Chronology and petrology in MIS4-2 of DSDP Site 94-609

Ice-rafting evidence for a '1500-year cycle' sparked considerable debate on millennial-scale climate change and the role of solar variability. Here, we reinterpret the last 70,000 years of the subpolar North Atlantic record, focusing on classic DSDP Site 609, in the context of newly available raw data, the latest radiocarbon calibration (Marine09) and ice core chronology (GICC05), and a wider range of statistical methodologies. A ~1500-year oscillation is primarily limited to the short glacial Stage 4, the age of which is derived solely from an ice flow model (ss09sea), subject to uncertainty, and offset most from the original chronology. Results from the most well-dated, younger interval suggest that the original 1500 ± 500 year cycle may actually be an admixture of the ~1000 and ~2000 cycles that are observed within the Holocene at multiple locations. In Holocene sections these variations are coherent with 14C and 10Be estimates of solar variability. Our new results suggest that the '1500-year cycle' may be a transient phenomenon whose origin could be due, for example, to ice sheet boundary conditions for the interval in which it is observed. We therefore question whether it is necessary to invoke such exotic explanations as heterodyne frequencies or combination tones to explain a phenomenon of such fleeting occurrence that is potentially an artifact of arithmetic averaging.

Use of the energy-release rate in a 2 scale damage analysis of a bonded joint

Stress singularities appear at the extremities of an adhesive bond. They can produce a damage mechanism that we assimilate in this Note to a crack. The energy release rate permits to characterize its evolution. But a very refined mesh would be necessary for a real structure. Using an asymptotic method based on the small thickness of the bond a limit model with a different local behaviour is suggested. It leads to an approximation of the energy release rate

Aluminum Induces a Decrease in Cytosolic Calcium Concentration in BY-2 Tobacco Cell Cultures1

Al toxicity is a major problem that limits crop productivity on acid soils. It has been suggested that Al toxicity is linked to changes in cellular Ca homeostasis and the blockage of plasma membrane Ca2+-permeable channels. BY-2 suspension-cultured cells of tobacco (Nicotiana tabacum L.) exhibit rapid cell expansion that is sensitive to Al. Therefore, the effect of Al on changes in cytoplasmic free Ca concentration ([Ca2+]cyt) was followed in BY-2 cells to assess whether Al perturbed cellular Ca homeostasis. Al exposure resulted in a prolonged reduction in [Ca2+]cyt and inhibition of growth that was similar to the effect of the Ca2+ channel blocker La3+ and the Ca2+ chelator ethyleneglycol-bis(β-aminoethyl ether)-N,N′-tetraacetic acid. The Ca2+ channel blockers verapamil and nifedipine did not induce a decrease in [Ca2+]cyt in these cells and also failed to inhibit growth. Al and La3+, but not verapamil or nifedipine, reduced the rate of Mn2+ quenching of Indo-1 fluorescence, which is consistent with the blockage of Ca2+- and Mn2+-permeable channels. These results suggest that Al may act to block Ca2+ channels at the plasma membrane of plant cells and this action may play a crucial role in the phytotoxic activity of the Al ion.

Identification of two evolutionarily conserved and functional regulatory elements in intron 2 of the human BRCA1 gene

Cross-species comparative genomics is a powerful strategy for identifying functional regulatory elements within noncoding DNA. In this paper, comparative analysis of human and mouse intronic sequences in the breast cancer susceptibility gene (BRCA1) revealed two evolutionarily conserved noncoding sequences (CNS) in intron 2, 5 kb downstream of the core BRCA1 promoter. The functionality of these elements was examined using homologous-recombination-based mutagenesis of reporter gene-tagged cosmids incorporating these regions and flanking sequences from the BRCA1 locus. This showed that CNS-1 and CNS-2 have differential transcriptional regulatory activity in epithelial cell lines. Mutation of CNS-1 significantly reduced reporter gene expression to 30% of control levels. Conversely mutation of CNS-2 increased expression to 200% of control levels. Regulation is at the level of transcription and shows promoter specificity. Both elements also specifically bind nuclear proteins in vitro. These studies demonstrate that the combination of comparative genomics and functional analysis is a successful strategy to identify novel regulatory elements and provide the first direct evidence that conserved noncoding sequences in BRCA1 regulate gene expression. (c) 2005 Elsevier Inc. All rights reserved.

Unidirectional inversion of ibuprofen in Caco-2 cells: Developing a suitable model for presystemic chiral inversion study

Intestinal chiral inversion of ibuprofen is still lacking direct evidence. In a preliminary experiment, ibuprofen was found to undergo inversion in Caco-2 cells. This investigation was thus conducted to determine the characteristics and influence of some biochemical factors on the chiral inversion of ibuprofen in Caco-2 cells. The effects of substrate concentration (2.5-40 mu g/ml), cell density (0.5-2 x 10(6) cells/ well), content of serum (0-20%), coexistence of S ibuprofen (corresponding doses), sodium azide (10mm), exogenous Coenzyme A (CoA) (0.1 - 0.4 mm),. and palmitic acid (5-25 mu m) on inversion were examined. A stereoselective HPLC method based on the Chromasil-CHI-TBB column was developed for quantitative analysis of the drug in cell culture medium. The inversion ratio (F-i) and elimination rate constant were calculated as the indexes of inversion extent. Inversion of ibuprofen in Caeo-2 cells was found to be both dose and cell density dependent, indicating saturable characteristics. Addition of serum significantly inhibited the inversion, to an extent of 2.7 fold decrease at 20% content. Preexistence of S enantiomer exerted a significant inhibitory effect (p < 0.01 for all tests). Sodium azide decreased the inversion ratio from 0.43 to 0.32 (p < 0.01). Exogenous CoA and palmitic acid significantly promoted the inversion at all tested doses (p < 0.01 for all tests). This research provided strong evidence to the capacity and capability of intestinal chiral inversion. Although long incubation times up to 120 h were required, Caco-2 cells should be a suitable model for chiral inversion research of 2-APAs considering the human-resourced and well-defined characteristics from the present study.

Oxidative and inflammatory status in Type 2 diabetes patients with periodontitis

Aim: To determine the impact of periodontitis on oxidative/inflammatory status and diabetes control in Type 2 diabetes. Materials and Methods: A comparative study of 20 Type 2 diabetes patients with periodontitis [body mass index (BMI) 31+5], 20-age/gender-matched, non-periodontitis Type 2 diabetes controls (BMI 29+6) and 20 non-diabetes periodontitis controls (BMI 25+4) had periodontal examinations and fasting blood samples collected. Oxidative stress was determined by plasma small molecule antioxidant capacity (pSMAC) and protein carbonyl levels; inflammatory status by total/differential leucocytes, fibrinogen and high sensitivity C-reactive protein (hsCRP); diabetes status by fasting glucose, HbA1c, lipid profile, insulin resistance and secretion. Statistical analysis was performed using SPSS. Results: pSMAC was lower (p=0.03) and protein carbonyls higher (p=0.007) in Type 2 diabetes patients with periodontitis compared with those without periodontitis. Periodontitis was associated with significantly higher HbA1c (p=0.002) and fasting glucose levels (p=0.04) and with lower ß-cell function (HOMA-ß; p=0.01) in diabetes patients. Periodontitis had little effect on inflammatory markers or lipid profiles, but Type 2 diabetes patients with periodontitis had higher levels of hsCRP than those without diabetes (p=0.004) and the lowest levels of HDL-cholesterol of all groups. Conclusion: Periodontitis is associated with increased oxidative stress and compromised glycaemic control in Type 2 diabetes patients.

Dapagliflozin add-on to metformin in type 2 diabetes inadequately controlled with metformin:a randomized, double-blind, placebo-controlled 102-week trial

Background: Management of type 2 diabetes with metformin often does not provide adequate glycemic control, thereby necessitating add-on treatment. In a 24-week clinical trial, dapagliflozin, an investigational sodium glucose cotransporter 2 inhibitor, improved glycemic control in patients inadequately controlled with metformin. The present study is an extension that was undertaken to evaluate dapagliflozin as long-term therapy in this population.Methods: This was a long-term extension (total 102 weeks) of a 24-week phase 3, multicenter, randomized, placebo-controlled, double-blind, parallel-group trial. Patients were randomly assigned (1:1:1:1) to blinded daily treatment (placebo, or dapagliflozin 2.5 to 5, or 10 mg) plus open-label metformin (=1,500 mg). The previously published primary endpoint was change from baseline in glycated hemoglobin (HbA1c) at 24 weeks. This paper reports the follow-up to week 102, with analysis of covariance model performed at 24 weeks with last observation carried forward; a repeated measures analysis was utilized to evaluate changes from baseline in HbA1c, fasting plasma glucose (FPG), and weight.Results: A total of 546 patients were randomized to 1 of the 4 treatments. The completion rate for the 78-week double-blind extension period was lower for the placebo group (63.5%) than for the dapagliflozin groups (68.3% to 79.8%). At week 102, mean changes from baseline HbA1c (8.06%) were +0.02% for placebo compared with -0.48% (P = 0.0008), -0.58% (P

Elevated serum free light chains predict cardiovascular events in type 2 diabetes

OBJECTIVE: Elevated polyclonal serum immunoglobulin free light chains (FLCs; combined FLCκ+FLCλ [cFLC]) are associated with adverse clinical outcomes and increased mortality; we investigated cFLC and cardiovascular disease (CVD) events in type 2 diabetes. RESEARCH DESIGN AND METHODS: In a cohort study of 352 south Asian patients with type 2 diabetes, serum cFLC, high-sensitivity C-reactive protein (hsCRP), and standard biochemistry were measured. CVD events over 2 years were recorded and assessed usingmultiple logistic regression. RESULTS: cFLC levels were elevated significantly in 29 of 352 (8%) patients with CVD events during 2 years of follow-up (50.7 vs. 42.8mg/L; P = 0.004). Inmultivariate analysis, elevated cFLC (>57.2 mg/L) was associated with CVD outcomes (odds ratio 3.3 [95% CI 1.3-8.2]; P = 0.012) and remained significant after adjusting for age, albumin-to-creatinine ratio, diabetes duration, or treatment. CONCLUSIONS: cFLC elevation is a novel marker for CVD outcomes in type 2 diabetes that warrants further investigation. © 2014 by the American Diabetes Association.

Global Results for Solution to the Mass-Critical Schrödinger Equation with Convolution Nonlinearity in R^n

Георги Венков, Христо Генев - Разглеждаме един клас от L^2 - критични нелинейни уравнения на Шрьодингер в R^(1+n) с конволюционна нелинейност от тип Хартри. Целта ни е да установим локалното и глобално съществуване на решенията, както и коректност на задачата на Коши в достатъчно малка околност на нулата в пространството L^2 (R^n). Като естествено следствие на глобалните резултати ние доказваме съществуване на оператор на разсейване за малки начални условия.

Gazdasági kórkép alulnézetből 2. rész (Syndrome of Hungarian Economy from Bottom-view - part 2.)

A magyar gazdaság új növekedési pályára állása a kilencvenes évek végére tehető, s ebben meghatározó szerepe volt a pótlólagos erőforrásként szolgáló külföldi működőtőke-befektetéseknek. A nemzetközi tőkeáramlás ezredfordulót követő módosulása (csökkenő volumen, változó irányultság) kedvezőtlenül érintette a hazai gazdaságot, aminek egyik következménye a beruházások csökkenése és a növekedési ütem lassulása, másik következménye viszont – a jövedelemkiáramlást semlegesítő hatás elmaradása miatt – a fizetési mérleg romlása. Ebben a helyzetben halaszthatatlanná vált az államháztartási egyensúlyromlás megállítása, illetve a gazdasági fejlődés új alapokra helyezése. A szerző elemzésében – a hazai versenyszektor eredményességi és vagyoni jellemzőinek értékelésével – azt szeretné jelezni, hogy az egyensúlytalansági állapot megszüntetése nem szorítkozhat az államháztartási rendszerre, vagyis az ország helyzetének stabilizálása, majd új növekedési pályára állás nem képzelhető el a gazdaság átfogó modernizációja nélkül. Vizsgálata a ténylegesen működő (343 ezer) hazai társas vállalkozás 2000–2008. évi pénzügyi beszámolóinak adataira épül. Álláspontja szerint a mintavétel nagysága ellensúlyozza az esetleges torzító hatásokat (lásd: helyenként előforduló kreatív beszámolók), így a vállalkozások mennyiségi gyarapodása, méret szerinti megoszlása, a gazdasági tevékenység jellege, a teljesítmények és eredmények alakulása, a vállalkozói vagyon módosulása megbízhatóan értékelhető, illetve a tapasztalatok alapján a korrekciós intézkedések igénye és azok tartalma is jól körvonalazható. Tanulmányát így ajánljuk a téma iránt érdeklődőknek, a versenyszektor szereplőinek, de leginkább a gazdaságpolitika formálóinak. _________ The economic performance during the transition period was characterized by the alternations of fulfilled hopes and unrealized expectations. The economic restructuring and changes in market relations took place during the first decade, while new – mostly foreign – investment groups entered on the new market. As a result the economy was stabilized and was put to a new growth path. But after the millennium the foreign investment based economy development strategy was no more adequate. The new engine for the growth should have been the domestic small and medium enterprise sector (SsME), but despite the subsidies this sector was not strengthened to take this role. The author – the researcher of BCE, and the ex-president of APpEH – analyses the characteristics of the domestic business demography, performance and effectiveness, based on the 2000–2008 annual financial statements of the business sector. In the author’s analysis – with assessment of the domestic business sector and financial performance characteristicst - he would like to point out that the imbalance can not be confined to the elimination of state government system, that is, the country’s situation to stabilize, and then post a new growth path is not conceivable without the modernization of the economy overall. In his view, the sample size outweighed the possible distortionary effects (see occurring in places of creative accounts), so the growth of business volume, size distribution, the nature of economic activity, the evolution of performance and results, a reliable assessment of changes in the business of property and the experience on the basis of the need for corrective action, and its contents are also well delineated. Sstudy it is recommended for those interested in the topic, the business sector actors, but most of the economic policy makers.

Resolution of deep venous thrombosis in type 2 diabetes mice model : implication of fibrinolytic and matrix metalloproteinase systems

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Resolution of deep venous thrombosis in type 2 diabetes mice model : implication of fibrinolytic and matrix metalloproteinase systems

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Reduced lipoapoptosis, hedgehog pathway activation and fibrosis in caspase-2 deficient mice with non-alcoholic steatohepatitis

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