The supersymmetric standard model

ABSTRACT This set of lectures introduces at an elementary level the supersymmetric Standard Model and discusses some of its phenomenological properties

Expansion-enhanced super-resolution radial fluctuations enable nanoscale molecular profiling of pathology specimens

Expansion microscopy physically enlarges biological specimens to achieve nanoscale resolution using diffraction-limited microscopy systems1. However, optimal performance is usually reached using laser-based systems (for example, confocal microscopy), restricting its broad applicability in clinical pathology, as most centres have access only to light-emitting diode (LED)-based widefield systems. As a possible alternative, a computational method for image resolution enhancement, namely, super-resolution radial fluctuations (SRRF)2,3, has recently been developed. However, this method has not been explored in pathology specimens to date, because on its own, it does not achieve sufficient resolution for routine clinical use. Here, we report expansion-enhanced super-resolution radial fluctuations (ExSRRF), a simple, robust, scalable and accessible workflow that provides a resolution of up to 25 nm using LED-based widefield microscopy. ExSRRF enables molecular profiling of subcellular structures from archival formalin-fixed paraffin-embedded tissues in complex clinical and experimental specimens, including ischaemic, degenerative, neoplastic, genetic and immune-mediated disorders. Furthermore, as examples of its potential application to experimental and clinical pathology, we show that ExSRRF can be used to identify and quantify classical features of endoplasmic reticulum stress in the murine ischaemic kidney and diagnostic ultrastructural features in human kidney biopsies.</p

Further delineation of Malan syndrome

Malan syndrome is an overgrowth disorder described in a limited number of individuals. We aim to delineate the entity by studying a large group of affected individuals. We gathered data on 45 affected individuals with a molecularly confirmed diagnosis through an international collaboration and compared data to the 35 previously reported individuals. Results indicate that height is > 2 SDS in infancy and childhood but in only half of affected adults. Cardinal facial characteristics include long, triangular face, macrocephaly, prominent forehead, everted lower lip, and prominent chin. Intellectual disability is universally present, behaviorally anxiety is characteristic. Malan syndrome is caused by deletions or point mutations of NFIX clustered mostly in exon 2. There is no genotype-phenotype correlation except for an increased risk for epilepsy with 19p13.2 microdeletions. Variants arose de novo, except in one family in which mother was mosaic. Variants causing Malan and Marshall-Smith syndrome can be discerned by differences in the site of stop codon formation. We conclude that Malan syndrome has a well recognizable phenotype that usually can be discerned easily from Marshall–Smith syndrome but rarely there is some overlap. Differentiation from Sotos and Weaver syndrome can be made by clinical evaluation only

A Suggestive Association of Fuchs Heterochromic Cyclitis with Cytotoxic T Cell Antigen 4 Gene Polymorphism

Background: Fuchs heterochromic cyclitis (FHC) is a chronic inflammatory eye disease, usually presenting as unilateral anterior uveitis. Up to date no disease susceptibility genes have been described for FHC. Methods: The allele frequency of HLA DRB1 and DQB1, polymorphisms of the tumour necrosis factor (TNF) _ promoter region (–376, –308, –238), the promoter (–318), first exon (+49) and (AT)n repeat polymorphism of the cytotoxic T cell antigen 4 (CTLA4) gene were analysed in 44 FHC patients and 139 healthy controls. Results: The CTLA4 –318 C/T genotype was increased in FHC patients [odds ratio (OR) 3.0, 95% confidence interval (CI) 1.4–6.5], as well as long CTLA4 (AT)n microsatellite alleles with more than 16 AT repeats (OR 2.6, 95% CI 1.3–5.3). A trend towards the –308 G/A TNF- _ genotype was found in the patient cohort, whereas no difference in HLA class II allele distribution was observed. Conclusion: CTLA4 but not TNF- _ or HLA class II DRB1 and DQB1 may represent a candidate gene for disease susceptibility in FHC

MÉTODO PARA FORMULAÇÃO DE PLANO OPERACIONAL APLICADO AO PLANEJAMENTO PORTUÁRIO: CONTRIBUIÇÃO PARA ELABORAÇÃO DOS PLANOS DE DESENVOLVIMENTO E ZONEAMENTO (PDZS) DOS PORTOS BRASILEIROS

Operational Plans, in the context of the Port Development and Zoning Plans (PDZs), are characterized as a group of actions that lead to the achievement of the national port sector strategic goals. This article proposes a method for its elaboration based on 5W2H approach and considering strategic guidelines of socio-environmental policy instruments, national transport policy, port sector planning tools, municipality territory planning and port authority planning instruments. The method was applied in the elaboration of Porto do Itaqui’s PDZ and resulted in 77 actions in line with the planning instruments, policies and guidelines mentioned.Los Planes Operativos, en el contexto de los Planes de Desarrollo y Zonificación Portuarios (PDZs), son conjuntos de acciones que conducen al logro de objetivos en el ámbito estratégico del sector portuario nacional. Este artículo propone un método para su elaboración, utilizando la técnica 5W2H como base y considerando las directrices estratégicas de los instrumentos de política socioambiental, política nacional de transporte, planificación del sector portuario, planificación del territorio municipal y los instrumentos de planificación de la autoridad portuaria. El método se aplicó en la preparación del PDZ de Porto do Itaqui y resultó en 77 acciones en línea con los instrumentos de planificación, políticas y directrices mencionadas.Planos Operacionais, no contexto dos Planos de Desenvolvimento e Zoneamento Portuário (PDZs), caracterizam-se como conjuntos de ações que conduzem ao atingimento dos objetivos no âmbito estratégico do setor portuário nacional. Neste artigo, propõe-se um método para sua elaboração utilizando como base na técnica 5W2H e considerando as diretrizes estratégicas de instrumentos de políticas socioambientais, política nacional de transportes, planejamento do setor portuário, planejamento do território do município e instrumentos de planejamento da Autoridade Portuária. O método foi aplicado na elaboração do PDZ do Porto do Itaqui e resultou em 77 ações alinhadas aos instrumentos de planejamento, políticas e diretrizes mencionados

Image3_A high-throughput drug discovery pipeline to optimize kidney normothermic machine perfusion.TIFF

Kidney transplantation is the only definitive therapy for end-stage kidney disease. The shortage of organs for transplantation is the main limitation of this life-saving treatment. Normothermic machine perfusion (NMP) is a novel preservation technique with the potential to increase the number of transplantable kidneys through reducing delayed graft function and organ evaluation under physiological conditions. To date, the cellular effects and possible pharmacological interventions during machine perfusion are incompletely understood. A major limitation is the technically complex, time-consuming, and small-scale replication of NMP in rodent models. To overcome this, we developed a 3D-printed, high throughput ex-vivo mouse kidney slice incubator (KSI) mimicking mouse kidney NMP by working under closely resembling conditions. KSI significantly reduced the time per experiment and increased the sample throughput (theoretical: 54 incubations with n = 500/day). The model recapitulated the cellular responses during NMP, namely increased endoplasmic reticulum stress (ER stress). Using KSI, five pharmacological interventions against ER stress taken from the literature were tested. While four were ineffective and excluded, one, β-Nicotinamide-adenine-dinucleotide (NADH), ameliorated ER stress significantly during KSI. The test of NADH in mouse kidney NMP replicated the positive effects against ER stress. This suggests that testing the addition of NADH during clinical kidney NMP might be warranted.</p

The use of an oral contraceptive containing ethinylestradiol and drospirenone in an extended regimen over 126 days

Objective: To assess the bleeding profile, acceptance and safety of an extended 126-day regimen of the oral contraceptive Yasmin(R) [30 mu g ethinylestradiol (EE) and 3 mg drospirenone (DRSP)]. Methods: Using daily diaries, 177 women recorded bleeding events throughout the 126-day cycle. At end of treatment, the women completed questionnaires reflecting their satisfaction with the extended regimen. A Subset of 30 women underwent endometrial histology sampling after completion of the extended regimen. Results: Of 177 women assigned to the extended regimen, 80.8% completed the extended 126-day regimen. Approximately 40% of the women reported complete absence of bleeding, while in 60% a shift towards less intense bleeding was observed. The first onset of bleeding occurred after a median of 99.0 days into the extended cycle. The acceptance of the extended regimen was high, with 68.4% of the women expressing satisfaction. The general safety profile with the extended use was comparable to that seen with the conventional 21+7-day regimen. All endometrial biopsies with sufficient material for analysis were normal and supported the endometrial safety of the extended regimen. Conclusion: This study showed that the continuous use of a 30-mu g EE and 3-mg DRSP formulation over 126 days was safe, efficacious, well accepted by the users and resulted in a considerable reduction of bleeding. (C) 2006 Elsevier Inc. All rights reserved