocarboxylate transporter (MCT) 4. Lactate is then taken up by the slow-twitch fibers expressing MCT1 and utilized as a substrate for oxidative phosphorylation [64, 65]. This form of metabolic coupling is known as the 'skeletal muscle lactate shuttle' .
As such, it is perhaps not surprising that tumors may have also developed a form of metabolic coupling, specifically involving tumor-stromal interactions. In further support of the existence of a 'lactate shuttle' in human tumors, we have now shown that CAFs express MCT4 (for lactate extrusion), while breast cancer cells express MCT1 (for lactate uptake) (Figure 3) . Interestingly, MCT4 expression in CAFs is induced by oxidative stress, and MCT4 is a known HIF1α target gene (see Discussion below) .
Evidence supporting a 'lactate shuttle' in human tumors: compartmentalized distribution of monocarboxylate transporter (MCT)1/4. (a) MCT4 is expressed in the fibroblastic stromal compartment of human breast cancers. Note that MCT4 staining is absent from the tumor epithelial cells, but is present in the surrounding stroma. MCT4 staining outlines the cancer-associated fibroblasts that surround nests of epithelial cancer cells. (b) MCT1 is expressed in the epithelial compartment of human breast cancers. Note that MCT1 staining is present in the tumor epithelial cells, but is absent in the surrounding stroma. (c) The lactate shuttle: an energy transfer mechanism in normal tissue and human cancers. MCT4 functions primarily as a transporter that extrudes lactate from cells that are undergoing aerobic glycolysis and lack functional mitochondria. After lactate is extruded by MCT4 in cancer-associated fibroblasts (CAFs), lactate is then taken up by MCT1 in adjacent cancer cells. Similarly, ketones are transported by the same MCTs that handle lactate. Our studies suggest that metabolic coupling occurs between CAFs and adjacent tumor cells. Modified and reproduced with permission from .
Recent studies have dissected the mechanism(s) by which a loss of stromal Cav-1 leads to an aggressive breast cancer phenotype, and have shown that oxidative stress plays a central role. The role of oxidative stress in sustaining tumor growth is underscored by the observation that reactive oxygen species (ROS)-mediated myo-fibro-blast conversion is sufficient to reduce tumor-free survival, and increases metastatic potential in a mammary tumor mouse model .
Gene expression profiling of Cav-1(-/-) null bone-marrow-derived stromal cells has shown the up-regulation of gene transcripts associated with ROS production, and over-expression of the transcriptional targets of HIF1α and NFκB, suggesting that a loss of stromal Cav-1 induces oxidative stress, mimics hypoxia, and stimulates inflammation .
Co-cultures of normal human fibroblasts and MCF7 cells indicate that cancer cells use oxidative stress as a weapon to trigger the conversion of adjacent fibroblasts into myo-fibroblasts . Cancer cell-induced oxidative stress potently perturbs the behavior of adjacent fibro-blasts, induces the lysosomal-mediated degradation of Cav-1, and promotes mitochondrial dysfunction, resulting in increased aerobic glycolysis . In turn, these glycolytic fibroblasts support tumor cell mitochondrial respiration and growth by actively transferring high-energy nutrients (such as lactate and pyruvate) to cancer cells.
In support of the 'reverse Warburg effect ', comparison of the tumor-promoting properties of two fibroblast lines (named CL3 and CL4) with either mitochondrial or glycolytic metabolism has revealed that aerobic glycolysis in CAFs greatly promotes tumor formation. CL3 fibroblasts show oxidative metabolism and increased mitochondrial mass, whereas CL4 fibroblasts display a shift towards aerobic glycolysis and increased lactate production . Interestingly, in a xenograft model, CL4 fibro-blasts enhance the growth of mammary tumors by approximately eight- fold compared to CL3 cells, without a detectable increase in angiogenesis. Consistent with this growth-promoting effect , CL4 fibroblasts also increase the mitochondrial mass of co-cultured breast cancer cells .
An oxidative-stress-rich micro-environment generates DNA damage in both cancer and stromal cells (Figure 1). We have shown that MCF7 cancer cells induce oxidative stress and promote DNA double-strand breaks in associated stromal cells, which are blocked by anti-oxidant treatments . Similarly, after three-dimensional co-culture with prostate cancer cells, bone-derived stromal cells undergo stable cytogenetic modifications by a ROS-mediated mechanism .
Conversely, in an MCF7-fibroblast co-culture model, MCF7 cancer cells undergo aneuploidy and random mutagenesis , suggesting that CAFs facilitate the dynamic search for a more aggressive 'mutator phenotype' in cancer cells (Figure 1). Functionally, fibroblasts provide cancer cells with a six-fold protection against cell death  (Figure 2), via the up-regulation of the anti-apoptotic protein TIGAR . Cav-1 knockdown fibroblasts provide even greater protection for cancer cells against apoptosis, clearly indicating that a loss of stromal Cav-1 in humans may greatly facilitate tumor growth by suppression of cancer cell death .
Thus, data supporting the 'reverse Warburg effect ' indicate that cancer cells and fibroblasts are metabolically coupled and mutagenically co-evolving [41, 73]. Cancer cells use oxidative stress to corrupt adjacent fibroblasts and to induce their metabolic re-programming . In this way, fibroblasts secrete energy rich metabolites that facilitate cancer cell survival. In addition, fibroblasts promote mutagenesis of cancer cells, leading to a more aggressive 'aneuploid' phenotype [41, 73]. Aneuploidy in cancer cells is known to be associated with poor clinical outcome.
Metabolomic profiling reveals that Cav-1(-/-) null mammary fat pads display a highly catabolic metabolism, with the increased release of several metabolites, such as amino acids, ribose and nucleotides, and a shift towards gluconeogenesis, as well as mitochondrial dysfunction . These changes are consistent with increased autophagy, mitophagy and aerobic glycolysis, all processes that are induced by oxidative stress . Autophagy or 'self- eating' is the process by which cells degrade their own cellular components to survive during starvation or to eliminate damaged organelles after oxidative stress. Mitophagy, or mitochondrial-autophagy, is particularly important to remove damaged ROS-generating mitochondria.
An autophagy/mitophagy program is also triggered by hypoxia [75, 76]. Hypoxia is a common feature of solid tumors, and promotes cancer progression, invasion and metastasis . Interestingly, via induction of autophagy, hypoxia is sufficient to induce a dramatic loss of Cav-1 in fibroblasts. The hypoxia-induced loss of Cav-1 can be inhibited by the autophagy inhibitor chloroquine, or by pharmacological inhibition of HIF1α [69, 78]. Conversely, small interfering RNA-mediated Cav-1 knock-down is sufficient to induce pseudo-hypoxia, with HIF1α and NFκB activation, and to promote autophagy/mitophagy, as well as a loss of mitochondrial membrane potential in stromal cells . These results indicate that a loss of stromal Cav-1 is a marker of hypoxia and oxidative stress. In a co-culture model, autophagy in cancer-associated fibroblasts was shown to promote tumor cell survival via the induction of the pro-autophagic HIF1α and NFκB pathways in the tumor stromal microenvironment . Finally, the mitophagy marker Bnip3L is selectively up-regulated in the stroma of human breast cancers lacking Cav-1, but is notably absent from the adjacent breast cancer epithelial cells .
Another study has shown that cell-specific induction of autophagy by HIF1α activation in fibroblasts or MDA-MB-231 cells differentially affects tumor growth. In a xenograft model, HIF1α activation in fibroblasts greatly enhances the tumorigenicity of co-injected MDA-MB-231 cells, whereas HIF1α activation in MDA-MB-231 cancer cells suppresses tumor growth . Importantly, in this experimental setting, the levels of tumor angiogenesis were unchanged. As HIF1α triggers autophagy in both fibroblasts and cancer cells, these data demonstrate that the role of autophagy in driving tumor formation is cell-type specific, and that stromal autophagy, and not cancer cell autophagy, favors tumor growth.
Several studies have demonstrated that the over-expression of autophagic markers, such as ATG16L and cathepsin K and D, in the stroma and not in tumor cells predicts poor prognosis [80–82]. Similarly, loss of autophagic markers, such as Beclin 1, in tumor cells correlates with poor clinical outcome, suggesting that activation of an autophagic program in tumor cells reduces tumor aggressiveness .
Metabolome profiling of several types of human cancer tissues versus corresponding normal tissues have consistently shown that cancer tissues are highly catabolic, with the significant accumulation of many amino acids and TCA cycle metabolites [84, 85]. The levels of reduced glutathione were decreased in primary and metastatic prostate cancers compared to benign adjacent prostate tissue, suggesting that aggressive disease is associated with increased oxidative stress . Also, these data show that the tumor microenvironment has increased oxidative-stress-induced autophagy and increased catabolism.
Taken together, all these findings suggest an integrated model whereby a loss of stromal Cav-1 induces autophagy/mitophagy in the tumor stroma, via oxidative stress. This creates a catabolic micro-environment with the local accumulation of chemical building blocks and recycled nutrients (such as amino acids and nucleotides), directly feeding cancer cells to sustain their survival and growth. We have termed this novel idea the 'autophagic tumor stroma model of cancer' . This new paradigm may explain the 'autophagy paradox', which is based on the fact that both the systemic inhibition and systemic stimulation of autophagy prevent tumor formation . We propose that vectorial energy transfer from the tumor stroma to cancer cells directly sustains tumor growth, and that interruption of such metabolic coupling will block tumor growth. Autophagy inhibitors (such as chloroquine) functionally block the catabolic transfer of metabolites from the stroma to the tumor, inducing cancer cell starvation and death . Conversely, autophagy inducers (such as rapamycin) promote autophagy in tumor cells and induce cell death . Thus, both inhibitors and inducers of autophagy will have a similar effect by severing the metabolic coupling of the stroma and tumor cells, resulting in tumor growth inhibition (cutting 'off ' the fuel supply).
This model may also explain why enthusiasm for anti-angiogenic therapy has been dampened. In most cases, the clinical benefits are short term, and more importantly, new data suggest an unexpected link between anti-angiogenic treatments and metastasis. In pre-clinical models, anti-vascular endothelial growth factor (anti-VEGF) drugs (sunitinib and anti-VEGFR2 blocking antibodies) were shown to inhibit localized tumor formation, but potently induced relapse and metastasis [90–92]. Thus, by inducing hypoxia in the tumor microenvironment, anti-angiogenic drugs may create a more favorable metastatic niche . Hypoxia-induced autophagy may play a role by generating a catabolic micro-environment rich in chemical building blocks that can be directly used by cancer cells to sustain malignant transformation and metastatic progression.
Finally, the autophagic tumor stroma model can also provide an explanation for systemic cachexia, which is progressive skeletal muscle and adipose tissue wasting, affecting up to 50% of all cancer patients and resulting in severe weight loss and shortened survival . Cachexia is the result of increased energy consumption and higher metabolic rates . Based on our data, we envision that cancer leads to a generalized catabolic state via an autophagic-mechanism that generates building blocks and starves the rest of the body. While the exact signaling pathways governing this phenomenon are not yet fully elucidated, it is clear that oxidative stress-induced autophagy functions as a driver of muscle wasting . For example, skeletal muscles from tumor-bearing mice showed impaired Akt activation and a more than 50-fold induction of Bnip3, a well recognized marker of autophagy/mitophagy . These findings also help explain why patients with metabolic syndrome and diabetes have an increased risk for the development of multiple epithelial cancers, due to their constitutive and systemic activation of the autophagic program, and the over-production of high-energy nutrients, such as lactate and ketones .
We have recently used laser-capture micro-dissection of the tumor stroma from human breast cancers to directly validate that a loss of stromal Cav-1 is transcriptionally associated with oxidative stress, hypoxia, autophagy, and mitochondrial dysfunction, via gene-set enrichment analysis (Figure 4) . In addition, we see that oxidative stress in CAFs induces cytokine production via NFκB activation, directly linking inflammation with autophagy/catabolism in the tumor stroma . So, cachexia may start locally as stromal autophagy, and then spread systemically via cytokine production and inflammation, which also drive autophagy .
Molecular profiling of a Cav-1 deficient tumor micro-environment in breast cancer patients. (a) The transcriptional profiles of caveolin-1 (Cav-1)-positive (+) tumor stroma (N = 4) versus Cav-1-negative (-) tumor stroma (N = 7) were compared, via laser-capture microdissection. We identified 238 gene transcripts that were up-regulated and 232 gene transcripts that were down-regulated in the stroma of tumors showing a loss of Cav-1 expression. Note that the two patient populations are transcriptionally distinct. (b) The Cav-1-deficient stromal gene signature is associated with poor survival in estrogen receptor-positive and luminal A breast cancer patients. Note that the Cav-1-deficient stromal signature is clearly associated with decreased overall survival. (c) Heat maps of the gene transcripts associated with the response to hypoxia, glycolysis, and autophagy. Note that Cav-1-deficient stroma shows the up-regulation of hypoxia target genes (65 transcripts), glycolysis/pyruvate metabolism (15 transcripts), and autophagy (22 transcripts). Modified and reproduced with permission from .
In direct support that cancer cells use mitochondrial oxidative metabolism, many investigators have shown that cancer cells are 'addicted' to glutamine [24, 100]. Glutamine is a non-essential amino acid that is metabolized to glutamate and enters the TCA cycle as alpha-ketoglutarate, resulting in high ATP generation via oxidative phosphorylation [2, 22, 101–103].
Recent studies also show that ammonia is a by-product of glutaminolysis [104–106]. In addition, ammonia can act as a diffusible inducer of autophagy [104–106]. Given these observations, glutamine addiction in cancer cells provides another mechanism for driving and/or maintaining autophagy in the tumor micro-environment (Figure 5). In support of this idea, we have previously shown that a loss of Cav-1 in the stroma is sufficient to drive autophagy, resulting in increased glutamine production in the tumor micro-environment .
Glutamine utilization in cancer cells and the tumor stroma. Oxidative mitochondrial metabolism of glutamine in cancer cells produces ammonia. Ammonia production is sufficient to induce autophagy. Thus, autophagy in cancer-associated fibroblasts provides cancer cells with an abundant source of glutamine. In turn, the ammonia produced maintains the autophagic phenotype of the adjacent stromal fibroblasts. See text for details. TCA, tricarboxylic acid.
Thus, this concept defines a new vicious cycle in which autophagy in the tumor stroma transfers glutamine to cancer cells, and the by-product of this metabolism, ammonia, maintains autophagic glutamine production (Figure 5). This model fits well with the 'autophagic tumor stroma model of cancer metabolism', in which energy-rich recycled nutrients (lactate, ketones, and glutamine) fuel oxidative mitochondrial metabolism in cancer cells.
We have recently proposed that cancer cells behave like 'parasites', by inducing oxidative stress in normal host fibroblasts, resulting in the production of recycled nutrients via autophagy [41, 69, 78]. This is exactly the same mechanism by which infectious parasites (such as malaria) obtain nutrients and are propagated by inducing oxidative stress and autophagy in host cells [107–109]. In this regard, malaria is an 'intracellular' parasite, while cancer cells may be thought of as 'extracellular' parasites. This explains why chloroquine is both an effective anti-malarial drug and an effective anti-tumor agent, as it functions as an autophagy inhibitor , cutting off the 'fuel supply' in both disease states.
Are there any examples of cancer cells that act as infectious parasites? Surprisingly, the answer is yes . There are four known types: canine transmissible venereal tumor (CTVT), which is a sexually transmitted disease that occurs in feral dogs  - it is transmitted through coitus, licking/biting, or sniffing; devil facial tumor disease, spread among Tasmanian devils via facial biting [113, 114]; contagious reticulum cell sarcoma, which is transmitted between Syrian hamsters via mosquito bites [115, 116]; and malignant fibrous histiocytoma, which was transmitted from a cancer patient to his surgeon  during an injury that occurred when the surgeon was operating.
These parasitic cancers are all transmitted by allografting, so the cancer cells literally 'metastasize' from one affected host to another 'naïve' host, in an infectious manner that does not involve a virus.
Experimentally, the most is known about CTVT. This disease is thought to have originated in ancient wolves or coyotes, and the tumor cells themselves act as the infectious agent. As such, these cancer cells are genetically distinct from their hosts, as determined by genomic sequence analysis of their nuclear DNA . CTVT represents the oldest known cancer cell line that has been continuously propagated, most likely for more than 10,000 years [118, 119].
Interestingly, it has recently been shown that CTVT tumor cells survive by periodically 'capturing' mitochondrial DNA from their hosts [119, 120]. Thus, it has been suggested that these CVCT tumor cells have survived for more than 10,000 years by maintaining and renewing their capacity for oxidative mitochondrial metabolism by 'stealing' host cell mitochondrial DNA [119, 120]. In accordance with this idea, CTVT is highly sensitive to adriamycin/doxorubicin therapy , a chemo-therapeutic agent that also functions as a mitochondrial poison.
Similarly, it has been independently shown that human cancer cells can 'steal' live mitochondria or mitochondrial DNA  from adjacent mesenchymal stem cells in culture, which then rescues aerobic glycolysis in these cancer cells . This is known as mitochondrial transfer . Interestingly, others have shown that metastatic breast cancer cells show the up-regulation of numerous mitochondrial proteins , specifically associated with oxidative phosphorylation, as seen by unbiased proteomic analysis .
Thus, increased mitochondrial oxidative metabolism may be a key driver of tumor cell metastasis. In further support of this argument, treatment of MCF7 cancer cells with lactate is indeed sufficient to induce mitochondrial biogenesis in these cells [41, 78] (Figure 6). To determine if these findings may be clinically relevant, a lactate-induced gene signature was recently generated using MCF7 cells . This gene signature shows that lactate induces 'stemness' in cancer cells, and this lactate-induced gene signature predicts poor clinical outcome (including tumor recurrence and metastasis) in breast cancer patients  (Figure 6). These findings are consistent with experiments showing that intraperitoneal injection of lactate in an MDA-MB-231 xenograft model results in an approximately ten-fold increase in lung metastasis .
Lactate treatment of estrogen receptor-positive breast cancer cells drives mitochondrial biogenesis, leading to poor survival in a subset of luminal A breast cancer patients. (a) Lactate-treated (10 mM) MCF7 cells show a significant increase in mitochondrial mass, as visualized by staining with antibodies against mitochondrial marker proteins. (b) Lactate-treated (10 mM) MCF7 cells were subjected to transcriptional profiling (exon-array) to generate a gene signature. Interestingly, this lactate-induced gene signature predicts poor clinical outcome in estrogen receptor-positive/luminal A breast cancer patients, which represent nearly 60 to 70% of cases, and is the most common type of breast cancer. Modified and reproduced with permission from .
MPL and his laboratory were supported by grants from the NIH/NCI (R01-CA-080250; R01-CA-098779; R01-CA-120876; R01-AR-055660), and the Susan G Komen Breast Cancer Foundation. FS was supported by grants from the WW Smith Charitable Trust, the Breast Cancer Alliance (BCA), and a Research Scholar Grant from the American Cancer Society (ACS). RGP was supported by grants from the NIH/NCI (R01-CA-70896, R01-CA-75503, R01-CA-86072, and R01-CA-107382) and the Dr Ralph and Marian C Falk Medical Research Trust. The Kimmel Cancer Center was supported by the NIH/NCI Cancer Center Core grant P30-CA-56036 (to RGP). Funds were also contributed by the Margaret Q Landenberger Research Foundation (to MPL). This project is funded, in part, under a grant with the Pennsylvania Department of Health (to MPL). The Department specifically disclaims responsibility for any analyses, interpretations or conclusions. This work was also supported, in part, by a Centre grant in Manchester from Breakthrough Breast Cancer in the UK (to AH) and an Advanced ERC Grant from the European Research Council. Dr MP Lisanti would especially like to thank Drs Craig B Thompson, Tak W Mak, Michel L Tremblay, and Robert S DiPaola (other participants of the ASBMB/AACR 2011 Meetings) for their feedback, thoughtful comments, and helpful suggestions. This review was recently presented as a lecture at the AACR 2011 Meeting in the Educational Session 'Autophagy and Cell Death' on 2 April 2011 (Orlando, FL). It was also presented as a lecture at the Experimental Biology 2011-ASBMB Meeting (Washington, DC) at the session on 'Metabolism and Cancer' on 13 April 2011.


MIAMI GARDENS, FL – Karl Glassman and Cathi Glassman's Apostle will make both his turf and stakes debut as he attempts to extend his win streak to three races in Saturday's $75,000 Showing Up at Gulfstream Park West.
The Showing Up for 3-year-olds and the $75,000 Cellars Shiraz for 3-year-old fillies, both at one mile on the grass, highlight a 10-race card and kick off the Fall Turf Festival's stakes program.
Trained by Eddie Plesa Jr., the 3-year-old Medaglia d'Oro colt is two-for-two at the Showing Up distance, both wins coming as the favorite and over older horses, the latter on Gulfstream West's main track Oct. 3.
Apostle, purchased for $900,000 as a 2-year-old, has worked twice since the win including a mile breeze on the grass at Palm Meadows, Gulfstream Park's satellite training facility in Palm Beach County.
"We took him up to Palm Meadows and worked him on the turf to make sure he didn't have a dislike for it, and he handled it fine," Plesa said. "I'm not saying he's going to be better on the turf than the dirt, but it's the end of the year. It's a 3-year-old stakes race, so we figured we'd give him an opportunity and see what happens.
Apostle drew Post 6 in a field of 15 that includes main-track-only entrant Royal Holiday and will carry 117 pounds including regular rider Edgard Zayas. Only three horses have previous experience over Gulfstream West's turf course, all with a win – Silent Citizen, Watschen and Nauti Buoy.
Gidu, Renaisance Frolic, Sand Dancer, Gemonteer and Nauti Boy all own grass stakes wins, the latter coming in the Juvenile Turf last November at Gulfstream West, also under Zayas.
Unraced at 2, Apostle ran in a pair of maiden special weights during Gulfstream's 2017-18 Championship Meet, finishing fifth going seven furlongs in his Jan. 6 debut and returning to be third at 1 1/16 miles Feb. 10. He didn't race again until graduating with a 1 ½-length triumph Aug. 23 at Gulfstream.
Gulfstream Park is the premiere venue in South Florida to watch and wager on all 14 Breeders' Cup races Friday and Saturday from Churchill Downs.
Silks simulcast center will open at 10 a.m. both Friday and Saturday for program and seat sales. Ten Palms will offer a Breeders' Cup Buffet Saturday from 11 a.m. to 5 p.m. for $49 plus tax. In addition, fans can watch the Breeders' Cup at Frankey's Sports Bar located in Gulfstream Village starting at 2 p.m. Friday and noon Saturday.
Friday's Breeders' Cup races start with the inaugural $1 million Juvenile Turf Sprint, with a post time of 3:21 p.m., and ends with the $2 million Juvenile (G1) which has a 6:05 p.m. post time.
Saturday's Breeders' Cup races begin with the $1 million Filly & Mare Sprint (G1) with a noon post time, and are capped by the $6 million Classic (G1) – featuring South Florida-based Gunnevera – with a 5:44 p.m. post time.
South Florida is also represented in the Breeders' Cup by Well Defined in the Juvenile and Stormy Embrace in the Filly and Mare Sprint, both trained by Kathleen O'Connell.
Gulfstream Park West will have live nine-race card Friday starting at 12:35 p.m. and a live 10-race program Saturday with a 12:15 p.m. first post.


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How to Activate Voice Access When Looking at Your Android Phone
September 2, 2021 ShaqHaxLeave a Comment on How to Activate Voice Access When Looking at Your Android PhoneArticles
Joe Fedewa is a Staff Writer at How-To Geek. He has close to a decade of experience covering consumer technology and previously worked as a News Editor at XDA Developers. Joe loves all things technology and is also an avid DIYer at heart. He has written thousands of articles, hundreds of tutorials, and dozens of reviews. Read more…
Android has some powerful accessibility tools that can make using a smartphone easier. "Voice Access" is one that can help if you have trouble manipulating a touch screen. We'll show you how to make it work only when you're looking.
"Voice Access" is an Android accessibility app that allows people to use their voice to open apps, navigate the user interface, and edit text. It's aimed at people who may have difficulty using their fingers to get around a touch screen.
It can do the basic things you'd expect, but there's also a lot more advanced stuff. Here's a short video to show off what it can do.
You can see how its capabilities go beyond simply opening apps. It can control many things on the screen and even scroll for you. Voice Access differs from Google Assistant in that you don't need to be conversational. Instead of saying "open subscriptions," you simply say "subscriptions."
There are several ways that you can use Voice Access, depending on how much you need it. Voice Access can be listening whenever the screen is on, be manually started with a shortcut, or activated with a Google Assistant command.
We'll show you a feature called "Gaze Detection" that will have it listen when you're actively looking at the display.
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At the time of writing in June 2021, Gaze Detection is in beta. You will need to opt-in to the beta in the Google Play Store. To do so, visit the Play Store listing for Voice Access and select "Join" from the Beta Program card.
Now you'll have to wait a few minutes for an update for the app to arrive. After that, we're ready to get started. When you first launch the app, you'll be asked to turn it on in the Accessibility Settings. Tap "OK."
Find "Voice Access" from the Accessibility Settings.
Toggle the switch on to "Use Voice Access."
You'll be asked to allow some pretty big permissions, which is necessary for Voice Access's powerful features. Tap "Allow" if you're okay with that.
Now we can go to the Voice Access Settings, found on the same screen.
Scroll all the way down to the "Setup" section and tap "More Options."
At the bottom, you'll see a toggle for "Gaze Detection." Turn it on.
Now, when Voice Access is running, you'll see a little face icon in the status bar area. Voice Command will only listen to your voice when it detects your face looking at the screen.
For anyone who relies on Voice Access to control their Android smartphone, this is a great little trick. You won't have to worry about the app listening when you're not actively using the device. For more information about what Voice Access can do, check out Google's full list of commands.
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