Helices by hydrogen bonding : folding and stacking of chiral supramolecular scaffolds

Zelfassemblage van synthetische, organische structuren leidt tot nieuwe ontwikkelingen, zowel binnen het vakgebied van de biologie, als dat van de materiaalkunde. In principe maakt het zelfassemblageproces het mogelijk op nano-schaal, snel goed-gedefinieerde architecturen op te bouwen, die hun reversibele karakter behouden. In een supramoleculaire architectuur is een optimale balans tussen stabiliteit en reversibiliteit essentieel. Wanneer niet-covalente interacties te sterk worden, belemmeren kinetische factoren de bewegingsvrijheid van de individuele bouwstenen. De supramoleculaire architectuur kan dan zijn optimaal geordende thermodynamische evenwichtssituatie niet meer bereiken. Een optimale balans tussen stabiliteit en reversibiliteit in de supramoleculaire architectuur houdt een optimale afstemming in van de verschillende niet-covalente interacties (bijvoorbeeld waterstofbrugvorming en ¿-¿ interacties). Om de bijdrage van iedere specifieke interactie in te kunnen schatten, is een diepgaand begrip van de relatie tussen de chemische structuur en de materiaaleigenschappen (vloeibaar kristalliniteit, gelvorming) noodzakelijk. Voor verschillende verbindingen (Figuur 1) is een samenhangend moleculair beeld gevormd over het totale concentratiegebied, van bulk, via gel tot geïsoleerd molecuul. Hierbij is gebruik gemaakt van een scala aan technieken, waaronder DSC, optische microscopie en röntgen diffractie in de vaste fase, terwijl in de gel fase AFM en SANS zijn gebruikt. In verdunde oplossing zijn geïsoleerde supramoleculaire architecturen aanwezig. Om (de mate van) ordening hierin te herkennen, is gebruik gemaakt van supramoleculaire chiraliteit, geïntroduceerd via chirale informatie in de perifere ketens. Circulair dichroïsme spectroscopie is het aangewezen instrument gebleken om inzicht en begrip te verkrijgen in het gedrag van de nieuwe chirale architecturen. In dit onderzoek ligt de nadruk op de helix-architectuur, mede vanwege de essentiële rol die de ¿-helix speelt in de expressie van eiwitfuncties. Recent zijn C3-symmetrische schijfvormige moleculen ontwikkeld, die zelf-assembleren tot kolommen. Heliciteit is gegenereerd door de schijven ten opzichte van elkaar te roteren met behulp van intermoleculaire waterstofbrugbinding en ¿-¿ stapeling. Om een optimale afstemming van deze interacties te verkrijgen is een reeks van twaalf C3-symmetrische schijven vergeleken, variërend in hun mogelijkheid tot waterstofbrugbinding (amide of ureum) en tot ¿-¿ stapeling (klein, gemiddeld, groot), al dan niet voorzien van een stereogeen centrum in de lipofiele zijstaarten. De schijven vertonen inderdaad een samenhangend gedrag over het hele concentratiegebied. In verdunde oplossing (CD) zelf-assembleren ze tot helische kolommen. Deze kolommen vormen een netwerk in de lyotrope gelfase (AFM, SANS), terwijl ze in de vloeibaar kristallijne fase hexagonaal geordend zijn (Xray). Bij alle concentraties is gebleken dat ureum waterstofbruggen een grotere stabiliteit geven dan amide waterstofbruggen. Tegelijkertijd wordt de kinetiek zichtbaar in het opbouwen van de meest geordende architectuur, een fenomeen aangeduid als hysterese. Amide schijven lijken direct een geordende helix te vormen. De ureum schijven vormen aanvankelijk een slecht gedefinieerde stapel, die vervolgens langzaam in een goed-geordende, chirale kolom verandert. De rigiditeit van de ureum kolom maakt de formatie van een n-heptaan solvent schil om de kolom mogelijk, in een medium van vertakt isooctaan. Asymmetrie in de bovengenoemde disks, maakt het in principe mogelijk de `secundaire¿ helices te incorporeren in `tertiaire¿ architecturen. Monoamide diureum disks vormen helices via uitsluitend amideamide en ureum-ureum interacties. Echter, een poging de monoamide diureum disks `aaneen te rijgen¿ tot een `foldamer¿ in een helixconformatie faalde. Al bij een lengte van vijf tot zes eenheden trad irreversibele en dus ongeordende a ggregatie op door `sterke¿ waterstofbruginteracties. Niettemin ligt de `foldamer¿ aanpak tot helixformatie dichter bij de natuurlijke ¿-helix dan de `selfassembly¿ benadering. Hier wordt immers gebruik gemaakt van covalente polymeermoleculen, die een helixconformatie aannemen met behulp van intramoleculaire, niet-covalente interacties. Een polyureïdoftaalimide met `zwakkere¿ intramoleculaire waterstofbruggen is ontworpen, gesynthetiseerd en onderzocht. Uit microscopische en optische metingen blijkt dat dit polymeer (~ 30 eenheden) een geordende, chirale supramoleculaire helix vormt in diverse oplosmiddelen en bij lage concentratie (10-5 M). Na chromatografische isolatie van de oligomeren (2 tot en met 8 eenheden), konden intra- en intermoleculaire opvouwprocessen geïdentificeerd worden. Met het oog op toepassing van het ureïdoftaalimide platform in nieuwe materialen is een eerste poging ondernomen om de kleurstof antrachinon op te nemen in de ftaalimide helix. Er zijn inderdaad geordende architecturen gevonden die zouden kunnen bijdragen aan een efficiënter ladingstransport in supramoleculaire elektronica

Developing Data Stories in Digital Humanities: Challenges and Protocol

This article discusses the development of data-driven stories and the editorial processes underlying their production. Such ‘data stories’ have proliferated in journalism but are also increasingly developed within academia. Within CLARIAH, the Common Lab Infrastructure for the Arts and Humanities, we are developing data stories based on analyses of data and metadata available via the Media Suite, an online resource providing access to a wide range of multimedia collections. Although ‘data stories’ lack a clear definition, there are similarities between the processes that underlie journalistic and academic data stories. However, there are also differences, specifically when it comes to epistemological claims. In this article we discuss data stories as phenomenon and their use in journalism and in the Humanities, based on the three main elements of data stories: data, visualisation, and narration. This provides the context in which we developed an editorial protocol for the development of CLARIAH Media Suite Data Stories, which includes four phases: exploration, research, review, and publication. While exploration focuses on data selection, research focuses on narration. Visualisation plays a role in both of these phases. Review is geared towards quality control, and in the publication phase the data story is published and monitored. By discussing our editorial protocol, we hope to contribute to the debate about how to develop and account for academic data stories

Multifocal occurrence of extra-abdominal desmoid type fibromatosis – A rare manifestation. A clinicopathological study of 6 sporadic cases and 1 hereditary case

Desmoid-type fibromatosis, also called desmoid tumor, is a locally aggressive myofibroblastic neoplasm that usually arises in deep soft tissue with significant potential for local recurrence. It displays an unpredictable clinical course. β-Catenin, the genetic key player of desmoid tumors shows nuclear accumulation due to mutations that preve

Psychosocial functioning of adult siblings of Dutch very long-term survivors of childhood cancer: DCCSS-LATER 2 psycho-oncology study

ObjectiveTo describe psychosocial outcomes among adult siblings of very long-term childhood cancer survivors (CCS), to compare these outcomes to reference populations and to identify factors associated with siblings' psychosocial outcomes. MethodsSiblings of survivors (diagnosed 5 years since diagnosis) of the Dutch Childhood Cancer Survivor Study DCCSS-LATER cohort were invited to complete questionnaires on HRQoL (TNO-AZL Questionnaire for Adult's HRQoL), anxiety/depression (Hospital Anxiety and Depression Scale), post-traumatic stress (Self-Rating Scale for Post-traumatic Stress Disorder), self-esteem (Rosenberg Self-Esteem Scale) and benefit and burden (Benefit and Burden Scale for Children). Outcomes were compared to a reference group if available, using Mann-Whitney U and chi-Square tests. Associations of siblings' sociodemographic and CCS' cancer-related characteristics with the outcomes were assessed with mixed model analysis. ResultsFive hundred five siblings (response rate 34%, 64% female, mean age 37.5, mean time since diagnosis 29.5) of 412 CCS participated. Siblings had comparable HRQoL, anxiety and self-esteem to references with no or small differences (r = 0.08-0.15, p < 0.05) and less depression. Proportions of symptomatic PTSD were very small (0.4%-0.6%). Effect sizes of associations of siblings' sociodemographic and CCS cancer-related characteristics were mostly small to medium (& beta; = 0.19-0.67, p < 0.05) and no clear trend was found in the studied associated factors for worse outcomes. ConclusionsOn the very long-term, siblings do not have impaired psychosocial functioning compared to references. Cancer-related factors seem not to impact siblings' psychosocial functioning. Early support and education remain essential to prevent long-term consequences.Metabolic health: pathophysiological trajectories and therap

Positive and negative survivor-specific psychosocial consequences of childhood cancer: the DCCSS-LATER 2 psycho-oncology study

Purpose: Numerous studies investigated generic psychosocial outcomes in survivors of childhood cancer (CCS). The present study aimed to describe survivor-specific psychosocial consequences in CCS, and to identify socio-demographic and medical associated factors. Methods: CCS from the Dutch Childhood Cancer Survivor Study (DCCSS)-LATER cohort (diagnosed 1963-2001) part 2 (age >= 18 years, diagnosed = 5 years since diagnosis) completed the Benefit & Burden Scale (BBSC) and the Impact of Cancer-Childhood Cancer (IOC-CS). Items were scored on a 5-point Likert scale (range 1-5). We examined outcomes with descriptive statistics, and socio-demographic and medical associated factors with regression analyses, corrected for multiple testing (p = 15 years since diagnosis, participated. On average, CCS reported 'somewhat' Benefit (M = 2.9), and 'not at all' to 'a little' Burden (M = 1.5) of childhood cancer. Average scores on IOC-CS' positive impact scales ranged from 2.5 (Personal Growth) to 4.1 (Socializing), and on the negative impact scales from 1.4 (Financial Problems) to 2.4 (Thinking/Memory). Apart from cognitive problems, CCS reported challenges as worries about relationship status, fertility, and how cancer had affected siblings. Female sex was associated with more Personal Growth, and more negative impact. CCS more highly educated, partnered, and employed had higher positive and lower negative impact. CCS older at diagnosis reported more positive impact. CNS tumor survivors and those who had head/cranium radiotherapy had higher negative impact. CNS tumor survivors reported less positive impact. Conclusion and implications: The majority of CCS reported positive impact of cancer while most CCS reported little negative impact. While this may indicate resiliency in most CCS, health care providers should be aware that they can also experience survivor-specific challenges that warrant monitoring/screening, information provision and psychosocial support.Metabolic health: pathophysiological trajectories and therap

Has the Rate of CD4 Cell Count Decline before Initiation of Antiretroviral Therapy Changed over the Course of the Dutch HIV Epidemic among MSM?

Introduction:Studies suggest that the HIV-1 epidemic in the Netherlands may have become more virulent, leading to faster disease progression if untreated. Analysis of CD4 cell count decline before antiretroviral therapy (ART) initiation, a surrogate marker for disease progression, may be hampered by informative censoring as ART initiation is more likely with a steeper CD4 cell count decline.Methods:Development of CD4 cell count from 9 to 48 months after seroconversion was analyzed using a mixed-effects model and 2 models that jointly modeled CD4 cell counts and time to censoring event (start ART

Non-AIDS defining cancers in the D:A:D Study-time trends and predictors of survival : a cohort study

BACKGROUND:Non-AIDS defining cancers (NADC) are an important cause of morbidity and mortality in HIV-positive individuals. Using data from a large international cohort of HIV-positive individuals, we described the incidence of NADC from 2004-2010, and described subsequent mortality and predictors of these.METHODS:Individuals were followed from 1st January 2004/enrolment in study, until the earliest of a new NADC, 1st February 2010, death or six months after the patient's last visit. Incidence rates were estimated for each year of follow-up, overall and stratified by gender, age and mode of HIV acquisition. Cumulative risk of mortality following NADC diagnosis was summarised using Kaplan-Meier methods, with follow-up for these analyses from the date of NADC diagnosis until the patient's death, 1st February 2010 or 6 months after the patient's last visit. Factors associated with mortality following NADC diagnosis were identified using multivariable Cox proportional hazards regression.RESULTS:Over 176,775 person-years (PY), 880 (2.1%) patients developed a new NADC (incidence: 4.98/1000PY [95% confidence interval 4.65, 5.31]). Over a third of these patients (327, 37.2%) had died by 1st February 2010. Time trends for lung cancer, anal cancer and Hodgkin's lymphoma were broadly consistent. Kaplan-Meier cumulative mortality estimates at 1, 3 and 5 years after NADC diagnosis were 28.2% [95% CI 25.1-31.2], 42.0% [38.2-45.8] and 47.3% [42.4-52.2], respectively. Significant predictors of poorer survival after diagnosis of NADC were lung cancer (compared to other cancer types), male gender, non-white ethnicity, and smoking status. Later year of diagnosis and higher CD4 count at NADC diagnosis were associated with improved survival. The incidence of NADC remained stable over the period 2004-2010 in this large observational cohort.CONCLUSIONS:The prognosis after diagnosis of NADC, in particular lung cancer and disseminated cancer, is poor but has improved somewhat over time. Modifiable risk factors, such as smoking and low CD4 counts, were associated with mortality following a diagnosis of NADC

Facile synthesis of a chiral polymeric helix; folding by intramolecular hydrogen bonding

In a single condensation step, a polyureidophthalimide is synthesized, which folds into a chiral, helical architecture according to CD spectroscop

Facile synthesis of a chiral polymeric helix; folding by intramolecular hydrogen bonding

In a single condensation step, a polyureidophthalimide is synthesized, which folds into a chiral, helical architecture according to CD spectroscop