prix compétitifs

tout cela

qu'à la qualité luxueuse qu'elle

que l'enseigne brille, s'appuyant sur le prestige

chic, plus proche de la boutique de luxe que du magasin

avec beaucoup de maisons établies et de

l'exception

des soins de la peau et des cheveux

des soins de la peau et des cheveux

instaure

L'enseigne propose un vaste choix de marques cultes de cosmétiques, produits capillaires et dermocosmétiques prisés des amateurs de beauté, aux côtés de maquillage et de parfum

Situé à la croisée de la boutique et du magazine, c'est autant un lieu où l'ont peu lire sur la beauté qu'acheter

soins de la peau et des cheveux

quand on sait ce qu'on veut, et qu'on recherche

que vous avez déjà choisi

Les prix sont toujours compétitifs, et ce large choix permet souvent de dénicher des références, des pépites ou d'anciens classiques difficiles à trouver ailleurs, ce qui en fait un favori des acheteurs qui savent

parfums, maquillage, soins du visage, du corps et des cheveux, sur un très large éventail de marques, des incontournables grand public aux grands noms de créateurs sélectifs

reflète

Si d'autres ont d'abord ouvert des boutiques, Notino a tout misé sur le web, et sa démarche

, l'un des détaillants beauté en ligne à la croissance la plus rapide en Europe, s'est taillé une réputation de spécialiste du commerce en ligne

Mêlant conseil personnalisé, boutiques physiques et solide gamme sélective, Marionnaud est une enseigne rassurante que l'on recommande naturellement à

Les nombreuses boutiques physiques prolongent le site en proposant des services et soins en institut, et la carte de fidélité permet de relier les expériences en ligne et en magasin avec des points et des offres membres

Sephora propose un large éventail de marques – maquillage, soins et aussi bien des parfums de prestige que des nouveautés qui font le buzz – et l'enseigne est souvent la première à référencer les marques dont tout le monde parle, portée par un impressionnant catalogue d'exclusivités

Le site est facile à parcourir et mise sur l'aide pour trouver le bon produit

Son catalogue offre une gamme sélective bien équilibrée entre soins, parfums et maquillage, couvrant aussi bien des marques prestige établies que des produits du quotidien accessibles

Sa Sephora Collection propose des produits du quotidien bien conçus et abordables. La gamme est ainsi variée, allant de l'accessible au haut de gamme

Le site et l'application sont faciles à utiliser

une solide implantation

l'enseigne a bâti

avec de vrais conseils

Le programme de fidélité simple (un point par euro, un bon de dix euros dès 200 points) ne fait qu'améliorer l'expérience

Grâce à

la force du service

pour passer d'une catégorie à une autre

Sa sélection « Parfums d'Exception » mêle des maisons de niche à l'élégance classique comme Serge Lutens, Tom Ford Private Blend, Armani Privé et Van Cleef & Arpels, à des noms plus récents tels qu'Essential Parfums et L'Atelier Parfum, ainsi que des lancements exclusifs que l'on ne trouve pas partout, notamment Orebella de Bella Hadid, LolaVie de Jennifer Aniston et about-face de Halsey.

Le choix est vaste et multimarque

Fondée à Lille en 1984, Nocibé est devenue l'une des destinations beauté les plus reconnues de France. Elle est construite

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Were they really leaving because of states' rights, or because they believed slavery wasn't being protected anymore? After reading this document, I think slavery was the main issue, and South Carolina believed compromise had already failed.

After reading that South Carolina thinks the North broke the deal first, maybe it proves that compromise had been falling apart for years before this even happened.

After reading this, it proves that South Carolina thinks the deal was already broken before they left. They thought that the North stopped following the Fugitive Slave Law for years.

This passage shows why compromise had broken down by 1860. South Carolina said that the Northern states had violated the constitution because they refused to enforce the Fugitive Slave Act. This went against many of the moral beliefs of the Northerners.

Does sonomer need to be defined here?

Not clear.

What It's Really Like to Leave MAGA Christianity<br /> by [[Molly Wadzeck]] in HuffPost Life<br /> accessed on 2026-07-27T23:17:52

Case#:2, 29-year-old woman

DiseaseAssertion:NR

FamilyInfo:NR

CasePresentingHPOs:

CaseHPOFreeText:decreased ability to focus, increasing difficulty to adapt in the dark, normal visual acuity in both eyes (logMar BCVA OD/OS: 0.02), PERG responses were diminished in both eyes.

CaseNotHPOs:

CaseNotHPOFreeText:

Genotyping Method: ”Analysis of the ABCA4 gene”

PreviouslyPublished:No

Variant:NM_000350.3:c.1805G>A, NM_000350.3:c.6079C>T

ClinVar: 99085, 7882

CAID:CA226933, CA119129

SupplementalData:

This variant is found on pg 2 in proband 11019. Compound heterozygous for c.4532C>A, (p.Pro1511His). JHU institute (US). Said to have Stargardt based on the following criteria: "(1) patients (at least 6 years old) with at least two ABCA4 variants or one ABCA4 variant associated with a typical STGD1 phenotype and (2) presence of a well-defined atrophic lesion with/without flecks at the most recent visit of at least 300 µm in diameter (the total area of all lesions <12 mm2)." No additional details provided

This variant is found on pg 21 in proband 13047. Compound heterozygous for c.5882G>A p.Gly1961Glu. Said to have Stargardt based on the following criteria: "(1) patients (at least 6 years old) with at least two ABCA4 variants or one ABCA4 variant associated with a typical STGD1 phenotype and (2) presence of a well-defined atrophic lesion with/without flecks at the most recent visit of at least 300 µm in diameter (the total area of all lesions <12 mm2)." No additional details provided

PMID: 10958763

Gene: ABCA4

Disease: Stargardt

PMID: 16917483

Gene: ABCA4

Disease: Stargardt

This paper was referenced by PMID: 23755871 as containing variant c.6410G>A (p.Cys2137Tyr), but this variant foes not appear to be in the text or tables

PMID: 34008801

Gene: ABCA4

HGNC ID: 34

PMID: 28559085

Gene: ABCA4

Disease: IRD

PMID: 26377081

Gene: ABCA4

Disease: ABCA4-Associated Retinal Degenerations

PMID: 17562343 GeneName: ABCA4

Case#: Patient 13, 35yo

DiseaseAssertion: STGD

FamilyInfo: Family 8

CasePresentingHPOs:

CaseHPOFreeText: Visual acuity=0.017. OCT ft (μm)=163. MP (dB)=0. Fundus=3(extensive atrophic-appearing RPE changes). ERG=3(abnormal responses involving both rods and cones). mfERG=4(subnormal mfERG in the entire test field (0°–30°) plus pathologic Ganzfeld ERG).

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: PCR of coding regions, intron/exon boundaries, and 5′ and 3′ regions of ABCA4; Standard cycle-sequencing reactions with BigDye Terminator

PreviouslyPublished:

Variant: L541P; R1098C

CAID: CA226911;

SupplementalData: n/a

Case#:48-year old man, onset at 13-years old

DiseaseAssertion: STGD1

FamilyInfo: n/a

CasePresentingHPOs: HP:0003621, HP:0025147, HP:0011507, HP:0030329, HP:0030610, HP:0007722, HP:0007703, HP:0007663

CaseHPOFreeText: BCVA was 20/200 bilaterally and refractive error was OD: −1.50/+0.50 × 149° and OS: −1.50/+0.25 × 161°. Hyperautofluorescent transitional zone in each eye more pronounced in right eye. The left eye showed a complete defect of the RPE-Bruch membrane complex with herniation of the outer retina. Maximum horizontal diameter of this RPE-Bruch membrane complex defect was 266um.

CaseNotHPOs: HP:0000510, HP:0000548, HP:0007984

CaseNotHPOFreeText: No defect observed in the RPE and Bruch membrane in right eye. Patient had normal cone and rod responses on ERG

Genotyping Method: ABCR 600 micro-array chip

PreviouslyPublished: n/a

Variant: NM_000350.3(ABCA4):c.4216C>T (p.His1406Tyr), NM_000350.3(ABCA4):c.5882G>A (p.Gly1961Glu)

ClinVar: 99259, 7888

SupplementalData: n/a

Case#: Case2, Sex:Female, Age:15

DiseaseAssertion: STGD

FamilyInfo: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: Clinical Notes: Few yellowish Flecks without autofluorescence. General notes: participant presented with atypical macular degeneration.

CaseNotHPOs:n/a

CaseNotHPOFreeText: n/a

Genotyping Method: Exome sequencing data generation. Additional sequencing targeted amplification fo PRPH2 and ELOVL4 using PCR.

PreviouslyPublished: n/a

Variant: Variant 1 given as p.G1961E; NM_000350.3:c.5882G>A p.(Gly1961Glu) . Variant 2 given as p.Q636X; NM_000350.3(ABCA4):c.1906C>T (p.Gln636Ter).

ClinVar: Variation ID: 7888 ; Variation ID: 265012

CAID: ; CA10588302

SupplementalData: Proband variant information given in Table 1.

PMID: 33846575

Gene: ABCA4

Disease: Stargardt disease and retinitis pigmentosa

PMID: 9973280

Gene: ABCA4

Disease: Stargardt

PMID: 17990484

Gene: ABCA4

Disease: Stargardt disease (STGD), Fundus flavimaculatus (FFM), Age-related macular degeneration 2 (ARMD2)

Case#: Patient #33, female, 64yo at baseline visit, "late" age of onset

DiseaseAssertion: ABCA4-related retinopathy with secondary RPE atrophy

FamilyInfo:

CasePresentingHPOs:

CaseHPOFreeText: Inclusion criteria were defined as 1) presence of at least one mutated allele in ABCA4 (NM_000350.2) in Sanger sequencing with multiplex ligation-dependent probe amplification analysis or next-generation sequencing,9 2) a compatible phenotype with flecks at the level of the RPE consistent with ABCA4 -related Stargardt disease,9 3) presence of RPE atrophy, and 4) serial examinations with an interval of at least 6 months. RPE atrophy to the end-stage (i.e., demarcated lesions with ≥90% darkness of the optic disc under short-wavelength excitation light, DDAF) that previously showed highest interreader agreement.7 The size of DDAF has to be at least 0.05 mm 2 (each single atrophic area in cases of multifocality), and the entire lesion must be completely visualized on the AF image at each visit to be advanced for analysis. Self-reported symptom onset into early-onset (≤10 years), intermediate-onset (11–44 years), and late-onset (≥45 years). ff-ERG based Category: Group 1 contained eyes with normal scotopic and photopic responses; Group 2, eyes with normal scotopic responses, but reduced (over 2 SDs) photopic B-wave and 30-Hz flicker amplitudes; and Group 3, eyes with impairment of both rod- and cone-driven responses. BCVA: OD=0.4, OS=1.1 [LogMAR] .

CaseNotHPOs:

CaseNotHPOFreeText: Insufficient pupil dilation, additional retinal pathology, previous retinal treatment, or other ocular comorbidities substantially affecting image quality led to exclusion from the study

GenotypingMethod: Sanger sequencing with multiplex ligation-dependent probe amplification analysis or next-generation sequencing

PreviouslyPublished: possible since Birtel is an author on this paper and the probands both have the same second variant as in PMID: 29555955

Variant: allele 1: c.3468C>G p.(Tyr1156*) allele 2: c.5059A>T p.(Ile1687Phe); c.4297G>A p.(Val1433Ile)

ClinVar: n/a

CAID: CA341290648

SupplementalData: The supplemental table linked here contains genotype and phenotype information.

When expressed in transfected HEK293T cells and quantified by Western blotting, this variant was in the range of 40%-52%. This variant has a basal ATPase activity of 63% ± 5% compared to WT (100%) and was categorized as class 2 (partial reduction in expression and basal ATPase activity that was modestly stimulated by N-Ret-PE) with a moderate/severe predicted severity.

PMID: 41063816

Gene: ABCA4

HGNC ID: 34

Case#: Case 3, 39yo

DiseaseAssertion: BEM, RCD

FamilyInfo: n/a

CasePresentingHPOs:

CaseHPOFreeText: a ring of increased AF surrounding decreased foveal AF, visual acuity= 6/6, 6/6

CaseNotHPOs:

CaseNotHPOFreeText: acquired toxic aetiology

GenotypingMethod: The entire coding sequence (50 exons), including exon–intron boundaries, of the ABCA4 gene of each patient was screened using single‐stranded conformational polymorphism (SSCP) analysis and direct sequencing.

PreviouslyPublished: n/a

Variant: Val552Ile heterozygous

CAID: CA239745

SupplementalData: n/a

Case#: Patient #42, female, 31yo at onset, German

DiseaseAssertion: macular dystrophy or cone-rod dystrophy

FamilyInfo: phase not confirmed, but assumed in case of parental consanguinity or if only siblings were affected

CasePresentingHPOs: HP:0012508

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText: syndromic retinal disease, age-related macular degeneration, central serous retinopathy, autoimmune retinopathy, retinal vascular disease, achromatopsia, X-linked retinoschisis, North Carolina macular dystrophy

PreviouslyPublished: n/a

Variant: c.3468C>G (p.Tyr1156Ter); c.5059A>T (p.Ile1687Phe) Sanger sequencing of ABCA4

ClinVar: n/a

CAID: CA341290648

SupplementalData: Supplementary table 1

Transparent Peer Review

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Potential topic/subtopic- Since learning Standard English in schools, African Americans students were taught to write SE and then encouraged to speak SE during school hours. But the students' use of AAVE vs. SE became controversial in schooling.

Potential theme- AAVE has close ties to Standard English (SE), African Americans were finally allowed to learn reading and writing and were also encouraged to through certain institutions.

AAVE was created by African American slaves from the south, living in isolated conditions, through interactions that had to be limited and not conversational with European Americans.

African-American Vernacular English (AAVE) = a variety of English spoken by many African American people

Most African Americans were living in the south as slaves in what is the U.S. now, around the late 1700's slaves could not learn to read or write because of harsh laws. Most of the African American literary traditions became oral and not written around that time. Their literature started to get past down to many people, and generations using the oral tradition.

The use of French in positions of power allowed the elite to maintain control and limited the ability of Creole-speaking Haitians to fully participate in government and society

French remained the language of government, education, and power because it was already established during colonial rule, while Creole was not recognized in formal settings because it lacked a written system.

A long time to have adopt the language 1918-1983

The recognition of Creole as a national language showed a shift toward valuing the language spoken by the majority of Haitians, although social and political factors influenced this change.

French was given official power in Haiti’s government, which reinforced the importance of French over Creole in formal settings.

The preference for French helped maintain beliefs that French speakers were more educated or important, while Creole speakers faced discrimination

Access to French education created social inequality because people who learned French gained more opportunities and influence.

French became associated with power and status because the educated elite used it in government, education, and other important settings while most Haitians spoke Creole.

As new generations were born in Haiti, Creole became their first language, showing how the language grew from a way to communicate into a complete language.

Different African groups who spoke different languages had to communicate with each other, which helped shape and develop Haitian Creole over time

Alleyne’s theory suggests that Africans combined European vocabulary with the grammar and structures of their own languages, which helped create new Creole languages.

Mufwene argues that Creole languages developed by changing and reorganizing existing languages as different groups interacted, especially during the period of slavery.

Bickerton argues that children create new grammatical structures when they learn a pidgin language, suggesting that Creole languages develop through the human ability to create and organize language.

A pidgin that becomes a full language when children grow up learning it as their first language and develop more complex grammar.

A communication system created between groups; usually learned as a second language and not spoken natively by children.

The substrate theory argues that African languages influenced the development of Creole languages, shaping their structure and vocabulary despite European influence.

Researchers have different explanations for how Creole languages developed from the interaction between African and European languages

Language reflected social class differences in Haiti, with Creole being spoken by the majority of the population and French associated with wealth and power.

Haiti’s independence was historically significant because it became the first nation in the Western Hemisphere led by formerly enslaved Black people.

The growth of plantations increased the demand for enslaved African labor, which contributed to the forced movement of Africans to Haiti.

Control of the island shifted from Spain to other European powers, especially France, which influenced the development of language and culture in Haiti.

Before Europeans arrived, Indigenous peoples already lived on the island and had their own cultures and languages.

Haitian Creole developed when different groups came into contact and combined elements of their languages, creating a new way of communication.

Researchers have started paying more attention to different Creole languages to better understand their history, development, and importance

Creoles influenced by languages other than English were studied less, even though they are an important part of Caribbean culture and communication

Early research focused mostly on Creole languages that were based on English, showing that some Creole varieties received more attention than others

Creole languages, which developed by blending different languages and cultures, have faced struggles to be recognized as official national languages because of historical prejudice and discrimination

Language ideology connects the way society is organized (power, inequality, social groups) with the way people speak and view different languages

People’s beliefs about language are influenced by social factors like race and class, which can determine which languages are viewed as valuable or acceptable

People are often judged and placed into social groups based on education, jobs, lifestyle, and material possessions

Language is affected not only by race but also by social class and economic status.

African languages and Creoles were looked down upon because they were not given the same recognition or power as European languages

European languages gained power because they were used in schools, government, and legal systems controlled by colonizers

Language can reflect social inequalities because some languages are viewed as more valuable or prestigious than others.

Racist beliefs created a hierarchy that gave white people more power and unfairly treated Black people as less valuable.

People of African descent were kept out of schools, government, and other systems that promoted European language and customs.

Over time, people came to believe that European (white) culture was better than African cultures.

Europeans held power, while the people they ruled had fewer rights and opportunities.

People's language or dialect became connected to how they were treated based on race.

Different languages mixed because people from many places were brought together in the Caribbean

Shenzhen Guanglijin Technology Co., 4.345.259.760 https://sc04.alicdn.com/kf/Ha5093be65386420090d853d2ed258a635.jpg ![(https://sc04.alicdn.com/kf/Ha5093be65386420090d853d2ed258a635.jpg)

It states where the passage is in the overall boo

Part A

sdf

这里有一些tile看上不去不对或者不典型, 能不能你用视觉来check一下下面的tile Cancer：第3、7张 TLS/lymphoid：第1、5张 Vessel：基本整行，尤其第2–8张 Adipose：第1、4、8张 Nerve：第1、3、4张

然后在一个约8*8个tile的放大视野区域把annotion的的区域也画上,来判断一下是不是位于annotion边界还是内部的不均匀区域?

final peer-reviewed publication: https://journals.flvc.org/selbyana/issue/view/6421

Great descriptive and informative material to demonstrate the struggles of urbanization, the desperately needed investment to these overcrowding/ densely populated tenements, and the reform that finally prevailed via justice

It is really important to show that police work is not what we see on tv and to show students the ways in which this kind of work is mundane. I feel that this section is incomplete without a discussion of contemporary police violence, which has been a major focal point for social movements in the US over the last decade. I would want students to seriously consider the role policing plays in Illinois. You gesture to some of the history of slave patrols, but the contemporary moment does get that type of balance. If assigning this chapter, I would feel the need to bring in a lot of supplemental material to give students a more nuanced understanding of contemporary policing and its connections to criminology.

Why did this take longer? Is there a connection to the colonization of Hawaii or resistance from natives or settlers?

and criminalized such practices? Created laws around these practices?

Say more on this! Can you draw on these citations to better show students how this is the case?

can you make a connection to crime here? Corruption and white collar crime, maybe?

Is there a connection to be made between these historical entities and current iterations of neighborhood watch? This is also a racialized entity in many communities.

Would they have wanted to participate in policing at that time? What about restrictions on their freedoms from these early policing entities? You gesture to slave patrols, but my assumption would be that there are more examples to draw on! How might we think about this type of policing and the study of criminology (who is getting criminalized, for example)?

While there are no federally recognized tribes in Illinois, could a bit more be said on this? The system for tribal nations is quite different from states, and involves a great deal more federal jurisdiction, with some state jurisdiction. It can also change based on tribal affiliation and lack thereof, which also shows how legal jurisdiction is able to change!

Can a bit more context be added for this? How is dual sovereignty related to the drinking age example? I feel that a student might see this as federal supremacy over the state laws, which I don't think is the point.

I find this section to be especially useful for getting students to think about the various governing bodies that affect their lives. While the focus on state, municipal, and other local governing bodies is clear, can there be a connection made to other governing bodies (for example, federal) that would also have jurisdiction? I think it would also be useful to clarify, whether in the text or during class discussion, that laws can change based on where one is (or reiterate here since it comes up in the prior chapter).

typo

wut?

Great paper! Really interesting results, especially the differences you see between the two disease presentations (CMD-LMNA and classical EDMD). I have a few questions/comments:

1. in section 'impaired cell-cell interactions in LMNA-CMD mutant muscle cells precursors' you conclude that impaired cell-cell adhesions are due in part to degradation of m-cadherin. do you have a hypothesis for why the cadherin is degrading? Is it because something else is impaired so there's just alot extra around that has no purpose?

2. Given such striking phenotypes in cell-cell adhesion, I'm kind of surprised that the functional overload testing for PLN mass and force doesn't create a bigger gap in the CMD-LMNA condition. Do you have any insight into why this might not be such a strong change?

3. Wow, figure 7 has a really cool result!

4. You worked out a really interesting mechanism for the defects observed in your cells and in the patient population. I'm wondering if you have any ideas on the direct connection between LaminA disruption and the downstream effects, like disrupted YAP signaling, impaired cell-cell junctions, etc. It is just presumed to be an effect of a poorly functioning nucleus structure (due to lamin deficiency), or is there something more specific?

This shows that many abolitionists saw Brown's raid as a response to an already violent system rather than the beginning of the violence.

Shifts the focus from John Brown's violent actions to the cause he fought for. She is saying that Brown's raid forced Americans to debate not only violence but also the morality of slavery.

John Browns raid created fear in the South rather than hope for freedom from slavery or compromise.

A big part of the culture at the time was being patriotic and the klansman were using this to their advantage and portraying their ideology in a positive light despite it being horrific.

Voici les jalons historiques a mettre 1999 : Lancement du projet d'automatisation de la compensation bancaire. 2003 : Création de l'ACCC 2004 : Naissance de l'ASIMT et lancement du SIMT 2009 : Généralisation de la télécompensation et fin des chambres de compensation. 2010 : Création du GSIMT sous forme de GIE. 2019 : Reconnaissance du GSIMT comme infrastructure d'importance systémique. 2023 : Lancement du virement instantané.

Remplacer le titre par Chiffres clés

Remplacer le titre par Le GSIMT en bref

Use a reward as motivation, set a goal for studying, or break it up into smaller and more manageable chunks.

Sachito should get her sister to babysit that way she can have time to study and go out with her husband.

James should learn how to manage his time more wisely and spend more time studying and doing his reading than hanging out with his friends, but still having breaks to do what he wants to do.

Becky should sort out a schedule that allows her to work on her senior thesis and planning the project while still being able to finish both. If she can't she could spend more time on the senior thesis and get someone to help with planning the project.

Set certain days to be able to visit his mom instead of studying.

With the upbeat friend I would have a lot of fun studying with them and we would get through all the material and retain it. With the negative friend we would not do a lot of studying if any and end up doing something else wasting time and not doing anything useful.

They start to believe the negative things they say so they start to do bad in classes. They don't want to study, but instead want to party leading them to do bad in classes.

2 because it sets a goal that's specific and time oriented.

My goals for college are to be accepted into Texas A&M, earn a bachelor and doctorate of vet med, get accepted into vet school, and become a licensed vet.

My goal this year is to pass all my classes with at minimum only one B. My goals for high school are to strengthen my relationships with everyone and to be top 10% of my class.

My goals for today are to get enough sleep and finish my work. My goal for the week is to get on top of my work so that I don't have to do it all at once. My goal for the month is to pass the class I'm in.

The performance of the Gamba models in comparison to much larger baselines is pretty remarkable! I also thought that introducing more difficult, less random versions of the classification experiments you ran was a smart way of investigating the models’ discriminative capabilities. However, I’m a little curious why the MEM training task predicts evolutionary rates for all tokens, rather than just the masked ones. Did you compare this performance to predicting only the masked positions? Or the performance if there was no mask, and the model predicted at all positions?

Prévoir au noiveaud e ce bloc la possinilité de détailler les différents rôles une phrase pour chaque rôle

Apres lorganigramme ajouter cette phrase L’ensemble des services repose sur :

Apres l'organigramme des comités ajouter cette phrase L’ensemble des services repose sur :

Really interesting work! The SAE analysis is a great analogue of the distributional hypothesis in NLP. I’ve seen papers calling for architectures and datasets built around the concept for genes, but it’s cool to see compelling evidence that biologically meaningful feature neighborhoods can be learned from sequence prediction alone. It’d be especially interesting to see how closely the distances in these neighborhoods correlate with co-occurrence in the training data versus independent structural, biochemical, or functional similarity.

I suggest to delete it

Toolchain part, make it even more concise, because it is public information

naming issue, draft of what ?

Do I need this ?

Its a comprehensive resequencing study of nearly 200 genotypes with broad genetic base including indigenous germplasm. Furthermore, the MAS give us the insight in to the genetic base in term of adaptability that can be used by breeders to develop new varieties.

Should say "96-Well"

Adoptar un lenguaje con sensibilidad de género es una forma influyente de promover la igualdad de género y luchar contra el sesgo basado en el género.

as the government dose less to protect its people the negativity towards people of color and its intensity has risen.

recruiters and companies should not be able to signup with non-company emails

Peut-être serait-il pertinent de signaler que l'interprétation des celle de Socken en plaçant le « race des noyés » entre guillements.

On ne comprend pas tout à fait à qui ou à quoi Marcotte est comparé par l'adverbe « également », puisque les opinions des deux critiques présentés précédemment s'opposent à la sienne, d'autant plus que la phrase est introduite par la locution adverbiale « Au contraire ». Je suggère de retirer « également ».

La négation surprend ici. La citation est-elle correctement retranscrite ? Une section qui explique cette tournure syntaxtique a-t-elle été tronquée ?

Même commentaire par rapport au dédoublement de la consonne n dans « résonance ». Par ailleurs, la même citation est recopiée au §28 avec l'orthographe attendue de « résonance ». Peut-être serait-il préférable de ne convoquer la citation qu'une seule fois, dans le corps du texte et de plutôt se contenter ici de « l'idée d'une “voix de la nature” étant un fait culturel particulièrement tenace, Rosa [considère qu'il] se doit de mobiliser ce concept dans son analyse ».

Je suggère « aux dires du directeur, du manque d'espace dans le journal » ou « aux dire du directeur du journal, du manque d'espace dans les pages, déjà monopolisées ... », pour éviter la répétition de « journal ».

Je suggère « des discours rappelant la guerre, des unes de journaux, des communications radiophoniques » pour éviter la répétition de « discours ».

La proposition principale est averbale. Je suggère : « Il demeure incapable, malgré ses tentatives ... »

Même commentaire que plus haut par rapport au dédoublement de la consonne n dans « résonance ».

À qui « son ami » fait-il référence ici ? La proposition précédente, « le monde ne lui répond pas » sans reprise d'un pronom (« et reste immobile ») porte à croire que le sujet de cette proposition est « le monde », ce qui insinuerait « son ami [au monde] ». La logique nous indique plutôt qu'il s'agit de Chenevert (par rapport à Godias). Il faudrait clarifier ce passage.

Erreur de syntaxe ici : il faudrait retirer la conjonction « et » ou ajouter un mot devant « ordinaire ».

Il s'agit de la première mention de Godias. On peut facilement déduire qu'il s'agit d'un personnage du roman, toutefois le lecteur n'a pas beaucoup de contexte auquel le rattacher. Je proposerais d'ajouter une information supplémentaire pour mieux guider le lectorat : « La relation d'amitié qu'entretient Chenevert avec son collègue [?] Godias est caractéristique ... »

Vous (hihi) revenez plus précisément sur le caractère insomniaque de Chenevert plus loin (§8). Je suggère de reformuler pour exclure cette caractéristique pour l'instant : « Sévère, nerveux, portant tous les malheurs du monde sur ses épaules, il apparaît dans le texte ... »

Le référent du pronon « en » semble un peu lointain ici. Je suggère de redonner le titre du roman ici : « qui font d'Alexandre Chenevert une œuvre encore absolument actuelle ».

On attendrait ici « résonance » avec un seul n. Si la citation a été correctement retranscrite, il faudrait ajouter un [sic].

Il semble manquer une virgule ici : on s'attendait plutôt à lire « Chenevert, caissier, est inquiet ». Cependant, on comprend mal le lien entre les autres qualificatifs, qui semblaient plutôt se rapporter à la fonction extradiégétique de personnage de Chenevert qu'à son rôle intradiégétique. Peut-être serait-il préférable de simplement lire « Chenevert est inquiet » ?

Le GDT associe ce syntagme au domaine de l'industrie automobile : il faudrait peut-être lui préférer « sujet de discorde » ou « point de désaccord ».

or "structures" since it is contemporary and not changes over time or you mean that consumer functional strategies are reshuffled across contemporary climate gradients?

from varm, wet and stable climates to colder and drier regions with more seasonality.

You see if that improves. I am not sure

species distributions and data on functional traits and pairwise mutualistic interactions to estimate....

I think this Scholarslop stat from many years but was not that clear as to day, it was good to use the Grammarly to correct the grammar for the writer and change some sentences but we can not use AI for paraphrase!? we can use the iPhone with our life but not use the App for other side of our life. The question now AI is good to generate ideas but not allow to write with is diffrent between them ?

Paper was officially peer-reviewed and accepted by Nature Chemical Biology. Please cite:

Müller M, Niemeyer K, Ojha NK, Porav SA, Vinayagam D, Urban N, Büchau F, Oleinikov K, Makke M, Bauer CC, Johnson AV, Muench SP, Zufall F, Bruns D, Schwarz Y, Raunser S, Leinders-Zufall T, Bon RS, Schaefer M, Thorn-Seshold O. Ideal efficacy photoswitches for chemocontrol of TRPC4/5 channel functions in live tissues. Nat Chem Biol. 2026 Feb;22(2):180-191.

PMID: 41545580 PMCID: PMC12858405 DOI: 10.1038/s41589-025-02085-x

most of this is on civil wars etc., and it can be more robust because the data is richer .. But for GCR/Xrisk there was not much found. Is there credible 'large-N' quant analysis worth targeting? -- maybe do a nother target5ed run for that?

do we want to support per account requests as we do in feed configuration? to deduce the account from request context?

merge these in the epxlanation

This method also seems to be fairly common

It is very affordable to do a project such as this one

I've experimented with garage band before

Gives me an idea

The purpose is to give students a different perspective on the english and writing they already know

eLife Assessment

This multimodal neuroimaging study leverages fMRI, PET, and deep learning to predict memory performance. The authors introduce the brain-cognition gap to link these different imaging modalities to cognition and evaluate their results in two independent cohorts. The results are solid and provide an important contribution to the literature and will be of interest to neuroscientists working at the interface of cognition, neuroimaging.

Reviewer #1 (Public review):

[Editor's Note: this version has been assessed by the Reviewing Editor without further input from the original reviewers. The authors have responded to the comments raised in the previous round of review.]

Summary:

The authors attempted to identify if a new deep learning model could be applied to both resting and task state fMRI data to predict cognition and dopaminergic signaling. They found that resting state and moving watching conditions best predict episodic memory, but only movie watching predicts both episodic and working memory. A negative 'brain gap' (where the model trained on brain connectivity predicts worse performance than what is actually observed) was associated with less physical activity, poorer cardiovascular function, and lower D1R availability.

Strengths:

The paper should be of broad interest to the journal's readership, with implications for cognitive neuroscience, psychiatry, and psychology fields. The paper is very well-written and clear. The authors use two independent datasets to validate their findings, including two of the largest databases of dopamine receptor availability to link brain functional connectivity/activity with neurochemical signaling.

Comments on previous version:

I thank the authors for their extensive efforts to revise the manuscript. I have no further concerns.

Reviewer #2 (Public review):

Summary:

The authors developed a deep learning model based on a DenseNet CNN architecture to predict two cognitive functions: working memory and episodic memory, from functional connectivity matrices. These matrices were recorded under three conditions: during rest, a working memory task, and a movie, and were treated as images for the CNN algorithm. They tested their model's performance across different conditions and a separate dataset with a different age distribution (using the same MRI scanner, scanning configurations, and cognitive tests). They also calculated the "brain cognition gap" based on the model trained on resting functional connectivity to predict working memory. Extending from the commonly used index "brain age," the brain cognition gap was defined as the difference between the working memory score predicted by their model (predicted working memory) and the working memory score based on the working memory test itself (observed working memory). This brain cognition gap was found to be associated with physical activity, education, and cardiovascular risk. The authors also conducted additional mediation tests to examine whether regional functional variability mediated the relationship between PET-derived measures of dopamine and the brain cognition gap.

Strengths:

The major strength of this manuscript is the extensive effort the authors have put into creating a new 'biomarker' that links deep learning with fMRI, PET, physical activity, education, and cardiovascular risk across two studies. This effort is impressive.

Concerns from the previous round of review:

(1) The primary issue is still the lack of baseline models against which to benchmark the predictive performance of the proposed DenseNet model. This concern was raised independently by two reviewers. Without such benchmarks, it is difficult to interpret the reported results in the context of prior work on MRI-based cognition prediction.

Notably, the authors state: "While we compared our model with the connectome predictive modeling (CPM) approach and observed better performance with our deep learning framework, we did not conduct a comprehensive benchmark across all available machine learning methods, nor was this the aim of the present study."

However, I could NOT find any discussion or results related to the CPM model in the manuscript. It is therefore unclear whether the DenseNet model was actually statistically compared with CPM, and, if so, how the comparison was conducted.

Note that the statement, "While Vieira et al. show that the majority (76%) of prior studies used linear modeling approaches, including CPM and penalized regressions, these models are often vulnerable to overfitting, especially when applied to high-dimensional fMRI data," is not entirely accurate. Linear models typically have far fewer parameters than deep-learning models and are therefore often less prone to overfitting. In fact, it is well established that deep-learning models are particularly susceptible to overfitting and usually require substantially larger sample sizes to achieve stable and reliable performance. Although deep-learning models may outperform shallower models once sufficient data are available and training is well controlled, this does not justify the authors' claim as stated. I therefore disagree with the argument put forward by the authors.

The authors further justify the absence of benchmarking by stating: "In this context, deep learning was employed as a flexible framework capable of modelling high-dimensional functional connectivity patterns across cognitive states, rather than as a claim of inherent methodological superiority. Thus, our goal was not to propose a universally superior prediction model, but rather to test how brain state influences predictive utility for WM and EM using a deep learning approach." However, most shallow models can likewise be applied across different brain states and cognitive targets. This rationale does not establish deep learning as a uniquely appropriate or necessary choice. If deep learning is indeed a better approach in this context, the authors should demonstrate this empirically through appropriate benchmarking against established baseline models.

(2) Additional analysis shows that "BCG is not significantly associated with cognition itself". This is the most perplexing result. This is like saying Brain Age Gap is not related to chronological Age. It is counterintuitive since the Brain Age Gap is calculated by chronological age minus actual age, and most research has shown a strong relationship between the Brain Age Gap and age.

If the brain cognition gap is not related to cognition, is it possible that the results found are mainly due to the predictive model not fitting well with another dataset? Regardless, the lack of association between BCG and cognition deserves a discussion.

(3) I still do not fully understand the rationale of the mediation analysis. The analysis and findings are still not related to aims 1 and 2, since DA and entropy are not part of the prediction models. But I appreciate the explanation that this part is related to the authors' previous work, and that the authors attempted to link to them somehow.

[Editors' note: the authors have responded to these points.]

Reviewer #3 (Public review):

Summary:

This paper by Esmaeili and co-authors presents a connectome prediction study to predict episodic memory and relate prediction errors to other phonotypic variables.

Strengths:

(1) A primary and external validation dataset.

(2) Novel use of prediction errors (i.e., brain-cognitive gap).

(3) A wide range of data was investigated.

Author response:

The following is the authors’ response to the previous reviews

Public Reviews:

Reviewer #1 (Public review):

Comments on revised version:

I thank the authors for their extensive efforts to revise the manuscript. I have no further concerns.

Reviewer #2 (Public review):

The authors have made several corrections to the original manuscript. For example, they revised the bootstrapping analysis to avoid arbitrarily inflating the degrees of freedom. However, most substantive concerns remain inadequately addressed.

(1) The primary issue is still the lack of baseline models against which to benchmark the predictive performance of the proposed DenseNet model. This concern was raised independently by two reviewers. Without such benchmarks, it is difficult to interpret the reported results in the context of prior work on MRI-based cognition prediction.

Notably, the authors state: "While we compared our model with the connectome predictive modeling (CPM) approach and observed better performance with our deep learning framework, we did not conduct a comprehensive benchmark across all available machine learning methods, nor was this the aim of the present study."

However, I could NOT find any discussion or results related to the CPM model in the manuscript. It is therefore unclear whether the DenseNet model was actually statistically compared with CPM, and, if so, how the comparison was conducted.

Note that the statement, "While Vieira et al. show that the majority (76%) of prior studies used linear modeling approaches, including CPM and penalized regressions, these models are often vulnerable to overfitting, especially when applied to high-dimensional fMRI data," is not entirely accurate. Linear models typically have far fewer parameters than deep-learning models and are therefore often less prone to overfitting. In fact, it is well established that deep-learning models are particularly susceptible to overfitting and usually require substantially larger sample sizes to achieve stable and reliable performance. Although deep-learning models may outperform shallower models once sufficient data are available and training is well controlled, this does not justify the authors' claim as stated. I therefore disagree with the argument put forward by the authors.

The authors further justify the absence of benchmarking by stating: "In this context, deep learning was employed as a flexible framework capable of modelling high-dimensional functional connectivity patterns across cognitive states, rather than as a claim of inherent methodological superiority. Thus, our goal was not to propose a universally superior prediction model, but rather to test how brain state influences predictive utility for WM and EM using a deep learning approach." However, most shallow models can likewise be applied across different brain states and cognitive targets. This rationale does not establish deep learning as a uniquely appropriate or necessary choice. If deep learning is indeed a better approach in this context, the authors should demonstrate this empirically through appropriate benchmarking against established baseline models.

We thank the reviewer for reiterating this point. As noted in both the manuscript and our previous response, the primary goal of the present study was not to benchmark predictive algorithms, but rather to compare the predictive utility of different brain states using a consistent modeling framework.

We did perform an exploratory CPM analysis using a conventional implementation that included correlation-based feature selection (p < 0.01), summarization of positive and negative networks, and robust regression for prediction using 3-fold validation. However, CPM performance can depend substantially on analytical choices, including feature-selection thresholds, treatment of positive and negative networks, cross-validation strategies, and model specification. Although we obtained CPM results (see below), we did not systematically evaluate how these choices influenced performance, nor did we optimize CPM to the same extent as would be required for a rigorous methodological comparison.

For this reason, we chose not to include a CPM-versus-DenseNet comparison in the manuscript. Any direct comparison could easily be overinterpreted as evidence for the superiority of one approach over another, despite the absence of a comprehensive benchmarking framework. We therefore deliberately avoided such claims and instead focused on the scientific question motivating the study: whether predictive performance differs across brain states when the same predictive framework is applied consistently. We agree that comparisons with CPM and other predictive approaches would be valuable, but we believe such analyses are better suited to a dedicated methodological benchmarking study.

(2) Additional analysis shows that "BCG is not significantly associated with cognition itself". This is the most perplexing result. This is like saying Brain Age Gap is not related to chronological Age. It is counterintuitive since the Brain Age Gap is calculated by chronological age minus actual age, and most research has shown a strong relationship between the Brain Age Gap and age.

If the brain cognition gap is not related to cognition, is it possible that the results found are mainly due to the predictive model not fitting well with another dataset? Regardless, the lack of association between BCG and cognition deserves a discussion.

We thank the reviewer for this comment. The absence of a significant BCG-cognition association might be unexpected. We agree it warrants careful interpretation. Theoretically, when a predictive model is trained and evaluated across samples with differing age distributions, the regression-to-the-mean dynamics that typically create BAG–age dependence may not transfer in the same way to BCG–cognition relationships, particularly in age-homogeneous cohorts such as COBRA. However, we acknowledge that the present findings alone are insufficient to resolve this question fully.

We have added additional findings as supplementary material (Figure S4).

(3) I still do not fully understand the rationale of the mediation analysis. The analysis and findings are still not related to aims 1 and 2, since DA and entropy are not part of the prediction models. But I appreciate the explanation that this part is related to the authors' previous work, and that the authors attempted to link to them somehow.

We appreciate the reviewer's comment. The mediation analysis was not intended as a replication of our previous work, but rather as a mechanistic analysis to examine whether the association between BCG and cognition operates indirectly through brain age. Given the established links between BCG, brain age, and cognitive function, mediation analysis provides a principled framework for testing this hypothesis. Essentially, this mediation analysis supports previous theoretical model and our own empirical data where we showed lower DA contributes to more noise in FC metric, which in turn results in less accurate prediction (i.e., larger gap).

Recommendations for the authors:

Reviewer #2 (Recommendations for the authors):

(1) I hope the authors report CPM analysis as they claimed in the response letter, with actual statistical tests to compare the performance of DenseNet vs. CPM. It will be better to compare DenseNet with other models as well.

We thank the reviewer for reiterating this point. As noted in both the manuscript and our previous response, the goal of the present study was not to benchmark DenseNet against alternative predictive frameworks, but rather to compare the predictive utility of different brain states using a consistent modeling approach. Although we explored CPM as a potential reference model, we found that its performance was sensitive to analytical choices, including feature-selection thresholds, summarization of positive and negative networks, and model specification. A rigorous CPM comparison would therefore require systematic optimization and validation of these choices, which would constitute a separate benchmarking analysis beyond the scope of the present study. We therefore deliberately avoided claims regarding methodological superiority and revised the manuscript accordingly. While comparisons with CPM and other machine-learning approaches would be valuable, we believe such analyses would constitute a separate benchmarking study beyond the scope of the present work.

(2) "n-back did not significantly predict EM in DyNAMiC, and rest did not significantly predict WM. For this reason, we highlighted only the conditions that showed meaningful predictive power in the original analyses."

These null results should also be reported; otherwise, this suggests the authors cherry-picked only the "meaningful" results, making the claims overly optimistic.

We thank the reviewer for this comment. We agree that reporting only significant findings could create the impression of selective reporting. However, this was not our intention. All within-dataset prediction results, including both significant and non-significant findings, are reported in Tables 1 and 2. For the cross-dataset analyses, we chose to evaluate only the best-performing models identified in the DyNAMiC dataset. This decision was made a priori to test whether the most reliable predictive models generalized to an independent dataset, rather than to maximize the number of significant findings. For example, resting-state FC emerged as the strongest predictor of episodic memory in DyNAMiC and was therefore selected for external validation in COBRA. Similarly, the movie-watching model showed the strongest performance for working memory and was consequently carried forward to the cross-dataset validation. We have clarified this rationale in the manuscript.

(3) I appreciate the correlation plots between BCG and physical activity and cardiovascular risk. The results are much weaker in COBRA (r = .17 and -.10 vs. .40 and -.27 in DyNAMIC). Perhaps this warrants discussion. Note that there are potential outliers in DyNAMIC. Perhaps the authors might like to include Spearman's rank.

We thank the reviewer for this helpful observation. We agree that although the associations between BCG and both physical activity and cardiovascular risk were statistically significant in COBRA, the effect sizes were smaller than in DyNAMiC. To assess whether the observed association was influenced by potential outliers, we repeated the analysis using Spearman’s rank correlation. The association remained the same after controlling for age using partial Spearman rank correlation - between GAP and physical activity (DyNAMiC: r =0.40, p =0.001; COBRA: r =0.17, p=0.03) and for GAP vs. CVD risk score (DyNAMiC: r =–0.27, p =0.03; COBRA: r = –0.10, p =0.40). Nevertheless, we have now tempered the interpretation in the Discussion (P.12) to clarify that the direction and significance of the associations were consistent across datasets, but that the magnitude of the effects was weaker in COBRA. This difference may reflect cohort differences, including age range, sample composition, and differences in how physical activity was assessed.

(4) Yes, adding figures comparing BCG and BAG in the main text would be helpful, given BAG's popularity.

We have added additional findings as a supplementary figure.

(5) The authors should provide this reason as a justification in the method: "We initially attempted to predict both episodic memory (EM) and working memory (WM). However, EM prediction was only reliable within and across samples for the resting state, whereas WM prediction generalized most strongly from the movie-watching condition. Because COBRA does not include a movie-watching paradigm, we could not evaluate WM prediction across datasets. For this reason, we focused on EM when examining the brain-cognition."

We thank the reviewer’s suggestion. This clarification is included in the method section of the revised manuscript [P 21].