https://www.centerforhealthsecurity.org/our-work/exercises/2022-catastrophic-contagion/

Catastrophic Contagion

The Johns Hopkins Center for Health Security, in partnership with WHO and the Bill & Melinda Gates Foundation, conducted Catastrophic Contagion, a pandemic tabletop exercise at the Grand Challenges Annual Meeting in Brussels, Belgium, on October 23, 2022.

The extraordinary group of participants consisted of 10 current and former Health Ministers and senior public health officials from Senegal, Rwanda, Nigeria, Angola, Liberia, Singapore, India, Germany, as well as Bill Gates, co-chair of the Bill & Melinda Gates Foundation.

The exercise simulated a series of WHO emergency health advisory board meetings addressing a fictional pandemic set in the near future. Participants grappled with how to respond to an epidemic located in one part of the world that then spread rapidly, becoming a pandemic with a higher fatality rate than COVID-19 and disproportionately affecting children and young people.

Participants were challenged to make urgent policy decisions with limited information in the face of uncertainty. Each problem and choice had serious health, economic, and social ramifications. 

Ethical Skeptic ☀

@EthicalSkeptic

Dr. Ho

Your enemy now is the passing of time, a lack of general panic-fear, and people seriously examining why 6,400 excess deaths are occurring each week right now.

We will be wise to your tradecraft going forward. This is not going to end well for you.

Quote Tweet

Prof Peter Hotez MD PhD

@PeterHotez

·

9h

For the record: Dr. Fauci has done nothing wrong, except serve our nation. In the meantime, Mr. Musk should know that 200,000 Americans needlessly lost their lives from Covid due to this kind of antiscience rhetoric and disinformation. Elon, I’m asking you to take down this Tweet twitter.com/elonmusk/statu…

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https://mobile.twitter.com/EthicalSkeptic/status/1601999322916311041

https://longevity.technology/news/ai-designed-protein-can-awaken-silenced-genes-one-by-one/

AI-designed protein can awaken silenced genes one-by-one

Gene therapy technique designed by the University of Washington can toggle on individual genes that regulate cell growth, development and function.

By combining CRISPR technology with a protein designed by AI, researchers from the University of Washington School of Medicine in Seattle have been able to awaken individual dormant genes by disabling the chemical “off switches” that silence them through gene therapy.

Longevity.Technology: This gene therapy approach, which is described in Cell Reports, will allow researchers to understand the role individual genes play in normal cell growth and development and diseases such as cancer; it will also broaden our understanding of aging at a genetic level. The new technique controls gene activity without altering the DNA sequence of the genome by targeting the epigenome – the chemical tags and modifications that help package genes in our chromosomes and regulate their activity. Epigenetic modifications affect gene activity and we collect them over time – this build-up of epigenetic markers contributes to aging, but can also affect of the health of future generations as they can be inherited.

Targeting the epigenome was an attractive prospect for the Washington team. “The beauty of this approach is we can safely upregulate specific genes to affect cell activity without permanently changing the genome and cause unintended mistakes,” Shiri Levy, a postdoctoral fellow in UW Institute for Stem Cell and Regenerative Medicine (ISCRM) and the lead author of the paper, says [1].

In the gene therapy research, Levy and her colleagues focused on a complex of proteins called PRC2 that silences genes by attaching a small molecule, called a methyl group, to a protein that packages genes called histones.

PRC2 is active throughout development but plays a particularly important role during the first days of life when embryonic cells differentiate into the various cell types that will form the tissues and organs of the growing embryo. PRC2 can be blocked with chemicals, but they are imprecise, affecting PRC2 function throughout the genome. The goal of the UW researchers was to find a way to block PRC2 so that only one gene at a time would be affected.

To do this, David Baker and his colleagues used AI to create a protein that would bind to PRC2 and block a protein the PRC2 uses to modify the histones. Ruohola-Baker and Levy then fused this designed protein with a disabled version of a protein called Cas9. Cas9 is the protein used in the gene editing process called CRISPR – Cas9 binds and uses RNA as an address-tag. The system allows scientists, by synthesising a specific “address-tag” RNA, to bring Cas9 to a precise location in the genome and cut and splice genes at very specific sites.

However, in this experiment the researchers disabled the cutting function of the Cas9 protein – calling it dCas9, for “dead”. This meant the genomic DNA sequence remained unaltered. However, it can no longer cut, dCas9 can still deliver, functioning as a transport for cargo and delivering it to a specific location. The AI-designed blocking protein was the cargo of the dCas9-RNA construct.

“DCas9 is like UBER,” explains Levy, “It will take you anywhere on the genome you want to go. The guide RNA is like a passenger, telling the UBER where to go [1]. In the new paper, Levy and her colleagues show that by using this technique, they were able to block PRC2 and selectively turn on four different genes. They were also able to show they could transdifferentiate induced pluripotent stem cells to placental progenitor cells by simply turning on two genes [2].

p1

>>17924290

“This technique allows us to avoid bombarding cells with various growth factors and gene activators and repressors to get them to differentiate,” Levy explains. “Instead, we can target specific sites on the gene transcription promoters’ region, lift those marks and let the cell do the rest in an organic, holistic manner [1].”

Finally, the researchers were able to show how the technique can be used to find the location of specific PRC2-controlled regulatory regions from where individual genes are activated – the location of many of these are unknown. In this case, they identified a promoter region –called a TATA box – for a gene called TBX18. Although current thinking is that these promotor regions are close to the gene, within in 30 DNA base pairs, they found for this gene the promoter region was more than 500 base pairs away.

“This was a very important finding,” said Ruohola-Baker. “TATA boxes are scattered throughout the genome, and current thinking in biology is that the important TATA boxes are very close to the gene transcription site and the others don’t seem to matter. The power of this tool is that it can find the critical PRC2 dependent elements, in this case TATA boxes that matter [1].”

Epigenetic modifications decorate broad regions of the genome in normal and abnormal cells. However, the minimal functional unit for the epigenetic modification remains poorly understood, Ruohola-Baker notes: “With these two advances, AI-designed proteins and CRISPR technology, we can now find the precise epigenetic marks that are important for gene expression, learn the rules and utilize them to control cell function, drive cell differentiation and develop 21st century therapies [1].”

[1] https://bitDOTly/3usm1x2

[2] https://www.cell.com/cell-reports/fulltext/S2211-1247(22)00184-X

>>17924290

https://www.cell.com/cell-reports/fulltext/S2211-1247(22)00184-X

dCas9 fusion to computer-designed PRC2 inhibitor reveals functional TATA box in distal promoter region

Highlights

•

EBdCas9 inhibits PRC2 function in precise genomic locations

•

EBdCas9 upregulates TBX18, p16, CDX2, and GATA3 by de-repression

•

EBdCas9 identifies PRC2-controlled, active TATA box >500 bp upstream of TBX18 TSS

•

EBdCas9 is sufficient to induce transdifferentiation and repress cancer cell cycle

Summary

Bifurcation of cellular fates, a critical process in development, requires histone 3 lysine 27 methylation (H3K27me3) marks propagated by the polycomb repressive complex 2 (PRC2). However, precise chromatin loci of functional H3K27me3 marks are not yet known. Here, we identify critical PRC2 functional sites at high resolution. We fused a computationally designed protein, EED binder (EB), which competes with EZH2 and thereby inhibits PRC2 function, to dCas9 (EBdCas9) to allow for PRC2 inhibition at a precise locus using gRNA. Targeting EBdCas9 to four different genes (TBX18, p16, CDX2, and GATA3) results in precise H3K27me3 and EZH2 reduction, gene activation, and functional outcomes in the cell cycle (p16) or trophoblast transdifferentiation (CDX2 and GATA3). In the case of TBX18, we identify a PRC2-controlled, functional TATA box >500 bp upstream of the TBX18 transcription start site (TSS) using EBdCas9. Deletion of this TATA box eliminates EBdCas9-dependent TATA binding protein (TBP) recruitment and transcriptional activation. EBdCas9 technology may provide a broadly applicable tool for epigenomic control of gene regulation.

https://www.cell.com/cell-reports/pdfExtended/S2211-1247(22)00184-X

>>17924314

see

>>17924290

and

A Nano 3D Printer That Prints Nano-Sized Objects

https://www.nanalyze.com/2020/04/nanotechnology-3d-printing-by-nanoscribe/

an Israeli 3D printing startup that’s developing their flagship machine “capable of micron-resolution printing, with the capability to print thousands of parts in a single build.” The ability to 3D print objects at a micro or nanoscale opens doors for many new applications. Today, we’re going to look at Nanoscribe, a company that’s built the “world’s highest resolution 3D printer designed for ultra-precise and rapid microfabrication.”

About Nanoscribe

Click for company website

Spun off from the Karlsruhe Institute of Technology in 2007, Nanoscribe’s founders are leading scientists in the field of nanophotonics. In other words, they’re experts in studying how light behaves at a nanoscale. (That’s one of the things that makes nanotechnology so interesting. Under 100 nanometers, everything starts to behave differently.) The German company has raised an undisclosed amount of funding to build what they’re calling the “highest resolution commercially available 3D printer” dubbed the “Photonic Professional GT2” which can create structures just 30 nanometers across. (To put this in scale, a human blood cell is 8000 nanometers across.) In August of last year, they opened an office in ‘Murica (Bahstun to be exact) and three months later sold their 200th machine. Let’s try to understand what their nano 3D printers do and the technology that powers them.

Two-Photon Polymerization

They say that you should be able to explain your business plan to a nine-year-old – during the duration of a 30-second elevator ride. For Nanoscribe, they create very tiny 3D objects that can’t even be seen with the naked eye using photons, the basics units of light. The technique is called 2–Photon Polymerization (2PP) and it’s kind of cool to visualize. Some fellow who wrote a book on the topic describes the process as follows:

The technique is also referred to as two-photon polymerization because the polymerization of the photoresist is initiated by a two-photon process—that is, it requires the absorption of two photons at the same location simultaneously (or within a very short time of one another). This only occurs in a small volume at the center of the laser focus where the intensity is high enough. By sweeping the laser beam through the photoresist, optical quality 3D structures can be reproducibly fabricated with voxel sizes down to ∼ 100 ×100 × 300 nm3.

Credit: Light Robotics: Structure-Mediated Nanobiophotonics

Nanoscribe offers an entire product family of resins and other materials that can be used to print the tiniest structures on a variety of different substrates like glass, silicon wafers, photonic, and microfluidic chips. The Nanoscribe website contains stories of some very remarkable applications for the technology including:

A filtering membrane that can capture circulating tumor cells

A 3D printed scaffold that enables tailor-made neuronal networks

A 3D-printed microscaffold cochlear implant

Self-propelled microscopic donuts that can transport particles

The world’s smallest microstents made of soft and responsive components

A 3D printed micro valve for treating glaucoma (see below)

In addition to the above examples, here are some areas of research that 2PP technology is actively being used in.

Microfluidics – Various microfluidic elements such as filters, mixers, and capillary pumps

MEMS Devices– Remotely controlled movable micromachines can be printed with the device

Biomedical Engineering – Their users commonly fabricate 3D scaffolds to study cell growth, migration or stem cell differentiation on biomimetic structures

3D Microoptics – Single micro-lenses, freeform optics, and compound lens systems can be printed without the need of post-print assembly

>>17924339

In addition to the Photonic Professional GT2 printer, Nanoscribe is also developing another machine that does equally cool things.

Nanoscribe’s Quantum X

The Nanoscribe Quantum X is the self-described “world’s first Two-Photon Grayscale Lithography system for maskless microfabrication of refractive and diffractive microoptics.” There’s a lot going on here, so let’s break down each item. We already understand how 2PP technology works for 3D printing, so how does it work for lithography? In fact, what is lithography anyways?

The entire semiconductor industry revolves around creating low-cost silicon chips that contain hundreds of millions of transistors using a technique called lithography. It’s best described as follows:

Lithography is the main tool used in IC manufacturing to record a binary image (pattern) on a layer of photosensitive material (photoresist) spun over a substrate, generally a semiconductor wafer.

Credit: Reference Module in Materials Science and Materials Engineering, 2016

There’s also something called “maskless lithography” which means you can skip some steps in the process which makes it easier to do research for low-volume, special purpose manufacturing. (This is literally the primary value proposition behind 3D printing – create prototypes quickly without having to create an entire manufacturing line to do so.) Turns out that something called “Beer’s law” imposes strong limitations on today’s maskless lithography devices. Nanoscribe has been able to bypass these limitations with their new machine which was released in Summer of 2019 and appears to be taking reservations still.

Credit: Nanoscribe

The fully-automated system uses a software wizard to guide designers and engineers through print job creation along with three cameras to monitor the progress.

Nanoscribe’s Growth

Nanoscribe isn’t a funded startup because they appear to be cash-flow positive having achieved profitability for twelve years in a row now while plowing back 25% of revenues into R&D. The company’s 70 employees provide the hardware, software, materials, and processes as a complete solution to more than 1,500 active operators of their systems located in over 30 countries. A key partner and investor for Nanoscribe is Carl Zeiss AG, a German manufacturer of optoelectronics and optical systems with over 7 billion in revenues for 2018. Says Nanoscribe, “ZEISS has supported Nanoscribe from the very beginning with technology and consulting and also made a major financial contribution through the acquisition of shares in September 2008.”

Conclusion

At some point, the investment community lost the term “nanotechnology” and just started to call it by different names. In a past article titled “Ginkgo Bioworks – Nanobots Are Finally Here,” we talked about how various aspects of synthetic biology bear a strong resemblance to how nanotechnology was originally envisioned by Eric Drexler in his book Engines of Creation. Ginkgo believes that biology itself is the most efficient manufacturing method on this planet, and they’re using it to create new organisms that do mankind’s bidding.

In the case of Nanoscribe, they’re able to create smooth 3D structures at a nano-level which is an incredible accomplishment. Much of this work appears to be in early stages, and the company mentions their research being highlighted in more than 700 peer-reviewed journal publications. Remember all that talk about nanobots? If you were going to build one, you’d probably want to start by looking at what Nanoscribe’s nano 3D printers can do.

Want to know what 30 tech stocks we own right now? Want to know which ones we think are too risky to hold? Become a Nanalyze Premium member and find out today!

>>17924326

Quantum AI is building proteins that can control genetic expression in humans

>>17924353

>>17924314

>>17924377

>>17924382

>>17924383

https://pubmed.ncbi.nlm.nih.gov/25207063/

In Vitro Effects of Ivermectin and Sulphadiazine on Toxoplasma gondii

Abstract

Objective: Ivermectin and sulphadiazine were tested individually to determine their in vitro effects on Toxoplasma gondii grown in human epidermoid larynx carcinoma (Hep-2) cell culture.

Study design: In-vitro study.

Material and methods: Toxoplasma growth was quantities by an enzyme immunoassay performed directly on the fixed cultures, using a rabbit anti-T. gondii immunoglobulin G as the first antibody and a phosphatase-labeled anti-rabbit immunoglobulin G as the second antibody. For each drug, regression models were used to quantify the relationship between optical density values and antimicrobial agent concentrations in the cultures.

Results: The 50% inhibitory concentrations (IC50) of ivermectin and sulphadiazine were found to be 0.2 μg/mL and 7.3 μg/mL after 48 h of exposure, respectively. None of the concentrations tested for each drugs demonstrated toxicity to Hep-2 cells after 72 h of incubation.

"Conclusion: These results indicate thativermectin significantly inhibited replication of the tachyzoites of T. gondii RH strain."

>>17924392

it can with some help

https://pubmed.ncbi.nlm.nih.gov/25207063/

In Vitro Effects of Ivermectin and Sulphadiazine on Toxoplasma gondii

Abstract

P-glycoprotein, which is encoded by the multi-drug resistance gene (MDR1), highly restricts the entry of ivermectin into the brain by an ATP-driven efflux mechanism at the blood-brain barrier.In dogs with a homozygous MDR1 mutation though, ivermectin accumulates in the brainand provokes severe signs of neurotoxicosis and even death. In contrast to ivermectin, selamectin is safer in the treatment of MDR1 mutant dogs, suggesting that selamectin is transported differently by P-glycoprotein across the blood-brain barrier. To test this, we applied selamectin to mdr1-deficient mdr1a,b(-/-) knockout mice and wild-type mice. Brain penetration, organ distribution, and plasma kinetics were analyzed after intravenous, oral, and dermal spot-on application in comparison with ivermectin.We found that in vivo both macrocyclic lactone compounds are substrates of P-glycoprotein and that these strongly accumulate in the brain of mdr1a,b(-/-) knockout micecompared with wild-type mice at therapeutic doses of 12 mg/kg selamectin and 0.2 mg/kg ivermectin. However, selamectin accumulates to a much lesser degree (5-10 times) than ivermectin (36-60 times) in the absence of P-glycoprotein. This could explain the broader margin of safety of selamectin in MDR1 mutant dogs. In liver, kidney, and testes, ivermectin and selamectin accumulated less than four times as much in mdr1a,b mutant mice as in wild-type mice. Breast cancer resistance protein (Bcrp)-deficient bcrp(-/-) knockout mice were also included in the application studies, but showed no differences in brain concentrations or organ distribution of either ivermectin or selamectin compared with wild-type mice. This indicates that Bcrp is not a relevant efflux carrier for these macrocyclic lactone compounds in vivo at the blood-brain barrier.

>>17924419

specialists on special lists..

And?

btw it is against many laws to target based on medical condition, mental capacity/IQ, or 'disability'.

>>17924422

>Get close to

children in Haiti

>>17924484

ain't no problem.