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COVID-19 and Social Media Content Moderation
Google, Facebook, Twitter, and more commit to battling coronavirus misinformation
In response to the coronavirus outbreak, the social networking giant ‘s content moderators were sent home due to the virus, forcing it to rely more on technology to police misinformation in the interim.
They announced they would be relying on automated tools more than normal as a result—and warned that this would result in more errors in moderation which would be rectified along the way.
According to the company update, full-time employees would be trained to devote “extra attention” to highly sensitive content, such as any involving suicide, child exploitation and terrorism.
Mark Zuckerberg acknowledging the decision on a media call with Washington Post said this could result in “false positives,” including removal of content that should not be taken down.
RECOMMENDED: COVID-19: 5 Ways to Do Smart & Responsible Marketing
“This means some reports will not be reviewed as quickly as they used to be and we will not get to some reports at all,”
YouTube’s announcement was in the same terms: “We will temporarily start relying more on technology to help with some of the work normally done by reviewers. This means automated systems will start removing some content without human review, so we can continue to act quickly to remove violative content and protect our ecosystem, while we have workplace protections in place. As we do this, users and creators may see increased video removals.” The same day, Twitter said it would do the same.
We are working closely together on COVID-19 response efforts. We’re helping millions of people stay connected while also jointly combating fraud and misinformation about the virus, elevating authoritative content on our platforms, and sharing critical updates in coordination with government healthcare agencies around the world. We invite companies to join us as we work to keep our communities healthy and safe.
Reducing the workforce also will alter the appeals process for users who believe their content was removed in error. People can still report they disagree with Facebook’s decision.
Stopping misinformation and harmful content would involve the following
- Combating COVID-19 misinformation across our apps
- Limiting misinformation and harmful content
- Banning ads for medical face masks
- Prohibiting exploitative tactics in ads
- Removing misinformation related to COVID-19 on Instagram
- Banning ads for hand sanitizer, disinfecting wipes and COVID-19 test kits
- Keeping our platform safe with remote and reduced content review
While for content creators and publisher, all monetized content goes through brand safety reviews. This includes Instant Articles and videos with in-stream ads. Since their ability to review new content is now limited, they won’t be able to approve all content for monetization.


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American rapper Jay-Z has released fourteen solo studio albums, four collaboration albums, ... Released: November 4, 1997 (US); Label: Roc-A-Fella, Def Jam; Formats: CD, LP, cassette, digital download. 3, 2, 36, —, —, —, —, —, —, 78. The albums discography of Roc Nation, an American company and record label, consists of three studio albums, one collaboration album, one compilation album and two mixtapes by Jay-Z, four studio albums and ... "Jay-Z – Creative Control Mixtape (Listen / Download)". mixtapes.tv.


ARMO Platform provides ways to integrate with third-party applications. Depending on the application, you can perform scanning tasks in the application and send the scan results to ARMO Platform to more easily visualize scan data and manage your controls, frameworks, or results.
You can integrate cluster scanning with Cloud providers, platforms, and monitoring apps. You can use repository scanning in your CI/CD pipelines and IDE. ARMO Platform can also send email notifications and tightly integrate with Atlassian Jira or Slack.
The following integrations are supported:
Updated about 1 month ago


About The Technology
Digestate enhancement and treatment technologies have become more important due to the increase in the number and capacity of AD plants and industrial processes. Due to growing environmental and regulatory concerns, there is a need to manage nutrients such as nitrogen, phosphorous and potassium in the digestate and how these are spread onto land.
Colloide have developed a digestate treatment system that not only targets effective management of ammonia emissions but by recovering valuable resources also enables a zero-waste solution. The recovered resources are products of agricultural value and present an opportunity to achieve a zero pollution digestate management system. We have a wealth of experience in providing both innovative solutions and upgrading existing systems. Our Digestate Treatment System is compliant with government regulations and codes of good practice.
Colloide’s main methods are vaporisation (flash distillation/evaporation/stripping), reverse osmosis (including pre-filtration), chemical dosing (used in conjunction with other technologies) and a combination of SBR and MBR treatments.
Enhanced solids separation and removal of suspended and dissolved solids.
Removal of COD, VOC, Potassium and Phosphorus.
Greenhouse gas reduction.
Vastly superior treated water quality and recovery of nutrients.
A flexible process which can be tailored to meet specific requirements.
Capture or removal of ammonia for spreading on land, storage as concentrated fertilizer or exporting off site.
Vaporisation: Flash distillation/evaporation/stripping
These different methods of vaporisation ensure that ammonia is removed (>75%) from whole digestate, allowing the solids to be spread on land at a much higher coverage and approved for exporting off site. Alternatively, the ammonia can be captured as a liquid product for storage as a concentrated fertilizer, which can also be transported off-site for other markets. These systems help reduce the production of greenhouse gases, such as methane and CO2 and target the removal of suspended solids and VOC.
Reverse Osmosis (including pre-filtration)
This treatment recycles the digestate waste water into water (clean water recovery >75%), that can be re‐used for washdown, irrigation, evaporative cooling or disposed directly to a watercourse, thus prolonging the availability of freshwater resources. It can remove microplastics, viruses, bacteria, pharmaceuticals and pesticides from treated water, as well as recovering specific nutrients. A pre‐filter is installed before the reverse osmosis (RO) membrane and extends the life of the more expensive RO membrane, thereby reducing our client’s overall operating cost. The treated effluent can be used as a concentrated liquid fertilizer for exporting from a digestor site.
Chemical dosing (used in conjunction with other technologies)
Colloide design and build customised chemical dosing systems for a wide range of chemicals and applications. These packages are tailored to suit our clients’ requirements while adhering to European Standards, Ciria and HSE guidance. Our chemical dosing systems in conjunction with other technologies aid in the removal of chemicals such as phosphorus and ammonia. This treatment also enhances the separation of solids from liquid digestate and/or removal of suspended and dissolved solids as well as improving overall sterilisation.
SBR & MBR
The Sequential Batch Reactor (‘SBR’) and Membrane Bioreactor (MBR) are extremely compact and flexible solutions to waste water treatment. They offer an extremely high quality of treated effluent and both technologies achieve the removal of ammonia, suspended solids and COD. Our specialist MBR systems can also remove microplastics. The liquid fraction of digestate from these processes can be disposed to sewers, land or pre-treatment for further technologies.


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26th January 2015
First ever Chinese gay workplace discrimination lawsuit ‘will definitely have an impact’
7:05 PM — What is believed to be the first ever lawsuit over anti-gay workplace discrimination has taken place in a Chinese court.
Owner of Vietnamese Attitude Magazine arrested as part of gambling ring
1:48 PM — Among ten people who were arrested in Ho Chi Min suspected of running an illegal gambling ring was the owner of Attitude Magazine's Vietnamese franchise.
21st January 2015
Actor tells Indian trans community: ‘Don’t get offended’
4:36 PM — An transgender actor from controversial Tamil film 'I' has spoken out, telling trans protesters to not be offended.
India: LGBT community want Obama’s support
12:07 PM — The Indian LGBT community is calling on Barack Obama to offer his support to them ahead of his visit to the country this weekend.
16th January 2015
Pope Francis: Same-sex marriage ‘disfigures God’s plan for creation’ 243
5:56 PM — Pope Francis has attacked same-sex marriage, saying those who support it are attempting "redefine the very institution of marriage".
Japan’s ex-PM debuts as a drag queen… could Gordon Brown be next? 8
3:42 PM — The former Prime Minister of Japan has debuted as a drag queen.
15th January 2015
European Parliament urges Kyrgyzstan to drop anti-gay bill
3:57 PM — Kyrgyzstan has been urged by the European Parliament to drop an anti-gay bill.
Goa minister claims he was ‘misquoted’ about trying to ‘cure’ LGBT teens 6
1:10 PM — A minister in Goa has denied that the government there plans to attempt to “cure” LGBT people and make them “normal”, using therapy and “medicines”.
Indian ruling party says it is ‘for decriminalising homosexuality’ 8
12:16 PM — The ruling party in India has vowed to decriminalise homosexuality, saying while gay people are rejected by some, they should be accepted.
Thailand to recognise third gender 1
11:37 AM — Thailand's new constitution will include references to a third gender for the first time.
13th January 2015
Ban Ki-moon: India’s gay sex ban is ‘intolerant’ 19
10:52 AM — UN Secretary General Ban Ki-moon has criticised India's gay sex ban, saying it is "intolerant".
12th January 2015
Goa to attempt to make gay youths ‘normal’ 25
4:54 PM — The government in Goa plans to attempt to "cure" LGBT people and make them "normal", using therapy and "medicines".
8th January 2015
Vietnam abolishes ban on same-sex marriage 4
11:26 AM — The Vietnamese government repealed a ban on same-sex marriage on New Year's Day.
7th January 2015
Nepal to allow third gender on passports 3
12:54 PM — The Nepalese government is to issue passports with a third gender option for citizens who do not identify as male or female.
5th January 2015
Meet India’s first ever out transgender mayor 3
9:39 AM — For the first time a transgender candidate has won a mayoral election in India.
3rd January 2015
Bollywood actor plans to release intimate photos to ‘prove’ he’s not gay 32
1:17 PM — Bollywood actor Sahil Khan has threatened to release "intimate" photos of him with his alleged female lover - after she claimed he is gay.
28th December 2014
Bisexual Kim Jong-un orgy scene cut from ‘The Interview’? 3
5:46 PM — Sony Pictures reportedly cut parts of a scene featuring a bisexual orgy out of the released version of The Interview.
22nd December 2014
Taiwanese Parliament considers same-sex marriage for the first time 4
10:40 AM — For the first time, the Taiwanese Parliament on Monday considered legislation to legalise same-sex marriage.
19th December 2014
China: court rules homosexuality doesn’t need to be ‘cured’ 3
11:48 AM — A court in China has ruled that a psychological clinic must re-pay costs to a gay man for trying to "cure" him.
18th December 2014
Malaysia: government stops funding organisation for trans women 1
1:50 PM — The Malaysian government has abruptly stopped funding an organisation that provides support for trans women, sex workers and people with HIV.

domain: law


The Esquire Swiss Octane range is the most affordable range of Movado watches. The battery powered quartz watches are manufactured in Switzerland and feature both analogue and digital time displays. The stainless steel case is complimented by the ABS composite rubber strap. The watch comes with a two year factory warranty. During the warranty period, take your watch to a registered dealer for battery changes. After the warranty has expired, you can change the battery yourself by following a few easy steps.
Things You'll Need
- Soft cloth
- Small flathead screwdriver (e.g. screwdriver used in computer and glasses repairs)
- Watch case wrench (available from craft and jeweler stores)
- Replacement battery
Lay the ESQ Swiss Octane watch face down on the soft cloth. This will prevent the face from getting scratched. Open the back of the watch. If the watch has two small grooves along the sides, simply slide the flathead screwdriver into one of the grooves. Apply upward pressure to pop off the back. If there are small screws in the back, use the watch case wrench to undo the screws.
Use the flathead screwdriver to slide the battery out from under the battery clip. Take care not to damage the other components of the watch when doing so. Take note of the orientation of the battery so that you can place the new battery in the same way the old one was situated.
Reset the circuit. Watches with digital displays need to have their circuit reset when the battery is replaced. Put one arm of the tweezers against the positive (+) terminal on the battery and the other on the silver or gold colored dot in the mechanism which is marked "AC".
Use the tweezers to place the new battery under the battery clip. Avoid touching the battery with your fingers as the salt and oil from your hands can cause corrosion. Make sure that all dust and dirt are removed from the mechanism and replace the watch back. If your watch back pops off, simply apply pressure until it clicks back into place. If your watch back has screws, use the wrench to replace the screws.
- Photo Credit Ryan McVay/Photodisc/Getty Images
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A unique probe designed to acquire nuclear magnetic resonance difference spectra of two samples is presented. The NMR Difference Probe contains two sample coils in a resonant circuit that switches between parallel excitation and serial acquisition to cancel common signals such as solvent peaks and impurities. Two samples containing a common analyte, acetonitrile, were used to demonstrate signal cancellation in a difference spectrum collected with a single pulse experiment. The cancellation was over 96% effective. The approach described has applications in the areas of solvent subtraction and spectral simplification.


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Welcome to Jason Pang Gallery, your premier destination to unlock the world of pre-wedding photography. We specialize in providing exceptional art classes and art galleries for enthusiasts and professionals alike in the field of photography. Join us on this artistic journey as we explore the beauty and significance of pre-wedding photography.
Art Classes and Workshops
At Jason Pang Gallery, we understand the importance of honing your photography skills. Our art classes cater to individuals of all skill levels, from beginners to advanced photographers. Led by industry professionals, our classes provide comprehensive guidance and practical hands-on experience.
Whether you aspire to become a professional pre-wedding photographer or simply want to improve your skills, our classes cover a wide range of topics. From composition and lighting techniques to post-processing and storytelling, we aim to equip you with the necessary tools to capture breathtaking pre-wedding moments.
One of the key elements in creating stunning pre-wedding photographs is mastering composition. Our expert instructors will teach you the art of framing, rule of thirds, and utilizing negative space to create visually pleasing and balanced compositions.
Playing with Lighting
Lighting plays a vital role in photography, and pre-wedding photography is no exception. In our classes, you will learn how to manipulate natural and artificial light sources to capture the desired mood and ambiance in your pre-wedding photographs. Understanding lighting techniques will enable you to enhance the romantic atmosphere and beauty of the couple.
Capturing remarkable pre-wedding photographs is only part of the equation. Our art classes also delve into post-processing techniques to enhance your images further. Learn the ins and outs of popular editing software, and discover how to retouch, enhance colors, and create stunning visual effects to make your pre-wedding photographs stand out.
Art Galleries and Exhibitions
Jason Pang Gallery takes pride in curating exceptional art galleries and exhibitions that showcase the captivating world of pre-wedding photography. Our galleries serve as a platform for budding and established photographers to exhibit their work and inspire others.
Immerse yourself in a world of creativity as you explore our carefully curated galleries. Each photograph tells a unique story, capturing moments of love, happiness, and anticipation. Pre-wedding photography is an art form that celebrates the beautiful bond between couples, and our galleries exemplify the artistry behind it.
Spotlight on Emotion
Our art galleries aim to evoke emotions that resonate with viewers. From the joyful laughter shared between couples to the tender moments of intimacy, you will find an array of emotions beautifully depicted in our curated exhibitions. We believe that pre-wedding photography is an art that should touch the hearts of those who experience it.
Regardless of whether you are an artist, a couple planning your wedding, or someone seeking inspiration, our art galleries will ignite your creativity. Witness the unique perspectives and creative approaches employed by our professional photographers, as they capture moments of love in the most enchanting ways.
In addition to our art galleries, we also organize engaging workshops conducted by renowned pre-wedding photographers. These workshops provide a platform for learning and networking, where you can gain insights, exchange ideas, and connect with fellow enthusiasts and professionals in the industry.
Contact Us Today
Are you ready to embark on a journey of creativity and passion with pre-wedding photography? Connect with the Jason Pang Gallery today to discover the artistry behind this beautiful art form. Whether you're interested in joining our art classes, exploring our art galleries, or attending our engaging workshops, we are here to guide and inspire you.
Visit https://jasonpanggallery.com to explore more about our offerings and take the first step towards capturing timeless pre-wedding memories.pre wedding photographer

domain: artistic


Regular borescope inspections are crucial for the proper working of steam and gas turbines. Turbines operate in severe industrial conditions where the temperature can exceed one thousand Fahrenheit. They require periodic maintenance to uphold their mechanical integrity.
Therefore, there is a need for a cost-effective way to address these challenges without exposing the plant to significant downtime. In recent years, borescope inspection services have adopted advanced technology. Different types of devices have varying solutions for a wide range of industrial applications. In this article, we’ll look at some of the benefits of the borescope for gas turbine inspections.
Detecting Obstructions and Dirt
If you are running a plant, the last thing you need is a machine that breaks down unexpectedly. You can prevent downtimes by strictly following maintenance routines. For the turbine inspection to be effective, the testing equipment ought to have the capacity to capture the relevant details.
If dirt gets into the combustor of gas turbines, it can cause a temperature differential in the unit. Oil, moisture, sand, and other types of debris may go past the filter. Different types of obstructions may accumulate and eventually cause the system to fatigue.
One advantage of inspecting turbines with a borescope is that the device allows for quick inspections. Modern devices can project images with full HD resolutions. As a result, finding the fault is much faster because the details are easy to discern without dismantling critical parts of the machinery.
Minimize Future Damage
Gas turbines need to be monitored closely to catch damages before they become problematic. For example, hot corrosion is triggered by oxidation that takes place at considerably high temperatures. The machine can generate temperatures of more than 500 degrees centigrade.
Hot corrosion is known to cause damage to the turbine in areas subjected to severe stress. Minerals and metallic parts can react during oxidation. As a result, certain parts of the turbine, such as the base of the blade, may become prone to cracking and breakage.
Turbine inspections can help pinpoint areas where oxidation may be weakening the system. There may be places where bolts will need to be tightened. It may be necessary for technicians to know exactly where the problem has occurred for effective parts retrieval.
Boroscopic inspection of a gas turbine does not leave a lot of room for errors in fault detection. It generates high-resolution images that are projected on an electronic screen. It allows technicians to work in the plant to diagnose the issue properly.
For example, if you detect cracks, your technician may be in a better position to understand its course. The cracks may be from stresses the machine is subjected to or it as a result of oxidation and fatigue.
With quality images, the plant can prescribe an effective remedy for the problem. If the issue is oxidation, the technicians may change the water and check for the presence of contaminants. You can use high-resolution images and videos to visualize the progression of the problem and how it may evolve in the future.
Objective Management and Timely Assessment
Other types of turbine inspections are not as specific as the video borescope evaluations. The data is specific, which allows for the condition-based maintenance of the machinery. Precise information ensures guesswork is eliminated from the process.
Additionally, the process of inspection and maintenance is timely. The plant can detect faults with the turbine at the earliest stages to prevent complications and downtime. The accuracy of the visuals enables the technician to understand the nature of the fault before it can manifest into an inefficiency.
All in all, advanced borescope inspections can make cleaning of the equipment more precise, and parts removal less complex. They are reliable, accurate, and simple to use for maintenance and repair tasks. They can improve the longevity of the gas turbines and boost the plant’s bottom line. If you have any questions about turbine inspections, do not hesitate to contact us today.


This 2012 Morganzo 55: Double Nickels on the Grime trip report was originally posted at The Bozeman Fix July 26th, 2012.
The purpose: the endless pursuit of beauty by bicycle
The challenge: impassible roads, unquenchable thirst
Matthew Thomsen wins the Morganzo Trophy as first overall unsupported badass cyclist.
Amy Chiuchiolo wins the Hardcore Trophy for killing it in the Morganzo and then riding the Bangtail Divide immediately after. Seriously.
Sam Haraldson wins the Troll Trophy for slaying the hilly Morganzo on only 8 gears.
Lincoln Jamrog wins the International Trophy for coming all the way from Livingston and building bridges made of gravel.
Jon Wareham wins the Spirit Award for his positive attitude during multiple mechanicals.


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Get the top-rated recipe for Gluten Free Red Velvet Cake at ...
Watch how to make a gluten-free red velvet cake with a soft texture and yummy chocolate flavor. Brown rice flour, coconut f
by Yummy Food & Fashion
by Kristin Omdahl
by Crazy Hacker BD
by Thrift Weddings

domain: food


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Reporting to the department manager, the position holder will be charged with creating, developing and producing advertising banners for our clients, to be displayed on our website. He/she will focus on the conception of graphic elements destined for online advertising, while taking into account the client’s corporate image. He/she will also design creative mock-ups within visual guidelines and size/weight limits.
Summary of Responsabilities:
- Creating and producing advertising banners (sizing and cutting images, Flash animations, animated gifs, etc.);
- Developing, conceiving and producing advertising mock-ups meeting clients’ guidelines, requests and expectations;
- Maintaining and updating advertising banners on our website;
- Communicating frequently with our representatives and with the clients as needed;
- Fulfilling computer graphic, HTML integration and graphic interface mandates, as needed;
- Collaborating closely with the production and programming teams;
- Completing, as needed, other related tasks.
Technical Competencies :
- Two years’experience with Photoshop software.
- Two years’experience with Flash animations.
- Two years’experience with Illustrator software.
- Experience with Flash (action script) programming, an asset.
- Knowledge of other Adobe products.
- D.E.C. in Graphic Design (Web) or the equivalent.
- Two years experience in Web design.
- Work experience in advertising, an asset.
- Knowledge of the parameters of HTML language and of graphic production elements for the Web and for other interactive media, an asset.
- Knowledge of referencing, an asset.
- Command of the latest Web technologies, and up-to-date on technological developments.
- Excellent sense of organization and of priorities, ability to manage several projects simultaneously.
- Ability to work autonomously and under tight deadlines, attention to detail, and a well-developed sense of aesthetics.
- Bilingualism, oral and written (French/English).
- Only candidates providing a portfolio online will be considered.
- Creativity, perfectionism, pro-active mindset, autonomy, team spirit, thoroughness, sense of urgency.

domain: design


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Thank you, Ernie, for that kind introduction, and good morning ladies and gentlemen. Alex Massad has asked me to extend his sincere regrets at not being able to be here with you this morning. Fortunately, from my point of view, his absence is a welcome opportunity for me to address this audience of fellow petroleum engineers.
This is the age of the acronym — with good reason. Consider for example, the poor newspaper headline writer who has to fit Intercontinental Ballistic Missiles into two columns of space while including a verb and a few other modifying words to boot. Thus, we all know what ICBM means . . . or UFO — even if we've never seen one. You didn't have to see the movie; either, to know what — or who — ET stands for.
While it may not be a household acronym just yet, I know everyone in the SPE recognizes EOR, Enhanced Oil Recovery, the subject of this morning's discussion. I must honestly admit, however, I would feel more confident in writing a believable sequel to ET, than in predicting what might happen down the road for EOR. ET may have gone home, but EOR is here to stay.
With the knowledge that oil is a finite resource, the art of getting more production from each known reservoir will depend heavily on EOR and remain of paramount importance to the future of the oil industry and the United States economy. My crystal ball remains a little clouded as to the exact impact specific future applications will have due to uncertain political and technical factors. Perhaps our discussion today can blow political and technical factors. Perhaps our discussion today can blow away some of the fog and give us an outlook for recovering more of what we have already found.
For this morning's discussion, I'll limit comments to the U.S. industry. We'll take a look at what has been found, cumulative production, current reserves, and what we might logically expect in reserve additions through application of existing and future EOR technology. We will also cover some of the economic factors involved.

domain: economics


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Bayern Munich Frauen were supposed to play Potsdam in the Frauen Bundesliga but had to be rescheduled due to a frozen pitch. In the meantime, the players will be going to their respective international teams during this break, with some of the players playing in tournaments. The rescheduling of the Potsdam game based on when said tournaments will conclude; the Potsdam game will now kick off on February 25.
Per Bayern’s official website, 18(!) Frauen players will be on international duty. Let’s see who they are:
Bayern’s Germany crew will be playing a friendly game against Ireland and then Sweden.
1. Carolin Simon
2. Klara Bühl
3. Linda Dallmann
4. Sydney Lohmann
5. Lea Schüller
6. Lina Magull
Bayern’s lone English representative Georgia Stanway will be competing in the Arnold Clark Cup, with the Three Lions taking on Korea (2/16), Italy (2/19), and Belgium (2/22).
7. Georgia Stanway
Japan and Brazil
Saki Kumagai and Tainara will play each other on the first matchday of the SheBelievesCup in the United States on February 16. Japan plays hosts USA and then Canada, while Brazil faces the same teams but in the reverse order; both teams play their succeeding games on February 19 and 22.
8. Saki Kumagai
The three Icelandic Bayern players will compete in the Pinatar Cup in Spain. They face Scotland (02/15), Wales (2/18), and the Philippines (2/21). Feels great to see the girls (of my homeland, the Philippines) making waves on the international stage.
10. Glódís Perla Viggósdóttir
11. Karólína Lea Vilhjálmsdóttir
12. Cecilía Rán Rúnarsdóttir
Austria, Croatia, and Norway
Three different players will play friendlies with their teams. Austria will play a double header with the Netherlands (February 17 and 21); Croatia will play against Finland (02/16), Romania (02/19), and Hungary (02/22) in the Cyprus Cup; Norway is in the Tournoi de France and take on Uruguay (02/15), Denmark (02/18), and hosts France (02/21).
13. Sarah Zadrazil (Austria)
14. Ivana Rudelić (Croatia)
15. Tuva Hansen (Norway)
U19 national teams (Germany and Norway)
Three youngsters are called up to their national teams: Franziska Kett and Laura Gloning for Germany and Emilie Bragstad for Norway. The Germany U19 team will play in the 10 Nations Cup against England (02/16), Italy (02/18), and Sweden (02/21) while Bragstad will face Portugal in a friendly.
16. Franziska Kett
17. Laura Gloning
18. Emilie Bragstad

domain: game


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Pancreatic ductal adenocarcinoma (PDAC) reportedly progresses very rapidly through the initial carcinogenesis stages including DNA damage and disordered cell death. However, such oncogenic mechanisms are largely studied through observational diagnostic methods, partly because of a lack of live in vitro tumour imaging techniques. Here we demonstrate a simple live-tumour in vitro imaging technique using micro-patterned plates (micro/nanoplates) that allows dynamic visualisation of PDAC microtumours. When PDAC cells were cultured on a micro/nanoplate overnight, the cells self-organised into non-spheroidal microtumours that were anchored to the micro/nanoplate through cell-in-cell invasion. This self-organisation was only efficiently induced in small-diameter rough microislands. Using a time-lapse imaging system, we found that PDAC microtumours actively stretched to catch dead cell debris via filo/lamellipoedia and suction, suggesting that they have a sophisticated survival strategy (analogous to that of starving animals), which implies a context for the development of possible therapies for PDACs. The simple tumour imaging system visualises a potential of PDAC cells, in which the aggressive tumour dynamics reminds us of the need to review traditional PDAC pathogenesis.
Despite accumulating evidence on the pathological features exhibited by cancer cells in various carcinomas, recent in vitro cancer cell studies have focused on the behavior of single cells in isolation. In contrast, in analyses conducted at the tumor tissue level, in vivo methodologies still largely depend on observational diagnostic methods such as histopathological analysis and in vivo imaging systems using fluorescent imaging probes. Consequently, the underlying pathophysiological tumor dynamics in tissue remains mostly unclear. Thus, in current cancer research, directly linking in vitro cell-based studies with in vivo tissue-based pathological studies could result in a huge gap in our understanding. Indeed, we have been confronted with numerous unexpected difficulties in clinical trials of molecular-targeted anticancer agents for which there should be near perfect evidence for targets from conventional evaluations undertaken both in vivo and in vitro. Recently, the importance of using three-dimensional (3D) cell culture systems has remarkably increased in the field of anticancer drug development1,2,3,4; 3D cell culture systems are expected to provide more physiologically relevant information to the in vivo setting as compared with traditional two-dimensional culture systems5,6,7,8.
PDAC, which constitutes approximately 90% of pancreatic cancers, is still one of the most lethal malignant tumours9. KRAS mutation is the initiating genetic event for pancreatic intraepithelial neoplasia (PanINs), premalignant lesions of PDACs10. Recent work has shown that once PDACs become detectable, they progress from T1 stage to T4 stage in approximately 14 months11. PDACs rapidly progress through highly frequent DNA damage and mitotic abnormalities through unknown catastrophic events12,13. Generally, the epithelial–mesenchymal transition (EMT) is believed to be one of the essential events for the acquisition of metastatic ability in a variety of carcinomas14,15,16,17,18. However, a recent study using genetically engineered mouse models of PDAC development reported that carcinoma cells could metastasise without activating EMT programs19,20. And while the extremely aggressiveness characteristics of PDACs are well established, the dynamics of PDAC tumours have not been well studied.
In this study, we developed a new type of cell culture micro/nanoplate, which elicits the ability of carcinoma cells to self-organise through the addition of a simple modification by micro-nanotechnology. We demonstrate here that anchorage-dependent PDAC microtumours on the micro/nanoplate show morphological polarity and exhibit active motility through filipoedia and lamellipoedia. Furthermore, the micro/nanoplate enables visualisation of live tumour dynamics; the microtumours endocytose debris-derived surface nucleosides directly into vacuoles and then accumulate dead cell-derived phosphatidylserine (PS) on their surfaces (resulting in PS externalisation, a cause of cancer immune evasion). Hence, the tumour dynamics visualised by our simple technology urge us to review the well-known pathogenesis of this intractable cancer and will contribute to the development of innovative new anticancer drugs.
Materials and Methods
Reagents and antibodies
We used 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer for glass (PC modifier-C, Daiichi Kigyo, Japan), Parylene-C (Specialty Coating Systems, USA) and positive photoresist (PR; S1818 Shipley, USA) for preparation of the micro/nanoplate. Mouse anti-human α-tubulin (clone DM1A, eBioscience), mouse anti-human dynein intermediate chain 1 (Abcam, Cambridge, UK) monoclonal antibodies (mAbs) were used for immunofluorescence staining. 5- (and 6-) carboxyfluorescein diacetate succinimidyl ester (CFSE; Dojindo Laboratories, Kumamoto, Japan), and PKH26 (Sigma-Aldrich, St. Louis, MO, USA) were used for live-cell labelling. Annexin V Alexa Flour® 488 (Molecular Probes, Inc., Eugene, OR, USA) and Ethidium Homodimer-1 (EthD-1; Molecular Probes, Inc.) were used for live and dead cell monitoring. Cell Navigator™ Lysosome Staining Kit Red Fluorescence (AAT Bioquest, Inc., Sunnyvale, CA, USA) was used for lysosome staining. FluoSpheres® Carboxylate-Modified Microspheres (0.2 µm, yellow-green fluorescent; Molecular Probes, Inc.) were used to track the flow of medium. Click-iT® Plus EdU (5-ethynyl-2′-deoxyuridine, a nucleoside analogue of thymidine) Alexa Fluor® 594 Imaging Kits (Molecular Probes, Inc.) were used to detect nucleosides. Nocodazole (Sigma-Aldrich) was used as a microtubule inhibitor. Formalin-fixed tissue sections were subjected to immunohistochemical staining using the LSAB2 Kit/HRP (Dako, Glostrup, Denmark).
Three human PDAC lines, PCI-55, PCI-24, and PCI-43, were used. These cell lines were established in our laboratory from PDAC tissues that were resected from primary sites at Hokkaido University Hospital21. LH Gene Mutation Detection Kit for KRAS Mutation Codons 12 and 13 (Wako, Osaka, Japan) was used for detection of KRAS mutation in these cell lines. Human oral squamous carcinoma cell lines, HSC-3 and SCC-9, lung adenocarcinoma cell lines, H1975 and A549, and colon adenocarcinoma cell lines, DLD-1 and WiDr, were purchased from JCRB cell bank (Osaka, Japan) and ATCC. KHYG-1, a human NK cell line, was purchased from JCRB and maintained in RPMI-1640, supplemented with 100 U of recombinant human IL-2 (Shionogi, Osaka, Japan), 10% FBS, and penicillin/streptomycin.
Preparation of the micro/nanoplate
In this research, we modified our previous patterning method22. The first step was forming 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer layer on a glass substrate23. We spun the MPC solution at 2000 rpm for 30 sec and then dried the substrate in a chamber with an ethanol atmosphere at room temperature for 20 min to form the polymer layer uniformly. Finally, the substrate was baked at 70 °C for 4 h to graft the MPC polymer covalently to the substrate by a dehydration reaction. We then deposited a 1-µm-thick poly(p-xylylene) (Parylene-C) dry film mask onto the MPC-grafted layer. Parylene forms a thin, flexible and transparent film when deposited by chemical vapour deposition with a Parylene deposition machine (Labcoter PDS2010, Specialty Coating Systems, USA). The deposition process consists of three steps: dimer (di-p-xylene) vaporization at approximately 150 °C, monomerization at 690 °C, and finally polymerization at room temperature. Next, a photoresist (PR) was patterned on the Parylene film using a standard photolithographic technique to define etching regions for both the Parylene film and MPC polymer. The PR was then spin-coated onto the substrate. After exposure to ultraviolet light through a glass mask (SUSS Micro Tes: MA-6, Germany), the PR was developed using NMD-3 (2.38% Tetramethyl Ammonium Hydroxide) developer. Both the Parylene film and MPC polymer were then etched away with O2 plasma (50 W for 4.5 min) at the defined regions using inductively coupled plasma etching system (EIS-700, ELIONIX INC, Tokyo, Japan). Roughness was measured using VK-X250 3D Laser Scanning Confocal Microscope (Keyence Corporation, Osaka, Japan).
Cell culture using the micro/nanoplate
The prepared micro/nanoplate has cell-adherable micro-circular islands, 30 µm in diameter, with nanoscale roughness. These patterned micro-circular islands with nanoscale roughness were glass substrates, which allowed cells to adhere; the rest was coated with MPC polymer, which inhibits protein adsorption and cell adhesion. The Parylene layer was gently peeled off, washed with distilled water once and sterilized with 70% ethanol for 10 min and dried in the clean bench. A small amount of petroleum jelly was applied at the four corners of a 40 mm petri dish and the 20 mm × 20 mm micro/nanoplate was then fixed on them. The micro/nanoplate fixed in the petri dish was washed three times with medium and soaked in the medium until cell culture to avoid drying. We suspended 1–3 × 106 PDAC cells in 3 ml of 10% FBS DMEM, gently poured this cell suspension on the micro/nanoplate fixed in the petri dish before incubation at 37 °C in a CO2 incubator. After overnight culture, anchorage-dependent PDAC microtumours self-organized on the micro/nanoplate and were used for subsequent experiments. To inhibit microtubules, anchorage-dependent PDAC microtumours were treated for indicated times with 1 µM nocodazole. Some plates received fresh medium without nocodazole by washing with PBS for 3 times.
We purchased C.B-17/lcr-scid/scidJcl mice from CLEA Japan, Inc. (Tokyo, Japan). These mice (severe combined immunodeficiency [SCID] mice) were bred and housed under specific pathogen-free conditions in our animal facility. Animal experiments were conducted according to the Guidelines for the Care and Use of Laboratory Animals at Hokkaido University Faculty of Medicine and approved by the Institutional Review Committee of Hokkaido University.
Intraperitoneal injection of PDAC cells
Male SCID mice (6–8 weeks old) were injected intraperitoneally with a mixture of CFSE- or unlabelled PCI-55 (total 5 × 106 cells) suspended in 200 µl of PBS. Peritonea were harvested at 3 days after injection and prepared for frozen sections with Tissue-Tek O.C.T. Compound (Sakura Finetek Japan, Tokyo, Japan).
Microtumours anchored to the micro/nanoplates were fixed with 4% paraformaldehyde for 20 min. For intracellular staining, cells were treated with PBS that contained 0.5% Triton-X-100 for 20 min and then fixed with ice-cold 70% methanol for 5 min. Nonspecific binding was blocked with PBT (0.05% Tween-20 in PBS) that contained 0.1% goat serum for 10 min. After incubation with primary Abs for each targeted protein, Alexa Fluor-conjugated goat polyclonal Ab was used as a secondary Ab. Time-lapse images and high resolution two-dimensional (2D) images were acquired by inverted fluorescence microscope (Keyence BZ-X700 and BZ-9000; Keyence Corporation). Three-dimensional (3D) analyses were reconstructed by images acquired by a spectral imaging confocal microscope (Nikon-A1R; Nikon Instech Co., Ltd., Tokyo, Japan) using NIS-Elements AR Ver 4.60.00 software (Nikon).
In this study, we enlisted 10 patients with histologically confirmed PDAC, whose tumours were surgically resected at Hokkaido Gastroenterology Hospital (Sapporo, Japan). All experiments using human specimens were approved by the Medical Ethics Committees of Hokkaido University Faculty of Medicine. Three-µm-thick human aorta sections were deparaffinized and antigen-retrieved by autoclaving at 121 °C for 20 min. Nonspecific binding was blocked with 3% goat serum in PBS for 30 min. To prevent endogenous peroxidase activity, sections were incubated in 3% hydrogen peroxide for 10 min. Sections were incubated with primary Ab for 1 h at room temperature, then with biotinylated secondary Ab and finally with streptavidin-HRP (LSAB2 kit; Dako). After incubation, specimens were developed with diaminobenzidine (Dako) and counterstained with Mayer’s haematoxylin.
Live and dead cell assay
Anchorage-dependent PDAC microtumours on the micro/nanoplate in the petri dish were cultured in 3 ml of DMEM culture medium supplemented with Annexin V Alexa Flour 488 (25 µl) and EthD-1 (2 µm). Time-lapse images were captured using an inverted fluorescence microscope (Keyence BZ-X700 and BZ-9000).
PCI-55 cells were cultured in 60-mm tissue culture dishes overnight. After washing with PBS 2 times, PCI-55 cells were UV-irradiated at 250 mJ/cm2 with Bio-Rad GS Gene Linker (Bio-Rad, San Jose, CA). After washing with PBS again, they were incubated with serum-free DMEM for 2 h. Dead PCI-55 cells and debris were harvested by a cell scraper and used for dead cell feeding.
PDAC cells (5 × 105) were cultured in 60-mm tissue culture dishes in medium containing 10 µM EdU for 24 h. Cells were then fixed in 4% paraformaldehyde in PBS with 0.05% Tween-20 for 20 min at room temperature, and them permeabilized in 0.5% Triton X-100 for 20 min. The EdU was then detected by following manufacturer’s instructions of the Click-iT EdU imaging Kits (Invitrogen), using Alexa Fluor® 555.
Data were analysed using Student’s t-test. P < 0.05 was considered significant.
PDAC cells self-organise into non-spherical microtumours anchored to the micro/nanoplate
To visualise live tumours and their dynamics, we devised a novel in vitro tumour imaging system using micro-patterned plates (micro/nanoplates) prepared according to a standard photolithography method22 (Fig. 1a). Specifically, we coated a glass substrate with MPC polymer, grafted the MPC polymer, deposited Parylene film onto the MPC polymer, and then deposited and patterned the photoresist (PR). These patterned plates were etched with both the Parylene and MPC polymer using oxygen (O2) plasma, and then the PR was removed before use (Fig. 1b). Using laser scanning microscopy, we performed quantitative analysis of the plate roughness. Arithmetical mean height (Ra), maximum height of profile (Rz) and arithmetic mean peak curvature (Spc) in the patterned circular islands with roughness (micro/nanoplate) were about twice that of conventional microplates, developed interfacial area ratio (Sdr) were about 4.8 times (Fig. 1c,d). These results indicated that the patterned circular islands in the micro/nanoplate had nano-scale roughness slightly higher than conventional microplates. To culture cancer cells using the micro/nanoplate, we employed three human PDAC cell lines (PCI-55, PCI-24, and PCI-43) with heterozygous KRASG12D mutation, the most common mutation in clinical PDAC24,25. When PDAC cells were cultured in micro/nanoplates overnight, they self-organised into three-dimensional (3D) non-spherical microtumours that were solidly anchored to multiple microislands across the plates’ non-adherable areas (Figs 1e, 2a,b and Supplementary Movie 1). When other carcinoma cell lines such as oral cancer, lung cancer and colon cancer cell lines were cultured, they self-organised into variously-shaped microtumours on the micro/nanoplate (Fig. 2c). This self-organisation was only efficiently induced in rough (i.e., adherable), small-diameter microislands (Figs 1e,g,h and 3a–c). When PDAC microtumours exceeded the bottom area size of a micro-island, the circularity of microtumours decreased sharply (r2 = 0.5271; Fig. 1f), exhibiting invasive expansion. Our 3D images clearly showed that PDAC microtumours anchored to multiple microislands had morphological polarity (Fig. 3d–f and Supplementary Movie 2). When anchorage-dependent PDAC microtumours exceeded their single microislands, they exhibited microtubules (MT)-based protrusions in the presumed direction of movement (Fig. 3g,h).
PDAC microtumours are triggered by a cell-in-cell structure anchored to a micro-island
Next, we investigated how self-organisation of anchorage-dependent PDAC microtumours was triggered on the micro/nanoplate. Time-lapse images showed that at least nine PCI-55 cells were anchored to a micro-island through entosis (cell-in-cell invasion; Fig. 4a, Supplementary Movie 3)26,27. Surprisingly, this entotic event was reversible and did not involve cell death (Fig. 4b, Supplementary Movie 4). Therefore, it was different from the entotic event often observed in carcinoma specimens where most internalized cells are eventually killed28. When PCI-55 cells were sparsely cultured, a few cells showed live cell entosis in microislands (Fig. 4c) and at least four cells formed papillary cell-in-cell structures (Fig. 4d). Our 3D images showed a CFSEHigh-labelled PCI-55 cell penetrating into CFSELow-labelled cells that formed a microtumour (Fig. 4e). Similarly, multinucleated giant PCI-55 cells whose green fluorescence intensity was almost halved contained at least six CFSEHigh-labelled PCI-55 cells (Fig. 4f); other PDAC cell lines also self-organised into cell-in-cell structures on the micro/nanoplate (data not shown). We also found PDAC microtumours anchored to single microislands to form MTs and actin filaments vigorously near the anchored parts (Fig. 4g), suggesting the possibility that the micro/nanoplate may induce differentiation into mature microtumours. Taken together, these results indicate that self-organisation of PDAC microtumours is triggered by cell-in-cell structures anchored to rough microislands.
Cells covering the surface of PDAC microtumours exhibit peri-membranous expression of α-tubulin
In 3D cultures, α-tubulin is expressed in the peripheral regions of spheroids29. Our results also indicated that PDAC microtumours were covered by cells exhibiting enhanced peri-membranous expression of α-tubulin (Fig. 4c–g). However, such peri-membranous expression of α-tubulin was not observed in mitotic cells that were located outside the surface of the microtumours (Fig. 4h,i). MT inhibitors are shown to be anticancer agents that target mitosis30. Nocodazole, an inhibitor of MT polymerisation, prevented PCI-55 microtumours from anchoring to the micro/nanoplate (Fig. 4j, Supplementary Movie 5). Most of the treated microtumours showed anchorage-independent spheroidal morphology, and many live PCI-55 cells were scattered outside of the disrupted microtumours (Fig. 4k). However, the disruption did not induce cell death even in scattered cells (Fig. 4l, Supplementary Movie 6). Furthermore, when PCI-55 cells were grafted intraperitoneally into SCID mice, similar peri-membranous expression of α-tubulin was also observed in PCI-55 microtumours that colonized in the peritoneum in vivo (Fig. 4m). These results suggest that MTs composed of α-tubulin are involved in the formation of anchorage-dependent PDAC microtumours. MT inhibitors are shown to be anticancer agents that target mitosis30. Next, we examined whether such peri-membranous expression of α-tubulin is a clinically relevant phenomenon. As expected, similar expression patterns and cell-in-cell structures formed by both live cells and dead cells were observed in PanIN lesions and invasive PDACs but not in normal pancreatic ductal epithelium (Fig. 5a–e). In 9 out of 11 PDAC specimens, we observed cell-in-cell structures within live cells (Fig. 5e, arrow heads) more frequently than within dead cells (Fig. 5e, arrows). Particularly, peri-membranous expression of α-tubulin was greater in higher grade PanIN lesions and invasive PDACs (Fig. 5d,e). Taken together, these results suggest that PDAC microtumours anchored to the micro/nanoplate mimic microscopic tumour lesions observed in human clinical PDAC specimens.
Live anchorage-dependent PDAC microtumours catch dead-cell debris and display the death phenotype
We found that anchorage-dependent PDAC microtumours on the micro/nanoplate integrally formed huge lamellipoedia (Fig. 6a), and the morphological polarity covered by membranous α-tubulin expression was very close to that of single cells (Fig. 6b). Thus, we next examined whether anchorage-dependent PDAC microtumours behave as single units. Time-lapse images showed live PCI-55 microtumours actively moving to catch debris in culture medium (Fig. 6c, Supplementary Movie 7). To examine whether live PDAC microtumours actively take in dead-cell debris, we used live- and dead-cell monitoring, using Annexin V (green) and EthD-1 (red)31. Time-lapse images showed live PCI-55 microtumours stretching to catch external floating apoptotic cells and dead-cell debris with huge lamellipoedia (Fig. 6d, Supplementary Movie 8).
Live PDAC microtumours secondarily show PS externalisation by sucking and catching dead-cell debris
Interestingly, before the debris was taken up by the PCI-55 microtumours, it accumulated in front of the microtumours, suggesting that PDAC microtumours suck and then catch debris (Fig. 6c). Indeed, we confirmed that in cultured medium, many floating green-fluorescent nanobeads drifted towards anchorage-dependent PCI-55 microtumours, which suggests that live PDAC microtumours have a strong suction force on their surface (Fig. 6g, Supplementary Movie 9). Consistent with this, we frequently observed that PDAC microtumours accumulated Annexin V on their external surfaces (Fig. 6e). Even when microtumour-forming PDAC cells were in a mitotic phase they were covered by the strong green fluorescence of Annexin V (Fig. 6f). When anchorage-dependent PCI-55 microtumours were harvested and cultured back in a culture dish, they stopped elongation and began removing PS from their surfaces (Fig. 6h, Supplementary Movie 10). Additionally, we confirmed that when PCI-55 microtumours were cocultured with KHYG-1, a human natural killer (NK) cell line, they were not attacked by KHYG-1 cells, suggesting that live PDAC microtumours might be misrecognised as non-viable tissue by immune cells (Fig. 6i,j, Supplementary Movie 11).
Live PDAC microtumours feed on dead-cell debris
Live imaging analysis using micro/nanoplates demonstrated that annexin V+/EthD-1+ live PDAC microtumours accumulated Annexin V on their external surfaces, whereas EthD-1 accumulated inside the cells (Fig. 7a,b, Supplementary Movie 12). Finally, we performed PDAC microtumour-feeding with their dead cell debris. Live PCI-55 microtumours treated with UV produced dead-cell debris (Fig. 7c). The microtumours took up this dead-cell debris, and began to display red EthD-1 fluorescence from their outer edges (Fig. 7d). Mature microtumours aggressively devoured dead-cell debris (Fig. 7e, Supplementary Movie 13). Consistent with this, PCI-55 microtumours significantly increased in size at 48 h after feeding on dead-cell debris compared with microtumours that did not feed (Fig. 7f). The cell death mechanism reportedly promotes PDAC tumour growth13, and our results suggest that external dead cell debris contributes to PDAC tumour growth as well. Our results also suggest that PDAC microtumours take in nuclear components, such as EthD-1 (which has a high affinity for nucleic acid), indicating that the increased autophagy and lysosomal catabolism extended to nuclear fragments32. Next, to find whether PDAC microtumours directly take in dead cell-derived nucleosides from their surfaces, we fed CFSE-labelled PCI-55 microtumours with UV-induced dead PCI-55 cells that had previously incorporated a nucleoside analogue of thymidine, Edu. As expected, we observed massive accumulation of Edu+ dead-cell debris around the microtumours (Fig. 7g). Cross-sectional images showed considerable Edu in microtumour vacuoles (Fig. 7h); some Edu was detected in lysosomes (Fig. 7i), indicating that Edu + dead-cell debris was endocytosed from the surface of the PDAC microtumour and then incorporated into lysosomes of the inner cells forming the microtumours. These results suggest direct recycling of external dead-cell debris-derived nucleotides by PDAC microtumours.
In this study, we developed a micro/nanoplate that promotes self-organisation in PDAC cells by micro-nanotechnology (Figs 1 and 2). We have demonstrated that anchorage-dependent PDAC microtumours on the micro/nanoplate show morphological polarity and aggressive motility (Fig. 3). Self-organisation of PDAC microtumours was triggered by cell-in-cell structures anchored to rough microislands (Fig. 4). Cellular internalization process entosis frequently observed in human tumours is known as a mechanism underlying the cancer cell competition, cell-in-cell structure or cannibalism26,27,33. Very limited cell-adherable microislands on the micro/nanoplate provide states susceptible to induce entosis to PDAC cells. It may be very similar to the malignant tumour lesion of PDAC showing abnormal multilayer proliferation in very restricted parts of the lumen of the pancreatic duct.
We also found that PDAC microtumours were covered by enhanced peri-membranous expression of α-tubulin both in vitro and in vivo (Figs 4 and 5). MT inhibitors are shown to be anticancer agents that target mitosis30,34,35. Our results showed that most of the MT-treated microtumours showed anchorage-independent spheroidal morphology, and many PCI-55 cells were scattered outside of the disrupted microtumours and were not dead (Fig. 4). Thus, these results suggest that the disruption of PDAC microtumours without cell death may be a side effect of MT inhibitors as anticancer agents, leading to scattering of living cancer cells and then recurrence.
Furthermore, we have demonstrated that the micro/nanoplate enables visualisation of live tumour dynamics, revealing that the microtumours endocytose debris-derived surface nucleosides directly into vacuoles and then accumulate dead-cell-derived phosphatidylserine (PS) on their surfaces (Figs 6 and 7). Externalisation of PS is an important well-known feature in cancer cells and has shown to be a cause of immune evasion in cancer36,37,38,39, but how it occurs in tumours is unclear. We found that live PDAC microtumours secondarily show PS externalisation by sucking and catching dead-cell debris. Our findings imply that PS externalisation might occur on live PDAC microtumour surfaces as a result of dead-cell debris absorption. At the present time, we do not have the technology to understand the phenomenon both in vitro and in vivo. This simple tumour imaging system will enable us to visualise more of the true nature of live PDAC microtumours; the observed tumour dynamics would urge us to review the traditional understanding of PDAC pathogenesis.
In this study, we also observed that nocodazole-inhibited MTs decreased externalisation of PS in the PDAC microtumours on the micro/nanoplate (Fig. 4). This result indicates that MT-inhibited PDAC microtumours stop exhibiting the apoptotic phenotype. Immune cells recognised PS-externalized PDAC microtumours as dead tissues, which may result in cancer immune evasion. Perhaps our results imply the possibility that MT-inhibitors may be useful for removing the secondary dead-cell phenotype in the PDAC microtumours to enhance cancer immunotherapy.
Our work has demonstrated that mature microtumours advanced like starving animals exhibited cannibalism to survive. It is most likely to occur in PDAC patients, but currently there are only approaches to deduce it in fixed samples in vivo. Consideration of this sophisticated survival strategy in malignant epithelial cells and inhibiting or exploiting the relevant pathophysiological events could lead to genuine therapeutic options against this intractable cancer. This simple, low-cost in vitro tumour imaging system could bridge the gap between cell-based and tissue-based analyses, leading to a better understanding of PDAC progression from cancer cells to microtumours.
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We thank K. Nakahata, Y. Higashi, T. Emoto, K. Ito, M. Susa, M. Sato, Y. Onodera, M. Kino and A. Honma for help in the development of the micro/nanoplate; T. Nemoto and K. Kobayashi for help with analysis of bioimaging at Nikon Imaging Center at Hokkaido University in ABiS, MEXT, Japan. This work was supported by JSPS KAKENHI Grant Number 26460464, JP16H06280, and NPJ Grant Number NPS15058 by Nanotechnology Platform of MEXT, Japan.
The authors declare no competing interests.
Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Miyatake, Y., Kuribayashi-Shigetomi, K., Ohta, Y. et al. Visualising the dynamics of live pancreatic microtumours self-organised through cell-in-cell invasion. Sci Rep 8, 14054 (2018). https://doi.org/10.1038/s41598-018-32122-w
- Pancreatic Ductal Adenocarcinoma (PDAC)
- PDAC Cells
- Dead Cell Debris
- Tumor Imaging Systems
Nature Reviews Gastroenterology & Hepatology (2021)

domain: medical


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A rich, ready-to-use potting mix recommended for a wide variety of bedding and potted plants grown indoors and out. It is fortified with a slow-release fertilizer that continues to feed plants for up to 6 months. This product contains RESiLIENCE®, which may improve resistance to wilting.
This all-purpose container mix with Moisture Pro™ water-holding crystals helps maintain mix moisture for longer and has an extended-release fertilizer to keep plants fed for up to four months. This product contains RESiLIENCE®, which may improve resistance to wilting.


Let’s face it, if your band officially formed in 1971, had significant roots going back to 1967 and is still a fully functioning unit, then every year will be a significant anniversary of something or other. This definitely seems to be the case with the Blue Öyster Cult, and the celebratory releases are coming thick and fast these days. This is great news for the fans as the iconic BÖC are one of those bands that seem to get bigger and better as each year passes, and they are quite probably the most ‘cult’ band ever (no pun intended). So, let’s pop back to 2017 when Blue Öyster Cult were playing a series of gigs in the UK and Europe and, on June 17th, they played the Stone Free Festival at the O2 Indigo in London, which they marked by playing their eponymous debut in full plus selected highlights from their illustrious career. The cameras were there to record the event and was filmed in spectacular 4K which has allowed for multiple releases including vinyl, CD/DVD and stand-alone Bluray which covers just about every base.
The 75-minute set kicks off with their debut album in full, and it is great to see a band that can still do it live on stage and not exist off past glories – plus it is testimony to such a strong debut album that many of the tracks have gone on to be staples of their live sets ever since. In fact, if it is a while since you last played the debut Blue Öyster Cult album then do yourself a favour and give it a whirl, you’ll be amazed at just how fresh and contemporary it still sounds and, of course, it contains Then Came The Last Days Of May – one of the greatest and most moving songs of all time! The version of BÖC that recorded this live album was Eric Bloom on vocals/guitar/keyboards, Donald “Buck Dharma” Roeser on guitar/vocals, Richie Castellano on keyboards/guitar/vocals, Danny Miranda on bass/vocals and Jules Radino on drums/percussion, and what a tight and compact unit they make too. As ever, it is critical that Bloom and Roeser remain to ensure the dynamic of the band as they are the heart and soul of the team.
The debut tracks are played with style and aplomb to a devoted audience and the band give a show stopping performance as they feed off the vibe and energy of the audience, and all too soon the debut tracks are completed and then it is a short yet thrilling ride to the end of the set as the band delivers stunning versions of Buck’s Boogie, Godzilla, (Don’t Fear) The Reaper, Tattoo Vampire and Hot Rails To Hell. It’s a cracking set pumped up with energy and suitably filled with crowd pleasing favourites simply designed to bring the roof down – and if Godzilla and The Reaper do not get you going then you are beyond redemption. The band are on fire and the video is beautifully shot, giving exemplary close-up shots, and puts you right in the front row, the best tickets in the house. The stage is rather minimalist and the lights used to enhance the audio performance i.e. they are not obtrusive which allows you to concentrate on the musicians. The sound is perfect and offered as either stereo or 5.1 mix which makes for a totally immersive experience. The only extra is a 5-minute clip of the band in a back stage lounge warming up which gives a taste of what it is like to be on the inside but is by no means essential. This is a band that has been around the block many, many times and they know how to deliver the knockout blow. This is heavy rock as it should be played with songs that are true classics from one of the greatest bands on the planet. Buy, settle down and simply revel in their genius!
Track List: Transmaniacon MC (3:34), I’m On The Lamb But I Ain’t No Sheep (316), Then Came The Last Days Of May (10:35), Stairway To The Stars (3:55), Before The Kiss A Redcap (5:30), Screams (3:06), She’s As Beautiful As A Foot (2:59), Cities On Flame With Rock And Roll (6:21), Workshop Of The Telescopes (3:48), Redeemed (3:48), Buck’s Boogie (7:34), Godzilla, (4:29), (Don’t Fear) The Reaper (7:02), Tattoo Vampire (2:47), Hot Rails To Hell (4:59).


National & International Drone Industry Leaders, Larsen, Meet
Washington, DC, September 30, 2016
Tags: Jobs & the Economy
Congressman discusses challenges & opportunities in drone industry
Rep. Rick Larsen (WA-02), the Ranking Member on the House Subcommittee on Aviation, met this week with the Small UAV (unmanned aerial vehicles) Coalition and the Association for Unmanned Vehicle Systems International (AUVSI) to discuss opportunities and challenges in the drone industry.
The Small UAV Coalition is a “partnership of leading consumer and technology companies who believe that U.S. leadership in the research, development, production, and application of unmanned aerial vehicles will benefit consumers in all walks of life.” AUVSI is the “world's largest nonprofit organization devoted to advancing the unmanned systems and robotics community.”
"As the drone industry continues to grow, businesses and regulators must work together to develop new rules to navigate uncharted territory,” said Larsen. “It was great meeting with the Small UAV Coalition and AUVSI to discuss how regulations can support companies that are pursuing innovations such as the use of drones for package delivery, while also ensuring high safety standards for the public, the environment and other aircraft.”
Earlier this month, Larsen delivered a keynote address at an aviation symposium in Seattle about the future of the drone industry.
Larsen has consistently called for a strong regulatory system to safely grow the drone industry. In 2015, Larsen praised the Federal Aviation Administration’s decision to create a registration process for unmanned aircraft systems and when the agency announced its final rule on small drones in June of this year, Larsen called it “an important first step in establishing rules of the road.”


text:
UEFA Champions League statistics
• Celtic FC's 3-2 win at Spartak on matchday two was their first in 21 away games in the UEFA Champions League.
• Juan Insaurralde serves a one-game ban following his red card on matchday two.
• Five Spartak players were on senior international duty: Dmitri Kombarov (Russia), Aiden McGeady (Republic of Ireland), Kim Källström (Sweden), Jano Ananidze (Georgia) and Emmanuel Emenike (Nigeria). Kombarov played all of Russia's 1-0 FIFA World Cup qualifying victory over Portugal at the Luzhniki Stadium on 12 October while half-time substitute Källström provided two assists as Sweden came from four down to draw 4-4 with Germany four days later.
• Emenike started Nigeria's 6-1 win against Liberia on 13 October, a victory which wrapped up an 8-3 aggregate triumph and secured the Super Eagles' place at the 2013 African Cup of Nations.
• Pavel Yakovlev ruptured ligaments in his right knee during the first leg of Russia's UEFA European Under-21 Championship play-off triumph against the Czech Republic on 12 October.
• Insaurralde's 94th-minute own goal consigned Spartak to a 2-1 defeat by FC Anji Makhachkala on Saturday, their third successive defeat. That represents their worst run since November 2009.
• Saturday marked the 30th anniversary of the Lenin Stadium disaster in which a reported total of more than 300 people died towards the end of the UEFA Cup second round game between Spartak and HFC Haarlem. The Anji game was preceded by a minute's silence while Spartak players entered the pitch in T-shirts bearing the words 'We remember'. Fans at the match replaced all their usual banners with ones bearing the legend 'We remember' while survivors of the disaster, fans and directors of Spartak's official fan club laid flowers at the memorial at the Luzhniki Stadium. Saturday also featured the fifth annual Memory Cup amateur tournament.
• Romulo will miss the UEFA Champions League group stage after being ruled out for six months with a torn anterior cruciate knee ligament sustained during the 3-1 win against FC Rostov on 23 September. Sergei Parshivlyuk and Soslan Gatagov are expected to be out until the new year after suffering knee ligament injuries in the summer.
• This season Spartak won their first three league games for only the fourth time. On the previous three occasions, in 1994, 1997 and 1999, they went on to win the title.
UEFA Champions League statistics
• Benfica have committed 43 fouls; more than any other team in the group stage.
• Benfica have scored 348 goals in the European Cup.
• Luisão is banned until 14 November following an incident involving the referee against Fortuna Düsseldorf 1895 in an August friendly. Bruno César and Nemanja Matić will incur a suspension with their next yellow cards.
• Benfica are in a third successive group stage campaign, equalling a club record set between 2005 and 2007.
• Four Benfica players were on senior international duty last week: Matić (Serbia), Ezequiel Garay, Enzo Peréz (Argentina) and Maxi Pereira (Uruguay). Pereira's Uruguay and an Argentina side featuring Garay went head-to-head in FIFA World Cup qualifying on 12 October, with Argentina winning 3-0 in Mendoza.
• Rodrigo scored four goals in Spain's 5-0 win against Denmark in the first leg of their UEFA European Under-21 Championship play-off on 11 October, a 3-1 second-leg triumph sending them through to next summer's finals.
• Paulo Lopes and Luisinho made debuts as Benfica beat second-tier SC Freamunde 4-0 in the Portuguese Cup third round on 18 October. Óscar Cardozo, out since 23 September with a thigh injury, made a goalscoring return.
• Jorge Jesus's team travelled to Abu Dhabi during the international break, Nolito scoring three goals in a 4-0 friendly win against Baniyas SC.
• Rodrigo agreed a four-year contract extension on 23 August, keeping him with the Eagles until summer 2019. He has a €45m release clause.
©UEFA.com 1998-2017. All rights reserved.

domain: news


text:
During the month of April you may read away fines associated with overdue items on your London Public Library account (excludes direct fees for lost or damaged items).
To participate, simply register at the library and begin logging your reading throughout the month. You must read at the library to have your minutes count. You will earn $10 for every hour you read. To receive credit for your reading, simply turn in your log at the end of the month or when you hit the total number of hours allowed, which is 10.
- You must register for the program. Adults register at the Main Service Desk and youth 17 years and younger register at the Children's Desk.
- You must bring your log sheet every time you visit the library to read and have a staff member log you in and out. It is your responsibility to secure your log. In the event that it is lost, you will have to start over.
- You must be actively reading the whole time you are logged in; however, a quick visit to the restroom is permitted.
- Parents may read to children that cannot read to themselves. (The Children's room is the preferred location for this activity).
- Reading from computers or smart phones are not permitted. However, you may use an e-reader device, as long as, you are reading a book.
- You may bring a book with you or you may use one of the library's books, magazines or newspapers to read.
If you have further questions, please see a staff member. Happy reading!

domain: library


CNN Go and Talk Asia have been interviewing some of Korea’s top entertainers for the G20 Seoul Summit that is happening this week.
CNN’s Anna Coren interviewed Super Junior and Nichkhun was covered their website.
In the latest clip released, Lee Hyori and Daniel Henney can be seen taking the show around Seoul and explaining the different places they visit.
Playful Kiss’s Kim Hyunjoong was also interviewed and he talked about the impact of youtube. His drama is currently airing episodes through a deal struck with Google and Youtube.
The production company behind Playful Kiss understands their target audience and they’re pioneering this new way of bringing dramas to the masses.
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Flowmeters, Flowmeter Pickup Coils
Generally speaking the pickup coil is selected based on meter size and desired turndown range. Hoffer offers many different types of magnetic pickup coils with different gauss levels. In addition, Hoffer offers modulated carrier pickup coils which provide turndown ranges of 100:1 in some configurations.
Engineering Guide – When a Hoffer Turbine Flowmeter is equipped with two pickup coils properly positioned on the flowmeter housing, it is possible to sense flow direction, flowrate and total flow as well as add/subtract options.
Miniflow – Sensed by the pickup coil and converted to a pulsing output signal where the frequency is related to the flow rate.
Intrinsically Safe Redi-Pulse Pickup Coil – The Redi-Pulse pickup coils are for use with turbine type flowmeters
Redi-Pulse Pickup Coil – Both magnetic and modulated carrier pickup coils are available.
About Hoffer Flow Controls Turbine Flowmeters
For over forty-five years Hoffer Flow Controls has been designing and manufacturing quality turbine flowmeters and related process instrumentation. Hoffer Flow Controls specializes in cryogenic flowmeters, magnetic flowmeters, ultrasonic flowmeters and electronic flowmeters. We have expanded our product line to include but not limited to; Aerospace flowmeters, Oil and gas flowmeters, Industrial custody transfer flowmeters, Gas and liquid flowmeters (Power generation), WFI water flowmeters, Sanitary flowmeters, Military grade flowmeters and Subsea flowmeters.
Hoffer Flow Controls is committed to the quality system established by ISO 9001 that ensures our ultimate success by continually satisfying customer needs, improving performance, and making us competitive in the world market.


text:
is our role with the City of Hartford Advisory Commission on Food Policy. The Hartford Advisory Commission on Food Policy was established by City ordinance in 1991 to implement recommendations from the Mayor’s Task Force on Hunger. Continuously operational since then, its purpose is to integrate all City agencies in a common effort to improve the availability of safe and nutritious food at reasonable prices for allHartford residents, particularly those in need.
to a happy, healthy, and productive life in the City;
of safe and nutritious food is available for City residents;
is not limited by economic status, location, or other factors beyond a resident’s control; and
of food in the City remains at a level approximating the level for the state.
As part of its advisory role to city officials, the Commission annually prepares a series of recommendations on food and nutrition issues. Recent recommendations include supporting mid-sized grocery stores, ensuring that all schools in Hartford have active gardens, and reducing food waste.
Hartford Food System was founded in 1978. Since then, we have been dedicated to finding long-term solutions for access to affordable and healthy food in our home city of Hartford.
190 Wethersfield Avenue Hartford, CT 06114


LEOMINSTER — Over the course of the past month, Leominster baseball skipper Rich Barnaby has raved about his team’s willingness to wait out the other team, to grind them out.
His mantra: Wait them out, get into the bullpen, and feast on the weaker pitching.
In Friday’s Central Mass. Division 1 semifinal, LHS flipped the script.
The top-seeded Blue Devils rapped nine hits and attacked No. 12 Algonquin Regional early and often, as Leominster posted a 7-0 win over the Tomahawks at Doyle Field.
The win lifts the Blue Devils to 17-1, with a trip to the Central Mass. set for Monday afternoon against No. 7 St. Paul’s of Worcester back at Doyle at 6 p.m.
“When you get into playoff games and the pressure is a little higher, it’s always good to get a couple of runs early,” Barnaby said. “That takes the pressure off your bat, you don’t squeeze the bat as tight, and your approaches get a little better.
“Our seniors led us today. Some teams’ seniors have lost focus; our seniors are about to play for another title. We have the chance to win the first Athletic Director’s Tournament and the last Central Mass. sectional; we’re going for 2-for-2.”
After LHS starter Brandon Arsenault (5 IP, 1 K, 3 H) set the side down on six pitches in the top of the first, the Blue Devil offense didn’t waste any time whatsoever: leadoff hitter Tyler Smith smoked the first pitch through the box for a base hit, before Sean Dutton took ball one.
On the next pitch, he drove it out of the ballpark for the first of two two-run bombs by the Blue Devils.
“Usually I bunt Sean in that situation, but I told him, ‘Today, we need runs, I’m not going to bunt you if Tyler gets on.’ I think that was a good decision,” Barnaby said. “That was the right call.”
Leominster’s offensive surge continued: Evan McCarthy ripped an infield single before Nick Garcia followed up with a single two pitches later, but LHS failed to capitalize.
But in the third, Smith led off the frame with a heroic at-bat, fouling off four pitches before earning a full-count walk. He then swiped second.
Two hitters later, McCarthy singled Smith all the way around, but the fielder’s throw home was offline. McCarthy went to second on the throw, but didn’t stop running as he noticed the offline toss.
He ended up at third.
He didn’t stay at third long, as Garcia absolutely obliterated the first pitch he saw for a two-run homer to deep left, giving LHS a 5-0 lead.
“That was crazy. That was out of any ballpark in America. Even Yellowstone,” Barnaby said.
Leominster added single runs in the fifth and sixth, as Arsenault singled Dutton in with two outs in the fifth, and Smith delivered Nico Martinez to wrap up the scoring.
Arsenault was efficient on the mound, as he only threw 56 pitches and started his last hitter while sitting on 53 pitches; that means he will be able to throw relief work Monday if necessary.
“Brandon’s efficient. He mixes in three pitches to contact, he trusts his defense, and we made some good plays out there; Evan McCarthy’s picking balls out at first base — Nick Garcia was looking like Brooks Robinson over at third. (Eamon) Darkan was chasing down anything in the air,” Barnaby said.
Freshman Angel Baez and sophomore Ryan Garner split the sixth and seventh for Leominster, with Garner battling out of a bases-loaded jam with three straight K’s to end the game.
In all, Leominster pitching allowed five hits, with only two runners reaching third.


text:
The Best Places to Experience "La La Land" in Los Angeles
Make your own magic in the "City of Stars"
The City of Angels once again gets a star turn courtesy of La La Land. The characters Mia and Sebastian, played by Emma Stone and Ryan Gosling, sashay around town in love with each other and Los Angeles.
Written and directed by Damien Chazelle, La La Land received 14 Oscar nominations, tying the record for most nods by a single film with All About Eve (1950) and Titanic (1997). At the 89th Academy Awards, La La Land won six Oscars, including Best Director for Chazelle (the youngest winner in the category), Best Actress (Stone) and Best Original Song ("City of Stars").
Read on for how to make your own magic during your La La Land tour of Los Angeles.
NOTE: Hours and opening dates change frequently. Check individual websites for updated information.
Spanning more than 4,300 acres, Griffith Park is the 11th-largest municipally owned park in the U.S. After a Hollywood Hills party, Sebastian and Mia discover a spectacular view of the San Fernando Valley, where they perform the showstopper “A Lovely Night.” The sequence was filmed in one take at "Cathy's Corner" off Mt. Hollywood Drive.
One of LA’s greatest cultural attractions, the Griffith Observatory has appeared in numerous TV shows and films, perhaps most famously in Rebel Without a Cause (1955), starring James Dean and Natalie Wood. As an homage, Sebastian and Mia visit the Observatory, where an unforgettable scene takes place in the Samuel Oschin Planetarium.
During a montage, Sebastian and Mia ride the landmark Angels Flight, located off Hill Street across from Grand Central Market in Downtown LA. Though the Bunker Hill funicular was closed at the time, the filmmakers got permission to use Angels Flight for a day.
Angels Flight has appeared in more than 100 movies, including the film noirs Criss Cross (1949) and Kiss Me Deadly (1955); and TV series like Bosch, Perry Mason (both the original and the 2020 HBO series) and the classic Dragnet.
Opened in 1917, the historic Grand Central Market houses a vibrant collection of classic and modern food vendors serving cuisines from around the world. In a montage, Sebastian and Mia stop by Sarita's Pupuseria at GCM. Sarita's serves handmade pupusas with dozens of different fillings, including vegetarian options.
The Lighthouse Cafe
Jazz plays an important role in La La Land - Sebastian is a jazz pianist who dreams of opening his own club and makes a living by playing cocktail party gigs. The Lighthouse Café in Hermosa Beach has showcased jazz since May 1949, featuring legendary musicians like Miles Davis, Chet Baker, Art Blakey, and Cannonball Adderley. Today the club books a wide range of music, from jazz to reggae and rock.
Hermosa Beach Pier
Extending over the Pacific Ocean, the Hermosa Beach Pier is a popular destination for fishing and gorgeous sunsets. After he and Mia visit The Lighthouse Cafe, Sebastian strolls the pier and sings the Oscar-winning "City of Stars."
Smoke House Restaurant
Thanks to its proximity to Warner Bros., the Smoke House Restaurant has been a favorite hangout for the entertainment industry since it was established in 1946. The legendary steakhouse stands in for the supper club where Sebastian plays holiday tunes.
Colorado Street Bridge
The Colorado Street Bridge was proclaimed the highest concrete bridge in the world upon its completion in 1913. With majestic arches rising 150 feet into the sky, this historic bridge has impressed travelers and locals from the day it opened, and is one of LA's most romantic landmarks.
Seen in a romantic montage, the world-famous Watts Towers were built by Italian immigrant construction worker Sabato (aka "Sam" or "Simon") Rodia in his spare time over a period of 33 years, from 1921 to 1954. Rodia built the towers by himself, using only hand tools and window washer's equipment. The monumental sculpture was declared a National Historic Landmark in 1990 and hosts annual events such as the Day of the Drum Festival and the Simon Rodia Watts Towers Jazz Festival.
NOTE: Watts Towers is currently inaccessible due to ongoing renovations. The Arts Center is open to the public during construction.

domain: entertainment


Hello Fajar Kurnia
Some GPO settings may control how user sessions are handled, especially in remote desktop environments. For instance, there are policies that dictate session timeouts, disconnection behavior, or even the ability to log off users after a certain period of inactivity. If any such policies are in place, they could influence the behavior you're experiencing. Certain security measures might also be set to restrict background processes when the user logs out. This is commonly done for security reasons to ensure that no unauthorized processes continue running in the background after a user disconnects. To narrow down the issue:
- Review the specific GPOs you applied for hardening and look for any settings related to user sessions, session management, or restrictions on background processes.
- Ensure that the GPOs are applied correctly to the user or computer.
If you have any further questions or concerns about this case, please let me know.
---If the Answer is helpful, please click "Accept Answer" and upvote it.


text: The effects of 7 weeks of sprint training (repeated 5-s all-out sprints) on maximal power output (Wv,max) determined during a force-velocity test and a 30-s Wingate test (Wpeak) were studied in ten students [22 (SD 2) years] exercising on a cycle ergometer. Before and after training, muscle biopsies were taken from vastus lateralis muscle at rest for the ten subjects and immediately after a training session for five of them. Sprint training induced an improvement both in peak performances by 25% (Wv,max and Wpeak) and in the 30-s total work by 16%. Before sprint training, the velocity reached with no load (v0) was related to the resting muscle phosphocreatine (PCr) stores (r = 0.87, P < 0.001). The training-induced changes in v0 were observed only when these PCr stores were lowest. This pointed to a possible limiting role of low PCr concentrations in the ability to reach a high velocity. The improvement in performances was linked to an increase in the energy production from anaerobic glycolysis. This result was suggested in muscle by the increase in lactate production measured after a training session associated with the 20% higher activity of both phosphofructokinase and lactate dehydrogenase. The sprint training also increased the proportion of slow twitch fibres closely related to the decrease in fast twitch b fibres. This result would appear to demonstrate an appropriate adaptive reaction following high-intensity intermittent training for the slow twitch fibres which exhibit a greater oxidative capacity.

domain: health


text:
Ericsson’s third quarter 2014 results explained.
Ericsson has announced the launch of the sixth annual Innovation Awards, a competition in which university students are given the opportunity to be drivers of fundamental change in society.
Sercomtel, a telecommunications company from Brazil, has selected Ericsson’s SSR 8010 solution to manage broadband users, aiming to modernize management and control of its network through a smart router.
Sixty new professionals join Ericsson’s 400 R&D specialists in Brazil; team is focused on Ericsson’s Business Support Systems (BSS) projects.
David Holecek, Connectivity Brand and Marketing Manager, Volvo Car Corporation, discusses his own and Volvo's thinking behind the Connected Car.
Hans Vestberg, President and CEO of Ericsson, is among confirmed Premium Keynote speakers for the event, which returns to São Paulo after two years in Rio de Janeiro.


text:
§ Mr. Faulds
asked the Secretary of State for Wales whether he will specify the sums paid under certificates of indemnity by the National Museum and Library in336W
—nursery, infant, primary and secondary—were completed in the constituency of Flint East, in the years March 1974 to March 1979; and what were the total estimated costs.
§ Mr. Michael Roberts
New school places completed in the East Flint Constituency between March 1974 and March 1979 were as follows:
Wales in respect of claims for loss of, or damage sustained by, objects let to it during the financial year ended 31 March 1979, divided between (a) claims satisfied in respect of long-term loans to the permanent collections and (b) claims satisfied in respect of loans to temporary exhibitions.
§ Mr. Wyn Roberts


text:
For weeks we've been subjected to advertisements, pamphlets and articles reminding us that Mother's Day is on Sunday. While all of this may be helpful for people who actually want to celebrate their mums, the hype around Mother's Day can be extremely distressing for some.
"Mother's Day can be triggering for all sorts of people - those who have lost their mums, those who have difficult relationships, and for those struggling with infertility," psychologist Sara Chatwin told Newshub.
- The real impact of kids using social media at the dinner table
- Should you make a habit of living mindfully?
It's why Chatwin believes the day could be re-defined as "caregiver celebration" day - a day to celebrate those who have had a positive influence in your life, from friends to extended family.
"Surround yourself with positive people and talk about your feelings and how the day may be affecting you. Don't internalise those emotions - you can make yourself physically sick if you do," she says.
"It's important not to detract from other's happiness if you're not celebrating your mum. Rather, create your own celebration."
No matter who you choose to spend the day with, Chatwin believes there's no need to buy into the materialism surrounding Mother's Day.
"Spending time with loved ones, having meaningful conversations about gratitude and relishing seeing the smiles on your child's face are all more important than posting a picture of eggs bene on Instagram."
Going into Mother's Day with big expectations could result in people feeling let down or disappointed, Chatwin says.
"These days we put a lot of emphasis on having things, or doing things, and there's no need to.
"Spending time with those you cherish is gift enough rather than buying into the one-upmanship on social media," she says.

domain: psychology