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Thus, dual specificity inhibitors and combinatorial drug target approaches have been considered. However, a challenge in the development of PI3K inhibitors for antitumor therapies has been the redundancy within the PI3K/AKT/mTOR pathway and the ability of compensatory pathways to emerge, resulting in clinical resistance ( 21). Tumors containing PIK3CA mutations may reflect enhanced dependence on this prosurvival pathway and may predict enhanced sensitivity to PI3K pathway inhibition ( 22). #Aarons cube signal path driversActivating mutations in the PI3K p110α (PIK3CA) subunit are major drivers of many cancer types, including endometrial, ovarian, colorectal, bladder, lung, and breast cancer ( 21). Like CHK1, PI3K is also involved in HRR class1A PI3K isoforms act as a sensor of genomic instability by regulating the recruitment of the Nbs1 sensor protein to double-strand breaks, and by promoting Rad51 recombinase foci formation ( 19, 20). The PI3K/AKT/mTOR signaling pathway controls many biological processes, including cell growth, survival, proliferation, and metabolism, both under normal physiologic conditions, as well as in pathologies, such as cancer ( 18). The clinical benefit rate at 3 months across all tumor types was a modest 29%, suggesting that further evaluations in SCC should focus on combination therapy and/or biomarker-selected populations ( 6, 7). In an expansion cohort of patients with advanced squamous cell carcinoma (SCC) who received prexasertib at the recommended phase II dose (RP2D) of 105 mg/m 2, the most common treatment-related treatment-emergent adverse event (TEAE) was grade 4 neutropenia (71% ref. The primary toxicities of prexasertib monotherapy in the dose escalation phase were hematologic and included neutropenia, leukopenia, anemia, and thrombocytopenia ( 6). In the phase I study (NCT01115790), single-agent prexasertib therapy was the first CHK1 inhibitor to achieve antitumor objective responses in patients with advanced cancer ( 6). Prexasertib (LY2606368) is an adenosine-5′-triphosphate competitive inhibitor of CHK1, which induces DNA damage, including double-strand breaks and chromosomal fragmentation ( 17). Because of this, CHK1 inhibitors have been explored as an antitumor strategy, not only as amplifiers of DNA damage in combination with radiotherapy and genotoxic chemotherapy, but also as monotherapy or in combination with other targeted agents ( 6–16). Inhibition of CHK1, therefore, abrogates checkpoint control, prevents DNA damage repair, and can promote mitotic catastrophe and subsequent apoptosis ( 1). Importantly, CHK1 also regulates homologous recombination repair (HRR) and promotes resolution of replication stress by stabilization of active replication forks ( 3, 5). In response to DNA damage, CHK1 phosphorylates and inactivates the substrate CDC25C, resulting in CDK1/cyclin B1 inhibition and culminating in G 2–M-phase cell-cycle arrest ( 4). Checkpoint kinase 1 (CHK1) is a serine threonine kinase activated downstream of the checkpoint transducer, ataxia telangiectasia mutated and Rad3 related (ATR refs. Stringent checkpoint control is a key cellular mechanism that prevents propagation of genotoxic lesions by pausing cell-cycle progression to allow for DNA repair prior to entering mitosis or to promote apoptosis in cells with unrepaired lesions ( 1). It is giving "Unable to load source file" error. But I couldn't get the data onto the map. I have downloaded the sample file from and placed it in the same folder as web page. I am trying to add a collection of pushpins to Virtual Earth using georss format. Getting "Unable to load source file" Error in Importing Data into shape layers Hi,. #Photostack api how to#As part of the integration, Windows Live Expo would have to provide the appropriate parameters to the InsertFP or CalculateFP library functions that are provided with the sample code.Īny idea how to implement this code snippet into Windows Live Expo Tag: PhotoStack Gadget Server-side scripting capability on the Windows Live Expo is required for this integration, as the script needs access to a secret transaction key that would be stored securely in the Windows Live Expo¡¯s Web server. The above example shows the call being made in an ASP scripting environment. This function would have to be called within a server-side script on the Windows Live Expo Web server. The function InsertFP is provided by the gateway and can be downloaded from the Merchant Interface (Virtual Terminal). API login ID (merchant ID) would be associated/linked with Windows Live Expo user ID. The transaction amount should not change after the fingerprint is generated. The function used to generate the fingerprint takes these fields (amount, transaction key, API login ID, and sequence number). A sequence number should be generated and the total amount of the transaction calculated before the call to generate the fingerprint is made. Clicking on the button will take the user to the gateway¡¯s secure Payment Form.Ī call to generate the fingerprint should be made when the button is clicked and before the Payment Form request is made to the gateway. The result of this HTML code snippet is a button. It shows that the fingerprint, time stamp, and the sequence number are inserted into the HTML form POST along with API login ID and other required fields. The following HTML code is recommended by Authorize.Net and along with the server-side script represents the minimum data that would need to be inserted into a page to provide a connection to the system (payment gateway). Simple Integration Method (SIM) is one of Authorize.Net¡¯s recommended connection methods uses scripting techniques to authenticate transactions with a unique transaction fingerprint. Authorize.Net and Windows Live Expo Integration Is there an API that would enable Authorize.Net (payment gateway) and Windows Live Expo integration. #Photostack api Pc#Uninstalling those and restarting PC helped - Messenger showed up and is forking fine (for now).
That was really the first air pollution problem that demonstrated to people that we could have an impact beyond our local environment. What inspired you to pursue this line of research, and what have been some of your key findings?Īt the time I was doing my graduate studies, acid rain was emerging as a big problem. There’s an opportunity to deal with both air pollution and climate change at the same time, and move us in a better direction for sustainability. I also plan to point out that those same pollutants play a big role in climate change as well. Even something like air pollution, which we have traditionally felt has been a local or regional problem, is really a global problem, and it is having a profound impact on the health of the planet-largely human health and ecosystem health. The main point I wish to make is to remind the audience that we all live in one environment. What are you hoping to convey to people during your lecture? What do you hope they might take away from it? Iowa Now caught up with Carmichael to discuss his upcoming lecture and the work that has spanned his entire career. Cecil Award in 2012, NASA Group Achievement Awards in 20, and the Regents Faculty Recognition Award in 1998. “I still have great fun doing this,” he says.Ĭo-director of the UI Center for Global and Regional Environmental Research since 1991, Carmichael has won numerous awards, including the American Institute of Chemical Engineers Lawrence K. A member of the UI faculty since 1978, Carmichael has not deviated much from the topic that fascinated him in his graduate studies. 19, in the fourth-floor assembly hall of the Levitt Center for University Advancement.Ĭarmichael earned a BS in chemical engineering from Iowa State University in 1974 and a PhD from the University of Kentucky in 1979. Growing up in a small town in Illinois, Gregory Carmichael had no idea that a career in engineering would take him all over the world while researching one of the most pressing issues facing our planet.įor nearly 40 years, the Karl Kammermeyer Professor of Chemical and Biochemical Engineering at the University of Iowa has been studying air quality and the worldwide impact of air pollution.Ĭarmichael, who also serves as director of the UI Informatics Initiative, will deliver the 34th annual UI Presidential Lecture, “What Goes Around, Comes Around: The Global Reach of Air Pollution,” at 3:30 p.m. #INKLET LOOM HOW TO#Like I said, if you're like me and want a Wacom but haven't had the cash or inclination to spend on it, Inklet could be the stepping stone you're looking for. Learning how to weave narrow patterned bands on an inkle loom allowed Kate Davies to reflect upon the interconnections between different cultures and. Weave intricate patterns and embellish with different types of yarns, beads and colors. The loom is designed to create long, very strong braids. Wood is unfinished New Zealand Silver Beech. The Pogo Sketch stylus is only required for pressure sensitivity, but it's a very reasonable $15. A smaller version of the Ashford Inkle loom, this is a small, very portable inkle loom for making belts, bracelets, ties, straps and trims. The software is $24.95, and their website has been brought to its knees by recent press, so you can download it from Apple's site if you can't reach it the official way. Inklet requires Snow Leopard to work, so if you're running anything pre-10.6, you're out of luck. It's not as big or probably as sensitive as a commercial Wacom tablet, but just for doodling and messing around, it's a much cheaper solution. Unfortunately, the trackpad doesn't have sensitivity built-in (it can only tell when you're touching, not how hard you're pushing), but with Ten One's Pogo Sketch stylus, which I presume sends pressure information back to your Macbook somehow, you can get that "line thickness" functionality - press harder for a thicker line, or less for a thinner line. The program uses the multitouch trackpad interface to sense where and when you're touching the pad, and then translates that into "drawing" marks just like a Wacom pen tablet. Now here's a fascinating app - Inklet is a new Mac app by Ten One Design that purports to turn your Macbook's trackpad into a tablet-style input. Start the game's launcher, go to 'Options', click 'DLC Settings' and make sure that 'yamc.dzip' is enabled at the very bottom. dzip files to The Witcher 2\CookedPC folder. #THE WITCHER 2 ASSASSINS OF KINGS VERSION 2 MOD#Yet Another Mod Compilation 1.1 - Extract the 2. Even if you have a strong graphics card, RTX gpus have some problems with the game, so keep that in mind. If you keep it turned off, you'll double or even triple your frames depending on the resolution you're playing on. Ubersampling makes the game less stable, and I can't recommend it unless you have a beastly pc. To prevent crashes, I advise you not to use the launcher and launch the game straight from witcher2.exe located in The Witcher 2\bin folder via a shortcut. I'll provide instructions that should work for most people. I did my testing on a couple of pcs and I'm satisfied with the results, but your mileage may vary. Crashes can occur, but its tough to say if you'll experience them until you do. The downside is that its stability is hardware dependent. It also increases the vegetation rendering distance - an engine limitation the game has been suffering from since release. The second optional step replaces the vanilla environment, character, weapon and armor textures with 4k textures. The game stability is identical with the vanilla game, so if ANY crashes happen, it's not mod related. The first optional step introduces only minor texture and animations changes. If you don't like either, you can just ignore them. The optional steps cancel each other out, so you must pick one. This modding guide is divided in three steps - 1 mandatory and 2 optional. I'll appreciate it if you take five minutes of your time and like/endorse the work of the modders that made this possible. 99% of the code in this compilation is other people's hard work, so I'll go into details about the fixes and I'll link every mod that has been used. That's why there's only 1 mandatory mod in this guide. For that reason, I've combined all conflicting mods and packed the edited scripts into one main mod compilation. Modding The Witcher 2 can be a slow, boring and even difficult process, especially if you have never done it before and you need to manually update, and combine outdated mods. It also includes lore-friendly character textures and additional animations as optional files. This guide's main goal is to provide a balanced experience by fixing gameplay bugs, introducing secondary gameplay mechanics and other quality of life features. #THE WITCHER 2 ASSASSINS OF KINGS VERSION 2 PATCH#It should be compatible with the steam and retail versions as long as they're patched to patch 3.4. This modding guide is written for The Witcher 2: Assassins of Kings Enhanced Edition version 3.5.0.26 (A) from GOG. #HALF LIFE SOURCE CODES FULL#This is a trailer for a Nightmare on Elm Street Platinum DVD which is in the main directory on the disc.Half-Life was the pioneer of interactive storytelling, allowing players to remain in full control of their character while engaging in memorable dialogue that would typically be relegated to a cutscene. This seems to be from an earlier version of the Shotgun when it had different colors, but the model used by the Scientist was never updated when the model was changed to the final's textures. It has a white rear, a gray stock, and a gray body, along with a much higher resolution texture. However, this shotgun uses a completely different texture than the actual Shotgun item model. The Scientist is armed with a Shotgun (with the internal name scigun.mdl) and will point it at the player before putting it down. Near the end of Lambda Core, the player will see a double glass door with a Scientist and a Security Guard on the otherwise. The game additionally only uses one frame of a full sprite animation. The Alien Grunt sprite used to simulate the horde of Alien Grunts in the bad ending appears to be based on the design seen in the 1997 prototype, not the final's. It is larger than the WON version and uses a solid orange color instead of orange with black borders. The in-game font in the Steam version is completely different. In the Steam version, it is now located on its own window and overlays the pause menu. In the pre-Steam versions of Half-Life, the console slides down from the top of the screen when activated. Steam Half-Life's GUI looks identical to the Steam GUI back during its 2003 launch. Also gone are many menu options, including Hazard Course, Custom Game, View Readme and Previews. Gone was a locked 640x480 menu with separate menu options, replaced with a menu that scaled with the game's resolution. When Valve re-released the game on their Steam service, they replaced the main menu. This was removed in versions 1.1.0.8 and after. In the older versions of retail Half-Life, taking fall damage or strafing left and right would result in the player's screen being tilted slightly. The Gina, Gordon, HGrunt, and Scientist multiplayer models were replaced with copies of the Helmet multiplayer model. The German version of the game removes the breasts (and the associated jiggle physics) the Female Assassins have. by shooting specific lights in a certain order, or performing some other secret action. #HALF LIFE SOURCE CODES MOD#Some map edits (or AMX Mod plugins) provide a way to open this door and enter the room - e.g. No one I told this believed it, by the way. The solution was to disable access to the room rather than deleting the room. It existed right up till the last minute before the map was released, and so when the decision to remove it was made, only a very minor change to the level was permitted. Pratt: Ok, once and for all, the “blue room” in crossfire - why is it there, and is there really any way in?ĭario: I could fill an encyclopedia with the number of emails I was sent about this blue room! There's actually no way in there. Inside the room is a spiral ramp leading to a crossbow, ammunition, and HEV suit batteries.ĭario Casali provides an explanation for the "Blue Room" in an interview with Planet Half-life from 2004. It is also visible when using render commands like r_drawflat, gl_wireframe, etc. It is visible in-game by setting off explosions around it (the scorch mark decals do not cross over from the wall to the blocking entity), but cannot be opened. In the room with the Longjump module and HEV charger, there is a "wall" entity blocking a passage to a secret room. Interestingly, if this triangle is touched while running Half-Life in the Xash3D source port, it will transport the player two maps ahead, however it'll properly position them near the starting elevator, albeit without their HEV suit, weapons, or ammunition, acting similarly to if the player attempted to directly load the map through the console. The switch also exists in the multiplayer level lambda_bunker, but will crash the game if used. #HALF LIFE SOURCE CODES HOW TO#Walking towards it will either crash the game (if you're running the game in Software mode, running in OpenGL or Direct3D mode will apparently stop the game from crashing) or send you 2 maps ahead (the map where you fire the tank to open the door that takes you to the lambda lab), floating on the ceiling, dead.Īttempting this in the Source version will exit the level and return to the main menu because the game doesn't know how to properly transition into the map the triangle sends you to. If one noclips inside, the player will see a red triangle. In the chapter 'Forget About Freeman', there is an elevator with a closed door at the beginning. Two English players have won the World Cup Golden Boot.Three people have won the World Cup as a player and as a coach.The record number of World Cup goals is 16, scored by who?.In which World Cup did Diego Maradona score his infamous 'Hand of God' goal?.The 2026 World Cup will be hosted across three different countries.Which country has appeared in three World Cup finals, but never won the competition?. Three countries have won the World Cup twice.Which country has won the most World Cups?.Which country won the first ever World Cup in 1930?.There have been two World Cup trophies.Shane Long (for Southampton vs Watford in 2018-19).Pierre-Emerick Aubameyang, Mohamed Salah and Sadio Mane.Patrick Vieira, Richard Dunne and Duncan Ferguson.Sadio Mane (2 minutes 56 seconds for Southampton vs Aston Villa in 2015).The fastest goal scored in Premier League history came in 7.69 seconds.Which three players shared the Premier League Golden Boot in 2018-19?.How many clubs competed in the inaugural Premier League season?.With 202 clean sheets, which goalkeeper has the best record in the Premier League?.Which team won the first Premier League title?.When was the inaugural Premier League season?.With 260 goals, who is the Premier League's all-time top scorer?. Three players share the record for most Premier League red cards (8).Which player, with 653 games, has made the most Premier League appearances?. Few onlookers could deny that it is a very well-proportioned and sculpted sedan. I was at the vehicle’s global reveal at the L.A Auto Show in November, and the audible buzz by the assembled media when the cover was pulled back was the kind of reception a supercar reveal elicits. What is a stroke of genius in the new Sentra is the styling, inside and out. Anecdotally, when I ask people who own cars with paddle shifters how much they use them, the typical response goes something like, “In the first month I used them but not much since then.” Again, a non-scientific study, but does indicate paddle shifters on non-performance vehicles falls into the just-because-you-can-do-it-doesn’t-mean-it-is-a-good-idea-category. Not that I’m a huge fan of them, just seems that it is a trend that has migrated from performance vehicles to more mundane rides. The CVT was perfectly suitable for the sedan, though I do find it puzzling that steering-wheel paddle-shifters are not available in any trim. #Nissan sentra reditr manual#Contributing to that fun-to-drive quality is the fact the new model is two inches wider and 2.2 inches lower than the 2019 version, providing a lower centre of gravity and a more stable stance.Īs the model name implies, it was outfitted with a continuously variable transmission (CVT), though the base S trim is available with…wait for it…a six-speed manual transmission (that cheering you hear is from automotive journalists the country over). These new updates were the highlights of my week in the Sentra SR CVT tester I had, the improved ride quality, handling and performance of the compact sedan evident from the first corner. This advertisement has not loaded yet, but your article continues below. |
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