Photoresponsive nutlin derivatives and uses thereof

The invention relates to the field of medicine and medicinal chemistry, more in particular to the design, manufacture and use of anti-cancer drugs that can be activated by an external stimulus that can be applied in a spatiotemporal fashion. Provided herein is a compound having the chemical structure or a pharmaceutically acceptable salt thereof

Distribution of Glycated Haemoglobin According to Early-Life and Contemporary Characteristics in Adolescents and Adults without Diabetes:The 1982 and 1993 Pelotas Birth Cohorts

AIM:Glycated haemoglobin (HbA1c), a marker of glucose control in individuals with diabetes mellitus, is also related with the incidence of cardiometabolic risk in populations free of disease. The aim of this study was to describe the distribution of HbA1c levels according to early-life and contemporary factors in adolescents and adults without diabetes mellitus. METHODS:HbA1c was measured in adults aged 30 years and adolescents aged 18 years who are participants in the 1982 and 1993 Pelotas Birth Cohorts, respectively. Bivariate and multivariate analyses were performed to describe the HbA1c mean values according to early-life and contemporary characteristics collected prospectively since birth. RESULTS:The distribution of the HbA1c was approximately normal in both cohorts, with a mean (SD) 5.10% (0.43) in the 1982 cohort, and 4.89% (0.50) in the 1993 cohort. HbA1c mean levels were significantly higher in individuals self-reported as black/brown skin color compared to those self-reported as white in both cohorts. Parental history of diabetes was associated with higher HbA1c mean in adults, while stunting at one year old presented an inverse relation with the outcome in adolescents. No other early and contemporary factors were associated with HbA1c levels in adults or adolescents. CONCLUSIONS:We found a consistent relationship between HbA1c and skin color in both cohorts. Further research is needed to understand the role of genomic ancestry on levels of HbA1c concentrations which may inform policies and preventive actions for diabetes mellitus and cardiometabolic risk

Pentagonal nanowires: a first-principles study of atomic and electronic structure

We performed an extensive first-principles study of nanowires in various pentagonal structures by using pseudopotential plane wave method within the density functional theory. Our results show that nanowires of different types of elements, such as alkali, simple, transition and noble metals and inert gas atoms, have a stable structure made from staggered pentagons with a linear chain perpendicular to the planes of the pentagons and passing through their centers. This structure exhibits bond angles close to those in the icosahedral structure. However, silicon is found to be energetically more favorable in the eclipsed pentagonal structure. These quasi one dimensional pentagonal nanowires have higher cohesive energies than many other one dimensional structures and hence may be realized experimentally. The effect of magnetic state are examined by spin-polarized calculations. The origin of the stability are discussed by examining optimized structural parameters, charge density and electronic band structure, and by using analysis based on the empirical Lennard-Jones type interaction. Electronic band structure of pentagonal wires of different elements are discussed and their effects on quantum ballistic conductance are mentioned. It is found that the pentagonal wire of silicon exhibits metallic band structure.Comment: 4 figures, accepted for publication in Phys. Rev.

Pengaruh pengencer komersial terhadap motilitas dan viabilitas spermatozoa semen babi landrace yang disimpan pada temperatur berbeda

The objective of this study was to determine the the effect diluent of commercial is diluent BTS® and MIII® in maintaining sperm motility and viability of landrace boars during storage at different temperatures at refrigerator (5 °C), AC (28 °C) and room temperature (32 °C). This experiment used a completely randomized design (CRD) with 6 treatment and 4 replications. Semen was collected twice a week from landrace boars. Semen Characteristic and their quality were evaluated macroscopically and microscopically. Good quality semen have motility >70%, sperm concentration 200 x 106 sperm/ml and morphological abnormality less than 20%, these semen were added with diluent commercial is diluent BTS® and MIII®. Sperm motility and viability were evaluated every 2 hours until 40% motility were evaluated. The result showed that fresh semen characteristic were good, with the presentage of sperm motility 85% with sperm concentration 242.50±16.5% and morphological abnormality 12.50±1.70%. The results showed that the liquid semen of landrace boar were stored at a temperature of 28 °C is better results temperature with the percentage motility of sperm 54.50% during 38 hours and temperature of 5 °C showed the second best result with the percentage of 46.32% motility during 36 hours of storage in the diluent BTS® . In conclusion : BTS® diluent is an appropriate diluent used to maintaining semen quality of landrace boars quality during preservasion

Diagnóstico da situação do aleitamento materno em área urbana do Sudeste do Brasil: utilização de metodologia simplificada

INTRODUCTION: The diagnosis of breastfeeding status in populations is necessary to define aims and to evaluate support and promotion programs related to this practice. Thus, the feasibility of undertaking such a diagnosis concomittantly with the National Multivaccination Campaign, was tested. METHOD: A simplified questionnaire was used (3 yes/no questions) to study the present feeding of 1,550 children under 1 year old (91.8% coverage) who attended the vaccination venues in August 19th, 1995. The medians and frequencies from three patterns of breastfeeding were calculated by probit analysis technique. RESULTS: The medians were: exclusive breastfeeding = 17 days (IC:4.6 - 28.7); complete breastfeeding = 64 days (IC: 53.0 - 74.5) and breastfeeding = 167 days (IC: 153.7 - 182.2). The good adjustment of three patterns was attested by R² values and by Kolmogorov-Smirnov tests (p < 0.05). CONCLUSIONS: The results confirmed the need for this program in the city. The simplified methodology was found to be available and is recommended for breastfeeding trend management and for studies on the impact resulting from intervention.INTRODUÇÃO: O diagnóstico da situação do aleitamento materno em populações é necessário para a definição de metas e avaliação de programas de promoção e apoio a esta prática. Neste sentido, testou-se a viabilidade de realizar tal diagnóstico concomitante à Campanha Nacional de Multivacinação, no Município de Botucatu, SP, Brasil. MÉTODO: Utilizou-se um questionário simplificado (3 questões tipo sim/ não) para estudar a alimentação atual de 1.550 crianças menores de um ano (91,8% de cobertura) que compareceram aos postos de vacinação, em 19 de agosto de 1995. As medianas e freqüências das três categorias de aleitamento materno foram calculadas pela técnica de análise de probitos. RESULTADOS: As medianas obtidas foram: aleitamento materno exclusivo = 17 dias (IC: 4,6 - 28,7); aleitamento materno completo = 64 dias (IC: 53,0 - 74,5) e aleitamento materno = 167 dias (IC:153,7 - 182,2). O bom ajuste dos três modelos foi evidenciado pelos valores de R² e pelos testes de Kolmogorov-Smirnov (p < 0,05). CONCLUSÕES: Os resultados confirmaram a necessidade do programa no município. A metodologia simplificada revelou-se viável. Recomenda-se sua utilização na monitorização da tendência do aleitamento materno e em estudos sobre o impacto de intervenções

Selectivity, efficacy and toxicity studies of UCCB01-144, a dimeric neuroprotective PSD-95 inhibitor

Inhibition of postsynaptic density protein-95 (PSD-95) decouples N-methyl-d-aspartate (NMDA) receptor downstream signaling and results in neuroprotection after focal cerebral ischemia. We have previously developed UCCB01-144, a dimeric PSD-95 inhibitor, which binds PSD-95 with high affinity and is neuroprotective in experimental stroke. Here, we investigate the selectivity, efficacy and toxicity of UCCB01-144 and compare with the monomeric drug candidate Tat-NR2B9c. Fluorescence polarization using purified proteins and pull-downs of mouse brain lysates showed that UCCB01-144 potently binds all four PSD-95-like membrane-associated guanylate kinases (MAGUKs). In addition, UCCB01-144 affected NMDA receptor signaling pathways in ischemic brain tissue. UCCB01-144 reduced infarct size in young and aged male mice at various doses when administered 30 min after permanent middle cerebral artery occlusion, but UCCB01-144 was not effective in young male mice when administered 1 h post-ischemia or in female mice. Furthermore, UCCB01-144 was neuroprotective in a transient stroke model in rats, and in contrast to Tat-NR2B9c, high dose of UCCB01-144 did not lead to significant changes in mean arterial blood pressure or heart rate. Overall, UCCB01-144 is a potent MAGUK inhibitor that reduces neurotoxic PSD-95-mediated signaling and improves neuronal survival following focal brain ischemia in rodents under various conditions and without causing cardiovascular side effects, which encourages further studies towards clinical stroke trials