Disease: Dystrophic epidermolysis bullosa (DEB) pruriginosa *Note: A novel vwf variant was found in this patient with these other variants in COL7A1 gene

Patient(s): 17 YO Korean male

Variant: VWF NM_000552.5: c.3310C>T p. (R1101W) Located in exon 26

Hadn't been reported previously Variant found to be inherited in trans from family analysis

According to the paper, they have classified with with ACMG guidelines as likely pathogenic.

Reasoning: Variant absent in the Korea Ref Genome Database and Allele Freq = 0.00086% in gnomAD (Evidence: PM2)

Variant detected in trans with another well-known pathologic variant (c.5797C>T) (Evidence: PM3)

Multiple missense variants are known to be pathogenic in RDEB (Evidence: PP2)

Various computational in silico predictive programs reported the variant as pathogenic (Evidence PP3)

for - t-SNE - youtube - t-SNE - high dimensionality space

for - t-SNE - youtube - t-SNE explanation - high dimensionality space - dimensional reduction

https://www.sclaz.com/

https://www.youtube.com/watch?v=x0h13Vq4rMc

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As the two man prepare to fight. Florinda is in a moral crisis, unsure whether to pray for her brother or her lover. This is another display of violence by man affecting the ladies.

Arle Lommel Senior Analyst at CSA ResearchSenior Analyst at CSA Research

One of the most interesting aspects of writing about AI and LLMs right now is that if I say anything remotely positive, some people will accuse me of being a shill for Big AI. If I say anything remotely negative, others will accuse me of being insufficiently aware of the progress AI has made.

So I will put out a few personal statements about AI that might clarify where I am on this:

1. AI is not intelligent, at least not in the human sense of the word. It is a sophisticated tool for drawing inference from binary data and thus operates below a symbolic level.

2. AI, at least in the guise of LLMs, is not going to achieve artificial general intelligence (AGI) now or in the future.

3. AI is getting much better at approximating human behavior on a wide variety of tasks. It can be extremely useful without being intelligent, in the same way that an encyclopedia can be very useful without being intelligent.

4. For some tasks – such as translating between two languages – LLMs sometimes perform better than some humans perform. They do not outperform the best humans. This poses a significant challenge for human workers that we (collectively) have yet to address: Lower-skilled workers and trainees in particular begin to look replaceable, but we aren’t yet grappling with what happens when we replace them so they never become the experts we need for the high end. I think the decimation of the pipeline for some sectors is a HUGE unaddressed problem.

5. “Human parity” is a rather pointless metric for evaluating AI. It far exceeds human parity in some areas – such as throughput, speed, cost, and availability – while it falls far short in other areas. A much more interesting question is “where do humans and machines have comparative advantage and how can we combine the two in ways that elevate the human?”

6. Human-in-the-loop (HitL) is a terrible model. Having humans – usually underpaid and overworked – acting in a janitorial role to clean up AI messes is a bad use of their skill and knowledge. That’s why we prefer augmentation models, what we call “human at the core,” where humans maintain control. To see why one is better, imagine if you applied an HitL model to airline piloting, and the human only stepped in when the plane was in trouble (or even after it crashed). Instead, with airline piloting, we have the pilot in charge and assisted by automation to remain safe.

7. AI is going to get better than it is now, but improvements in the core technology are slowing down and will increasingly be incremental. However, experience with prompting and integrating data will continue to drive improvements based on humans’ ability to “trick” the systems into doing the right things.

8. Much of the value from LLMs for the language sector will come from “translation adjacent” tasks – summarization, correcting formality, adjusting reading levels, checking terminology, discovering information, etc. – tasks that are typically not paid well.

44:17 Private Balance + Government Balance + Foreign Balance = 0 (I-S)+(G-T)+(X-M)=0

In the black southern community, daughters were punished more severely than their brothers. This is because of the already existing gender expectations placed on black women. The girls were always expected to remain quiet, however, it is sometimes possible for boys to interject as they have the possibility to preach in a church.

The only speech that was deemed orthodox for women to use, was talking into thin air. By doing that it inherently silenced their voice while giving them the illusion of actually being heard. On the contrary, black male preachers were to be heard and remembered.

The southern black community had a hierarchy for gender roles and children. Black males typically dominated preaching within the church which led to the women being dominate in "preaching" within the household. The kids were not allowed to give their own opinions on the topics discussed within the house as it was seen as them trying to be "equals" with the adults.

https://www.repubblica.it/economia/2024/08/26/news/energia_gas_geopoltica_impatto_su_politiche_di_aziende_su_clima_emissioni-423457597/

Scadden, David T. Approved Home Study Course in Typewriter Repair and Service. Little Falls, NJ: Typewriter Repair School, 1959. https://site.xavier.edu/polt/typewriters/homestudycourse.pdf.

2024 werden 6% mehr Menschen auf Kreuzfahrtschiffen unterwegs sein als vor der Pandemie. Neue Studie von Transport & Environment zum Wachstum dieses besonders energieintensiven Teils der Tourismusindustrie. https://www.theguardian.com/environment/article/2024/aug/07/cruisezilla-passenger-ships-have-doubled-in-size-since-2000-campaigners-warn

Case: Female Patient #1, Female, Japanese

DiseaseAssertion: UCD/OTCD

FamilyInfo: N/A

CasePresentingHPOs: Childhood onset (HP:0011463)

CaseHPOFreeText: Onset at 2 years

CaseNOTHPOs:

CaseNOTHPOFreeText: 16% OTC activity

CasePreviousTesting:

Variant: NM_000531.5:c.67C>T (p.Arg23*)

ClinVarID: 97292

CAID: CA224742

gnomAD:

Case: Patient #38, Female, Chinese

DiseaseAssertion: UCD/OTCD

FamilyInfo: No family history of disease, mutation is inherited

CasePresentingHPOs: Hyperammonemia (HP:0001987), oroticaciduria (HP:0003218), vomiting (HP:0002013), coma (HP:0001259), lethargy (HP:0001254), seizures (HP:0001250), childhood onset (HP:0011463)

CaseHPOFreeText: Elevated plasma ammonia at 190 umol/L (Normal: 9-30 umol/L), Elevated urinary orotate at 202 mmol/mmol creatinine (Normal: 0-1.5 mmol/mmol creatinine)

CaseNOTHPOs:

CaseNOTHPOFreeText: Normal plasma glutamine at 13.5 umol/L (Normal: 6-30 umol/L), Normal plasma citrulline at 15.75 umol/L (Normal: 7-35 umol/L)

CasePreviousTesting: gDNA extracted from peripheral blood leukocytes. PCR all coding exons and exon–intron boundaries of the OTC gene using 9 pairs of synthetic oligonucleotide primers, and the primer sequences and annealing temperature. PCR products were then purified and bidirectionally sequenced. The library was sequenced using Illumina HiSeq4000 and generated 150 bp paired-end reads. Data analysis was performed as previously described [Sun Y, Hu G, Liu H, Zhang X, Huang Z, Yan H, et al. Further delineation of the phenotype of truncating KMT2A mutations: the extended Wiedemann–Steiner syndrome. Am J Med Genet A. 2017;173:510–4.]. Multiplex ligation-dependent probe amplification analysis was performed for samples in which Sanger sequencing or WES failed to detect any disease-causing mutation.

Variant: NM_000531.6:c.67C>T (p.Arg23*)

ClinVarID: 97292

CAID: CA224742

gnomAD:

Case: Patient #4, Female, Caucasian

DiseaseAssertion: UCD/OTCD

FamilyInfo: N/A

CasePresentingHPOs: Hyperammonemia (HP:0001987),

CaseHPOFreeText: Elevated plasma ammonia concentration at 123 uM/L

CaseNOTHPOs:

CaseNOTHPOFreeText: Anxiety, plasma citrulline at 2 uM/L

CasePreviousTesting: N/A

Variant: NM_000531.5:c.67C>T (p.Arg23*)

ClinVarID: 97292

CAID: CA224742

gnomAD:

Case: Patient #85, Male

DiseaseAssertion: UCD/OTCD

FamilyInfo: N/A

CasePresentingHPOs:

CaseHPOFreeText:

CaseNOTHPOs: Late Onset

CaseNOTHPOFreeText: Milder phenotype

CasePreviousTesting: N/A

Variant: NM_000531.6: c.298+1G>T

ClinVarID: 97160

CAID: CA224544

gnomAD:

Case: patient#5 , female, Italian

Disease Assertion: UCD/OTCD

Family Info:

Case Presenting HPOs: irritability(HP:0000737), lethargy(HP:0001254), vomiting(HP:0002013), Oriticaciduria (HP:0003218), low plasma citrulline (HP:0003572), Elevated circulating alanine aminotransferase concentration(HP:0031964), Elevated circulating aspartate aminotransferase concentration (HP:0031956), childhood onset (HP:0011463)

Case HPO FreeText:

Case NOT HPOs:

Case NOT HPO Free Text:

Case Previous Testing: Total RNA was isolated from peripheral blood lymphocytes or lymphoblastoid cell lines and from frozen liver biopsy as described in Chomczynski and Sacchi (1987). For each patient two cDNA syntheses were performed: 10mg of total RNA with 800-1000 ng of oligo dT or 500ng of specific primer NR, mapping in the 3’UTR of OTC cDNA Identification of genetic lesions by amplification of the OTC mRNA, expressed in the liver tissue and intestine, from a non-specific tissue like PBL or lymphoblastoid cell lines. Some mutations, particularly those affecting splicing sites, may have a different expression in liver and PBL . In females, including manifesting carriers, this method allows the identification of deletions and gene rearrangements with certainty, but mutations, decreasing mRNA stability, are unlikely to be detected because the normal allele will constitute the majority of the RNA available for RT-PCR and will be preferentially amplified.

Supplemental Data: Case report section Notes: Hepatomegaly. This mutation, previously reported (Reish et al., 1993), has been correlated with a lethal disease form in a male patient, therefore the mild phenotype in our patient could be explained by a not completely unfavorable X-lyonization

Variant: NM_000531.6: c.928G>T(p.Glu310*)

ClinVarID: 97361

CAID: CA224838

gnomAD:

Gene Name: OTC (ornithine transcarbamylase)

Case: no patient #ID, female Disease Assertion: UCD/OTCD

Family Info: NA

Case Presenting HPOs: NA

Case HPO FreeText:

Case NOT HPOs:

Case NOT HPO Free Text:

Case Previous Testing: NA

Supplemental Data: TABLE 1, Notes: NA

Variant: NM_000531.6: c.77+1G>T

ClinVarID: 97314

CAID: CA224774

gnomAD:

Gene Name: OTC (ornithine transcarbamylase)

DOI: 10.1091/mbc.E20-04-0237-T

Resource: RRID:BDSC_28691

Curator: @bpowell22

SciCrunch record: RRID:BDSC_28691

What is this?

DOI: 10.1091/mbc.E20-04-0237-T

Resource: BDSC_38260

Curator: @bpowell22

SciCrunch record: RRID:BDSC_38260

What is this?

Case: patient #573, male

Disease Assertion: UCD/OTCD

Family Info:

Case Presenting HPOs:hyperammonemia (HP:0001987), Neonatal onset (HP:0003623)

Case HPO FreeText:

Case NOT HPOs:

Case NOT HPO Free Text:

Case Previous Testing: GDNA extracted from blood leukocytes using the proteinase K/phenol extraction procedure on a model 340 A nucleic acid extractor (Applied Biosystems). 5mg samples of DNA were digested with BamHI, MspI, or TaqI restriction endonuclease, electrophoresed through 1 % agarose gels, and transferred to a nylon membrane by standard procedures. The blots were then hybridized with a radiolabeled full-length cDNA probe for human OTC.

Supplemental Data: TABLE 3,

Variant: NM_000531.6: c.67C>T(p.Arg23*)

ClinVarID:97292

CAID: CA224742

gnomAD:

Gene Name: OTC (ornithine transcarbamylase)

Case: patient SM, male

Disease Assertion: UCD/OTCD

Family Info:

Case Presenting HPOs: Hyperammonemia (HP:0001987), Neonatal onset (HP:0003623)

Case HPO FreeText:

Case NOT HPOs:

Case NOT HPO Free Text:

Case Previous Testing: GDNA extracted from blood leukocytes using the proteinase K/phenol extraction procedure on a model 340 A nucleic acid extractor (Applied Biosystems). 5mg samples of DNA were digested with BamHI, MspI, or TaqI restriction endonuclease, electrophoresed through 1 % agarose gels, and transferred to a nylon membrane by standard procedures. The blots were then hybridized with a radiolabeled full-length cDNA probe for human OTC.

Supplemental Data: TABLE 3,

Variant: NM_000531.6: c.274C>T(p.Arg92*)

ClinVarID:97151

CAID: CA224530

gnomAD:

Gene Name: OTC (ornithine transcarbamylase)

Case: patient #188, male

Disease Assertion: UCD/OTCD

Family Info: N/A

Case Presenting HPOs: Neonatal onset (HP:0003623)

Case HPO FreeText:

Case NOT HPOs:

Case NOT HPO Free Text:

Case Previous Testing: gDNA testing involves PCR amplification of all 10 exons and exon/intron boundaries followed by screening for mutations or sequencing of all fragments, For these patients, confirmation of the diagnosis requires enzymatic assays. No specifications about the test

Supplemental Data: TABLE 1

Variant: NM_000531.6: c.835C>T(p.Gln279*)

ClinVarID: 97341

CAID: CA224811

gnomAD:

Gene Name: OTC (ornithine transcarbamylase)

Case: patient #303, female

Disease Assertion: UCD/OTCD

Family Info: N/A

Case Presenting HPOs:

Case HPO FreeText:

Case NOT HPOs:

Case NOT HPO Free Text:

Case Previous Testing: No specific functional tests indicated

Supplemental Data: In supplemental data files

Variant: NM_000531.6: c.766G>T(p.256Gly*)

ClinVarID: 870326

CAID: CA412722685

gnomAD:

Gene Name: OTC (ornithine transcarbamylase)

Case: patient #198, male

Disease Assertion: UCD/OTCD

Family Info: N/A

Case Presenting HPOs: Neonatal onset (HP:0003623)

Case HPO FreeText:

Case NOT HPOs:

Case NOT HPO Free Text:

Case Previous Testing: No specific functional tests indicated

Supplemental Data: In supplemental data files

Variant: NM_000531.6:c.538C>T(p.Gln180*)

ClinVarID: N/A

CAID: CA412724187

gnomAD:

Gene Name: OTC (ornithine transcarbamylase)

Case: patient #16, female, Japanese

Disease Assertion: UCD/OTCD

Family Info: N/A

Case Presenting HPOs:

Case HPO FreeText:

Case NOT HPOs:

Case NOT HPO Free Text:

Case Previous Testing: The severity of missense mutations was assessed using conservation and solvent accessible area of the replaced amino acid, calculated destabilization of mutant proteins and their SIFT and PolyPhen2 scores

Supplemental Data: Kido_et_al_2022_fgene_Data Sheet 2

Variant: NM_000531.6:c.77+1G>T

ClinVarID: 97314

CAID: CA224774

gnomAD:

Gene Name: OTC (ornithine transcarbamylase)

Case: patient #56, female, Japanese

Disease Assertion: UCD/OTCD

Family Info: N/A

Case Presenting HPOs: ,Hyperammonemia (HP:0001987)

Case HPO FreeText: N/A

Case NOT HPOs:

Case NOT HPO Free Text:

Case Previous Testing: The mRNA ref seq were, wherein the “A” nucleotide of the start codon ATG constituted as +1 numbering of the cDNA sequence. Met encoded by the start codon ATG also represented +1 for the amino acid numbering as set forth by the preprotein seq. PolyPhen-2, SIFT, and I-Mutant 3 tools were used for predicting the potential impact of an amino acid alteration in missense mutations on the function of each enzyme.

Supplemental Data: Table 1, patient had a liver transplant at 12yo.

Variant: NM_000531.6:c.940G>T(p.Glu314*)

ClinVarID: N/A

CAID: CA412726302

gnomAD:

Gene Name: OTC (ornithine transcarbamylase)

Case: no patient ID, Female

Disease Assertion: UCD/OTCD

Family Info: N/A

Case Presenting HPOs: HP:0003623, HP: 0001987

Case HPO FreeText: Neonatal onset, hyperammonemia

Case NOT HPOs:

Case NOT HPO Free Text:

Case Previous Testing: "Genomic DNAs were extracted from leukocytes, The ten exons and intron-exon boundaries of the OTC gene were PCR amplified and analyzed by Sanger sequencing on an ABI3100 sequencer. Intragenic deletions/duplications were searched for by Multiple Ligation Probe Dependent Amplification assay. Potential impact of non truncating variants on mRNA and protein was predicted using Splice Site Prediction. OTC variants were split into two groups, “severe” and “mild,” based on their impact on the clinical phenotype and on the OTC protein.

Supplemental Data: Table 3, All nuclear family members were tested but no information about their genotype. the condition to be part of this study was the presence of at least one heterozygous female in the pedigree of the patient.

Variant: NM_000531.6:c.766G>T(p.Gly256*)

ClinVarID: 870326

CAID: CA412722685

gnomAD:

Gene Name: OTC (ornithine transcarbamylase)

Case: Patient #35, female, Korean

Disease Assertion: UCD/OTCD

Family Info: N/A

Case Presenting HPOs: HP:0011463, HP:0003218, HP: 0001987

Case HPO FreeText: childhood onset, oroticaciduria, hyperammonemia

Case NOT HPOs:

Case NOT HPO Free Text:

Case Previous Testing: "Potential impact of mutations on OTC function and/or folding assessed by multiple alignments of orthologous protein sequences and human OTC and structural data from Protein Data Bank (1C9Y and available orthologs). In M patients, the approximate extent of the deletions assessed by inspection of presence/absence of PCR products. In F patients, the deletions determined by the SALSA multiplex ligation probe amplification (MLPA) KIT P079 OTC (MRC-Holland, Amsterdam, the Netherlands) and the Affymetrix Human SNP 6.0 array (Santa Clara, CA). Sequence spanning 38,211,736 – 38,300,703 bp region on chromosome X (GRCh37) and including OTC was scanned for motifs CCTCCCT, CCTCCTT, CCTCCCTT, CCCCACCCC, CCNCCNTNNCCNC, GGNGGNAGGG and their complements known as being associated with recombination hotspots. Repeats capable of non-B DNA structure formation implicated in double strand breaks (DSBs) were sought by complexity analysis . X-inactivation ratio determined by analysis of methylation status of the human androgen-receptor locus (HUMARA)

Supplemental Data: Table 1&2, This is a large deletion. The minimum plasma ammonia, orotic acid and Gln+Glu concentrations depends on certain age range: Plasma ammonia: neonates <90μmol/l, other <60μmol/l. Urinary orotic acid: 0–1year <6.6mmol/mol creatinine, 1 – 10 years <3.5 mmol/mol creatinine, over 10 years <2.4 mmol/mol creatinine. Serum glutamate + glutamine: 0 – 1 month 200–1200μmol/l, 1 month–1year 200–1100μmol/l, 1year–18years 200–900μmol/l, over 18years 200–800μmol/l.

Variant: NM_000531.6:c.853C>T(p.Gln285*)

ClinVarID: N/A

CAID: CA412723777

gnomAD:

Gene Name: OTC (ornithine transcarbamylase)

Case: Patient #34, female, Korean

Disease Assertion: UCD/OTCD

Family Info: N/A

Case Presenting HPOs: HP:0011463, HP:0003218, HP: 0001987

Case HPO FreeText: childhood onset, oroticaciduria, hyperammonemia

Case NOT HPOs:

Case NOT HPO Free Text:

Case Previous Testing: "Potential impact of mutations on OTC function and/or folding assessed by multiple alignments of orthologous protein sequences and human OTC and structural data from Protein Data Bank (1C9Y and available orthologs). In M patients, the approximate extent of the deletions assessed by inspection of presence/absence of PCR products. In F patients, the deletions determined by the SALSA multiplex ligation probe amplification (MLPA) KIT P079 OTC (MRC-Holland, Amsterdam, the Netherlands) and the Affymetrix Human SNP 6.0 array (Santa Clara, CA). Sequence spanning 38,211,736 – 38,300,703 bp region on chromosome X (GRCh37) and including OTC was scanned for motifs CCTCCCT, CCTCCTT, CCTCCCTT, CCCCACCCC, CCNCCNTNNCCNC, GGNGGNAGGG and their complements known as being associated with recombination hotspots. Repeats capable of non-B DNA structure formation implicated in double strand breaks (DSBs) were sought by complexity analysis . X-inactivation ratio determined by analysis of methylation status of the human androgen-receptor locus (HUMARA)

Supplemental Data: Table 1&2, This is a manifesting heterozygote. Serum Gln+Glu was considered elevated. The minimum plasma ammonia, orotic acid and Gln+Glu concentrations depends on certain age range: Plasma ammonia: neonates <90μmol/l, other <60μmol/l. Urinary orotic acid: 0–1year <6.6mmol/mol creatinine, 1 – 10 years <3.5 mmol/mol creatinine, over 10 years <2.4 mmol/mol creatinine. Serum glutamate + glutamine: 0 – 1 month 200–1200μmol/l, 1 month–1year 200–1100μmol/l, 1year–18years 200–900μmol/l, over 18years 200–800μmol/l.

Variant: NM_000531.6:c.717+1G>T(IVS7+1G>T)

ClinVarID: 97298

CAID: CA224753

gnomAD:

Gene Name: OTC (ornithine transcarbamylase)

Case: Patient #42, female, Korean

DiseaseAssertion: UCD/OTCD

FamilyInfo: N/A

CasePresentingHPOs: HP:0011463, HP:0001987, HP:0003218

CaseHPOFreeText: Childhood onset, hyperammonemia, oroticaciduria

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: Genomic DNA was extracted from peripheral blood leukocytes. A total of 10 coding exons and exon–intron boundaries of the OTC gene were amplified by PCR with customized primers. PCR products were directly sequenced with the same primers . Sequencing results were compared with the established human OTC sequences(NM_000531.5). Multiplex ligation-dependent probe amplification analysis was performed for patients in whom no OTC mutations were identified by direct sequencing using the OTC MLPA kit.

Supplemental Data: Table 1, no range was given for blood ammonia concentration, range given in the tables for glutamine and urine orotate is slightly different than the one in the results paragraphs.

Variant: NM_000531.6:c.958C>T(p.Arg320*)

ClinVarID: 97371

CAID:CA285809

gnomAD:

GeneName: OTC (ornithine transcarbamylase)

Case: Patient #52, female, Chinese

DiseaseAssertion: UCD/OTCD

FamilyInfo: family history of the disease, variant in probands mother and father

CasePresentingHPOs: HP:0011463, HP:0001987, HP:0003218, HP:0003572

CaseHPOFreeText: childhood onset,, hyperammonemia, oroticaciduria, low plasma citrulline

CaseNOTHPOs:

CaseNOTHPOFreeText: neurological damage

CasePreviousTesting: gDNA extracted from peripheral blood leukocytes. PCR all coding exons and exon–intron boundaries of the OTC gene using 9 pairs of synthetic oligonucleotide primers, and the primer sequences and annealing temperature. PCR products were then purified and bidirectionally sequenced. The library was sequenced using Illumina HiSeq4000 and generated 150 bp paired-end reads. Data analysis was performed as previously described [Sun Y, Hu G, Liu H, Zhang X, Huang Z, Yan H, et al. Further delineation of the phenotype of truncating KMT2A mutations: the extended Wiedemann–Steiner syndrome. Am J Med Genet A. 2017;173:510–4.]. Multiplex ligation-dependent probe amplification analysis was performed for samples in which Sanger sequencing or WES failed to detect any disease-causing mutation.

SupplementalData: Table 3, inherited mutation, drug treatment(L-arginine, L-Citrulline, sodium benzoate, and sodium phenylbutyrate), low protein diet treatment, and continuous veno venous hemodialfiltration

Variant: NM_000531.6:c.703C>T

ClinVarID: N/A

CAID: CA412721652

gnomAD:

GeneName: OTC (ornithine transcarbamylase)

https://www.att.com/support/article/wireless/KM1041824/

How to Use the Dial Phone, 1927. http://archive.org/details/HowtoUse1927.

下降幅度最大的 3 個類別是寫作、翻譯和客戶服務工作

寫作職位數量下降了 33%，翻譯職位數量下降了 19%，客戶服務職位數量下降了 16%

翻譯絕對是受打擊最嚴重的工作，每小時工資下降了 20% 以上

https://www.afro-impact.com/dot-en-afrique-un-legendaire-commerce-des-temps-modernes/#:~:text=Institu%C3%A9e%20dans%20les%20coutumes%20africaines%20depuis%20des%20mill%C3%A9naires%2C,preuve%20juridique%20du%20mariage%20au%20sein%20des%20familles.

for - CAR T cells - anti aging - eliminate senescent cells in mice. - quote - anti aging - CAR T cells

quote - (see below)

• If we give it to aged mice, they rejuvenate.
• If we give it to young mice, they age slower.
• No other therapy right now can do this,
• author: Amor Vegas

for - CAR T cells - research - anti aging - adjacency - CAR T cells - Michael Levin - Cold Spring Harbor Lab - Corina Amor Vegas - senescent cells - fountain of youth

Silverman, Joseph H., and John T. Tate. Rational Points on Elliptic Curves. 2nd ed. Undergraduate Texts in Mathematics. 1992. Reprint, New York: Springer, 2015.

urn:x-pdf:e59b1cd55350541e359fbb11896edd0c

annotations at: https://jonudell.info/h/facet/?user=chrisaldrich&max=100&exactTagSearch=true&expanded=true&url=urn%3Ax-pdf%3Ae59b1cd55350541e359fbb11896edd0c

https://www.youtube.com/playlist?list=PLxgUkHTvXNob8166Ezozo8NpcJ2Idn7Kw

tagline for AT&T commercials.

I saw one today watching football.

Appreciation

Neue, gigantische Fracking-Projekte in den USA („monster fracks“) verbrauchen enorme Mengen Wasser, so dass die Öl- und Gasfirmen inzwischen auch nach Wasser bohren. Damit wird die durch Übernutzung und globale Erhitzung prekäre Wasserversorgung in vielen Gegenden der USA zusätzlich belastet. Analyse und Reportage in der New York Times, die herazusgefunden hat, dass die monster fracks in Texas inzwischen zwei Drittel der Fracking-Projekte ausmachen. https://www.nytimes.com/interactive/2023/09/25/climate/fracking-oil-gas-wells-water.html

给目标服务器配置别名

on the matilda movie she has to do that

i once saw a serie (flash) where the protagonist blamed herself for everything

mom asks me how school was and this is always how it plays out

my mother told me this berfore aswell

i agree

this same thing happens when augusto shouts "BREEEK"

right when i was going to sleep my mother made me write and practice to pass a test

when i get exited or sad the same happens to me

when i take a bath i look 10x prettier aswell

famous quote

my cousin has once been in this situation

doctors ask the exact same questions to my mother when i go to a hospital

i do homework in the middle of the night

ive done this before

i do this with a tenis ball and i catch it with a punch to practice

This was a huge problem for me when i didnt have a ventilator, i would have to sleep in the couch but sometimes they followed

i had a dream i was escaping a ghost

i also met a girl in 5th grade which i loved, and i cared about her like i met her my whole life, but she left...

my father is also a good fisherman

this happened once in a sleepover

seems like the procrastinator version of me

i once did that because i thought it would go to space and find aliens

this was said by Matthew west

this is just like an event of a movie i watched

this is exactly what skellig used to do

heard that before

i recognize this prayer and i used to preach it in the USA

on skellig whisper was at her heels

this situation happened to my family when we went to egypt

i tried to learn that when i was in a school on the USA

there is a movie where dogs are prohibited in a hotel but someone manages to sneak one in

seems like my fridge

i like swimming

same, cant help petting my dog no matter what

My dog loves to bite

how i felt when going to the nr

the smell of crabs makes me feel that way

i have been to ubers that have this function

On Breaking Bad the mother would never tell, despite desperately wanting to tell her husband's secret

My father also gave me a wrapped present once

On a book i read a person died because they were too scared to go to the doctor for the same reason.

This situation is similar, when my father arrives his footsteps are heavy so i know he arrived.

I have eaten something like this.

The Kennedy administration became culturally associated with Camelot because Jacqueline Kennedy mentioned her husband's affinity for the show in an interview with Theodore H. White for LIFE Magazine following his death and quoted the show's closing lyric: “Don’t let it be forgot, that once there was a spot, for one brief shining moment, that was known as Camelot.”

Somewhat curious that there's T. H. White of The Once and Future King and a separate Theodore H. White who interviewed Jackie Kennedy following her husband's death with mentions of Camelot.

https://www.investopedia.com/terms/t/t-test.asp A t-test is an inferential statistic used to determine if there is a significant difference between the means of two groups and how they are related. T-tests are used when the data sets follow a normal distribution and have unknown variances, like the data set recorded from flipping a coin 100 times.

How to TTEST

https://www.usgo.org/news/2016/11/aga-president-andy-okuns-father-milton-t-okun-music-producer-for-john-denver-peter-paul-and-mary-dies/

Andy Okun's father

https://www.bartleby.com/nonfiction/

Pg. 52, 53, & 54

• Dietrich Bonheoffer, the 1st German lutheran Pator and theologians opposed Adolf Hitler's anti-semitic legislation called the Aryan Clause on April 7, 1933
• Reich church damded loyalty oath from all German Protestants who held church offices
• Bonheoffer refused and took lead in the alternative, confessing church movement
• he helped many jews escape the Germans as well as training other church leaders to do the same
• In June 1939 Bonhoeffer went to the U.S for the sake of his safety
• Bonheoffer specializes in theology
• He felt a calling to be involved in church and national affairs
• Bonheoffer worried that he is leaving god behind because he is not following his calling by staying to the U.S
• He was not allowed to return to Germany and this worried him
• June 20th, he feels uneasy and wishes to return home because God is giving him a sign "The reasons one gives for an action to others and to one's self are certainly inadequate... In the last resort one acts from a level which remains hidden from us. So we can only ask God to judge and forgive us.. it is now in his hands" (Cahalan, 54)
• July 9, 1939 he returns to Germany and resumes his efforts to resit hitlier and the Reich
• He wanted to assassinate Hitler (pg. 54)
• April 5, 1943 he was arrested for his activity in the underground resistance movement

This is what Dr. Herring meant by "fatter tails."

Below is why.

Thomas, L. (2021, October 14). SARS-CoV-2 induces tissue immune memory. News-Medical.Net. https://www.news-medical.net/news/20211014/SARS-CoV-2-induces-tissue-immune-memory.aspx

Beaumont, P. (2021, December 17). T-cells in Pfizer Covid jab recipients stay robust against severe illness. The Guardian. https://www.theguardian.com/world/2021/dec/17/t-cells-pfizer-covid-jab-robust-against-severe-illness-south-africa-research

https://findmymobile.samsung.com/

Gene: DICER1 PMCID: PMC8451242 PMID: 34552563 Pathogenic Inheritance Pattern: Autosomal Dominant MultipleDiseaseEntities Disease Entity: DICER1 syndrome, multinodular goitre, cystic nephroma, anaplastic renal sarcoma, Wilms tumour, differentiated thyroid carcinoma, gynandroblastoma, ciliary body medulloepithelioma, embryonal rhabdomyosarcoma, pineoblastoma, pituitary blastoma, kidney cyst, pulmonary cyst, Sertoli-Leydig Cell Tumor. Mutation: Germline MultipleGeneVariants Variant & Clinvar IDs: c.3452_3453del (485534), c.316del (no ClinVar ID), c.171_172insAC (no ClinVar ID), c.3434del (no ClinVar ID), c.988C>T (933007), c.5388dup (no ClinVar ID) Zygosity: None provided. Case: At time of operation, the goitre patients living in Denmark were ages 21, 12, 21, 8, 14, and 16. Four underwent total thyroidectomies, and two underwent partial thyroidectomies. The patient originally aged 21 previously had a kidney cyst at age 14 and a pulmonary cyst at an unknown age. The patient aged 14 at time of partial thyroidectomy later manifested a Sertoli-Leydig Cell Tumor at age 15. All six patients were female. CasePresentingHPO: None provided. CasePreviousTesting: thyroidectomy gnomAD: ENSG00000100697.10, https://gnomad.broadinstitute.org/gene/ENSG00000100697 Mutation Type: Frameshift, Nonsense

Gene Name: DICER1 PMCID: PMC5443331 PMID: 28323992 HGNCID: not found Inheritance Pattern: autosomal dominant Disease Entity: thyroid cancer and familial multinodular doiter Mutation: germline loss-of-function mutation Zygosity: not provided Variant: c.1870C>T; p.Arg624a, c.1870C>T; p.Arg624a, c.1870C>T; p.Arg624a, c.1870C>T; p.Arg624a, c.3726C>A; p.Tyr1242a, c.3675C>G; p.Tyr1225a, c.3675C>G; p.Tyr1225a Family Information: 145 individuals with a DICER1 germline mutation and 135 controls from 48 families Case: family members used; both males and females used and no significant differences seen among sex; ages range from 20-40 with carriers being significantly younger than controls; no significant differences seen among ethnicity but participants located from the US, UK, and Great Britain CasePresentingHPOs: thyroid cancer or MNG diagnosis common to those with a DICER! mutation but with no chemotherapy or radiation treatment yet CasePreviousTesting: tested levels of thyroid-stimulating hormone, thyroxine, thyroxine-binding globulin, and serum albumin; thyroid palpation; thyroid ultrasound; Sanger or next-generation sequencing assays gnomAD: n/a Mutation Type: missense

HGNCID:

Payne, R. P., Longet, S., Austin, J. A., Skelly, D. T., Dejnirattisai, W., Adele, S., Meardon, N., Faustini, S., Al-Taei, S., Moore, S. C., Tipton, T., Hering, L. M., Angyal, A., Brown, R., Nicols, A. R., Gillson, N., Dobson, S. L., Amini, A., Supasa, P., … Zawia, A. A. T. (2021). Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine. Cell, 184(23), 5699-5714.e11. https://doi.org/10.1016/j.cell.2021.10.011

Edward Nirenberg 🇺🇦 [@ENirenberg]. (2021, November 30). This is also not limited to the vaccine- any infection we encounter will do the same thing. It’s how we evolved to get around a massive genetic and bioenergetic challenge and it’s brilliant and it’s happening all the time regardless of any vaccines we get. [Tweet]. Twitter. https://twitter.com/ENirenberg/status/1465698637434933254

difference between SD and SEM

statistical significance should be less than 5%

tf your confidence that the results are not due to chance is 95%

99% confident that the true average (result) is between these two numbers;

at 1% (0.01) significance, we can scientifically assume there is a causal relationship

Bellesi, S., Metafuni, E., Hohaus, S., Maiolo, E., Marchionni, F., D’Innocenzo, S., La Sorda, M., Ferraironi, M., Ramundo, F., Fantoni, M., Murri, R., Cingolani, A., Sica, S., Gasbarrini, A., Sanguinetti, M., Chiusolo, P., & De Stefano, V. (2020). Increased CD95 (Fas) and PD-1 expression in peripheral blood T lymphocytes in COVID-19 patients. British Journal of Haematology, 191(2), 207–211. https://doi.org/10.1111/bjh.17034

Eric Topol. (2022, February 28). A multimodal #AI study of ~54 million blood cells from Covid patients @YaleMedicine for predicting mortality risk highlights protective T cell role (not TH17), poor outcomes of granulocytes, monocytes, and has 83% accuracy https://nature.com/articles/s41587-021-01186-x @NatureBiotech @KrishnaswamyLab https://t.co/V32Kq0Q5ez [Tweet]. @EricTopol. https://twitter.com/EricTopol/status/1498373229097799680

https://deadline.com/2022/03/discovery-sets-board-of-directors-warnermedia-merger-1234979430/

New board for Warner Bros. Discovery after $43 billion merger.

Anthony J Leonardi, PhD, MS. (2022, February 28). Damn, nice find https://t.co/cJRhB2k4zH [Tweet]. @fitterhappierAJ. https://twitter.com/fitterhappierAJ/status/1498113886846914567

Hall, V. G., Ferreira, V. H., Wood, H., Ierullo, M., Majchrzak-Kita, B., Manguiat, K., Robinson, A., Kulasingam, V., Humar, A., & Kumar, D. (2022). Delayed-interval BNT162b2 mRNA COVID-19 vaccination enhances humoral immunity and induces robust T cell responses. Nature Immunology, 1–6. https://doi.org/10.1038/s41590-021-01126-6

Paolucci, S., Cassaniti, I., Novazzi, F., Fiorina, L., Piralla, A., Comolli, G., Bruno, R., Maserati, R., Gulminetti, R., Novati, S., Mojoli, F., Baldanti, F., Bruno, R., Mondelli, M., Brunetti, E., Matteo, A. D., Seminari, E., Maiocchi, L., Zuccaro, V., … Ferrari, A. (2021). EBV DNA increase in COVID-19 patients with impaired lymphocyte subpopulation count. International Journal of Infectious Diseases, 104, 315–319. https://doi.org/10.1016/j.ijid.2020.12.051

T-test tutorial

Townsend, L., Dyer, A. H., Naughton, A., Kiersey, R., Holden, D., Gardiner, M., Dowds, J., O’Brien, K., Bannan, C., Nadarajan, P., Dunne, J., Martin-Loeches, I., Fallon, P. G., Bergin, C., O’Farrelly, C., Cheallaigh, C. N., Bourke, N. M., & Conlon, N. (2021). Longitudinal Analysis of COVID-19 Patients Shows Age-Associated T Cell Changes Independent of Ongoing Ill-Health. Frontiers in Immunology, 12. https://www.frontiersin.org/article/10.3389/fimmu.2021.676932

Los linfocitos T no nos salvarán del coronavirus, pero ayudarán a resolver el puzle inmunitario. (n.d.). Agencia SINC. Retrieved January 17, 2022, from https://www.agenciasinc.es/Reportajes/Los-linfocitos-T-no-nos-salvaran-del-coronavirus-pero-ayudaran-a-resolver-el-puzle-inmunitario

Halliday, J., & correspondent, J. H. N. of E. (2022, January 17). ‘Christmas was awful’: On the Omicron frontline at the Royal Preston hospital. The Guardian. https://www.theguardian.com/world/2022/jan/17/christmas-was-awful-on-the-omicron-frontline-at-the-royal-preston-hospital