Coherent beam combining of high power quasi continuous wave tapered amplifiers.

We demonstrate coherent beam combining of four high brightness tapered amplifiers in pulsed, quasi continuous wave (QCW) operation, seeded by a 976 nm laser diode. The maximum power of 22.7 W was achieved with > 64% combining efficiency in a close to diffraction limited beam. We discuss turn-on dynamics of tapered amplifiers operated in pulsed mode in detail.

ATP5H/KCTD2 locus is associated with Alzheimer's disease risk.

To identify loci associated with Alzheimer disease, we conducted a three-stage analysis using existing genome-wide association studies (GWAS) and genotyping in a new sample. In Stage I, all suggestive single-nucleotide polymorphisms (at P<0.001) in a previously reported GWAS of seven independent studies (8082 Alzheimer's disease (AD) cases; 12 040 controls) were selected, and in Stage II these were examined in an in silico analysis within the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium GWAS (1367 cases and 12904 controls). Six novel signals reaching P<5 × 10(-6) were genotyped in an independent Stage III sample (the Fundació ACE data set) of 2200 sporadic AD patients and 2301 controls. We identified a novel association with AD in the adenosine triphosphate (ATP) synthase, H+ transporting, mitochondrial F0 (ATP5H)/Potassium channel tetramerization domain-containing protein 2 (KCTD2) locus, which reached genome-wide significance in the combined discovery and genotyping sample (rs11870474, odds ratio (OR)=1.58, P=2.6 × 10(-7) in discovery and OR=1.43, P=0.004 in Fundació ACE data set; combined OR=1.53, P=4.7 × 10(-9)). This ATP5H/KCTD2 locus has an important function in mitochondrial energy production and neuronal hyperpolarization during cellular stress conditions, such as hypoxia or glucose deprivation.

Tuberculosis in pregnancy:a challenging differential diagnosisfor inflammatory bowel disease.

OBJECTIVE: To describe a case of tuberculosis with intestinal variant in a pregnant woman in the 17th week of pregnancy. DESIGN: Case report. SETTING: Department of Obstetrics, Federal University of São Paulo (UNIFESP), São Paulo-SP, Brazil. CONCLUSION: Tuberculosis is a public health problem that concerns many countries in the world. It was declareda public emergency by the World Health Organization in 2005. Its presence during pregnancy brings maternal risk and fetal impairment if not treated quickly and properly. The intestinal variant is not the most common form of the disease and may be confused with inflammatory bowel diseases, especially Crohns disease. Knowledge of the specific characteristics, combined with a detailed medical history and appropriate diagnostic methods can make all the difference in gestational prognosis. We report the case of a pregnant woman who wrongly underwent treatment for inflammatory bowel disease at another service. After admission to our university hospital, fruitful diagnostic clarification was achieved and the patient was diagnosed and treated for tuberculosis. We describe the details of the investigation and, in particular, review the main characteristics in the literature for differentiating the two diseases.

Absence of allelic imbalance involving EMSY, CAPN5, and PAK1 genes in papillary thyroid carcinoma.

Papillary thyroid cancer (PTC) accounts for 80% of all thyroid malignancies, and genetic alterations associated to its etiology remain largely unknown. Chromosomal band 11q13 seems to be one of the most frequently amplified regions in human cancer, providing several candidate genes that need detailed characterization. The aim of our study was to investigate the existence of allelic imbalance at EMSY, CAPN5, and PAK1, as candidate genes within 11q13.5-q14 region using a single nucleotide polymorphism-based analysis. We selected a panel of 9 polymorphisms that were analyzed in 41 thyroid carcinoma samples, their contralateral non-pathological tissue and 178 controls from the general population. We did not detect allelic imbalance at these loci in our series. However, we observed a difference in the EMSY-haplotype distribution among PTC patients when compared to controls (odds ratio=2.00; p=0.02). We conclude that 11q13.5-q14 is not imbalanced in PTC, but there is evidence suggesting that EMSY might be of relevance in PTC etiology.

Genotoxic activity of mebendazole in Aspergillus nidulans.

Mebendazole is an anthelmintic drug widely used in Cuba and in Mexico. Its interaction with tubulin interferes with the assemblage of the mitotic apparatus in the parasite cells, thus suggesting a possible genotoxic activity leading to chromosomal malsegregation. The heterozygous diploid strain D30 of Aspergillus nidulans was used to establish the ability of mebendazole to induce mitotic recombination and/or chromosomal non-disjunction, and the haploid strain FGSC #219 of A. nidulans was used to study the ability of mebendazole to induce point mutations in the methG suppressor system. Our results show that mebendazole can induce chromosomal non-disjunction but it fails to promote point mutations.

Membrane-bound ATP-dependent energy systems and the development of the gastric mucosal damage in rats produced by 0.2 M NaOH, 25% NaCl, 0.6 M HCI and 96% ethanol.

Damage to the gastric fundic mucosa was produced in rats by intragastric administration of 1 ml 0.2 M NaOH, 25% NaCl, 0.6 M HCl or 96% ethanol; a control group received 1 ml saline solution. The animals were killed 1 h later, and the number and severity of ulcers (lesions) noted. The gastric fundic mucosa were excised and frozen, and assayed enzymatically for adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and lactate, while the tissue level of cyclic adenosine monophosphate (cAMP) was estimated by radioimmunoassay. It was found that: (i) the number and severity of gastric lesions (ulcers) increased significantly in all the groups treated by the 4 necrotizing agents, (ii) the extent of ATP breakdown into ADP increased significantly, while the ATP transformation into cAMP by adenylate cyclase, and of cAMP into AMP by phosphodiesterase, decreased, (iii) the tissue level of lactate increased only in the 0.6 M HCl groups. It was concluded that: (i) the mucosal damage develops in consequence of a very active metabolic adaptation of the rat gastric fundic mucosa, notably the significantly increased ATP transformation into ADP, which is not the consequence of hypoxaemia, (ii) the feed-back mechanism system between the membrane-bound ATP-dependent energy systems is broken as the mucosal damage develops, the main changes being a significantly increased ATP transformation into ADP, a significantly decreased ATP transformation into cAMP, and significant alterations by neural, hormonal and pharmacological influences in the membrane-bound ATP-dependent energy systems.

Membrane-bound ATP-dependent energy systems and gastric cytoprotection by prostacyclin, atropine and cimetidine in the rat.

The effects were studied of different doses of prostacyclin (PG12), atropine and cimetidine on the gastric secretory responses of four-hour pylorus-ligated rats and on the gastric mucosal damage produced by intragastric administration of 0.6 M HCl, to determine the cytoprotective doses of PG12, atropine and cimetidine. In another series of observations, gastric mucosal damage was produced by intragastric administration of 0.6 M HCl and the effects were studied of cytoprotective doses of PG12, atropine and cimetidine on the number and severity of gastric lesions, in connection with the biochemical changes of the rat gastric fundic mucosa. The drugs were given intraperitoneally 30 min before the application of the necrotizing agent, and the animals were killed one hour later. During the experiments, the tissue levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and lactate were measured enzymatically, and the tissue content of cyclic adenosine monophosphate (cAMP) was determined by radioimmunoassay. The specimens were taken from the gastric fundic mucosa of groups of animals treated with saline solution (absolute control), with 0.6 M HCl (pathological control) and with 0.6 M HCl plus PG12, atropine and cimetidine (given in cytoprotective doses). The ratio of ATP.ADP-1, adenylate pool (ATP + ADP + AMP) and energy charge (ATP + 0.5 ADP.ATP + ADP + AMP-1) were calculated in all groups of animals. It was found that: (i) PG12 (in a dose of 5 micrograms.kg-1) atropine (in a dose of 0.025 mg.kg-1) and cimetidine (in a dose of 2.5 micrograms.kg-1) have cytoprotective effects; (ii) the gastric fundic mucosal damage produced by intragastric administration of 0.6 M HCl appears as a result of a positive metabolic adaptation of the gastric fundic mucosa; (iii) the development of gastric cytoprotection by PG12, atropine and cimetidine give rise to very different changes in the tissue levels of ATP, ADP, AMP and cAMP.(ABSTRACT TRUNCATED AT 400 WORDS)

Evidence of the gastric cytoprotective effects of vitamin A, atropine and cimetidine on the development of gastric mucosal damage produced by administration of indomethacin in healthy subjects.

Certain compounds such as prostaglandins, atropine, cimetidine and carotenes are able to prevent the development of gastric mucosal damage produced in experimental animals or in man by intragastric administration of necrotizing agents such as indomethacin without significantly inhibiting gastric acid secretion. The clinical background of this gastric cytoprotection and its importance for man is not yet known, although the beneficial effects of these compounds have been demonstrated in human therapy. In the present study, carried out in 66 healthy human subjects, it was found that vitamin A at a dose of 100,000 IU i.m., atropine at 0.125 mg i.m., and cimetidine at 12.5 mg i.m., which doses do not inhibit the gastric basal secretion nor the maximal secretory response to pentagastrin stimulation, each prevented the gastric microbleeding produced by the oral application of indomethacin. It is concluded that this gastric cytoprotection, characteristic of prostaglandins but extending to atropine, cimetidine and vitamin A, holds good in man as well as experimental animals. Thus the potential clinical significance of gastric cytoprotection induced by these compounds may be considerable.

Gastric cytoprotective effects of vitamin A and other carotenoids.

The effects of vitamin A and some carotenoids (beta-carotene, beta-cryptoxanthin, zeaxanthin, lutein, capsorubin, capsanthin, capsanthol and lycopene) were studied (a) on the development of acute gastric mucosal lesions produced by topical application of 0.6 M HCl and (b) on gastric secretion in 4-h pylorus-ligated rats. It was found (a) that vitamin A, beta-carotene, beta-cryptoxanthin, zeaxanthin and lutein significantly inhibited the development of gastric mucosal lesions produced by 0.6 M HCl, while capsorubin, capsanthin, capsanthol and lycopene failed to prevent the development of such lesions; and (b) that vitamin A, beta-carotene, beta-cryptoxanthin, zeaxanthin and lutein, i.e., the carotenoids which exerted a cytoprotective effect, had no inhibitory effect on gastric acid secretion in 4-h pylorus-ligated rats. The possible relationship between chemical structure and gastric cytoprotection is discussed.

Cytoprotective effect of vitamin A and its clinical importance in the treatment of patients with chronic gastric ulcer.

The effects of vitamin A were studied on the basal and maximal gastric secretory responses of 12 patients; and on healing in 60 patients with chronic gastric ulcer. The effect of vitamin A on ulcer healing was evaluated by a multiclinical, multicentre, randomized, prospective study in which the patients were divided into three groups. In group A the patients were treated with antacids only; in group B the patients were given antacids plus vitamin A (in doses of 3 X 50.000 U orally); and in group C the patients received antacids, vitamin A plus cyproheptadine (in doses of 3 X 4 mg orally). The treatment lasted four weeks. At the beginning and the end of treatment endoscopies were performed and ulcer sizes were measured planimetrically. Various other parameters such as ulcer index, antacid consumption and laboratory parameters were also evaluated during the four-week treatment. It was observed that: (i) vitamin A (given in doses of 100.000 U i.m.) decreased neither basal nor maximal gastric secretory responses; (ii) the number of patients with completely healed gastric ulcer was significantly higher (P less than 0.05) in groups B and C than in group A; (iii) the extent of ulcer reduction was significantly higher (P less than 0.01) in groups B and C than in group A; (iv) no significant changes were observed in ulcer index and antacid consumption during the four-week treatment in the different groups of patients; (v) the reduction of ulcer size was significantly greater (P less than 0.01) in the group treated with antacids plus vitamin A than in the group treated with antacids only, at two weeks of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

[Methylation and expression of the FMR1 gene]. / Metilación y expresión del gen FMR1.

OBJECTIVE: In this paper we present a brief review on DNA methylation, the enzymes and proteins involved in the repression complex and the importance of methylation of FMR1 gene in fragile X syndrome. DEVELOPMENT: Methylation status of control region in the genome plays a critical role in the regulation of gene expression. In susceptible genes containing CpG island in the promoter, cytosine methylation favors a repressive chromatin structure that prevents the binding of transcriptional activators to the promoter. The enzyme DNA methyltransferase transfers a methyl group from the S-adenosylmethionine to the 5 carbon of cytosine in the CG sequences. Several proteins have been described that recognize the methyl cytosine and recruit the co-repressor and the histones deacetylases. The lost of the acetyl groups produces the compacting of the chromatin. Fragile X syndrome is due, in the majority of the cases, to the expansion above a threshold of the CGG repeats in the first exon of FMR1 gene. These expansions are concomitant with the methylation of the promoter and the silencing of FMR1. CONCLUSIONS: DNA methylation is a tag that enables different phenotypic expression from an identical nucleotide sequence. Aberrant methylation is the cause of different pathologies including fragile X syndrome. The comprehension of the mechanisms by which methylation induces the silencing of the genes and the study of agents that could revert this process are important for the treatment of these diseases.

Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease.

Eleven susceptibility loci for late-onset Alzheimer's disease (LOAD) were identified by previous studies; however, a large portion of the genetic risk for this disease remains unexplained. We conducted a large, two-stage meta-analysis of genome-wide association studies (GWAS) in individuals of European ancestry. In stage 1, we used genotyped and imputed data (7,055,881 SNPs) to perform meta-analysis on 4 previously published GWAS data sets consisting of 17,008 Alzheimer's disease cases and 37,154 controls. In stage 2, 11,632 SNPs were genotyped and tested for association in an independent set of 8,572 Alzheimer's disease cases and 11,312 controls. In addition to the APOE locus (encoding apolipoprotein E), 19 loci reached genome-wide significance (P < 5 × 10(-8)) in the combined stage 1 and stage 2 analysis, of which 11 are newly associated with Alzheimer's disease.

An oscillator circuit to produce a radio-frequency discharge and application to metastable helium saturated absorption spectroscopy.

We present a rf gas discharge apparatus which provides an atomic frequency reference for laser manipulation of metastable helium. We discuss the biasing and operation of a Colpitts oscillator in which the discharge coil is part of the oscillator circuit. Radiofrequency radiation is reduced by placing the entire oscillator in a metal enclosure.

Detecting inertial effects with airborne matter-wave interferometry.

Inertial sensors relying on atom interferometry offer a breakthrough advance in a variety of applications, such as inertial navigation, gravimetry or ground- and space-based tests of fundamental physics. These instruments require a quiet environment to reach their performance and using them outside the laboratory remains a challenge. Here we report the first operation of an airborne matter-wave accelerometer set up aboard a 0g plane and operating during the standard gravity (1g) and microgravity (0g) phases of the flight. At 1g, the sensor can detect inertial effects more than 300 times weaker than the typical acceleration fluctuations of the aircraft. We describe the improvement of the interferometer sensitivity in 0g, which reaches 2 x 10-4 ms-2 / √Hz with our current setup. We finally discuss the extension of our method to airborne and spaceborne tests of the Universality of free fall with matter waves.

Learning the nodal stations in the abdomen.

The normal pathways of lymphatic drainage from the abdominal organs have been well described in the classic anatomy literature. Knowledge of the location and nomenclature of the common nodal stations in the abdomen are essential for complete report of radiological findings. CT is ubiquitous in the evaluation of oncology patients. Utilizing colour-coded CT images of the abdomen we will present the nomenclature and location of the nodal stations for common abdominal neoplasms, including those of the stomach, pancreas, liver, colon and the kidney. Understanding the nomenclature and the usual lymphatic pathways of metastasis will help radiologists detect disease spread from abdominal tumours. The goal of this pictorial review is to present the nodal stations, nomenclature and location of regional lymph nodes for the most common abdominal neoplasms. In addition, the reader can use this document as a handbook to learn and review this information.

The gastric fundic mucosal energy systems and the HCl-induced lesions in rats in dependence on starvation.

Gastric mucosal lesions were produced by intragastric administration of 0.6 M HCl (1 ml) to rats starved for 48 or 24 h, and to unstarved rats which received 5 or 20% glucose solution ad libitum. The number and severity of gastric lesions were recorded and the mucosal levels of ATP, ADP, and AMP were enzymatically measured, cAMP was determined by RIA. Adenylate pool, energy charge, and ATP X ADP-1 were rated. It has been found that: the 20% glucose fed rats showed the highest levels of biochemical constituents, but the lowest number and severity of gastric lesions; there were significant negative correlations between the number and severity of lesions and the mucosal levels of ADP, AMP and cAMP; significant positive correlations were found between the number and severity of gastric lesions and the ratios of ATP X ADP-1 and energy charge. It has been concluded that: the energy turnover processes of the fundic mucosa were significantly higher in the animals fed 20% glucose; the increased energy turnover in the gastric mucosa may produce a better metabolic adaptation against the necrotizing effect of HCl.

Effects of cimetidine administered in cytoprotective and antisecretory doses on the membrane-bound ATP-dependent energy systems in the gastric mucosal lesions induced by HCl in rats.

CFY strain rats (both sexes, 180-210 g) were fasted for 24 hr. Different doses of cimetidine (2.5, 10 and 50 mg X kg-1 i.p.) were given 30 min prior to the gastric mucosal lesions induced by the intragastric application of 0.6 M HCl. Animals were sacrificed 1 hr after the administration of the necrotizing agent. The number of gastric lesions was determined and their severity scored. Samples from the gastric fundic mucosa were taken for biochemical analysis. The tissue levels of adenosine-5'-triphosphate (ATP), adenosine-5'-diphosphate (ADP), adenosine-5'-monophosphate (AMP) and L-(+)-lactate were determined enzymatically, while the tissue contents of cyclic 3',5' adenosine monophosphate were measured by radioimmunoassay. The values for adenylate pool (ATP + ADP + AMP)-1 were calculated. All biochemical results were computed for 1.0 mg mucosal protein. We found that (1) the levels of ADP and lactate rose significantly, while ATP, AMP, cAMP, ATP X ADP-1 and energy charge decreased during the development of gastric lesions induced by HCl: (2) cimetidine decreased dose-dependently the number and severity of lesions: (3) the levels of ATP, ADP X ADP-1, and energy charge were increased dose-dependently by cimetidine, while AMP and lactate were decreased: (4) the levels of ADP, adenylate pool and cAMP did not change significantly by cimetidine.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytoprotecting-effect of cimetidine: experimental evidence in the rat gastric mucosal lesions induced by intragastric administration of necrotizing agents.

Contradictory data have been found on cimetidine-induced gastric cytoprotection. In our paper the effect of cimetidine administered intraperitoneally in doses of 2.5, 10 and 50 mg X kg-1, on: 1. The gastric acid secretory responses in 1 and 4 hr pylorus-ligated rats, and 2. The rat gastric mucosal lesions induced by intragastric administration of 0.6 M HCl, 0.2 M NaOH, 96% ethanol and 25% NaCl is discussed. It was found that: 1. Cimetidine dose-dependently inhibited the gastric acid secretion in 1 and 4 hr pylorus-ligated rats, but a dose of 2.5 mg X kg-1 did not exert any significant inhibition; 2. All doses of cimetidine significantly prevented the gastric lesion development induced by different necrotizing agents (0.6 M HCl, 0.2 M NaOH, 96% ethanol, and 25% NaCl); 3. The cytoprotecting dose of cimetidine was of 2.5 mg X kg-1; and 4. The duration of cimetidine-induced cytoprotection was 1 hr long before the administration of the necrotizing agent. These results suggest a real cimetidine-induced gastric cytoprotection.