Metastatic parathyroid carcinoma in the MEN2A syndrome

We report a patient with a metastatic parathyroid carcinoma and medullary carcinoma of the thyroid. This patient represents a variation of the multiple endocrine neoplasia syndrome (MEN) type 2A. There was no evidence of a phaeochromocytoma. The case illustrates the difficulties that may be encountered in localising the source of PTH secretion; the patient underwent four unsuccessful exploratory operations of the neck and mediastinum before further investigations revealed a single metastatic deposit of parathyroid carcinoma involving the first thoracic vertebra. PCR amplification and sequencing of the RET oncogene from the metastatic parathyroid carcinoma and genomic DNA revealed a heterozygous mutation (Cys634Tyr) in exon 11, as has previously been described to occur in MEN 2A. In addition, loss of tumour heterozygosity was demonstrated at loci from chromosomes 1, 2, 3p, 13q and 16p. This represents the first report of a parathyroid carcinoma in a MEN2A patient, in which the multiple allelic deletions are consistent with the generalised losses observed in aggressive tumours.     

蓝青蛙酒廊与录音棚

Serie建筑师事务所是一个国际化事务所,涉及的领域包括建筑、城市的设计。事务所关注于当代城市中建筑类型的进化和变异以及这些智慧形式在空间解决方案上的应用。类型学式的研究,或者用他们的名词,“连续”（SERIES）的思考和探索（利用建筑类型的累积智慧）是Serie作品的关键。     

Mutational analysis of PHEX gene in X-linked hypophosphatemia

Hypophosphatemic rickets is commonly an X-linked dominant disorder (XLH or HYP) associated with a renal tubular defect in phosphate transport and bone deformities. The XLH gene, referred to as PHEX, or formerly as PEX (phosphate regulating gene with homologies to endopeptidases on the X-chromosome), encodes a 749-amino acid protein that putatively consists of an intracellular, transmembrane, and extracellular domain. PHEX mutations have been observed in XLH patients, and we have undertaken studies to characterize such mutations in 46 unrelated XLH kindreds and 22 unrelated patients with nonfamilial XLH by single stranded conformational polymorphism and DNA sequence analysis. We identified 31 mutations (7 nonsense, 6 deletions, 2 deletional insertions, 1 duplication, 2 insertions, 4 splice site, 8 missense, and 1 within the 5' untranslated region), of which 30 were scattered throughout the putative extracellular domain, together with 6 polymorphisms that had heterozygosity frequencies ranging from less than 1% to 43%. Single stranded conformational polymorphism was found to detect more than 60% of these mutations. Over 20% of the mutations were observed in nonfamilial XLH patients, who represented de novo occurrences of PHEX mutations. The unique point mutation (a-->g) of the 5'untranslated region together with the other mutations indicates that the dominant XLH phenotype is unlikely to be explained by haplo-insufficiency or a dominant negative effect.     

Localisation of X linked recessive idiopathic hypoparathyroidism to a 1.5 Mb region on Xq26-q27

Natural bovine seminal RNase possesses a potent antitumor action. We have mutagenized monomeric bovine pancreatic RNase A, devoid of any cytotoxic action, to insert residues present at corresponding positions in the subunit of dimeric, antitumor, seminal RNase. Like naturally dimeric seminal RNase, the mutant dimeric RNases display selective toxicity for malignant cells, which is absent in the monomeric mutants.     

How can primary health care influence patients' alcohol drinking habits. "Simple intervention" results in a new therapeutic perspective

A review of findings in randomised trials with at least one-year follow-up suggests that primary care physicians can intervene briefly and successfully for patients manifesting symptoms of excessive drinking but no serious dependence. The risk level can be assessed by summing the preceding week's intake of spirits, wine and beer in standard measures and then convert it into grams of pure alcohol. Denial is minimised by using a non-judgmental lifestyle approach, and defining problems in terms of lifestyle habits and its consequences. Nervous problems, hypertension and dyspepsia are the most common diagnoses in the target group. Measurement of biochemical markers can be used, the serum gamma-glutamyl transpeptidase (GGT) level being still the most useful. Questionnaires are of limited value as they are associated with high false-positive rates. To motivate patients to reduce alcohol consumption, an intervention strategy with feedback is proposed, mainly based on the monitoring of symptoms and clinical findings including biochemical markers, and a self-help pamphlet is recommended. It is emphasised that the goal should be realistic to the patient, and that controlled drinking is an acceptable goal even in cases of mild dependence.     

Application of Numerical Simulation Method to Predict the Performance of Wave Energy Device with Impulse Turbine

This paper presents the work carried out to predict the behavior of a 0.6 m Impulse turbine with fixed guide vanes with 0.6 hub-to-tip (H/T) ratio under real sea conditions. In order to predict the true performance of the actual Oscillating Water Column (OWC), the numerical technique has been fine tuned by incorporating the compressibility effect. Water surface elevation verses time history based on Pierson Moskowitz Spectra was used as the input data. Standard numerical techniques were employed to solve the non-linear behavior of the sea waves. The effect due to compressibility inside the air chamber and turbine performance under unsteady and irregular flow condition has been analyzed numerically. Considering the quasi-steady assumptions, unidirectional steady flow experimental data was used to simulate the turbine characteristics under irregular unsteady flow conditions. The results show that the performance of this type of turbine is quite stable and efficiency of air chamber and the mean conversion     

Systematic fatigue spectrum editing by fast wavelet transform and genetic algorithm

Fatigue testing is critical in order to establish the service life of load-bearing components and structures. The extensive time associated with full fatigue spectrum testing can lead to prohibitive costs. A significant need exists for a fatigue load spectrum editing methodology, based on the mechanics of fatigue, that produces load spectra that can replicate service damage in laboratory testing and can lead to compressed testing times and reduced costs. In this work, a wavelet genetic (WAVEGEN) algorithm is developed to edit fatigue loading spectra using wavelet analysis to greatly reduce the length of a spectrum while retaining the same damage accumulation characteristics. In addition, an optimization protocol using a genetic algorithm is included within this process to automatically select the best wavelet editing parameters. The algorithm is designed to identify the most suitable wavelet type, filter, and level to optimally edit a given fatigue spectrum and ensure equivalence between edited and unedited spectra from a damage perspective. The algorithm was applied to two well-known aircraft fatigue spectra: Fighter Aircraft Loading Standard for Fatigue evaluation (FALSTAFF) and Transport Wing Standard (TWIST). The proposed approach has demonstrated that both spectra can be compressed significantly even while ensuring equivalence from a damage perspective.     

Computed effects of tip clearance on performance of impulse turbine for wave energy conversion

This paper depicts numerical analysis on Impulse turbine with fixed guide vanes for wave energy conversion. From the previous investigations, it is found that one of the reasons for the mismatch between computed and experimental data is due to neglecting tip clearance ef fect. Hence, a 3-D model with tip clearance has been generated to predict the internal flow and performance of the turbine. As a result, it is found that the comparison between computed and experimental data is good, quantitatively and qualitatively. Computation has been carried out for various tip clearances to understand the physics of tip leakage flow and effect of tip clearance on performance of such unconventional turbine. It is predicted that the turbine with 0.25% tip clearance performs almost similar to the case of without tip clearance for the entire flow coefficients. The designed value of 1% tip clearance has been validated numerically and computed that the efficiency of the turbine has been reduced around 4%, due to tip clearance flow at higher flow coefficients.     

Mechanism of intestinal absorption of ranitidine and ondansetron: transport across Caco-2 cell monolayers

We have investigated the transport of ranitidine and ondansetron across the Caco-2 cell monolayers. The apparent permeability co-efficients (Papp) were unchanged throughout the concentration range studied, indicating a passive diffusion pathway across intestinal mucosa. No metabolism was observed for ranitidine and ondansetron during the incubation with Caco-2 cell monolayers. Papp values for ranitidine and ondansetron (bioavailability of 50 and approximately 100% in humans, respectively) were 1.03 +/- 0.17 x 10(-7) and 1.83 +/- 0.055 x 10(-5) cm/sec, respectively. The Papp value for ranitidine was increased by 15- to 20-fold in a calcium-free medium or in the transport medium containing EDTA, whereas no significant change occurred with ondansetron, indicating that paracellular passive diffusion is not rate determining for ondansetron. Uptake of ondansetron by Caco-2 cell monolayers was 20- and 5-fold higher than that of ranitidine when the uptake study was carried out under sink conditions and at steady state. These results suggest that ranitidine and ondansetron are transported across Caco-2 cell monolayers predominantly via paracellular and transcellular pathways, respectively.     

Preserved number of entorhinal cortex layer II neurons in aged macaque monkeys

The perforant path, which consists of the projection from the layer II neurons of the entorhinal cortex to the outer molecular layer of the dentate gyrus, is a critical circuit involved in learning and memory formation. Accordingly, disturbances in this circuit may contribute to age-related cognitive deficits. In a previous study, we demonstrated a decrease in N-methyl-D-aspartate receptor subunit 1 immunofluorescence intensity in the outer molecular layer of aged macaque monkeys. In this study, we used the optical fractionator, a stereological method, to determine if a loss of layer II neurons occurred in the same animals in which the N-methyl-D-aspartate receptor subunit 1 alteration was observed. Our results revealed no significant differences in the number of layer II neurons between juvenile, young adult, and aged macaque monkeys. These results suggest that the circuit-specific decrease in N-methyl-D-aspartate receptor subunit 1 reported previously occurs in the absence of structural compromise of the perforant path, and thus may be linked to an age-related change in the physiological properties of this circuit.