Paula Meehan’s Cell: The Imprisoned Dialogue of Female Discourses

The paper discusses Paula Mehan’s play Cell with focus on the female discourses present in the context of this literary work and the multifold metaphorisation that both the title of the work and the contents invite. The discourses are analysed against the relevant social background and critical literature. The focal types of discourses under discussion involve imagery from maternal and familiar discourse, the “biological” discourse related to hygiene, the sexual discourse, the mock feminist discourse, the discourse of the military and the propaganda of the common good, and the discourse related to the animal world

Validation and Improvement of High Nature Value Farmland Identification - National Approach in the Walloon Region in Belgium and in the Czech Republic

The concept of High Nature Value (HNV) farmland has been evolving over the last fifteen years in Europe. In the European Union this has been closely linked to the aim of integrating environmental concerns in the Common Agricultural Policy. The idea that nature values, environmental qualities, even cultural heritage are linked to or dependent on farming, also underlies and supports the concept of a multifunctional 'European model of farming which provides benefits beyond food production. The objective of this study is to better identify and characterise HNV farmland at national level (the Walloon Region in Belgium) with a Farm System Approach based on FSS statistical data and specific national surveys, taking into account the whole farm with the total agricultural area and its characteristics. The methodology is built on two different approaches: the natural zones approach and the farm system approach. The natural zones approach uses spatial data to define agricultural zones with a verified high biodiversity interest, based on a reference biodiversity layer for the Walloon Region (WR) called the principal ecological structure (SEP). The farm system approach analyses the farm structure and farming practices on the basis of data available in the WR agricultural database. In the first step relevant variables have been selected to calculate the HNV indicators for the farm system approach at NUTS 5 level: 1) crop diversity and grassland presence, 2) extensive practices, and 3) landscape elements. In the second step the three indicators were combined to calculate the HNV score. In the third step the areas delimited through the farm system approach were overlaid with a map resulting form the natural zones approach. In the last step HNV farmland was analysed with regard to prevailing trends in farming practices and production types with the aim of identification of farming systems which might be associated with HNV farmland occurrence in the WR in Belgium. The analysis of spatial distribution of HNV farmland delimited in the study shows that 91% of the HNV farm system zone identified in the study is located in Ardenne, Fagne and Fammenne. The dominant farming system types are grazing livestock system specialised in milk or meat production, depending on the region. The average livestock density is less than 2.0 LU/ha. Over 60% of UAA is used as permanent grassland. The strength of the Farm System Approach methodology is the possibility of producing a map at the NUTS 5 level with an accurate description of the farm systems. The methodology can be improved by crosschecking the results with regional experts and getting feedback on the thresholds and the weighting of the indicators. The weaknesses of the Farm System Approach methodology are mainly due to the way agricultural practices are modelled. The lack of comprehensive and reliable data on landscape elements and grassland management hampers further validation of HNV farmland identification results. A development of additional relevant surveys is therefore recommended. An attempt at assessing the applicability of the FSA for HNV farmland identification was undertaken for the Czech Republic. Statistical data on farming practices are still incomplete and insufficient to build the methodology similar to the Walloon Region FSA. Conversely, biodiversity and habitat data are abundant and of high quality and currently are the best datasets for HNV farmland identification in the Czech Republic.JRC.H.5-Rural, water and ecosystem resource

Versatile Protecting-Group Free Tetrazolomethane Amine Synthesis by Ugi Reaction

The use of ammonia in the Ugi reaction is often problematic due to low yields and multiple side reactions. Here, we report the use of ammonia in the tetrazole Ugi variation providing a clean, good-to-high yielding reaction, especially with ketones as oxo components. The scope and limitations of this reaction and a structure–reactivity relationship are provided by performing >85 reactions. The primary amine component of the α-amino tetrazole is a versatile starting material for further reactions

Rayleigh-Jeans thermalization vs beam cleaning in multimode optical fibers

Classical nonlinear waves exhibit, as a general rule, an irreversible process of thermalization toward the Rayleigh-Jeans equilibrium distribution. On the other hand, several recent experiments revealed a remarkable effect of spatial organization of an optical beam that propagates through a graded-index multimode optical fiber (MMF), a phenomenon termed beam self-cleaning. Our aim here is to evidence the qualitative impact of disorder (weak random mode coupling) on the process of Rayleigh-Jeans thermalization by considering two different experimental configurations. In a first experiment, we launch speckle beams in a relatively long MMF. Our results report a clear and definite experimental demonstration of Rayleigh-Jeans thermalization through light propagation in MMFs, over a broad range of kinetic energy (i.e., degree of spatial coherence) of the injected speckle beam. In particular, the property of energy equipartition among the modes is clearly observed in the condensed regime. The experimental results also evidence the double turbulence cascade process: while the power flows toward the fundamental mode (inverse cascade), the energy flows toward the higher-order modes (direct cascade). In a 2nd experiment, a coherent laser beam is launched into a relatively short MMF length. It reveals an effect of beam cleaning driven by an incipient process of Rayleigh-Jeans thermalization. As discussed through numerical simulations, the fast process of Rayleigh-Jeans thermalization observed in the 1st experiment can be attributed due to a random phase dynamics among the modes, which is favoured by the injection of a speckle beam and the increased impact of disorder in the long fiber system

Diagnostic workup of childhood interstitial lung disease

Interstitial and orphan lung diseaseEnfermedad pulmonar intersticial y huérfanaMalaltia pulmonar intersticial i orfeChildhood interstitial lung diseases (chILDs) are rare and heterogeneous diseases with significant morbidity and mortality. An accurate and quick aetiological diagnosis may contribute to better management and personalised treatment. On behalf of the European Respiratory Society Clinical Research Collaboration for chILD (ERS CRC chILD-EU), this review summarises the roles of the general paediatrician, paediatric pulmonologists and expert centres in the complex diagnostic workup. Each patient's aetiological chILD diagnosis must be reached without prolonged delays in a stepwise approach from medical history, signs, symptoms, clinical tests and imaging, to advanced genetic analysis and specialised procedures including bronchoalveolar lavage and biopsy, if necessary. Finally, as medical progress is fast, the need to revisit a diagnosis of “undefined chILD” is stressed

Concise synthesis of tetrazole macrocycle

A concise two step synthesis of tetrazole containing macrocycles from readily accessible starting materials is presented. The first step comprises a chemoselective amidation of amino acid derived isocyanocarboxylicacid esters with unprotected symmetrical diamines to afford diverse α-isocyano-ω-amines. In the second step, the α-isocyano-ω-amines undergo an Ugi tetrazole reaction to close the macrocycle. Advantageously, this strategy allows short access to 11–19-membered macrocycles in which substituents can be independently varied at three different positions

‘Atypical Ugi’ tetrazoles

Amino acid-derived isocyano amides together with TMSN3, oxocomponents and 1° or 2° amines are common substrates in the Ugi tetrazole reaction. We surprisingly found that combining these substrates gives two different constitutional isomeric Ugi products A and B. A is the expected classical Ugi product whereas B is an isomeric product ('atypical Ugi') of the same molecular weight with the tetrazole heterocycle migrated to a different position. We synthesized, separated and characterized 22 different isomorphic examples of the two constitutional isomers of the Ugi reaction to unambiguously prove the formation of A and B. Mechanistic studies resulted in a proposed mechanism for the concomitant formation of A and B

Pathophysiological and clinical aspects of dopamine

W artykule podsumowano najnowsze doniesienia dotyczące roli dopaminy w patofizjologii nadciśnienia tętniczego pierwotnego, eksperymentalnego modelu nadciśnienia tętniczego oraz guza chromochłonnego. Zwrócono uwagę na antyproliferacyjne działanie dopaminy na komórki mięśni gładkich naczyń krwionośnych. Przytoczono dyskusję dotyczącą potencjalnej roli dopaminy i jej metabolitów jako substancji wskaźnikowych dla złośliwego nadciśnienia tętniczego i paraganglioma, szczególnie u pacjentów z mutacją SDHB. Omówiono kliniczne znaczenie selektywnego agonisty receptora D1 — fenoldopamu. Nadciśnienie Tętnicze 2011, tom 15, nr 1, strony 37–41This article summarizes the recent views on the role of dopamine in the pathophysiology of essential hypertension, experimental hypertension and pheochromocytoma. The studies on antiproliferative action of dopamine on VSMC (vascular smooth muscle cell) are mentioned. The authors discuss the potential role of dopamine and its metabolites as a marker of malignant hypertension and paraganglioma, especially in patients with SDHB (succinate dehydrogenase complex subunit B) gene mutations. The clinical implication of specific D1 agonist fenoldopam is also discussed. Arterial Hypertension 2011, vol. 15, no 1, pages 37–4

The MLL-Menin Interaction is a Therapeutic Vulnerability in NUP98 -rearranged AML

Chromosomal translocations involving the NUP98 locus are among the most prevalent rearrangements in pediatric acute myeloid leukemia (AML). AML with NUP98 fusions is characterized by high expression of HOXA and MEIS1 genes and is associated with poor clinical outcome. NUP98 fusion proteins are recruited to their target genes by the mixed lineage leukemia (MLL) complex, which involves a direct interaction between MLL and Menin. Here, we show that therapeutic targeting of the Menin–MLL interaction inhibits the propagation of NUP98-rearrranged AML both ex vivo and in vivo. Treatment of primary AML cells with the Menin inhibitor revumenib (SNDX-5613) impairs proliferation and clonogenicity ex vivo in long-term coculture and drives myeloid differentiation. These phenotypic effects are associated with global gene expression changes in primary AML samples that involve the downregulation of many critical NUP98 fusion protein-target genes, such as MEIS1 and CDK6. In addition, Menin inhibition reduces the expression of both wild-type FLT3 and mutated FLT3-ITD, and in combination with FLT3 inhibitor, suppresses patient-derived NUP98-r AML cells in a synergistic manner. Revumenib treatment blocks leukemic engraftment and prevents leukemia-associated death of immunodeficient mice transplanted with NUP98::NSD1 FLT3-ITD-positive patient-derived AML cells. These results demonstrate that NUP98-rearranged AMLs are highly susceptible to inhibition of the MLL–Menin interaction and suggest the inclusion of AML patients harboring NUP98 fusions into the clinical evaluation of Menin inhibitors

Compromised white matter is related to lower cognitive performance in adults with phenylketonuria.

Despite increasing knowledge about the effects of phenylketonuria on brain structure and function, it is uncertain whether white matter microstructure is affected and if it is linked to patients' metabolic control or cognitive performance. Thus, we quantitatively assessed white matter characteristics in adults with phenylketonuria and assessed their relationship to concurrent brain and blood phenylalanine levels, historical metabolic control and cognitive performance. Diffusion tensor imaging and 1H spectroscopy were performed in 30 adults with early-treated classical phenylketonuria (median age 35.5 years) and 54 healthy controls (median age 29.3 years). Fractional anisotropy and mean, axial and radial diffusivity were investigated using tract-based spatial statistics, and white matter lesion load was evaluated. Brain phenylalanine levels were measured with 1H spectroscopy whereas concurrent plasma phenylalanine levels were assessed after an overnight fast. Retrospective phenylalanine levels were collected to estimate historical metabolic control, and a neuropsychological evaluation assessed the performance in executive functions, attention and processing speed. Widespread reductions in mean diffusivity, axial diffusivity and fractional anisotropy occurred in patients compared to controls. Mean diffusivity and axial diffusivity were decreased in several white matter tracts and were most restricted in the optic radiation (effect size rrb = 0.66 to 0.78, P < 0.001) and posterior corona radiata (rrb = 0.83 to 0.90, P < 0.001). Lower fractional anisotropy was found in the optic radiation and posterior corona radiata (rrb = 0.43 to 0.49, P < 0.001). White matter microstructure in patients was significantly associated with cognition. Specifically, inhibition was related to axial diffusivity in the external capsule (rs = -0.69, P < 0.001) and the superior (rs = -0.58, P < 0.001) and inferior longitudinal fasciculi (rs = -0.60, P < 0.001). Cognitive flexibility was associated with mean diffusivity of the posterior limb of the internal capsule (rs = -0.62, P < 0.001), and divided attention correlated with fractional anisotropy of the external capsule (rs = -0.61, P < 0.001). Neither concurrent nor historical metabolic control was significantly associated with white matter microstructure. White matter lesions were present in 29 out of 30 patients (96.7%), most often in the parietal and occipital lobes. However, total white matter lesion load scores were unrelated to patients' cognitive performance and metabolic control. In conclusion, our findings demonstrate that white matter alterations in early-treated phenylketonuria persist into adulthood, are most prominent in the posterior white matter and are likely to be driven by axonal damage. Furthermore, diffusion tensor imaging metrics in adults with phenylketonuria were related to performance in attention and executive functions