The Austrian Constitutional Convention: continuing the path to reform the Federal State

Aquest article tracta els diferents debats i intents de reforma del sistema federal austríac dels darrers quinze anys. L’article parteix d'una perspectiva històrica que descriu els desenvolupaments més rellevants del federalisme austríac en el decurs del segle XX, i destaca la importància del procés de centralització a través de la constant transferència de competències des dels Länder al Govern federal, així com els diversos debats en aquest sentit. Segons l’autora, des de 1995, any de l’accés d’Àustria a la Unió Europea, s’han perdut dues grans oportunitats per dur a terme una reforma general del sistema federal que pogués contribuir a compensar el procés de centralització. La primera oportunitat perduda té referència directa amb la Unió Europea. Els Länder van accedir a l’adhesió amb la condició que la Constitució federal preveiés des de diverses dimensions la seva participació en els processos europeus de presa de decisions, tot deixant de banda l’oportunitat d’aprofitar el debat i pressionar per a una reforma estructural del sistema federal. La segona oportunitat perduda té a veure amb la dispersió de propostes resultants dels treballs de la Convenció Constitucional Austríaca. La Convenció, creada el 2003, tenia la missió de discutir la reforma de la Constitució en els aspectes que regulen l’estructura federal del país i, en conseqüència, elaborar- ne un primer esborrany. La incapacitat d’establir i definir eixos comuns de reforma, juntament amb la manca de flexibilitat i de cerca de compromís polític, van desdibuixar el paper de la Convenció.This article discusses the different debates and attempts to reform the Austrian federal system over the last fifteen years. The article is based on a historical perspective that describes the most relevant developments of Austrian federalism during the 20th century, highlighting the importance of the centralisation process through the constant transfer of powers from the Länder to the Federal Government, as well as various debates in this regard. According to the author, since 1995, the year of Austrian adhesion to the European Union, two opportunities have been missed to carry out a general reform of the federal system which could contribute to compensating the centralisation process. The first missed opportunity is directly related to the Austrian adhesion to the European Union. The Länder agreed to the adhesion under the condition that the Federal Constitution would include their participation in European decision-making processes. By focussing on this point, the Länder set aside the opportunity to take advantage of the debate and, as a consequence, press for structural reform of the federal system. The second missed opportunity was related to the dispersion of proposals resulting from the work of the Austrian Constitutional Convention. The Convention, created in 2003, had the mission of discussing those aspects of the reform of the Constitution that regulated the federal structure of the country and, as a consequence, of making a first draft reform. The incapability of establishing and defining common ground for reform, together with the lack of flexibility and of seeking political commitment, weakened the role of the Convention and, thus, any possibility to carry on with the reform

Introduction: Federalism, local government and policy-making

This special issue examines local government; one of the less explored and yet most relevant aspects of federal studies. The special issue looks at cases that demonstrate how the growing role of local government has a considerable impact on federal systems

"Treća razina vlasti" u Austriji. Pravna regulacija i trendovi u lokalnoj samoupravi

Unlike other constitutions, the Austrian Federal Constitution not only recognizes the municipalities (Gemeinden) explicitly, but also regulates their organisation and functions in principle, whilst details are left to the legislation of the nine Länder. In accordance with the European Charter of Local Self-Government, all local authorities are elected democratically, deriving their mandate either directly or indirectly from the local citizens. Numerous local functions are performed on an autonomous basis, where local authorities cannot be bound to instructions, although they are under state supervision. Whereas the constitutional status of the municipalities does not generally approach that of the Länder, they are recognised as a »third partner« in the system of fiscal equalisation and national budgeting, where co-operation between the federation, the Länder,and the municipalities is closer than in other areas. Their general admittance to the traditional »dual system« of Austrian federalism is still refused, though.U mnogim državama sve se češće traži ustavno priznavanje činjenice da je djelovanje lokalnih sa moup rav nih je di ni ca od ključne važnos ti za opće dob ro na ra zi ni naj bližoj građani ma. U fe de ral nim država ma to čes to do vo di do na petosti iz među ra zi ne fe de ral nih je di ni ca i lo kal ne ra zi ne bu dući da lo kal na samoupra va zah ti je va da ju se priz na kao trećeg par tne ra u sus ta vu fe de ra ci je,što se kla sičnoj fe de ral noj dok tri ni čini po put he re ze. Aus trij ski fe de ral ni Us tav re gu li ra or ga ni za ci ju i pos lo ve općina (Ge mein den) u načelu, no de talj nu pravnu re gu la ci ju pre pušta na bri gu de vetorima fe de ral nim je di ni cama (Länder). U skla du s Eu rop skom po ve ljom o lo kal noj sa moup ra vi, sve lo kal ne vlas ti iza bi ru se na de mok rat ski način, a man dat im je iz rav no ili neiz rav no ute me ljen na vo lji građana lo kal ne je di ni ce. Ve lik broj lo kal nih pos lo va obav lja se au to nom no, u skla du s načelom sup si dijar nos ti. O obav lja nju pos lo va pre ne se nog dje lok ru ga lo kal ne su vlas ti pod ložne upu ta ma fe de ral nih ti je la ili ti je la fe de ral nih je di nica (Länder). Ia ko ustav ni sta tus općina općeni to ni je jed nak sta tu su fe de ral nih je di ni ca (Länder), njih se priz na je kao »trećeg par tne ra« u sus ta vu fis kal nog po rav na nja i do nošenja držav nog pro računa, gdje je su rad nja iz melu fe de racije, općina i fe de ral nih je di ni ca (Länder) tješnja ne go u dru gim pod ručji ma. Međutim, općeni to go vo reći, lo kal ne sa moup rav ne je di ni ca još ni su us pje le postići da ih se tre ti ra kao kon sti tu tiv ne je di ni ce fe de ral nog sus ta va ia ko već go di nama traže zas tup lje no st u Gor njem do mu fe de ral nog Par la men ta. Važan us tav ni aman dman ko ji je ne dav no us vo jen iz rav no se ne tiče lo kal nih sa moup rav nih je di ni ca, a još se ne zna hoće li se pla ni ra na re for ma fe de ra liz ma i aus trij skog up rav nog sus ta va pro ves ti u blis koj bu dućnos ti, što bi mog lo ko ris ti ti bu dućem po ložaju lo kal ne sa moup ra ve

Structural basis for +1 ribosomal frameshifting during EF-G-catalyzed translocation [preprint]

Frameshifting of mRNA during translation provides a strategy to expand the coding repertoire of cells and viruses. Where and how in the elongation cycle +1-frameshifting occurs remains poorly understood. We captured six ∼3.5-Å-resolution cryo-EM structures of ribosomal elongation complexes formed with the GTPase elongation factor G (EF-G). Three structures with a +1-frameshifting-prone mRNA reveal that frameshifting takes place during translocation of tRNA and mRNA. Prior to EF-G binding, the pre-translocation complex features an in-frame tRNA-mRNA pairing in the A site. In the partially translocated structure with EF-G, the tRNA shifts to the +1-frame codon near the P site, whereas the freed mRNA base bulges between the P and E sites and stacks on the 16S rRNA nucleotide G926. The ribosome remains frameshifted in the nearly post-translocation state. Our findings demonstrate that the ribosome and EF-G cooperate to induce +1 frameshifting during mRNA translocation

Structural basis for +1 ribosomal frameshifting during EF-G-catalyzed translocation

Frameshifting of mRNA during translation provides a strategy to expand the coding repertoire of cells and viruses. How and where in the elongation cycle +1-frameshifting occurs remains poorly understood. We describe seven ~3.5-A-resolution cryo-EM structures of 70S ribosome complexes, allowing visualization of elongation and translocation by the GTPase elongation factor G (EF-G). Four structures with a + 1-frameshifting-prone mRNA reveal that frameshifting takes place during translocation of tRNA and mRNA. Prior to EF-G binding, the pre-translocation complex features an in-frame tRNA-mRNA pairing in the A site. In the partially translocated structure with EF-G*GDPCP, the tRNA shifts to the +1-frame near the P site, rendering the freed mRNA base to bulge between the P and E sites and to stack on the 16S rRNA nucleotide G926. The ribosome remains frameshifted in the nearly post-translocation state. Our findings demonstrate that the ribosome and EF-G cooperate to induce +1 frameshifting during tRNA-mRNA translocation

Monitoring physical and psychosocial symptom trajectories in ovarian cancer patients receiving chemotherapy

<p>Abstract</p> <p>Background</p> <p>Diagnosis and treatment of ovarian cancer (OC) entail severe symptom burden and a significant loss of quality of life (QOL). Somatic and psychological impairments may persist well beyond active therapy. Although essential for optimal symptom management as well as for the interpretation of treatment outcomes, knowledge on the course of QOL-related issues is scarce. This study aimed at assessing the course of depressive symptoms, anxiety, fatigue and QOL in patients with OC over the course of chemotherapy until early after-care.</p> <p>Methods</p> <p>23 patients were assessed longitudinally (eight time points) with regard to symptom burden (depression, anxiety, fatigue, and QOL) by means of patient-reported outcome instruments (HADS, MFI-20, EORTC QLQ-C30/-OV28) and clinician ratings (HAMA/D) at each chemotherapy cycle and at the first two aftercare visits.</p> <p>Results</p> <p>Statistically significant decrease over time was found for depressive symptoms and anxiety as well as for all fatigue scales. With regard to QOL, results indicated significant increase for 11 of 15 QOL scales, best for Social (effect size = 1.95; <it>p </it>< 0.001), Emotional (e.s. = 1.62; <it>p </it>< 0.001) and Physical Functioning (e.s. = 1.47; <it>p </it>< 0.001). Abdominal Symptoms (e.s. = 1.01; <it>p </it>= 0.009) decreased, Attitudes towards Disease and Treatment (e.s. = 1.80; <it>p </it>< 0.001) improved significantly over time. Analysis of Sexual Functioning was not possible due to a high percentage of missing responses (61.9%).</p> <p>Conclusions</p> <p>The present study underlines the importance of longitudinal assessment of QOL in order to facilitate the identification of symptom burden in OC patients. We found that patients show high levels of fatigue, anxiety and depressive symptoms and severely impaired QOL post-surgery (i.e. at start of chemotherapy) but condition improves considerably throughout chemotherapy reaching nearly general population symptoms levels until aftercare.</p

The EORTC emotional functioning computerized adaptive test:phases I-III of a cross-cultural item bank development

Background: The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group is currently developing computerized adaptive testing measures for the Quality of Life Questionnaire Core-30 (QLQ-C30) scales. The work presented here describes the development of an EORTC item bank for emotional functioning (EF), which is one of the core domains of the QLQ-C30. Methods: According to the EORTC guidelines on module development, the development of the EF item bank comprised four phases, of which the phases I-III are reported in the present paper. Phase I involved defining the theoretical framework for the EF item bank and a literature search. Phase II included pre-defined item selection steps and a multi-stage expert review process. In phase III, feedback from cancer patients from different countries was obtained. Results: On the basis of literature search in phase I, a list of 1750 items was generated. These were reviewed and further developed in phase II with a focus on relevance, redundancy, clarity, and difficulty. The development and selection steps led to a preliminary list of 41 items. In phase III, patient interviews (N = 41; Austria, Denmark, Italy, and the UK) were conducted with the preliminary item list, resulting in some minor changes to item wording. The final list comprised 38 items. Discussion: The phases I-III of the developmental process have resulted in an EF item list that was well accepted by patients in several countries. The items will be subjected to larger-scale field testing in order to establish their psychometric characteristics and their fit to an item response theory model

Time-resolved cryo-EM visualizes ribosomal translocation with EF-G and GTP

During translation, a conserved GTPase elongation factor-EF-G in bacteria or eEF2 in eukaryotes-translocates tRNA and mRNA through the ribosome. EF-G has been proposed to act as a flexible motor that propels tRNA and mRNA movement, as a rigid pawl that biases unidirectional translocation resulting from ribosome rearrangements, or by various combinations of motor- and pawl-like mechanisms. Using time-resolved cryo-EM, we visualized GTP-catalyzed translocation without inhibitors, capturing elusive structures of ribosome•EF-G intermediates at near-atomic resolution. Prior to translocation, EF-G binds near peptidyl-tRNA, while the rotated 30S subunit stabilizes the EF-G GTPase center. Reverse 30S rotation releases Pi and translocates peptidyl-tRNA and EF-G by ~20 Å. An additional 4-Å translocation initiates EF-G dissociation from a transient ribosome state with highly swiveled 30S head. The structures visualize how nearly rigid EF-G rectifies inherent and spontaneous ribosomal dynamics into tRNA-mRNA translocation, whereas GTP hydrolysis and Pi release drive EF-G dissociation

Multi-site Neurogenin3 Phosphorylation Controls Pancreatic Endocrine Differentiation

The proneural transcription factor Neurogenin3 (Ngn3) plays a critical role in pancreatic endocrine cell differentiation, although regulation of Ngn3 protein is largely unexplored. Here we demonstrate that Ngn3 protein undergoes cyclin-dependent kinase (Cdk)-mediated phosphorylation on multiple serine-proline sites. Replacing wild-type protein with a phosphomutant form of Ngn3 increases α cell generation, the earliest endocrine cell type to be formed in the developing pancreas. Moreover, un(der)phosphorylated Ngn3 maintains insulin expression in adult β cells in the presence of elevated c-Myc and enhances endocrine specification during ductal reprogramming. Mechanistically, preventing multi-site phosphorylation enhances both Ngn3 stability and DNA binding, promoting the increased expression of target genes that drive differentiation. Therefore, multi-site phosphorylation of Ngn3 controls its ability to promote pancreatic endocrine differentiation and to maintain β cell function in the presence of pro-proliferation cues and could be manipulated to promote and maintain endocrine differentiation in vitro and in vivo

A chemical synthesis of LNA-2,6-diaminopurine riboside, and the influence of 2′-O-methyl-2,6-diaminopurine and LNA-2,6-diaminopurine ribosides on the thermodynamic properties of 2′-O-methyl RNA/RNA heteroduplexes

Modified nucleotides are useful tools to study the structures, biological functions and chemical and thermodynamic stabilities of nucleic acids. Derivatives of 2,6-diaminopurine riboside (D) are one type of modified nucleotide. The presence of an additional amino group at position 2 relative to adenine results in formation of a third hydrogen bond when interacting with uridine. New method for chemical synthesis of protected 3′-O-phosphoramidite of LNA-2,6-diaminopurine riboside is described. The derivatives of 2′-O-methyl-2,6-diaminopurine and LNA-2,6-diaminopurine ribosides were used to prepare complete 2′-O-methyl RNA and LNA-2′-O-methyl RNA chimeric oligonucleotides to pair with RNA oligonucleotides. Thermodynamic stabilities of these duplexes demonstrated that replacement of a single internal 2′-O-methyladenosine with 2′-O-methyl-2,6-diaminopurine riboside (DM) or LNA-2,6-diaminopurine riboside (DL) increases the thermodynamic stability (ΔΔG°37) on average by 0.9 and 2.3 kcal/mol, respectively. Moreover, the results fit a nearest neighbor model for predicting duplex stability at 37°C. D-A and D-G but not D-C mismatches formed by DM or DL generally destabilize 2′-O-methyl RNA/RNA and LNA-2′-O-methyl RNA/RNA duplexes relative to the same type of mismatches formed by 2′-O-methyladenosine and LNA-adenosine, respectively. The enhanced thermodynamic stability of fully complementary duplexes and decreased thermodynamic stability of some mismatched duplexes are useful for many RNA studies, including those involving microarrays