20 research outputs found
Innovative AnsĂ€tze der Daseinsvorsorge in lĂ€ndlichen RĂ€umen - Lernen von Erfahrungen anderer europĂ€ischer LĂ€nder fĂŒr Deutschland (InDaLE)
Das Forschungsprojekt InDaLE (Innovative AnsĂ€tze der Daseinsvorsorge in lĂ€ndlichen RĂ€umen â Lernen von Erfahrungen anderer europĂ€ischer LĂ€nder fĂŒr Deutschland) untersuchte innovative AnsĂ€tze der Daseinsvorsorge in Ăsterreich, Schweden, Schottland sowie Deutschland und prĂŒfte deren Ăbertragbarkeit bzw. Anwendbarkeit auf lĂ€ndliche RĂ€ume in Deutschland.
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Stable Carbon and Nitrogen Isotopes in a Peat Profile Are Influenced by Early Stage Diagenesis and Changes in Atmospheric CO2 and N Deposition
In this study, we test whether the ÎŽ13C and ÎŽ15N in a peat profile are, respectively, linked to the recent dilution of atmospheric ÎŽ13CO2 caused by increased fossil fuel combustion and changes in atmospheric ÎŽ15N deposition. We analysed bulk peat and Sphagnum fuscum branch C and N concentrations and bulk peat, S. fuscum branch and Andromeda polifolia leaf ÎŽ13C and ÎŽ15N from a 30-cm hummock-like peat profile from an Aapa mire in northern Finland. Statistically significant correlations were found between the dilution of atmospheric ÎŽ13CO2 and bulk peat ÎŽ13C, as well as between historically increasing wet N deposition and bulk peat ÎŽ15N. However, these correlations may be affected by early stage kinetic fractionation during decomposition and possibly other processes. We conclude that bulk peat stable carbon and nitrogen isotope ratios may reflect the dilution of atmospheric ÎŽ13CO2 and the changes in ÎŽ15N deposition, but probably also reflect the effects of early stage kinetic fractionation during diagenesis. This needs to be taken into account when interpreting palaeodata. There is a need for further studies of ÎŽ15N profiles in sufficiently old dated cores from sites with different rates of decomposition: These would facilitate more reliable separation of depositional ÎŽ15N from patterns caused by other processes
AI is a viable alternative to high throughput screening: a 318-target study
: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNetÂź convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNetÂź model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery
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3-amino thioacridone inhibits DNA synthesis and induces DNA damage in T-cell acute lymphoblastic leukemia (T-ALL) in a p16-dependent manner
In T-cell Acute Lymphocytic Leukemia (T-ALL), the inhibitors of cyclin-dependent kinases (CDK) 4 and 6, p16 and p15, are inactivated almost universally at the DNA, RNA and protein levels. This suggests that CDK-targeting may be an effective therapeutic approach for T-ALL and other cancers. In this study, we tested 3 inhibitors of CDK4, 3-aminothioacridone (3-ATA), thioacridone (TA), and oxindole, for their effects on DNA synthesis and viability in primary T-ALL. Each compound was an effective inhibitor, with overall IC50s in similar ranges. In colony formation assay, leukemic cells were approximately 10-fold more sensitive to 3-ATA than normal bone marrow cells. When sorted by G1 protein status of T-ALL, p16(+), p15(+) or pRb(-) samples were significantly less sensitive to 3-ATA and TA, but not to oxindole, than p16(-), p15(-) or pRb(+) samples. There was no relationship of sensitivity with ARF expression. Despite their in vitro function as inhibitors of CDK4, 3-ATA did not inhibit pRb phosphorylation or cause G1 arrest, but did cause DNA damage and result in the induction and phosphorylation of p53. We conclude that 3-ATA efficacy can be predicted by p16 status in T-ALL, but the mechanism of action may be distinct from their in vitro ability to regulate CDK4 kinase activity
Innovative AnsĂ€tze der Daseinsvorsorge in lĂ€ndlichen RĂ€umen - Lernen von Erfahrungen anderer europĂ€ischer LĂ€nder fĂŒr Deutschland (InDaLE): Projektabschlussbericht: Learning from the experiences of other European countries for Germany (InDaLE)
Das Forschungsprojekt InDaLE (Innovative AnsĂ€tze der Daseinsvorsorge in lĂ€ndlichen RĂ€umen â Lernen von Erfahrungen anderer europĂ€ischer LĂ€nder fĂŒr Deutschland) untersuchte innovative AnsĂ€tze der Daseinsvorsorge in Ăsterreich, Schweden, Schottland sowie Deutschland und prĂŒfte deren Ăbertragbarkeit bzw. Anwendbarkeit auf lĂ€ndliche RĂ€ume in Deutschland.
Die Analyse von Erfahrungen im europĂ€ischen Ausland zur Anpassung von Infrastrukturen wird fĂŒr die Entwicklung innovativer AnsĂ€tze in Deutschland genutzt und kann neue Lösungen bieten.:ABBILDUNGSVERZEICHNIS VII
TABELLENVERZEICHNIS VIII
VORWORT 9
1 EINLEITUNG 12
1.1 Problemdarstellung und Motivation 12
1.2 Innovationen in der lÀndlichen Daseinsvorsorge: Forschungsstand 12
1.3 ProjektverstÀndnis 14
2 VERSTETIGUNG, ĂBERTRAGBARKEIT UND GOVERNANCE: KONZEPTIONELLE VORĂBERLEGUNGEN 15
2.1 Verstetigung 15
2.2 Ăbertragbarkeit 23
2.3 Governance von Daseinsvorsorge 28
3 METHODISCHES VORGEHEN: PROJEKTAUSWAHL, DATENERHEBUNGEN UND -ANALYSE 31
3.1 Vorauswahl und Checkliste 31
3.2 Finale Projektauswahl 31
3.3 Datenerhebung zu den Projekten 34
3.4 Datenauswertung der leitfadengestĂŒtzten Interviews 36
4 RAHMENBEDINGUNGEN IN DEN UNTERSUCHUNGSLĂNDERN 38
4.1 Deutschland 38
4.2 Ăsterreich 41
4.3 Schottland 45
4.4 Schweden 48
5 GOVERNANCE UND HERAUSFORDERUNGEN DER DASEINSVORSORGEBEREICHE IN LĂNDLICHEN RĂUMEN 53
5.1 Nachschulische Bildung 53
5.2 Medizinische Versorgung und Pflege 56
5.3 Nichtpolizeiliche Gefahrenabwehr 60
6 PROJEKTSTECKBRIEFE 67
6.1 Nachschulische Bildung 67
6.2 Medizinische Versorgung und Pflege 74
6.3 Nichtpolizeiliche Gefahrenabwehr 82
7 VERSTETIGUNG INNOVATIVER PROJEKTE: FĂRDERLICHE UND HEMMENDE FAKTOREN 89
7.1 Nachschulische Bildung 89
7.2 Medizinische Versorgung und Pflege 101
7.3 Nichtpolizeiliche Gefahrenabwehr 114
8 VERSTETIGUNG NACH WIRKUNGSBEREICHEN: ĂBERGREIFENDE ERKENNTNISSE AUS DEN BEISPIELPROJEKTEN 123
8.1 Inhaltlicher Wirkungsbereich 123
8.2 Organisationsstruktureller Wirkungsbereich 125
8.3 Politisch-administrativer Wirkungsbereich 126
8.4 Finanzieller Wirkungsbereich 127
9 INNOVATIVE LĂSUNGEN UND ANSĂTZE DER DASEINSVORSORGE IN LĂNDLICHEN RĂUMEN 129
9.1 Thesen zum inhaltlichen Wirkungsbereich 129
9.2 Thesen zum organisationsstrukturellen Wirkungsbereich 132
9.3 Thesen zum politisch-administrativen Wirkungsbereich 135
9.4 Thesen zum finanziellen Wirkungsbereich 139
10 HANDLUNGSEMPFEHLUNGEN 142
10.1 Empfehlungen fĂŒr die untersuchten Daseinsvorsorgebereiche 142
10.2 Checkliste fĂŒr ProjekttrĂ€ger zur Verstetigung 147
11 ZUSAMMENFASSUNG ZENTRALER ERGEBNISSE 149
11.1 Zentrale Erkenntnisse aus den drei untersuchten Daseinsvorsorgebereichen 149
11.2 Schlussfolgerungen fĂŒr die Forschung 154
12 LITERATURVERZEICHNIS 157
ANHANG I: PROJEKTBETEILIGTE UND PROJEKTVERANSTALTUNGEN 171
ANHANG II: INDALE-GLOSSAR 173
ANHANG III: INTERVIEWLEITFĂDEN 175The research project InDaLE (Innovative approaches to services of general interest in rural areas - learning from the experiences of other European countries for Germany) analysed innovative approaches to services of general interest in Austria, Sweden, Scotland and Germany and examined their transferability and applicability to rural areas in Germany.
The analysis of experiences in other European countries regarding the adaptation of infrastructures is used for the development of innovative approaches in Germany and can offer new solutions.:ABBILDUNGSVERZEICHNIS VII
TABELLENVERZEICHNIS VIII
VORWORT 9
1 EINLEITUNG 12
1.1 Problemdarstellung und Motivation 12
1.2 Innovationen in der lÀndlichen Daseinsvorsorge: Forschungsstand 12
1.3 ProjektverstÀndnis 14
2 VERSTETIGUNG, ĂBERTRAGBARKEIT UND GOVERNANCE: KONZEPTIONELLE VORĂBERLEGUNGEN 15
2.1 Verstetigung 15
2.2 Ăbertragbarkeit 23
2.3 Governance von Daseinsvorsorge 28
3 METHODISCHES VORGEHEN: PROJEKTAUSWAHL, DATENERHEBUNGEN UND -ANALYSE 31
3.1 Vorauswahl und Checkliste 31
3.2 Finale Projektauswahl 31
3.3 Datenerhebung zu den Projekten 34
3.4 Datenauswertung der leitfadengestĂŒtzten Interviews 36
4 RAHMENBEDINGUNGEN IN DEN UNTERSUCHUNGSLĂNDERN 38
4.1 Deutschland 38
4.2 Ăsterreich 41
4.3 Schottland 45
4.4 Schweden 48
5 GOVERNANCE UND HERAUSFORDERUNGEN DER DASEINSVORSORGEBEREICHE IN LĂNDLICHEN RĂUMEN 53
5.1 Nachschulische Bildung 53
5.2 Medizinische Versorgung und Pflege 56
5.3 Nichtpolizeiliche Gefahrenabwehr 60
6 PROJEKTSTECKBRIEFE 67
6.1 Nachschulische Bildung 67
6.2 Medizinische Versorgung und Pflege 74
6.3 Nichtpolizeiliche Gefahrenabwehr 82
7 VERSTETIGUNG INNOVATIVER PROJEKTE: FĂRDERLICHE UND HEMMENDE FAKTOREN 89
7.1 Nachschulische Bildung 89
7.2 Medizinische Versorgung und Pflege 101
7.3 Nichtpolizeiliche Gefahrenabwehr 114
8 VERSTETIGUNG NACH WIRKUNGSBEREICHEN: ĂBERGREIFENDE ERKENNTNISSE AUS DEN BEISPIELPROJEKTEN 123
8.1 Inhaltlicher Wirkungsbereich 123
8.2 Organisationsstruktureller Wirkungsbereich 125
8.3 Politisch-administrativer Wirkungsbereich 126
8.4 Finanzieller Wirkungsbereich 127
9 INNOVATIVE LĂSUNGEN UND ANSĂTZE DER DASEINSVORSORGE IN LĂNDLICHEN RĂUMEN 129
9.1 Thesen zum inhaltlichen Wirkungsbereich 129
9.2 Thesen zum organisationsstrukturellen Wirkungsbereich 132
9.3 Thesen zum politisch-administrativen Wirkungsbereich 135
9.4 Thesen zum finanziellen Wirkungsbereich 139
10 HANDLUNGSEMPFEHLUNGEN 142
10.1 Empfehlungen fĂŒr die untersuchten Daseinsvorsorgebereiche 142
10.2 Checkliste fĂŒr ProjekttrĂ€ger zur Verstetigung 147
11 ZUSAMMENFASSUNG ZENTRALER ERGEBNISSE 149
11.1 Zentrale Erkenntnisse aus den drei untersuchten Daseinsvorsorgebereichen 149
11.2 Schlussfolgerungen fĂŒr die Forschung 154
12 LITERATURVERZEICHNIS 157
ANHANG I: PROJEKTBETEILIGTE UND PROJEKTVERANSTALTUNGEN 171
ANHANG II: INDALE-GLOSSAR 173
ANHANG III: INTERVIEWLEITFĂDEN 17
The SIDECAR project : S-IcD registry in European paediatriC and young Adult patients with congenital heaRt defects
AIMS: Subcutaneous-implantable cardiac defibrillators (S-ICDs) are used increasingly to prevent sudden cardiac death in young patients. This study was set up to gain insight in the indications for S-ICD, possible complications, and their predictors and follow-up results. METHODS AND RESULTS: A multicentre, observational, retrospective, non-randomized, standard-of-care registry on S-ICD outcome in young patients with congenital heart diseases (CHDs), inherited arrhythmias (IAs), idiopathic ventricular fibrillation (IVF), and cardiomyopathies (CMPs). Anthropometry was registered as well as implantation technique, mid-term device-related complications, and incidence of appropriate/inappropriate shocks (IASs). Data are reported as median (interquartile range) or mean ± standard deviation. Eighty-one patients (47% CMPs, 20% CHD, 21% IVF, and 12% IA), aged 15 (14-17) years, with body mass index (BMI) 21.8 ± 3.8 kg/m2, underwent S-ICD implantation (primary prevention in 59%). This was performed with two-incision technique in 81% and with a subcutaneous pocket in 59%. Shock and conditional zones were programmed at 250 (200-250) and 210 (180-240) b.p.m., respectively. No intraoperative complications occurred. Follow up was 19 (6-35) months: no defibrillation failure occurred, 17% of patients received appropriate shocks, 13% of patients received IAS (supraventricular tachycardias 40%, T-wave oversensing 40%, and non-cardiac oversensing 20%). Reprogramming, proper drug therapy, and surgical revision avoided further IAS. Complications requiring surgical revision occurred in 9% of patients, with higher risks in patients with three-incision procedures [hazard ratio (HR) 4.3, 95% confidence interval (95% CI) 0.5-34, P = 0.038] and BMI 20 showed better outcome
The SIDECAR project: S-IcD registry in European paediatriC and young Adult patients with congenital heaRt defects
AIMS: Subcutaneous-implantable cardiac defibrillators (S-ICDs) are used increasingly to prevent sudden cardiac death in young patients. This study was set up to gain insight in the indications for S-ICD, possible complications, and their predictors and follow-up results. METHODS AND RESULTS: A multicentre, observational, retrospective, non-randomized, standard-of-care registry on S-ICD outcome in young patients with congenital heart diseases (CHDs), inherited arrhythmias (IAs), idiopathic ventricular fibrillation (IVF), and cardiomyopathies (CMPs). Anthropometry was registered as well as implantation technique, mid-term device-related complications, and incidence of appropriate/inappropriate shocks (IASs). Data are reported as median (interquartile range) or mean ± standard deviation. Eighty-one patients (47% CMPs, 20% CHD, 21% IVF, and 12% IA), aged 15 (14-17) years, with body mass index (BMI) 21.8 ± 3.8 kg/m2, underwent S-ICD implantation (primary prevention in 59%). This was performed with two-incision technique in 81% and with a subcutaneous pocket in 59%. Shock and conditional zones were programmed at 250 (200-250) and 210 (180-240) b.p.m., respectively. No intraoperative complications occurred. Follow up was 19 (6-35) months: no defibrillation failure occurred, 17% of patients received appropriate shocks, 13% of patients received IAS (supraventricular tachycardias 40%, T-wave oversensing 40%, and non-cardiac oversensing 20%). Reprogramming, proper drug therapy, and surgical revision avoided further IAS. Complications requiring surgical revision occurred in 9% of patients, with higher risks in patients with three-incision procedures [hazard ratio (HR) 4.3, 95% confidence interval (95% CI) 0.5-34, P = 0.038] and BMI 20 showed better outcome