Fantastic Totem Poles at the top of Stanley Park.
When we travel overseas we often choose bicycle riding to really get in touch with the area we are exploring and Vancouver is one of the most bicycle friendly cities we have visited. There were literally thousands of bikes riding around the Seawall in Stanley Park the day we set off on our adventure. We hired our bikes from Bicycle Sports Pacific or BSP, just one block from Davie Street. After a false start with a bike seat problem and a few adjustments we were on our way.
There are many places around the park renting bikes.
First stop was English Bay Beach, the best of Vancouver's city beaches. Further on at Second Beach the bike trail takes a right turn and then its 'one way' all the way around Stanley Park. However, we missed the turn and for some reason decided to take the dirt track called the Bridle Trail, and suddenly no other bikers.
English Bay Beach is very close to the centre of Vancouver.
The trail took us uphill and further uphill but our reward was seeing a magnificent forest with towering redwoods hundreds of years old and we had the trail to ourselves. After a stop or two and a lot of huffing and puffing we reached the top at Prospect Point. Here we had magnificent views over English Bay and the Lionsgate Bridge.
Prospect Point is good for lunch in Stanley Park.
At Prospect Point there are a number of places to eat and drink and, as the Canadians would say, there are also 'washrooms'. From here we walked our bikes down an incredibly steep, rough gravel path to the Seawall and, surprisingly again, there were no other tourists on this trail. How did we manage to get it so wrong? But we had a lot of fun along the way.
At last, back on the Seawall Trail we were feeling relieved until we realised the bike trail was only 'oneway' and we were going the wrong way. We wanted to see the famous Totem Poles and they were further back, in the wrong direction of course. So, feeling a little naughty, we decided to break the rules and rode the opposite way to everyone else, and after a few near misses with oncoming bicycles and pedestrians, we finally arrived at the Totem Poles.
Riding the Bridal Trail among the red woods in Stanley Park.
The Totem was the British Columbia Indian's 'Coat of Arms'. The Totem Poles are unique to the North West Coast of BC and lower Alaska. Carved from western red cedar each Totem tells of a real or mythical event. Don't miss them.
The Totem Poles are unique to North West BC.
With lots of pics of the Totems we decided to go 'mainstream' and ride in the same direction as everyone else. The whole ride around and through Stanley Park took us about three hours and it was truly a great ride. Did we find anything gay? Of course there were a few hunky daddies and a scattering of cute joggers. However, we have it on good authority that if we had taken the Eagle Trail we may have been even more entertained. Maybe something for next time.
If you are visiting Vancouver for the first time, get right in touch with the city from the outset by taking a relaxing and thoroughly scenic ride through beautiful Stanley Park.
Break Bakery is great for coffee and cake in Davie Village.
Tip: It can be very hard for Australians to find coffee in Canada which suits the style they enjoy to drink. The Canadians prefer their coffee large and weak. If you are staying in Davie Village we found the best place for coffee is Breka Bakery and Café on the corner of Hornby and Davie Streets. They will make the coffee the way you like it and their baked goods are sensational. Give yourself a little treat before heading out for your excursion.


Students of grade XI and the teaching staff bid grade XII students adieu on 30th January with a grand and gala party. XI graders displayed great degree of creativity in each element of the program, whether it was decoration or various events. Where as the boys of grade XII looked handsome in their designer suits, girls looked ravishing in sarees !
Seventeen students were conferred with beautiful 'Star Modernite' mementos for their conduct and contribution during the years of schooling. All the students of the outgoing batch were also given interesting titles by their juniors. An energetic dance performance and melodious songs by the school band added to the mood of the evening.
With number of rounds, Nishant Hyanki of XII science was chosen as Mr. Eve and Kripali Suri of XII was elected as Ms. Eve by grade XI. The evening was concluded with cutting a good luck cake. Sumptuous food and dance on peppy dance numbers by DJ was the perfect ending to the program.


← Fundraiser & Dinner Tickets On Sale Starting Today!
Bring in a Bottle of Wine and Receive an Extra Fundraiser Drink Ticket!
The SW Charter Annual Fundraiser is just around the corner on Sunday, March 19th. We have a great opportunity for you and your guest to receive an extra drink ticket by helping to stock our Wall of Wine for fundraiser night!
This Thursday 3/2 and Friday 3/3, the school is closed for parent-teacher conferences. If you bring a bottle of wine with a value over $15, you will receive 1 extra drink per guest. Just bring a bottle with you the day of your conference, drop it off in the designated spot located in Amanda's office.
Make sure to write down your name, how many guests and the type of wine you brought. We will handle the rest. We really appreciate all of your help in making our annual fundraiser and the Wall of Wine such a huge success. See you on the playground!
This entry was posted in Auction, Events, Fundraising and tagged wall of wine. Bookmark the permalink.


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His love did not go sour: a sweet tribute to Barry Norman
Andrew Collins quotes from his teenage diary while remembering the film critic on BBC Radio 5 Live.
By Antonia Quirke
"Film '81 is my favourite programme!" The writer and broadcaster Andrew Collins was quoting from his teenage diary during a sweet tribute to Barry Norman on Stephen Nolan's BBC Radio 5 Live show (1 July, 9pm). "Not only for its info," wrote his 15-year-old self, "but for its natural, witty, honest, reliable presenter . . ."
Much has been made since Norman's recent death aged 83 of his remaining a "natural and reliable" critic to the end. No small thing. I heard elsewhere that Norman had estimated he had seen around 13,000 movies during his lifetime. Yet, during his career, he was rarely tempted to contextualise the movies within their industry, as did Pauline Kael, who stepped into film production for a while as though in a defeated response to the powerful realisation that it's all about the money.
Norman did not imagine himself as a lone crusader for truth, unlike Alexander Walker, freaking out about David Cronenberg's Crash and calling for a ban. He also appeared to do things that didn't involve movies, perhaps unlike (the missed) Philip French, whose work ethic was no less than Stakhanovite. (French's Thatcherite hours!) Norman didn't start talking, like Gilbert Adair, with the sort of longing for old movies that one has for exes who got away, bitter at their loss.
And he never quite declined into a burble of approbation. Now that is remarkable, because film critics are lovers. They want the masterpiece so much. The movies – being the most mimetic form and the easiest to muddle with reality – can inspire the most passionate confusion. Hence film critics can watch something OK-ish through a shimmer of tears because it's not actively terrible and declare it "FUNNY AND MOVING!" all over the side of buses, like a drunken text sent to an entire contacts list.
In short: Norman didn't burn out. His love did not go sour. But then again, Norman was at his pomp at the tail end of a time of explosive cinema. His top films of 1981 were The Long Good Friday, Raging Bull and Gregory's Girl. Collins had noted in his teenage diary that this haul was "not too embarrassing". A lovely way of putting it. No, Andrew, not too embarrassing at all.
› Could China be the new best friend for a post-Brexit Britain?
Antonia Quirke is an author and journalist. She presents The Film Programme on BBC Radio 4. She writes a column on radio for the New Statesman.
This article appears in the 06 July 2017 issue of the New Statesman, Corbyn mania
What do we want from the Mayor when it comes to housing?
By John Dickie
The dizzying highs and painful lows of Cheer
Gwyneth Paltrow's Goop Lab is one of the creepiest things I've ever seen on television
Terry Jones might have been the most important Python of them all

redpajama_set_name: RedPajamaCommonCrawl


text:
123rd Airlift Wing Environmental Policy
Aircraft Noise
Online Information Request
KEEP - Kentucky Enlistment Enhancement Program
123rd Airlift Wing
220421-Z-VT419-0084
A U.S. Air Force pilot guides his F-22 Raptor to a parking spot on the flight line of the Kentucky Air National Guard Base in Louisville, Ky., April 21, 2022. The two-ship Raptor Demonstration Team will be among the highlights of this year's Thunder Over Louisville air show, to be held on the banks of the Ohio River in downtown Louisville on April 23. The event, which celebrates the 75th anniversary of the United States Air Force, is slated to feature more than 30 military and civilian aircraft, including the B-2 Spirit, C-17 Globemaster III, CV-22 Osprey, CH-53 Sea Stallion, F-16 Viper and UH-60 Blackhawk, in addition to eight historic warbirds like the B-24 Liberator, B-29 Superfortress and P-51 Mustang. (U.S. Air National Guard photo by Dale Greer)
Aircraft arrive at Kentucky Air Guard Base for Thunder air show
By Dale Greer
123rd Airlift Wing Public Affairs
LOUISVILLE, Ky. -- Military aircraft began arriving at the Kentucky Air National Guard Base here today for this weekend's Thunder Over Louisville air show, including the U.S. Air Force F-22 Raptor Demo Team.
The two-ship team will be among the highlights of this year's air show, to be held on the banks of the Ohio River in downtown Louisville on April 23. The event, which celebrates the 75th anniversary of the United States Air Force, is slated to feature more than 30 military and civilian aircraft, including the B-2 Spirit, C-17 Globemaster III, CH-53 Sea Stallion, CV-22 Osprey, F-16 Viper and UH-60 Blackhawk, in addition to historic warbirds like the B-24 Liberator, B-29 Superfortress and P-51 Mustang.
"We're set up for the best Thunder we've ever had," said Lt. Col. Josh Ketterer, air show coordinator for the Kentucky Air Guard. "It's going to be a fantastic 75th-anniversary salute, given all the current and historic Air Force planes on display."
The air show will kick off at 3 p.m. when 10 Airmen from the Kentucky Air Guard's 123rd Special Tactics Squadron parachute into the Ohio River from a Kentucky Air Guard C-130J Super Hercules, landing in front of the Great Lawn at Waterfront Park.
The jump team, which features pararescuemen; combat controllers; and a search, evasion, resistance and escape specialist, will perform a high-altitude, low-opening jump from about 5,000 feet while descending with an American and Kentucky flag, said Maj. Nate Tingle, the squadron's combat rescue officer.
The demonstration will showcase techniques used by Air Force special operators to insert themselves behind enemy lines or into challenging environments for combat operations, rescue missions or other contingencies.
Later in the show, aircrews from the Kentucky Air Guard's 165th Airlift Squadron will perform a two-ship aerial demonstration of the unit's new C-130J Super Hercules aircraft. The aircraft, which began arriving at the unit in November, will replace a fleet of eight C-130H Hercules transports dating to the early 1990s.
The C-130J Super Hercules features many improvements over its predecessor, including modern instrumentation, more efficient engines and a stretched fuselage for additional payload capacity, according to Lt. Col. Penn Brown, commander of the 165th Airlift Squadron. It is among the most versatile aircraft ever built, supporting a broad range of missions from special operations to air cargo with legendary capabilities that allow it to land on austere runways where other airlifters can't go.
"We're really proud of these new aircraft and are looking forward to showing them off during Thunder," Brown said. "It's a great opportunity for us to show the public what we do and how we serve our country's citizens."
Once again, the Kentucky Air Guard is serving as the base of operations for Thunder's military aircraft, providing logistical and maintenance support from its facilities at Louisville Muhammad Ali International Airport.
This year, Thunder marks its return to downtown after a two-year absence. The air show and evening fireworks display, which has drawn up to 1 million spectators to the waterfront in past years, was cancelled outright in 2020 because of COVID-19. A scaled-down air show with no public attendance was telecast from Bowman Field in 2021, while fireworks displays were staged at various locations around the community rather than downtown.
Kentucky Air National Guard Thunder over Louisville F-22 Raptor Demo Team 123rd Special Tactics Squadron 123rd Airlift Wing
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text:
1666426 Susy Hiroshi Nakagawa hn2360@cumc.columbia.edu 2021-11-19 12:28:19 2021-11-19 12:28:19
216392 sf3070@cumc.columbia.edu Samuel Flashner No 2021-10-26 04:44:52 2021-10-26 04:44:52
216393 ky2004@cumc.columbia.edu No 2021-10-26 04:44:52 2021-10-26 04:44:52
75130 hn2360@cumc.columbia.edu Hiroshi Nakagawa 1 2021-10-26 04:44:52 2021-11-19 12:28:19
79927 nora.tang@mdpi.com Nora Tang 2 2021-11-23 10:17:35 2021-11-23 10:17:36
3D Organoids
Subjects: Cell & Tissue Engineering
Hiroshi Nakagawa
The 3D organoid model system represents a powerful tool for capturing the physiology of the normal or neoplastic esophagus. These 3D organoids are easily manipulatable, require little patient material, and are amenable to medium- or high-throughput screening. While no studies have yet leveraged the 3D organoid system to characterize the functional consequences of microbiome alterations in esophageal neoplasia, this system has been applied to other cancer types.
In this review, we will briefly summarize the relationship between the microbiome and esophageal neoplasia, discuss 3D organoid models of esophageal malignancies, highlight analogous GI models of host–pathogen interactions, and underscore the value of applying such models to esophageal disease.
ESCC is the predominant histological subtype of esophageal cancer worldwide, accounting for >90% of all esophageal cancers [1][2]. In recent years, there has been considerable progress documenting the genetic and epigenetic changes promoting ESCC initiation and development of esophageal cancer [3][4][5][6]. Despite these advancements, overall survival remains poor at approximately 20% [7]. Therefore, more work is needed to characterize both the intrinsic and extrinsic factors that promote ESCC tumorigenesis and to translate these findings into actionable therapeutic strategies.
Ultimately, the esophagus harbors a stable bacterial microbiome that is altered in esophageal neoplasia. Critically, whether these alterations have a causal role in promoting esophageal neoplasia is unclear. Few studies have addressed the functional consequences of alterations to these microbiomes on the identity and behavior of the underlying esophageal squamous epithelium. Such studies have utilized co-culture models of specific bacteria and esophageal epithelial cells in monolayer. While valuable, such models fail to recapitulate the dynamic esophageal squamous epithelium ( Section 1.1 ) and therefore offer an incomplete understanding of the impact of the microbiome on the underlying tissue. Faithful characterization of this impact will isolate the salient changes in these microbiomes as well as reveal novel therapeutic strategies to more effectively treat two devastating diseases.
In addition to ASC or cell line-based organoids, iPSC-based esophageal organoid models have recently been developed [8][9]. Esophageal progenitor cells (EPCs) can be generated through sequential specification of human pluripotent stem cells. EPCs can then be differentiated to recapitulate the normal development of the esophageal squamous epithelium. This system is generally used to study the development of the fetal esophagus, but organoids take several weeks to form, which is significantly slower than the formation of organoids from ASCs or cell lines. Together, there are several methods for forming 3D esophageal organoids, each with their strengths and weaknesses.
2. Organoid and Microbiome Co-Culture Models of GI Cancer-Relevant Processes
Elsewhere in the GI tract, co-culture models of 3D organoids and the gut microbiome have enabled the faithful characterization of the consequences of microbe–epithelial interactions [10][11][12]. These studies have focused on the effect of specific bacteria or bacterial metabolites on cancer-relevant processes in the gastric or intestinal epithelium, including proliferation, viability, inflammatory signaling, immunogenicity, genomic stability, and cell fate determination ( Table 1 ). To date, most studies have focused on the effect of Helicobacter pylori , a causative agent of gastric cancer, on gastric 3D organoids [13]. However, there is growing interest in modeling the interactions of the GI epithelia and other bacterial species using 3D organoids. We will highlight the GI cancer-relevant studies below and discuss how the 3D organoid system facilitates research in this clinically relevant and incompletely understood field.
Table 1. Organoid and microbiome co-culture models of GI cancer-relevant processes.
Microbe
Cancer-Associated Phenotype
Gastric H. pylori Pathogenic Whole bacteria Luminal microinjection Human Increased PD-L1 expression, increased survival [8]
Increased inflammatory cytokine production (CXCL2, CXCL16, CXCL17, and CCL20), DC recruitment [9]
Increased proliferation through c-Met signaling [14]
Increased inflammatory cytokine production through the NF-κB pathway [11]
Mouse Increased proliferation through β-catenin signaling, mislocalization of Claudin-7 [12]
Human; Mouse Increased CD44-dependent proliferation and EMT [13]
Intestinal pks + E. coli Pathogenic Whole bacteria Luminal microinjection Human Increased DNA damage and mutational burden [15]
Mouse Increased proliferation, decreased differentiation, increased chromosomal alterations, increased DNA mutational burden [16]
E. coli Commensal Whole bacteria Luminal microinjection Human Increased proliferation (transient), enhanced barrier integrity through IL-6 and IL-8 signaling [17]
LPS Supplemented into media Mouse Decreased proliferation, increased apoptosis through TLR4 signaling [18]
Acinetobacter, Stenotrophomonas, and Delftia genera Commensal LPS Supplemented into media Mouse Decreased proliferation, increased necroptosis, increased differentiation through TLR4 signaling [19]
L. reuteri D8 Commensal Whole bacteria, indole-3-aldehyde Supplemented into media Mouse Increased proliferation, enhanced barrier integrity through IL-22 signaling [20]
Common commensal metabolites Commensal Gallic acid Supplemented into media Mouse Increased WNT signaling, Increased proliferation, decreased differentiation in mutant p53 epithelial cells [21]
Unconstrained proliferation is a common feature of cancer cells. Recent studies have leveraged the 3D organoid platform to better characterize the influence of the microbiome on epithelial cell growth and have identified several different species that promote the proliferation of both gastric and intestinal epithelial organoids ( Table 1 ). An early study determined that microinjection of H. pylori into the lumen of human gastric organoids results in increased epithelial proliferation through c-Met signaling [15]. A similar study corroborated these findings, demonstrating that H. pylori microinjection into the lumen of murine-derived gastric organoids induced proliferation in a CagA- and β-catenin-dependent manner [16]. Further, H. pylori resulted in the mislocalization of claudin-7, a tight junction protein required to maintain mucosal epithelial integrity [16]. Further evidence from 3D organoid models suggests that H. pylori infection results in both increased proliferation of both patient- and murine-derived gastric organoids and increased epithelial –mesenchymal transition in a CD44-dependent manner [17]. Pretreatment of patient-derived organoids with a CD44 peptide inhibitor resulted in the loss of epithelial proliferation following exposure to H. pylori , demonstrating how findings from 3D co-culture models can reveal potential clinic targets for the treatment of microbiome-associated gastric cancers. Together, these studies demonstrate how 3D organoids can be utilized to characterize the molecular consequences of cancer-relevant microbe–epithelial interactions. Beyond H. pylori infection, recent evidence suggests that commensal microbiome metabolites can greatly influence the tumorgenicity and proliferative capacity of transformed epithelial tissue [18]. Intestinal tumor organoids derived from mice harboring oncogenic p53 mutations exhibit normal and balanced growth and differentiation in the absence of the microbiome through the disruption of the WNT pathway. However, treatment of these organoids with the bacterial metabolite gallic acid was sufficient to restore T-cell factor-mediated WNT signaling, increase organoid proliferative capacity, and result in a loss of organoid differentiation consistent with transformation. Removal of gallic acid from the culture medium reversed the transformed phenotype, highlighting the plasticity of these cells and presenting the intriguing possibility that modulation of the gut microbiota may be a potential therapeutic avenue for p53-mutated intestinal cancers. Highlighting the value of the 3D organoid system, the authors performed a coarse screen of the effect of many differential bacterial metabolites on intestinal tumor organoid growth and proliferation. This screen was possible because organoids capture the physiology of the original tissue and are easily treated and tracked. Ultimately, 3D organoids facilitated the discovery of a novel and highly cancer-relevant phenotype. In other contexts, 3D organoids have been utilized to demonstrate that bacterial products result in reduced proliferation and increased stem cell death. Treatment of murine intestinal crypt organoids with E. coli -derived endotoxin lipopolysaccharide (LPS) results in increased levels of the apoptotic marker cleaved caspase 3 and decreased levels of the proliferation marker PCNA [19]. LPS stimulation had no effect on Toll-like receptor 4 (TLR4) knockout mice. A similar study corroborated these results, demonstrating that LPS stimulation of murine intestinal organoids results in decreased proliferation, increased necroptosis (a programmed form of inflammatory cell death) of stem cells, and increased cell differentiation through a TLR4-dependent program [20]. This study is an elegant example of how the 3D organoid platform can be utilized to identify the molecular mechanisms and consequences of microbe–epithelial interactions. The authors isolated a crypt-specific core microbiota (CSCM) and hypothesized that this bacterial population affects epithelial generation. The authors first determined that the CSCM affected epithelial proliferation and survival in mice, and then employed the 3D organoid system to identify the salient molecular processes driving this change. The authors incubated organoids with sonicates and with purified LPS from four representative CSCM species ( S. maltophilia , A modestus , A. radioresistens , and D. tsuruhatensis ) and measured proliferation, death, and differentiation of epithelial cells. The authors determined that, while LPS from all CSCM species resulted in decreased organoid maturation, LPS from S. maltophilia specifically induced epithelial cell differentiation and RIPK3-dependent necroptosis of intestinal stem cells. The use of 3D organoids facilitated these studies by providing a physiologically-relevant platform to measure intestinal epithelial homeostasis using short (7 day) cultures that were easily scaled to include a variety of different bacterial byproducts. Together, these studies demonstrate that 3D GI organoids are a valuable platform for identifying the molecular mechanisms regulating epithelial proliferation and survival.
Inflammation is an enabling characteristic of cancer [21]. Recent studies have demonstrated that the co-culture of GI organoids and common GI microbes results in a strong inflammatory response ( Table 1 ). Microinjection of H. pylori into the lumen of gastric organoids results in a rapid (2 h) increase in NF-κB -regulated proinflammatory genes, including IL-8 [22]. Contradicting data from 2D cell lines, IL-8 expression in gastric organoids did not depend on bacterial cytotoxicity-associated gene pathogenicity island ( cag PAI) [22][23][24]. These data highlight how experiments performed in 3D organoids and 2D cell lines can produce different results. Organoid co-culture models have also revealed that the pro-inflammatory response to commensal bacterial metabolites can promote epithelial homeostasis. Co-culture of intestinal organoids and the commensal bacteria Lactobacillus reuteri ( L. reuteri ) D8 revealed that D8 metabolites stimulate IL-22 expression following intestinal injury, which accelerates epithelial proliferation and promotes barrier integrity [25]. Consistent with these data, microinjection of nonpathogenic E. coli into the lumen of intestinal organoids results in increased secretion of IL-6 and IL-8, a transient increase in proliferation, and improved epithelial barrier function [26]. These experiments demonstrate how organoid co-culture contextualizes the effects of the microbiome on the GI epithelium by faithfully recapitulating epithelial barrier function. Avoiding immune destruction is an emerging hallmark of cancer [21]. Recent evidence from microbiome and organoid co-culture has demonstrated that the microbiome can promote immune evasion ( Table 1 ). A co-culture model of H. pylori infection in patient-derived organoids and autologous patient cytotoxic T lymphocytes and dendritic cells (DCs) revealed that H. pylori induces programmed death-ligand 1 (PD-L1) expression through the Shh signaling pathway [27]. PD-L1 upregulation was rapid (within 48 h) and promoted epithelial cell survival. Treatment with an inhibitor of PD-L1 or programmed cell death protein 1 (PD-1) resulted in epithelial cell death, indicating that H. pylori -associated gastric tumors may be susceptible to immunotherapy. An additional study examined the co-culture of patient derived gastric organoids, luminally-microinjected H. pylori , and human monocyte-derived dendritic cells [28]. The authors demonstrated that H. pylori infection resulted in the recruitment of DCs to the gastric epithelia following the production of multiple chemokines, including CXCL2, CXCL16, CXCL17, and CCL20. These results indicate that the gastric epithelium can recruit DCs for immunosurveillance following H. pylori infection. Together, these data highlight how organoid co-culture models can be used to characterize important and targetable mechanisms underlying microbiome-associated GI cancers.
Loss of genomic stability is an enabling characteristic of cancer [21]. How bacteria may promote mutagenesis is unclear, in part due to the challenges performing long term co-culture experiments with human epithelial cells and microbiomes. To address this knowledge gap, a recent study performed a long term (5 months) co-culture through repeated microinjection of pathogenic polyketide synthetase ( pks ) + E. coli into healthy human intestinal organoids [29]. The authors demonstrated that pks + E. coli generate DNA damage and a distinct mutational signature that is commonly identified in colorectal cancer. Further, short-term infection of primary murine colon organoids with pks + E. coli results in phenotypes consistent with malignant transformation, including chromosomal aberrations, increased mutational burden, enhanced proliferation, and impaired differentiation [30]. Together, these findings leverage the 3D organoid platform to suggest that a pathogenic bacteria strain has a causal role in GI cancer transformation.
3. Discussion and Future Directions
3D organoids provide an intriguing platform for the study of epithelial–microbiome interactions for a variety of reasons. These organoids can be rapidly generated (<14 days) and passaged multiple times [31]. Additionally, the equipment and reagents required to culture 3D organoids are available in a modern molecular biology laboratory that performs 2D tissue culture [31]. Further, 3D organoids recapitulate the dynamic proliferation-differentiation gradient of the esophageal mucosa and are embedded in Matrigel, which simulates the basement matrix [31]. Therefore, this system is more physiologically relevant than 2D cell culture. Further, organoids can be established from patient samples or from isogenic mouse models. This versatility enables organoids to be used as a platform for personalized medicine or for targeted interrogation of the interaction of specific genes with the microenvironment [31]. Building on this versatility, 3D organoids are amenable to CRISPR-mediated or RNA interference (RNAi)-mediated genomic engineering and can be used for high-throughput screening in the presence of bacteria or bacterial metabolites added to the cell culture media [32]. Ultimately, 3D organoids represent a powerful tool for modeling epithelial–bacterial microbiome interactions in a physiologically relevant way.
However, there are limitations to 3D organoids as platforms for studying epithelial–microbiome interactions. There is a significant learning curve for generating 3D organoids from single cells [33]. Further, maintaining the oxygen gradient and/or anaerobic conditions required for the cultivation of specific aerobic/anaerobic bacterial species is challenging in the setting of tissue culture [12][33]. Additionally, microinjection of bacterial species into the organoid lumen is not well-suited to high-throughput screening. Further, the cell of origin for EAC and BE is controversial and may not be of esophageal origin, so co-culturing normal esophageal organoids with potentially pathogenic bacteria may be exploring early neoplastic changes in the wrong lineage [34]. Finally, reductionist approaches of co-culturing a single or a select few bacterial species with 3D organoids may occlude a common function of commensal bacteria: preventing the colonization of pathogenic bacteria [35]. Therefore, while the co-culture of 3D organoids and the bacterial microbiome is a promising and novel approach for studying host–microbiome interactions in esophageal neoplasia, there are limitations to this model system.
This approach can be applied to study the direct impact of the microbiome on esophageal neoplasia. Several specific bacterial phyla or species have been implicated as risk factors for ESD and ESCC progression, including increased levels of Fusobacteria and decreased levels of Actinobacteria [36][37]. Characterizing the effect of these and other phyla or species derived from normal, dysplastic, or ESCC tissue, as discussed in Section 2.2 and Section 2.3 on organoids, could provide insight into a potential role for bacteria in the pathobiology of ESCC initiation and development. Similar studies can address the effect of common microbial alterations in EAC and BE. Specifically, the co-culture of 3D organoids from BE or EAC patients with bacteria from the Campylobacter genera would enable insight into the mechanistic effects of a common alteration associated with BE. Further, altering the Streptococcus:Prevotella ratio in co-culture models of BE organoids could identify the molecular changes that accompany a common microbial alteration [38][39]. Finally, co-culture of EAC-derived organoids with Veillonella could provide evidence that a controversial alteration is or is not contributing to EAC pathobiology [40][38]. Each proposed experiment would clarify the consequences of common microbial alterations in esophageal neoplasia.
Ultimately, the microbiome is an emerging co-factor in esophageal health and disease. While many studies have documented common components of normal and transformed esophageal epithelial cells, the current understanding of the role of the bacterial microbiome in esophageal homeostasis remains largely descriptive. The co-culture of 3D organoids with both individual bacterial species or the bacterial microbiome isolated from patients will enable functional annotation of these changes ( Figure 1 ).
Figure 1. Leveraging 3D organoids to study host–microbiome interactions in esophageal cancers. Patient-derived esophageal tissue can be dissociated into single cells and used to generate organoids. In parallel, the host bacterial microbiome can be isolated and specific bacteria species or products can be cultured or purified, respectively. These cultures or products can then be combined with patient-derived organoids. The ascribed endpoints can be used to assess the effect of the microbiome on the salient biological features of the esophageal stratified epithelium. Created with BioRender.com (accessed on 15 October 2021).
The microbiome is an emergent co-factor in the pathobiology of esophageal neoplasia [41]. Within the past two decades, several studies have determined that the composition of the esophageal or oral microbiome is altered in ESCC and EAC as well as their respective precursor lesions ESD and BE. These alterations may have both prognostic and therapeutic value; however, more work is needed to characterize the functional consequences of these changes. The 3D organoid model system represents a powerful tool for capturing the physiology of the normal or neoplastic esophagus. These 3D organoids are easily manipulatable, require little patient material, and are amenable to medium- or high-throughput screening. While no studies have yet leveraged the 3D organoid system to characterize the functional consequences of microbiome alterations in esophageal neoplasia, this system has been applied to other cancer types. Elsewhere in the GI tract, co-culture models of gastric or intestinal 3D organoids have enabled mechanistic insights into how the bacterial microbiome can promote cancer-specific processes such as proliferation, inflammation, immune escape, and mutagenicity. These insights have provided potential therapeutic targets. Therefore, there is growing interest in applying 3D organoid technology to unravel the mechanistic consequences of epithelial–bacterial microbiome interactions in esophageal neoplasia. Additionally, 3D organoid esophageal organoids can be used to identify the functional consequences of epithelial interactions with other elements of the microbiome, including viruses such as HPV. Further, by expanding co-culture models of esophageal organoids with the microbiome and with other stromal or immune cell elements, researchers can better recapitulate the native environment of the human esophagus. This platform would be ideal for personalized medicine. Ultimately, the co-culture of esophageal organoids and the bacterial microbiome is an untapped platform with the potential to provide actionable insight into the pathobiology of a leading cause of cancer worldwide.
This entry is adapted from 10.3390/microorganisms9112182
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Huntington Can't Afford Grant with Half Million Dollar Match, Scale Down Proposed by Finance Committee
Feb 2 2011 - 12:01am
HUNTINGTON, WV (HNN) – The Finance Committee rendered a tough decision on a prospective grant that would add ten firefighters to the payroll. The first two years of the new hires salaries are covered by the grant, but in the third year (and beyond) , the city would need $515,000 for the positions. Read more
TAKE TWO: Weekend First, Weekly Movie Comings/Goings
Feb 1 2011 - 11:59pm
Beckley, Charleston, Huntington, Logan, Wheeling
HUNTINGTON, WV (HNN) – Here's the first update on movies ending Thursday Feb 3 and those opening Friday, Feb. 4 in Huntington. *This is subject to modification at this time, but it is a good planner for film buffs. Read more
Marshall Alumni and Friends Tennis in Charleston
CHARLESTON, WV (HNN) – Marshall University's Greater Kanawha chapter has scheduled an alumni and friends tennis tournament beginning Friday, Feb. 25 at 5 p.m. in the Charleston YMCA. The tournament continues Feb. 26-27. Read more
AAA FUEL GAUGE: Less than a penny drop in West Virginia gasoline prices
Feb 1 2011 - 4:14pm
Whether the Groundhog sees his shadow or not, he definitely will find West Virginia gas prices have dropped less than a penny a gallon this week. The average price for a gallon of self-serve, regular unleaded gasoline is now $3.139 at the pump.
Financial Crisis Inquiry Commission Releases Report on the Causes of the Financial Crisis
Commission: Crisis was Avoidable: a Result of Human Actions, Inactions and Misjudgments; Warning Signs Were Ignored Read more
BOOK REVIEW: Teach For America founder Wendy Kopp tells how principles that drive the organization can transform America's Schools in 'A Chance to Make History'
"Silver bullets" and "silver scapegoats" drive much of the debate over what's wrong with America's schools and both forms of "silver" are false gods, all wrong and generally irrelevant, writes Wendy Kopp (with Steven Farr) in "A Chance to Make History: What Works and What Doesn't in Providing an Excellent Education for All" (PublicAffairs, 304 pages, $25.99). Read more
Cabell Huntington Hospital sponsors "Love Your Heart" Wednesdays at Huntington Mall
Feb 1 2011 - 5:37am
HUNTINGTON, WV - Cabell Huntington Hospital's Cardiac Services and
Senior Services will host a series of free heart health activities at
the Huntington Mall Food Court each Wednesday in February from 9 a.m. to
11 a.m. Read more
TAMARACK LINES UP SWEET EVENTS FOR FEBRUARY
February is a sweetheart of a month for winter activities at TAMARACK: The Best of West Virginia.
The month starts with the sweet sounds of Simply Jazz and Blues, celebrating its one year anniversary on February 5 at 7 p.m. The hour long radio show featured on Groovy 94 locally, goes live on Tamarack's stage featuring Platinum, John Yurick, Lewisburg songstress Susanna Robinson, Beckley singer Tia Martin Davis, bassist Holden Toler and Robert Gray. Ten dollar tickets, on sale now, must be reserved in advance. Read more
Goodwill offering medical office skills training course beginning March 7
Goodwill Industries will begin its next 20-week course of Medical Office Skills Training on March 7, 2011. Financial aid is available. Students should enroll as early as possible and complete the necessary FAFSA documentation to determine eligibility for funding, however, the enrollment deadline is February 2. Read more
No Major Huntington Financial Snarls, But Numerous Little Gremlins That Could Bite Approved Budget
HUNTINGTON, WV (HNN) – Patience , listening and learning appears to be occurring when members of the administration set down with members of Huntington council's Finance Committee. However, both revenue and expenses for the city are both only a few percentage points above or below estimates, according to a December 31, 2010 unaudited line by line City of Huntington financial report. Read more
A Dad's Point-of-View: I Hate When I Do That
Isn't that one of the things we often say to ourselves, "I Hate When I Do That"? As a general rule, I dislike using the word "hate" as casually as it is generally used. I prefer to reserve "hate" for someone or something more serious; for instance, I hate the guy who shot all those innocent people in Arizona (his name should ever be forgotten). But, as the use of this phrase is so ubiquitous, I will make an exception and take this literary license this time and use the word "hate." Read more
Huntington Mayor Wolfe Acknowledges Veto Speculation
HUNTINGTON, WV (HNN) – The clock tickets on whether Huntington Mayor Kim Wolfe will veto the modified no council approval spending limit ordinance. Read more
Portsmouth Diffusion Plant 50 Miles from Huntington
PORTSMOUTH, OHIO (HNN) – As early as 1979 when the radiated Huntington Pilot uranium processing plant was buried on the grounds of the Piketon, Ohio, gaseous diffusion plant, Portsmouth community members had concerns that the burial signaled the beginning of disposal of nuclear waste from other sites in Piketon. Read more
"King's Speech" "Black Swan" Win SAG "Actor" Awards
LOS ANGELES (Jan. 30, 2011) - Screen Actors Guild presented its coveted Actor® statuette for the outstanding motion picture and primetime television performances of 2010 at the "17th Annual Screen Actors Guild Awards®" in ceremonies attended by film and television's leading actors, held Sunday, Jan. 30, at the Los Angeles Shrine Exposition Center. Read more
Huntington Mayor Wolfe May Veto Spending Ordinance, According to Some Members of Council
If it happens, veto likely to be delivered to clerk Monday, Some Council Members Say
HUNTINGTON, WV (HNN) – Call it speculation, rumor or just counting the votes, but several members of Huntington City Council would not be surprised if Mayor Wolfe vetoes the spending reduction ordinance. Passed at the Monday, Jan. 23 council meeting, the ordinance reduces from $15,000 to $7,500 the purchasing amount which requires a prior approval of council. Read more
Finance Committee Chairman "Excited" About Upcoming Budget Number Crunching
Do you find excitement running down percentages and other numeric comparisons on an Excel spreadsheet? How about crunching for a challenge solution from within reported numbers? Read more
DEVOTION: You're Blessed
It's only natural that wholeness and healing is our constant desire. Of course when school is closed... students most always rejoice. Read more
Bayer, Baxter pay multimillion indemnity to haemophiliacs
From a Coalition Against Bayer Dangers Release
The news agencies AFP and dpa today confirmed a report by the Coalition against BAYER Dangers according to which the pharmaceutical companies BAYER, Baxter, Behring and Alpha are paying a multimillion dollar compensation to haemophiliacs from 22 countries. Read more
WV Legislature Considers Disciplinary Oversight of Law Enforcement Officers
Huntington Council's Public Safety Chair Would Support if Fair and Tweaked
CHARLESTON, WV (HNN) – Nine House of Delegates members, including Kelli Sobonya (R- Cabell) have brought forth proposed legislation that would require the reporting of so-called 'problem' officers to the State of West Virginia. Read more
BREAKING… Alpha Natural Resources Purchasing Massey for $8.5 Billion
From the Business News Wire...
ABINGDON, Va. & RICHMOND, Va.--(HNN)-- Alpha Natural Resources, Inc. ("Alpha") and Massey Energy Company ("Massey") announced today that they signed a definitive agreement under which Alpha will acquire all outstanding shares of Massey common stock, subject to customary closing conditions including stockholder approval of both companies. Read more
Frayed Nerves, Odor Follow WV Bayer Plant Power Failure
INSTITUTE, WV (HNN) – Area fire departments have found no air quality issues following a two hour power failure at the Bayer CropScience plant, Institute, WV. After the electricity had been restored around 12:45 p.m., Kanawha 911 reported that no injuries had been reported and that no shelter in place recommendations were issued on or off site. Read more
Marshall 12th Worst for "Highly Restrictive" Free Speech Policies; Dean Schedules Monday Meeting
Marshall University has made one of those lists you do not want to be on.
Specifically, a Top 12 list of university's that have policies that potentially violate free speech. Officially, the website, http://thefire.org called the Huntington institution's standards "highly restrictive." Read more
Huntington Drug Dealer Pleads Guilty
Weed and Seed Program Credited
HUNTINGTON, W.Va. – A Huntington man pleaded guilty in federal court before United States District Judge Robert C. Chambers to distribution of cocaine base. Keival L. Kelly, 27, of Huntington admitted to selling cocaine base to a confidential informant. On Sept. 23, 2009, after a prearranged drug buy. Read more
Massey Energy Argues to Families That Natural Gas Triggered Explosion
CHARLESTON, WV (HNN) – Massey Energy has shared results of its own investigation into the causes of the Upper Big Branch Mine disaster in April which claimed the lives of 29 miners. Read more
Huntington Council Finance Committee Chairman Asks About New Hire Funding After the Proposed Grant Ceases
HUNTINGTON, WV (HNN) – Council's Finance Committee chairman pursued a daunting question --- How to support the Huntington Fire Chief and stay within the budget. Read more
Show Up Early for Video Games Live
Gamers Come to the Keith Albee Performing Arts Center
Thursday, February 3, at 6:00 PM, one and a half hours prior to Video Games Live at the Keith Albee Performing Arts Center is your chance to become greatness among gamers. Play among the community and compete in a variety of classic and bestselling games including Guitar Hero III and Space Invaders. Read more
Huntington St. Joseph Girls Topple Ashland 59-39 in Invitational Basketball Tournament
HUNTINGTON-WV (HNN) Host Huntington St. Joe won 59-39 over Ashland to advance in the Girls Gold Bracket of the SJI Basketball Tournament at Veteran's Memorial Field House on Thursday night, Jan. 28
Wayne's Women Defeat Buffalo Putnam in St. Joe Invitational
HUNTINGTON-WV (HNN) Wayne High School advanced to the finals of the Girls Blue Bracket in the Saint Joe Invitational Basketball Tournament with a 55-46 win over Read more
Foreign Persons Must Report U.S. Agricultural Land Holdings
(Morgantown, WV) - January 28, 2011-- WV USDA Farm Service Agency (FSA) State Executive Director Alfred Lewis reminds foreign persons with an interest in agricultural lands in the United States that they are required to report their holdings and any transactions to the U.S. Secretary of Agriculture. Read more
Rahall Calls for Review of Huntington, Beckley Postal Closures
WASHINGTON, D.C. (HNN) – U.S. Rep. Nick Rahall (D-W.Va.) today appealed to the U.S. Postal Regulatory Commission to review the Postal Service's process for consolidating and suspending mail services in southern West Virginia. Read more
Martin Luther King, Jr., West Virginia Holiday Commission presents awards during annual celebration on Jan. 15
Twenty-one young people, five individuals and three service organizations were honored Saturday, Jan. 15, with awards from the Martin Luther King, Jr., West Virginia Holiday Commission as part of the state's observance of the Martin Luther King, Jr. holiday weekend. The awards ceremony was held during an invitation-only luncheon at the Culture Center, State Capitol Complex in Charleston. Read more
Kim Cattrall on Ricky Gervais: 'Cheap Jokes'
COURTESY OF EXTRA
"Extra" recently caught up with Kim Cattrall and asked if she thought Golden Globes host Ricky Gervais crossed the line with his snarky comment about the "Sex and the City" gal pals being too old.
"I didn't watch it so I can't really comment on it. Ageism is out there and I fight it every day in my own way," said Cattrall. "So, I think that's kind of a cheap joke... Maybe some people feel that needs to be out there. I don't particularly think so." Read more
RECALLS THIS WEEK: Paintball gun/markers, cribs, toy tanks, and other product recalls
Special to Huntingtonnews.net, with information from www.Recalls.org, a private 501 (c) (3) foundation.
KEE Action Sports LLC is recalling BT SA-17 Paintball Gun/Marker sold
nationwide from May 2010 to August 2010. When users attempt to pierce the
CO2 cartridge by closing the lever to the cartridge chamber, the cartridge
can fly out of the marker, posing an injury hazard. Read more
Jason Statham Tallks Shop on "The Mechanic"
Courtesy of EXTRA:
The Real Weapons of Mass Destruction: Methane, Propaganda & the Architects of Genocide: Part III


text:
Q: SDL 2.0 - OpenGL ES context problems I'm assuming that it is a context problem, but I can't figure out what the problem is...
SDL_Window *window = SDL_CreateWindow("Default", 0, 0, 480, 320, SDL_WINDOW_SHOWN | SDL_WINDOW_FULLSCREEN | SDL_WINDOW_BORDERLESS | SDL_WINDOW_OPENGL);
Assert(window, "Could not create window");

SDL_GLContext context = SDL_GL_CreateContext(window);
Assert(context, "Could not create context");

glViewport(0, 0, 480, 320);
if(glCheckFramebufferStatus(GL_FRAMEBUFFER) != GL_FRAMEBUFFER_COMPLETE){
  Assert(0, "Failure with framebuffer generation");
}

glClearColor(0, 104.0/255.0, 55.0/255.0, 1.0);
if(glGetError() != GL_NO_ERROR){
  Assert(0, "Could not set clear color");
}
glClear(GL_COLOR_BUFFER_BIT);

GLuint shaderHandle = glCreateShader(GL_VERTEX_SHADER);
Assert(shaderHandle, "Could not create shader handle");
Assert(glGetString(GL_SHADING_LANGUAGE_VERSION), "Cant get glstring, somethings wrong");

The shader handle is 0, which means it didn't work and from what I've read it's a bad sign when glGetString returns NULL. What's wrong?

A: The fine folks at forums.libsdl.org gave me the answer. A call to both
SDL_GL_SetAttribute(SDL_GL_CONTEXT_PROFILE_MASK, SDL_GL_CONTEXT_PROFILE_ES);
SDL_GL_SetAttribute(SDL_GL_CONTEXT_MAJOR_VERSION, 2);

is necessary.

redpajama_set_name: RedPajamaStackExchange


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There are many options to manage data in Windows RT and Windows Phone. You can store data locally on the device using XML o JSON files, you can store data on the Cloud using Azure Mobile Services, you can use local databases, etc. Each one of these solutions have their advantages and disadvantages. In this article I will focus on the use of local databases, specifically using the SQLite database. You can find more information about SQLite on their web site www.sqlite.com. The good thing about SQLite is that it works on almost any platform you can think of, including of course Windows RT and Windows Phone. If you want to effectively use PCL and have most of the logic of the app shared between Windows RT and Windows Phone, then your best option (at least, at the time I write this article) is to use SQLite.
SQLite has SDK packages for both Windows RT (8.0 and 8.1) and Windows Phone (8) that can be installed as a .vsix package into Visual Studio. These are just wrappers to the sqlite library (written in C++) and their syntax is not what we would expect if our project is using C#/XAML. Besides, both SDKs are not suitable for a PCL project and we can't have all the data access logic in our PCL project. Nick Randolph's blog has a very good 4-article series on how to use SQLite in a PCL library. He basically sets four goals: the project has to be blendable, has to use SQLite, all the data access logic needs to be in a PCL project, and the data access needs to be done using objects (LINQ style). I highly recommend reading the articles since it gives a step-by-step guide on how to install SQLite SDKs, and a bunch of nuget packages to achieve the goal. You will see that it is not easy to have it all configured, and having to do that every time you start a new project might be cumbersome. But, hey! there was no other alternative at the time he wrote the article, so kudos to him.
Fortunately, there is now a nuget package that will make things easier for you: SQLite.Net PCL. This is actually a set of packages you need to install (depending on the platform) in order to use SQLite. The thing is that setting it up is not trivial, you need to take the information from a bunch of blog posts, github docs, and even some source files, and there are some gotchas you need to be aware of. In this article I will summarize my experience in setting things up, hopefully to save time to those who would like to use the package. This is a step-by-step guide, so grab a cup of coffee and be ready to spend some time reading since it is a long article.
As with Nick's articles, we will have the same 4 goals in mind (blendable, SQLite, PCL and LINQ). Of course, if we want to effectively achieve these goals we need to architecture our projects to use MVVM. I'm a big fan of MVVM Light, and this is what I will use in this guide.
SampleApp.PCL: this is where all the logic for the app, including the data access layer, will be developed.
The last article presents a sample application that uses device isolated storage for the data access layer. I will use the code in that article to change the data layer to SQLite. You can download the sample project from here.
In the case of WinRT, when submitting the app in the Windows Store, you need to upload both x86 and x64 versions of your app.
SQLite.Net is actually a set of nuget packages. There is a common package for the PCL project, and then there is a package for each of the platforms you want to target. Let's us start with our PCL project. On the PCL project, using the nuget package manager, install both SQLite.Net PCL (SQLite.Net-PCL) and SQLite.Net.Async PCL (SQLite.Net.Async-PCL) packages.
For the WinRT project we need to install the same packages, plus the device specific package. The device specific package is the SQLite.Net PCL - WinRT Platform (SQLite.Net.Platform.WinRT). This package depends on a package called SQLite for Windows Runtime (Windows 8.1) – Redistribution (SQLite.WinRT.redist), which installs the SQLite SDK for the WinRT platform. The problem with this package (at the time of this writing) is that it targets a version of SQLite that is not the current one (when I write this article the latest SQLite SDK is version 3.8.4.3, and the version used by the nuget package is 3.8.4.1), so if you have already installed SQLite SDKs you will get an error when installing the nuget package. To workaround this, first uninstall the version of the SQLite SDK for the WinRT platform, and then add the nuget package.
Open Visual Studio, go to "Tools" menu, and then select "Extensions and Updates…".
On the dialog box, on the tree that is displayed on the left, select "Installed –> SDK".
Locate the extension called "SQLite for Windows Runtime (Windows 8.1)" and click Uninstall.
Now you're ready to install the nuget packages. On the WinRT project, install the SQLite.Net.Platform.WinRT package. This will attempt to install first SQLite.WinRT.redist and you will notice that a .vsix package for the SQLite SDK is installed. Unfortunately the package will fail to install the first time, I guess because VS and the nuget package manager are not aware of the newly installed SDK. The workaround is to restart VS and then attempt to install the nuget package again. This time it should install without any problems.
Uninstall the version of the SQLite SDK that was installed with the SQLite.WinRT.redist package using the steps outlined above. Close VS.
Download the latest .vsix package from the SQLite download page. At the time of this writing is version 8.3.4.3. You will probably download a .zip file, that's ok, just change the file extension to .vsix. Install this package.
Of course, if you do this, you need to repeat all the above every time you start a new project that uses SQLite. I whish that the SQLite.Net package would not depend on the SQLite.WinRT.redist, because this whole process is a pain in the a..., but anyway… let's move on.
The SQLite.Net.Platform.WinRT will also install the base SQLite.Net-PCL package. For consistency, let's add the SQLite.Net.Async-PCL as well. The figure shows how the WinRT project references should be at this point.
If you haven't done so before, install the SQLite SDK for the Windows Phone platform first. Download the latest .vsix package from the SQLite download page. At the time of this writing is version 8.3.4.3. You will probably download a .zip file, that's ok, just change the file extension to .vsix and then install this package. Make sure you restart VS.
Now, on your WP project use the nuget package manager to install the the SQL.Net PCL – WindowsPhone8 Platform (SQLite.Net.Platform.WindowsPhone8) package. The SQLite.Net.Platform.WindowsPhone8 will also install the base SQLite.Net-PCL package. For consistency, let's add the SQLite.Net.Async-PCL as well.
The figure shows how the WP project references should be at this point.
Compile to make sure everything works fine.
Now for the fun part, let's change or data access to use SQLite. If you've followed along with my project we will make changes to our existing model and configure a new data access to be injected in our IoC container. If you're not following along with my project, that's ok, just create the files with the full code below.
Notice the use of the PrimaryKey and AutoIncrement attributes (which are self explanatory).
Notice the use of StorageFile API to create the file, and the CreationCollisionOption.OpenIfExists option used. For SQLite to work the file needs to exist. If the file doesn't exists you will get an error when trying to use the SQLite API. This is one of the gotchas to be aware of. Notice also that the file is created on the application local folder.
There are a couple of things to notice here. Remember that we are using the PCL version of the SQLite.Net package. This PCL version actually relies on the platform specific implementation of SQLite. All PCL methods are based on the ISQLitePlatform interface. Each platform implements this interface and handles the platform's specific details for SQLite. In our case we are injecting the specific platform implementation using our IoC container. Notice how the constructor expects a ISQLitePlatform object which is assigned to a local property (lines 18 and 24).
The other thing to notice is the initialization of the database. First we get a reference to the file using our storage service (line 34) and then a SQLiteAsyncConnection is instantiated by passing the ISQLitePlatform implementation and the full path to the database file (line 35). I'm using the async implementation of the API, but you can use the synchronous one as well. The key thing is the platform specific object passed on the constructor.
The other parts of the file don't deserve a details explanation since they just use the SQLite API (for more info refer to the SQLite docs or to the SQLite.Net docs).
Notice the use of compiler directives, which is another trick to share files between WP and WinRT projects. In our case the LocatorService.cs file is a shared file (the WP project as a link to it from the WinRT project). We register the appropriate ISQLitePlatform interface: on WinRT we use SQLitePlatformWinRT and on WP we use SQLitePlatformWP8. With this, the IoC container will inject the appropriate SQLite implementation in the PCL data service.
Compile and make sure everything works fine. You should now be able to add objects to your SQLite database on both WinRT and WP, and all the data access logic developed on the PCL project. You can see the contents of your SQLite database using a tool such as sqlitebrowser.


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Cafe Rio opening new locations in Denver area
The first Cafe Rio Mexican Grill opened in 1997 in Southern Utah.
Credit: Cafe Rio Mexican Grill
Updated: 8:23 AM MDT October 14, 2022
DENVER — The home of Sweet Pork Barbacoa has announced it will open two new locations in Colorado this fall.
Cafe Rio Mexican Grill plans to open new restaurants in Greenwood Village and Highlands Ranch, bringing its total to 10 locations in Colorado.
A grand opening for a restaurant at 9531 East Arapahoe Road, near Interstate 25, will be held Friday, Oct. 14 and Saturday, Oct. 15.
Cafe Rio said the first 100 dine-in customers will receive free gifts and an additional 100 will win a free meal. Chips and salsa or chips and queso will also be offered for $1.99.
The Highlands Ranch location at 9215 South Broadway, near East Highlands Ranch Parkway, is planning a December opening.
The first Cafe Rio opened in Southern Utah in 1997 before expanding to Colorado in 2010.
"We're thrilled to be opening two new locations in Colorado where we've been part of the greater Denver community for over 12 years," Cafe Rio CEO Steve Vaughan said. "With these openings, we'll be able to offer more locations to Coloradans to experience our fresh, award-winning, and flavor-packed recipes in their own neighborhoods."
Cafe Rio is known for its full menu of burritos, salads, tacos, enchiladas, quesadillas, and Sweet Pork Barbacoa.
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RAW: John Fielder talks nature photography, decision to donate life's work


In 32 years of my life I haven't created anything of lasting value. Nothing that would last even during my lifetime, insignificant as it it. Have you?
I define 'lasting value' as having a major contribution in creating something significant that would last during one's lifetime or some time beyond. Try to fit anything you did into that definition – for most of us the answer would be 'no'.
You could argue that worrying about creating anything significant or leaving something after you is a harmful ego-driven thinking. I agree. I'm not happy about thinking about it and I wish I could make it go away. But I can't. And feeling guilty doesn't help.
My work in the army was interesting but locked inside the military complex it will slowly rot into an anonymous irrelevance. My startup hasn't bear fruits yet, and if it will in the future, it won't be anymore because of my work. My blog posts are ephemeral, little drops of words falling into an ocean of opinions, dissolving without ripples. My volunteering work in a psychological crisis line has helped people in distress get some relief, but limited to one-off online conversations the effect would have been temporary at best.
And so here I was – 32 and completely creatively bankrupt. But that just might have changed when I did the most unimaginative thing of all… and became a parent.
There is nothing "creative" in having a baby, no more than what a cat bearing a kitten can be credited with. Parenthood is an semi-automatic script imprinted in us by nature and culture, and played by us often due to a lack of imagination or courage to be different.
But once the child pops out and moves away from the animalistic, unconscious world of infancy and towards the human world of symbols, words and ideas we can start creating. The kind of life we build – the life that our child absorbs growing up in our care – is an absolute act of creation that will affect his memories, his personality, his basic assumptions about the world and ultimately his life. Of course parents don't get a credit for the miracle of life. But they might get some for a child that grows into a decent, caring and happy human being.
If all goes well, my child has a good chance of living long after me. Is there anything I could create that would match this? Is there a book I could write that would still be read in 40 years? Impossible. Is there a business or an organization I could found that would still go strong in 40 years? When the average lifespan of a small business is 8 years, and of a public company 15 years, the chances for this are slim.
I'm not saying that we should abandon our creative projects and start popping out children. But as a target for our energy and creativity, at least in terms of longevity a child seems to be a pretty good investment.


I may be an outlier in a world full of tech talking heads, many of which who really, really love to listen to themselves talk, but I don't have a hot take on the current situation involving Apple, the FBI, encryption, what other players in tech have or have not said on the matter, and what all of those combined mean for you. That's not because I don't care, it's just not an area of life that I have ever really put much focus or effort into. Is that me burying my head in the sand? I don't think so. The world is full of controversies and this is one, at least at the moment, I just don't have much to offer on. So, if that disappoints you, I apologize.
With that said, you need to know what's going on in case you need to take a stand, make choices about the products you use now and in the future, and whether or not there is anything you can do.
Confused at what the f*ck I'm talking about? Let's catch up!
On December 2, 2015, two pieces of absolute human garbage walked into a building in San Bernardino, CA and killed 14 people, while seriously injuring 22 others. These two, who I don't care to acknowledge by name because they don't deserve that reward, have terrorist ties or were at the very least, inspired by terrorist groups. The two were killed within hours of the attack, leaving the FBI with an investigation into why they could perform such a terrible act.
During the investigation, the FBI obtained a phone from one of the attackers and thinks that it may contain critical information leading up to the terrorist attack. That phone is an iPhone 5c. Since it is an Apple product, it is encrypted and the FBI has no way of getting inside of it. Because that is the case, they asked Apple to help them do so. Apple declined. Shortly after Apple declined, a federal judge ordered them to cooperate. Apple opposed that order.
In an open letter to customers, Apple CEO Tim Cook laid out his company's reasons for not helping the FBI. The entire letter is worth your time, but the basics are as follows. The FBI, for the most part, wants a backdoor into iOS. They want Apple to create a special version of iOS that allows them to brute force their way into the iPhone 5c that they obtained in this investigation. Apple argues that by doing so, they are opening up a "dangerous precedent" that could allow for any iPhone in someone's physical possession to be unlocked. Their reasoning? Because once you create a key or backdoor, it is "only as secure as the protections around it." In other words, because it exists and could unlock your phone, your neighbor's phone, my phone, and everyone else's phone, it poses a serious risk. There is no guarantee that the FBI or Apple or anyone else that is supposedly using this backdoor for a single use, could keep it safe enough.
I'll let that soak in for a second.
Of course, today, we're talking about iPhones. Should the FBI be given this sort of access, we'll likely be talking about Android phones, your computers, and everything else that you probably want kept secret in life, as well.
While Apple has penned this letter to customers, as far as I know, they still need to officially respond to the federal judge's order. They have a couple of days still to do that and likely will shortly.
At this point, we don't know how this will all shake out, but once Apple tells a judge "No," things should heat up quickly. Until then, you have some time to form an opinion on the matter. If you need help finding out all of the facts, you could read this NPR article. You should also know that WhatsApp's CEO and founder is backing Tim Cook. Google's Sundar Pichai says, through a series of tweets, that allowing for hacking of customer devices and data could "be a troubling precedent." This article on Gizmodo is also a quick read on why this whole situation matters to you.
So that's where we stand with a topic that is quite important to the future of security and encryption on your personal computing devices, as well as government overreach.
As we learn more and this all shakes out, we'll be sure to keep you updated.
Video: Samsung Shares a Brief History Lesson in "Unpacking Samsung"


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En psychologie et en économie, le cadrage est la façon de présenter une décision.
 Concernant la photographie, le cinéma, la télévision, la vidéo, le cadrage désigne l'opération qui consiste à délimiter le champ de la prise de vues.

Voir aussi : cadre, encadrement

redpajama_set_name: RedPajamaWikipedia


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Special Device Help Prevent Suddent Infant Death
Researchers from Germany's Fraunhofer Institute for Reliability and Microintegration IZM in Berlin has developed a new breathing sensor system that help prevent Sudden Infant Death Syndrome (SIDS). This syst...
University Installs Grass Lawn in School Library
Cornell University has built a grass lawn inside their school library as a part of a project of their institution's Department of Design and Environmental Analysis. The department is currently conducting a r...
Wash Your Clothes in a Portable Washing Machine [Video]
Meet, the Scrubba, a portable washing machine, in form of a bag. This wash bag, allows people to do their laundry, on-the-go. The Scrubba is a lightweight, foldable bag that features small nodules to help sc...
Fart-Deodorizing Underwear Sold in Japan
Thanks to Japan's new invention, the Deoest underwear, extreme farters can now release their foul smelling gas and prevent people near them from fainting. It is a fart-deodorizing underwear, created by Profe...
Real Angry Birds, Real Fun
Written on May 18, 2011 by R. Depp
Angry Birds just gets even better -- with 'real" birds invading real life.
Rovio, the creator of the Angry Birds mobile phone game, has made playing even more exciting. Angry Birds has become so popular that customized birthday cakes and plush toys were sold and even a fake movie was created. The latest is a real life version of the game.
The giant version was set up and filmed in Spain's Plaça Nova de Terrassa to promote Deutsche Telekom's new services. As with the mobile version, pigs and their barricades get destroyed in a rather amazing fashion as a street band plays the game's theme song. Watch video after the break!
Read the rest of the article »
Mattel to Produce Angry Birds Toys
Written on January 11, 2011 by R. Depp
After banking on dolls, toy maker Mattel invests on birds and pigs.
After the company earned millions selling Barbie dolls, Mattel likely saw the potential in the one of the top-selling mobile games of the new century. During the recent CES 2011, Mattel presented an Angry Birds-branded playset called "Angry Birds: Knock On Wood." It is consisted of plastic pieces which resemble the red, yellow and black bomb birds. Also included are wooden columns, pig pieces and slingshot launcher. There are point cards for keeping record of the score.
The Angry Birds: Knock On Wood playset will be released in May with a price tag of $15. A card-based Angry Birds game is also planned to be launched.
View Article Source »
Written on October 30, 2013
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La Marcha del Orgullo de las Diversidades Sexuales y Genéricas de Bolivia, es un evento anual que se celebra para conmemorar el Día Internacional del Orgullo LGBT y para promover la visibilidad y el respeto por la diversidad sexual y de género en el país. La primera Marcha del Orgullo LGBT en Bolivia se celebró en la ciudad de Santa Cruz en el año 2000 y desde entonces se ha convertido en una tradición anual en varias ciudades del país. Además de la movilización, se realizan actividades lúdicas y culturales.

A lo largo de los años, la Marcha del Orgullo LGBT en Bolivia ha enfrentado muchos desafíos y ha sido objeto de controversia. Ha sido objeto de críticas por parte de grupos conservadores y ha sido blanco de ataques y amenazas de violencia por parte de algunos individuos y grupos. Sin embargo, la Marcha del Orgullo LGBT ha sido una oportunidad para que la comunidad LGBT en Bolivia se reúna y celebre su diversidad y su orgullo.

En general, la historia de la Marcha del Orgullo LGBT en Bolivia refleja la lucha de la comunidad LGBT por el respeto y la igualdad en un país en el que aún existen muchos prejuicios y discriminación. A pesar de los desafíos, la Marcha del Orgullo LGBT ha sido una oportunidad para que la comunidad LGBT se una y lucha por sus derechos y su visibilidad en la sociedad boliviana.

Historia
Se realizó por primera vez en el año 2000 en la ciudad de Santa Cruz. La fecha elegida fue el 27 de junio, día previo al día internacional del Orgullo LGBT+, que conmemora la violenta intervención policial en el bar Stonewall Inn de Nueva York y el inicio de la lucha moderna por los derechos LGBT. En dicha ocasión se produjeron hechos de violencia, donde una persona arrojó una bomba de gas lacrimógeno en tanto que un grupo de personas persiguió a manifestantes travestis para agredirlas.

En el año 2002 se sumó la ciudad de La Paz.

En las primeras dos marchas por los derechos LGBT en La Paz, en 2003 y 2004, se observan en algunos miembros, muestras de temor de manifestar sus identidades sexuales, donde los manifestantes llevaban máscaras para cuidar su anonimato.

En 2005, se creara el "Movimiento Arcoíris", una alianza orgánica que plantea críticas y cambios a la marcha del movimiento LGBT. Buscando resignificar el carácter político de las marchas (alejándose de ser solo un desfile) así como también cuestiona la idea del "Día del Orgullo Gay" ligado a dichas marchas hasta el momento, porque resultaba excluyente para la diversidad habida entre las personas LGBT; de esta forma, las marchas pasaron a denominarse "Marcha del Orgullo de las Diversidades Sexuales y Genéricas".

En la marcha del año 2007 en La Paz, una bomba molotov estalló dejando varios heridos.

En Sucre, la primera marcha se realizó en 2007; entre 2008 y 2010 se suspendió la marcha, y desde 2011 se reactivó.

En el año 2009, comienzan las marchas en El Alto.

Debido a la pandemia de covid-19, las marchas en los años 2020 y 2021 se suspendieron y se realizaron actividades en línea.

En el año 2022, se realizó la Primera Marcha Internacional de la Mujer, Género-Diversidad y del Orgullo entre localidades bolivianas en conjunto con la zona norte de la provincia de Jujuy de Argentina.

Véase también

 Diversidad sexual en Bolivia
 Día Internacional del Orgullo LGBT
 Matrimonio entre personas del mismo sexo en Bolivia
 Anexo:Cronología de la historia LGBT en Bolivia

Referencias

Enlaces externos
 Queer Fiesta. Hybridity, drag and performance in Bolivian folklore

LGBT en Bolivia
Bolivia
Diversidad Sexual de Bolivia
Historia LGBT de Bolivia
Manifestaciones y protestas en Bolivia
LGBT en 2000


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July 23, 2020 Jessie Kincaid Leave a comment
Today is Glioblastoma Awareness Day. We wanted to share some facts with you all (scroll to end if you just want to see Tom's current status).
Glioblastoma Facts & Figures
Glioblastoma (or GBM) is one of the most complex, deadly, and treatment-resistant cancers.
More than 13,000 Americans are expected to receive a GBM diagnosis in 2020.
GBM accounts for 48 percent of all primary malignant brain tumors.
It is estimated that more than 10,000 individuals in the United States will succumb to glioblastoma every year.
The five-year survival rate for glioblastoma patients is only 6.8 percent, and the average length of survival for glioblastoma patients is estimated to be only 12 to 18 months.
Survival rates and mortality statistics for GBM have been virtually unchanged for decades.
Despite first being identified in the scientific literature in the 1920's, there have only been four drugs and one device ever approved by the FDA for the treatment of glioblastoma.
None of these treatments have succeeded in significantly extending patient lives beyond a few extra months.
Some patients have a glioblastoma upon diagnosis (de novo or primary GBM), while other patients' tumors start as another, lower-grade type of brain tumor and over time progress into a glioblastoma (secondary GBM). A vast majority of GBM diagnoses are de novo.
Mean age at diagnosis is 64.
In addition to being life-threatening, GBM – and its harsh treatments – inflict devastation upon the brain, which controls cognition, mood, behavior, and every function of every organ and body part.
Many patients will lose their ability to work, drive, and a host of other functions that contribute to one's sense of self and independence.
Glioblastoma is also one of the more expensive cancers to treat, often leaving patients and families with major financial hardship on top of the burdens of the disease.
Prominent Americans who've been lost to this type of cancer include: Beau Biden (son of former Vice President Joe Biden, and former Attorney General for the state of Delaware); Gary Carter (Hall of Fame Major League Baseball player); U.S. Senator Edward "Ted" Kennedy (Democratic politician); U.S. Senator John McCain (Republican politician and former presidential nominee); and Edward "Tug" McGraw (Major League Baseball player and father of country music star and actor, Tim McGraw).
Here's the link to today's presentation if you would like to hear more lf the latest on glioblastoma and hear from other survivors and providers:
Watch the Virtual GBM Awareness Day
And now for the update:
It's been just over 4 years since Tom's diagnosis. We recently had Tom's MRI and two spots have persisted. While they don't present as typical tumor, one has grown about 1mm from his last scan while the other faded somewhat. We discussed the option of surgery to remove and analyze the spot with his care team but we all came to the conclusion this week that the spot is too small to warrant surgery and again is not indicative of tumor. Hopefully it will go away on its own like the other spots have. We will re-evaluate at the next scan. We are also going to work on getting a second opinion in the event we need a more in-depth consult in the future. Tom feels great, has no symptoms and is still riding his bike as often as possible. As always, thanks for all of your amazing support!
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