Synthesis of H2 in dirty ice mantles by fast ion energy loss: New experimental results increase the relevance of this mechanism

Recent experimental results support the importance of H2 production in molecular clouds by cosmic ray bombardment of the mantles of grains. The formation of molecules different from those originally present in the irradiated layer can be explained by the production of molecular fragments induced by the release of energy if the impinging fast particle. One way of considering the process is in terms of a transiently hot cylinder, initially about 50 A in diameter, that exists around the track of an individual fast ion. Since ice has a relatively low thermal conductivity, energy lost by the ion in the ice layers remains confined around the track for time long enough to be thermalized. The hot cylinder increases in diameter and decreases in temperature on a time scale of 10(exp -11) to 10(exp -10) sec. Molecular fragments that are formed in this high temperature region acquire enough mobility to recombine with different partners, forming new molecules. A Monte Carlo simulation of the interaction between cosmic rays and grain mantles, at various depths in the core of a spherical molecular cloud, was performed. The simulation was continued until 40,000 ions had hit each grain of the type and size chosen. During the performed experiments thin icy films made of H2O and CD4 mixed in the gas phase and deposited on a cold finger at 9 K were irradiated with 1.5 MeV helium beams. Among synthesized molecules were found H2, HD, and D2

Ezetimibe/simvastatin 10/20 mg versus simvastatin 40 mg in coronary heart disease patients

BACKGROUND: Reducing low-density lipoprotein cholesterol (LDL-C) is the primary goal of therapy in patients with hypercholesterolemia and coronary heart disease (CHD). METHODS: This double blind placebo-controlled study enrolled patients 18 to 75 years of age with primary hypercholesterolemia and establishedCHDwhowere taking a stable daily dose of simvastatin 20 mg. Patients were randomized to ezetimibe/simvastatin 10/20 mg (eze/simva; n 5 56) or simvastatin 40 mg (simva; n 5 56) for 6 weeks. Percent change from baseline in LDL-C, total cholesterol, high-density lipoprotein cholesterol (HDL-C), and triglycerides were assessed by use of the Student t test. The percent of patients achieving LDL-C less than 100 mg/dL (,2.6mmol/L) or less than 80 mg/dL (,2.0 mmol/L) was analyzed via logistic regression with terms for treatment, baseline LDL-C, age, and gender. RESULTS: Baseline characteristics were similar between groups. Treatment with eze/simva combination resulted in significantly greater reductions in LDL-C, total cholesterol, and triglycerides versus doubling the dose of simva to 40 mg (all P , .01). Significantly more patients achieved LDL-C less than 100 mg/dL (,2.6mmol/L) and less than 80 mg/dL (,2.0mmol/L) with ezetimibe/simvastatin versus doubling the dose of simva to 40 mg (73.2% vs 25.0%; P,.001) for simvastatin. Changes in HDL-C were similar between treatments. Both treatments were generally well tolerated. CONCLUSION: In high-risk CHD patients with hypercholesterolemia, treatment with eze/simva combination resulted in significantly greater reductions inLDL-C, total cholesterol and triglycerides, as well as greater achievement of recommended LDL-C targets, compared with doubling the simvastatin dose to 40 mg over the 6-week period

DeepSRE: Identification of sterol responsive elements and nuclear transcription factors Y proximity in human DNA by Convolutional Neural Network analysis

SREBP1 and 2, are cholesterol sensors able to modulate cholesterol-related gene expression responses. SREBPs binding sites are characterized by the presence of multiple target sequences as SRE, NFY and SP1, that can be arranged differently in different genes, so that it is not easy to identify the binding site on the basis of direct DNA sequence analysis. This paper presents a complete workflow based on a one-dimensional Convolutional Neural Network (CNN) model able to detect putative SREBPs binding sites irrespective of target elements arrangements. The strategy is based on the recognition of SRE linked (less than 250 bp) to NFY sequences according to chromosomal localization derived from TF Immunoprecipitation (TF ChIP) experiments. The CNN is trained with several 100 bp sequences containing both SRE and NF-Y. Once trained, the model is used to predict the presence of SRE-NFY in the first 500 bp of all the known gene promoters. Finally, genes are grouped according to biological process and the processes enriched in genes containing SRE-NFY in their promoters are analyzed in details. This workflow allowed to identify biological processes enriched in SRE containing genes not directly linked to cholesterol metabolism and possible novel DNA patterns able to fill in for missing classical SRE sequences

Formation of Hydrogen, Oxygen, and Hydrogen Peroxide in Electron Irradiated Crystalline Water Ice

Water ice is abundant both astrophysically, for example in molecular clouds, and in planetary systems. The Kuiper belt objects, many satellites of the outer solar system, the nuclei of comets and some planetary rings are all known to be water-rich. Processing of water ice by energetic particles and ultraviolet photons plays an important role in astrochemistry. To explore the detailed nature of this processing, we have conducted a systematic laboratory study of the irradiation of crystalline water ice in an ultrahigh vacuum setup by energetic electrons holding a linear energy transfer of 4.3 +/- 0.1 keV mm-1. The irradiated samples were monitored during the experiment both on line and in situ via mass spectrometry (gas phase) and Fourier transform infrared spectroscopy (solid state). We observed the production of hydrogen and oxygen, both molecular and atomic, and of hydrogen peroxide. The likely reaction mechanisms responsible for these species are discussed. Additional formation routes were derived from the sublimation profiles of molecular hydrogen (90-140 K), molecular oxygen (147 -151 K) and hydrogen peroxide (170 K). We also present evidence on the involvement of hydroxyl radicals and possibly oxygen atoms as building blocks to yield hydrogen peroxide at low temperatures (12 K) and via a diffusion-controlled mechanism in the warming up phase of the irradiated sample.Comment: ApJ, March 2006, v639 issue, 43 pages, 7 figure

Wiki Web per il Problem Solving in Matematica

La necessità di affrontare l’emergenza evidenziata dalle recenti indagini OCSE-PISA sulle competenze dei quindicenni in matematica spinge ricercatori ed insegnanti ad elaborare metodologie sempre nuove e diverse di insegnamento/apprendimento. Tutti i tipi di risorse e le TIC in particolare diventano mezzi efficaci per proporre la matematica come strumento di pensiero capace di sollecitare il ragionamento. La creazione di una piccola comunità di apprendimento in rete, in cui i ragazzi possono imparare a cimentarsi con la scrittura collaborativa con la guida dei loro insegnanti, può essere un modo per stimolare quel confronto di idee tra i discenti che è base per un apprendimento attivo

LINEE GUIDA CLINICHE PER LA PREVENZIONE DELLA CARDIOPATIA ISCHEMICA NELLA IPERCOLESTEROLEMIA FAMILIARE Una patologia sotto-diagnosticata e sotto-trattata

AIMS. Familial hypercholesterolaemia (FH) is a common genetic cause of premature coronary heart disease (CHD) due to lifelong elevated plasma low-density lipoprotein (LDL) cholesterol levels. This paper aims to describe the problem of FH underdiagnosis and undertreatment and to promote CHD prevention providing recommendations for the screening and treatment of patients with FH. Methods and results. In many countries, less then 1% of FH patients are diagnosed, although the estimated prevalence of this condition is about 1/500 for heterozygous FH and the results of FH screening in a general population of Northern Europe suggest a prevalence of 1/200. Studies on FH patients agree on a widespread failure to achieve recommended target of LDL-cholesterol and on a 12-fold increased CHD risk. With a theoretical prevalence between 1/500 and 1/200, it is estimated that 14 to 34 million subjects worldwide have FH. With evidence of plasma cholesterol ≥8 mmol/L (≥310 mg/dL) in an adult or ≥6 mmol/L (≥230 mg/dL) in a child, premature CHD, tendon xanthomas, or sudden premature cardiac death, we recommend the screening for FH of this subject and of all first-degree relatives. The treatment of a patient with diagnosis of FH should have LDL targets of <3.5 mmol/L (<135 mg/ dL) for children, <2.5 mmol/L (<100 mg/dL) for adults, and <1.8 mmol/L (<70 mg/dL) for adults with known CHD or diabetes. Beside life-style and dietary modifications, first line therapies are statins, ezetimibe, and bile acid binding resins in children, and maximal potent statin dose, ezetimibe, bile acid binding resins, and fibrates in adults. Homozygotes FH and in treatment-resistant heterozygotes FH with CHD should be referred for LDL-apheresis. Conclusion. Familial hypercholesterolemia is a common condition that carries a high risk of CHD. The underdiagnosis and undertreatment of FH require a focused intervention that implements the screening and promote the early and aggressive treatment of these patients

Familial hypercholesterolemia: The Italian Atherosclerosis Society Network (LIPIGEN)

Primary dyslipidemias are a heterogeneous group of disorders characterized by abnormal levels of circulating lipoproteins. Among them, familial hypercholesterolemia is the most common lipid disorder that predisposes for premature cardiovascular disease. We set up an Italian nationwide network aimed at facilitating the clinical and genetic diagnosis of genetic dyslipidemias named LIPIGEN (LIpid TransPort Disorders Italian GEnetic Network)

Identification of a novel mutation of MTP gene in a patient with abetalipoproteinemia

Abetalipoproteinemia (ABL), or Bassen-Kornzweig syndrome, is a rare autosomal recessive disorder of lipoprotein metabolism, characterized by fat malabsorption, hypocholesterolemia retinitis pigmentosa, progressive neuropathy and acanthocytosis from early infancy. We describe the clinical and molecular characterization of a 6-month-old infant born of consanguineous, apparently healthy parents from Iran. The patient was hospitalized because of failure to thrive, greasy stool and vomiting. The patient's serum lipid profile, the clinical phenotype and the duodenal histology suggested the clinical diagnosis of ABL. The MTP gene analysis by direct sequencing revealed a novel homozygous mutation (c.1586 A > G-H529R). The parents were heterozygotes for the same mutation and interestingly the father showed a lipid profile characterized by a slight reduction of total and LDL-cholesterol plasma levels

Plasma levels of lipoproteins and apolipoproteins in congenital hypothyroidism: effects of L-thyroxine substitution therapy

Thyroid status in humans is an important factor in the regulation of lipoprotein metabolism. There are several data on hypothyroidism in the adult population, but less information is available about congenital hypothyroidism. Since lipid metabolism at birth is substantially different from that of adults, it is not likely that the same abnormalities that occur in adult hypothyroidism are also present when this is diagnosed at early life. We studied 16 subjects with congenital hypothyroidism, seven at the time of diagnosis and also after normalization of thyroid hormone levels over a period of 2.0 +/- 1.0 months of substitution therapy with L-thyroxine (5.9 +/- 1.2 micrograms/kg/d) and nine already on L-thyroxine therapy for a period of 4.7 +/- 3.2 months. Thirty-nine apparently healthy subjects matched for age were selected as controls. In all subjects, total cholesterol (CHO), triglycerides (TG), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol (HDL-C), apolipoproteins (apo) A-I and B, lipoprotein(a) [Lp(a)] thyrotropin (TSH), (LDL-C), total and free thyroxine (T4), and triiodothyronine (T3) were determined. CHO, HDL-C, and apo A-I levels were significantly higher in patients at the time of diagnosis than in controls (respectively, P = .0079, .0007, and .0004), whereas TG, LDL-C, apo B, and Lp(a) levels were not significantly different. During L-thyroxine substitution therapy in these subjects, HDL-C and apo A-I levels significantly decreased (respectively, by a mean of -36.2% and -24.4%), with similar behavior in all subjects.(ABSTRACT TRUNCATED AT 250 WORDS

RT-PCR and in situ hybridization analysis of apolipoprotein H expression in rat normal tissues

In this study, by using different techniques (i.e. Northern blot hybridization, RT-PCR and Southern blot hybridization) on various normal rat tissues, we were able to identify liver, kidney, heart, small intestine, brain, spleen, stomach and prostate as tissues in which the ApoH gene is transcribed. Moreover, for some of these tissues, by in situ hybridization, we found a specific localization of apoH transcripts. For instance epithelial cells of the bile ducts in liver and of the proximal tubules in kidney are the major sites of apoH synthesis. Our data suggest that some of the different physiological roles proposed for apoH could correlate with its direct expression, while others could correlate with its absorption from bloodstream or adjacent cells