"In a first-ever human clinical trial, an mRNA cancer vaccine developed at the University of Florida successfully reprogrammed patients’ immune systems to fiercely attack glioblastoma, the most aggressive and lethal brain tumor.

The results in four adult patients mirrored those in 10 pet dog patients suffering from brain tumors whose owners approved of their participation.

The discovery represents a potential new way to recruit the immune system to fight treatment-resistant cancers using an iteration of mRNA technology and lipid nanoparticles, similar to COVID-19 vaccines, but with two key differences: use of a patient’s own tumor cells to create a personalized vaccine, and a newly engineered complex delivery mechanism within the vaccine.

“Instead of us injecting single particles, we’re injecting clusters of particles that are wrapping around each other like onions,” said senior author Elias Sayour, M.D., Ph.D., a UF Health pediatric oncologist who pioneered the new vaccine, which like other immunotherapies attempts to “educate” the immune system that a tumor is foreign.

“These clusters alert the immune system in a much more profound way than single particles would.”

Among the most impressive findings was how quickly the new method spurred a vigorous immune-system response to reject the tumor, said Sayour, principal investigator at the University’s RNA Engineering Laboratory and McKnight Brain Institute investigator who led the multi-institution research team.

“In less than 48 hours, we could see these tumors shifting from what we refer to as ‘cold’—very few immune cells, very silenced immune response—to ‘hot,’ very active immune response,” he said.

“That was very surprising given how quick this happened, and what that told us is we were able to activate the early part of the immune system very rapidly against these cancers, and that’s critical to unlock the later effects of the immune response,” he explained in a video (below).

Glioblastoma is among the most devastating diagnoses, with median survival around 15 months. Current standard of care involves surgery, radiation and some combination of chemotherapy.

The new report, published May 1 in the journal Cell, is the culmination of seven years of promising studies, starting in preclinical mouse models.

In the cohort of four patients, genetic material called RNA was extracted from each patient’s own surgically removed tumor, and then messenger RNA (mRNA)—the blueprint of what is inside every cell, including tumor cells—was amplified and wrapped in the newly designed high-tech packaging of biocompatible lipid nanoparticles, to make tumor cells “look” like a dangerous virus when reinjected into the bloodstream to prompt an immune-system response.

The vaccine was personalized to each patient with a goal of getting the most out of their unique immune system...

While too early in the trial to assess the clinical effects of the vaccine, the patients either lived disease-free longer than expected or survived longer than expected. The 10 pet dogs lived a median of 4.5 months, compared with a median survival of 30-60 days typical for dogs with the condition.

The next step, with support from the Food and Drug Administration and the CureSearch for Children’s Cancer foundation, will be an expanded Phase I clinical trial to include up to 24 adult and pediatric patients to validate the findings. Once an optimal and safe dose is confirmed, an estimated 25 children would participate in Phase 2."

-via Good News Network, May 11, 2024

-video via University of Florida Health, May 1, 2024

The most popular browsers in different countries in 2012 and 2022.

by @theworldmaps_

Nope! When Chrome first came to popularity, people switched over to it cause it was “faster” (turns out, it just eats through your device’s CPU) but since then Firefox has upped its game in a major way. Chrome just doesn’t measure up anymore. Plus, nowadays Chrome is just a data harvester designed to show hyper targeted ads - so even if Firefox ain’t for you, it’s still worth ditching Google for a different browser.

Legit though I switched to Firefox and it’s so so so much better

i’m gonna keep reblogging this ad infinitum so yall might as well convert now

Srsly, use Firefox. It's great. If you really do need to do something hat you can only do on Chrome loke a specific plugin, use Chromium instead. It's open-source and handles like chrome.

Also, if you're currently using (desktop) Outlook for e-mail, consider switching to Thunderbird instead. Outlook has reduced support for non-big tech mail-accounts to basically 0. Thunderbird can literally do things outlook can't. Also: no ads!

Renaming "sale price" to "Quarter Tile" in SimPe

Notes on how to change "sale price" in the OBJD resource to "Quarter Tile" in SimPe for versions of SimPe up to and including 0.75.68

The OBJD entry 0x0022 is mis-named in versions of SImPe prior to 0.75.69 as it is used to determine if an object can be placed at quarter-tile offsets and not its "sale price".

Fortunately, it's fairly easy to both rename this entry and move which section it is in. (As it sits better within the "User Placement" section, not the "Catalog Price" section.)

1) Before starting SimPe find out its directory path, you can do this by right-clicking the shortcut and selecting Properties. The info you need is the "Start in:" directory.

2) Start SimPe

3) From the File menu, select Open…

4) Navigate into the "Start in:" directory noted above, then into the "Plugins\pjse.coder.plugin" sub-directory and select the GlobalStrings.package file.

5) Sort the resources (they should all be STR#) by Instance and scroll down to 0x00CC "ObjectDefinition (GLUA) Correct to BV" and select it.

6) In the Plugin View tab, scroll down to entry 0x0022(34) and change it from "sale price" to "Quarter Tile".

(If you want you can change any other entries here, for example, 0x0061(97) from "Vacation Sort" to "Holiday Sort" depending on your language preference.)

7) Commit, save and exit SimPe.

8) With a plain text editor, for example, Notepad, open the file "{Start in:}\Data\objddefinition.xml"

9) In the "<category name="02. Catalog Price">" block, find the block of text <property type="short"> <name>sale price</name> <help>sale price</help> <default>0</default> <index>34</index> </property>

and Cut and Paste it into the "<category name="05. User placement">" block.

10) Change "sale price" to "Quarter Tile". (This step is not strictly necessary as the displayed text is taken from the GlobalStrings.package file, but it's good to keep things consistent.)

11) Save your changes and exit the text editor.

12) Restart SimPe, open a .package file with an OBJD resource and check that it has worked.

I’m begging of you even if you disagree with Israel (rightly so), do not fall into the enemy of my enemy is my friend mentality. Do not forget the atrocities that the Islamic Republic has committed and is committing against its own people, including children. Do not forget Mahsa Amini and Nika Shahkarami and the millions killed by the Islamic Republic.

Sincerely, an Iranian.

hey guys! am i correct in assuming that if my ts2 game crashes in build/buy after a few minutes/ changing categories, that i have too many custom items in game? i don't think it's conflicts because the categories don't matter, and it happens if i take out the new folder of build/buy only and put other new stuff in, but it's solved if i take the new folder out and don't add any new objects.

i need to clean out my objects anyway (i have about 20gb of cc and don't use most of it LOL) so if that's the fix then i will go ahead and put the effort in tomorrow and declutter the catalogs

boost!

Depends, are you regenerating thumbnails? If so, that's totally normal for your game to crash. It just got overloaded with thumbnails. To avoid it, do just tiny bits of going through the catalog, then exit the lot and enter again to do the next batch.

Another possible reason is GUID conflicts (often straight up duplicates, like say, 5 copies of the BB Niche). They cause a surprisingly large number of crashes and resolving those could really help. I recommend picknmix' HCDU+ to look for them.

If neither works, yeah, either some new cc is hella borked or it's time to start cleaning out your dl folder

Words can't describe how much I'm enjoying this

DO NOT USE TEMPLATES TO MAIL YOUR REPRESENTATIVES!

So in case you want to use some sort of template to mail your representatives about the ongoig genocide in Gaza, don't!

To be clear: if you're planning on mailing your representatives about Gaza, DO IT! But DO NOT use a template!

Mail filters are easy to set up and deploy and WILL filter on specific sentences or patterns using regular expressions. If a mail server receives thousands of nearly-identical mails, chances are either the machine employs some sort of machine learning and it'll mark it as spam and disregard them immediately and/or some engineer will type up some extra filters to prevent more mails from coming through and cluttering up inboxes. Make no mistake: this is not hard to do and can be done within minutes.

If you want to get through mail filters, write it yourself. Do not erase typos, do not base your words on templates, but get personal. Do not let your voice get lumped in with spam runs!

Kind regards,

- Someone who has to deal with e-mail filters on a regular basis

So is this like a "don't bother if you can't do this" or a "templates are better than nothing but please try not to" kinda advice?

Super short answer: you can always try with a template, but your odds are better with a personalized mail.

Less short answer: Template mails are much more likely to get filtered as you can just reject all mails containing a selection of phrases, but that doesn't mean there is 0 chance they will get through. There is always a chance. After all, someone does have to bother to set up filters or something that auto-learns. Your odds are much (much much much) better with a personalized mail though.

Detailed answer aka Mail filters 101

So, the way you generally set up mail filters is to go for specifics. You do not want to discard anything legit, after all. For example: what can make phishing difficult to filter, is that you cannot just reject any mail that has the words "paypal" and "password reset" in them. That would filter legit mails too.

This is why filtering on a something like the sentences: "as part of our monthly user inspection program, we have discovered that your password is out of date" + "PASSWORD EXPIRY NOTICE " is a much better approach. Take a few very specific, relatively unique phrasings that keep appearing in the spammy mail and filter on that. It will block that specific "spam run" while still letting legit mails through.

If I were to have to set up a mail filter against "spammy" Palestine mails, I would grab a selection of identical-looking mails and find what they have in common. Then I will select specific phrasings to filter on that would pose a minimal risk of rejecting legit mail that the people or organization I'm setting it up for do want.

Filtering mails on singular words like "Palestine" or "Gaza" or "genocide" is way too broad and would also affect legit mail. By writing your own email, you are more difficult to filter and more likely to get through as your mail will probably not contain the exact same phrasing as other mails.

If your template mail gets filtered, it will either get marked as spam and probably be sent to the spam folder, or it will just be another number increasing the "mails rejected" count in the server logs.

All of this is assuming that the people setting up the filters know what they're doing and are not complete idiots.

Plumb Bob Keep Birthday Screenshot Contest

As part of the birthday festivities, we're having a screenshot contest! Our main page slideshow is both beautiful, and dated. We would like some new images to add to it, and that's where you come in. Put together your best screenshots of any sort of Plumb Bob Keep downloads, and then the community will vote for their top five!

So what are you waiting for? Get out there and start styling those scenes. We want to see your very best efforts to show off what Keepers can do! Questions? Ask one of the mods or in this thread. Be sure to submit your entries to rugrat0ne at the Keep (don't post them here) by April 15th.