THEORETICAL AND EXPERIMENTAL STUDIES ON DISKS CENTRIFUGAL SEPARATORS

The paper presents an extension of classical thin shell theory to those with moderate thickness, having simplex order h/R ≤ 0.2 ... 0.33. The application of the flexibility matrix method is studied to realise a computerised analysis of centrifugal disks separators for the influence of the central load Fa induced for assembling the bowl and for the critical area junctions. In the first time, the separator's bowl is divided in structural elements; each of the structural elements is at first considered separately and then the global generalised forces and bending moments are obtained from the displacement compatibility conditions at each element junction. Comparative experimental investigations based on recording surface strains at selected locations of the bowl performed with strain gauges reveal a reasonable agreement. The main features of the method as, (1) reasonable accuracy of the results, (2) reasonable positioning of the critical junctions, (3) low computational cost, give a real possibility in the design work

Rolul oxidului nitric în boala de reflux gastroesofagian

Conferinţa naţională în medicina internă din Republica Moldova cu participare internaţională, 19-20 mai 2011, Chişinău, Republica MoldovaSummary. Nitric oxide is a simple heterodiatomic molecule, composed by an atom of Nitrogen and one of Oxygen, with multiple and various effects in human biology; an biologic mediator, which is involved in various pathological and pathophysiological processes. In GERD the NO participates in the esophagian dysmotility adjustment, could be appreciated as a marker of inflammatory process in esophagus; it plays an citopretective role.Oxidul de azot sau oxidul nitric (NO) este o moleculă simplă heterodiatomică recunoscută recent, formată dintr-un atom de oxigen şi un atom de azot, cu multiple şi variate efecte în biologia umană. Este unul dintre cei mai importanţi mediatori biologici, implicat în multiple procese fiziologice şi patofiziologice. Oxidul nitric este una dintre cele mai mici molecule din natură, cu masă moleculară egală cu 30 Daltoni, de aceea trece uşor prin membrana celulară. Durata de viaţă a oxidului nitric este scurtă: în ţesuturile biologice – până la 5- 6 sec, în sol. NaCl – de la 6 până la 30 sec. Un aspect intrigant al moleculei NO este posibilitatea sa de a media evenimentele fiziologice normale şi, în acelaşi timp, de a fi foarte toxic. În sistemele biologice oxidul nitric se formează din reacţia de transformare a aminoacidului L-argininei în L-citrulină în prezenţa oxigenului şi a NADPH, proces catalizat de sintezele oxidului nitric (NOS). Izoenzimele neuronală (nNOS) şi endotelială (eNOS) sunt constitutive, citoplazmatice, prezente în permanenţă în celule şi activitatea lor depinde direct de concentraţia intracelulară a ionilor de calciu şi calmodulină. Oxidul nitric sintetizat de iNOS participă la instalarea proceselor inflamatorii în diverse maladii ale canalului digestiv: colita ulcerohemoragică, boala Cron, gastrita de reflux, esofagita de reflux. Efectele oxidului nitric în sistemul digestiv: asigură activitatea motorie a tractului gastrointestinal, participă in transmiterea impulsurilor neuronali (nNOS), reglează tonusul vascular al sistemului digestiv (eNOS), posedă acţiune citoprotectoare. Boala de reflux gastroesofagian (BRGE) reprezintă o maladie cronică recidivantă, cauzată de mecanisme complexe de perturbare a motilităţii tractului digestiv superior, cu retropulsia conţinutului gastric sau intestinal în esofag. În esenţă, BRGE este o afecţiune motorie esofagiană, care apare în urma relaxării inadecvate a sfincterului esofagian inferior. În ultimele 2 decenii, cunoştinţele referite la BRGE au făcut un salt enorm. Patogenia BRGE este complicată. Este constatat faptul că incapacitatea SEI (scăderea presiunii bazale) şi relaxarea spontană a esofagului sunt determinate de nivelul oxidului nitric. În BRGE cantitatea de NO este crescută şi depinde de severitatea esofagitei. NO provoacă relaxarea spontană a esofagului în faza interdigestiei, influenţând complexul motor migrant. Inervaţia esofagului este complicată. De rând cu sistemele nervoase simpatic şi parasimpatic, au fost descoperiţi neuronii neadrenergici-necolinergici (NANC), mai târziu numiţi nitroxidergice. Relaxarea esofagului şi SEI este determinată de receptori NANC, în care rolul de mediator îl joacă oxidul nitric. Acesta este eliberat de neuronii speciali (NANC), localizaţi in plexul intramural, numiţi de tip Dogheli. Stimularea neuronilor măreşte sinteza oxidului nitric, care pătrunde în stratul muscular şi activează guanilatciclaza solubilă care, la rândul ei, activează sinteza guanidinmonofosfat ciclaza (cGMF). Creşterea nivelului de cGMF micşorează concentraţia ionilor de calciu în citoplazmă şi afectează legătura dintre actină şi miozină, astfel provocând relaxarea SEI. Concluzie. Oxidul nitric joacă un rol important în reglarea motricităţii esogastrice, participă in reglarea microcirculaţiei esofagiene, poate fi considerată ca marker al procesului inflamator din esofag

Rolul bolii de reflux gastroesofagian în dezvoltarea bronhopneumopatiei cronice

Conferinţa naţională în medicina internă din Republica Moldova cu participare internaţională, 19-20 mai 2011, Chişinău, Republica MoldovaSummary. The gastro-oesophageal regurgitation is a disease which include all the symptoms from oesophagus regurgitation caused by the disturbance of the superior gastro-intestinal motility with the gastric or intestinal content retropulsion in oesophagus. The BRGE is represented by the typical symptoms: dysphagia, regurgitation, oesophagus pain,and atypical symptoms: cardiac-pain,respiratory-pain, ORL manifestations. These symptoms are accompanied or not by the oesophageal mucosa-lesions.Prevalenţa refluxului gastroesofagian este puţin cunoscută, dar are o incidenţă foarte mare. După cum arată numeroase studii epidemiologice, 30-44% din subiecţi au pirozis o dată în lună, asociat în mai mult de ¼ din cazuri cu alte simptome. În prezent este evidentă creşterea incidenţei afecţiunilor esofagiene, influenţată de sporirea factorilor de risc legaţi de stilul de viaţă (fumatul, obezitatea, mesele cu volum mare şi tardive), a factorului genetic (a cărui prezenţă este estimată în 18-31% din cazurile de boală), descoperind mai multe aspecte ale acestei maladii. Boala de reflux gastroesofagian (BRGE) este o entitate clinică independentă, cauzată de mecanisme complexe de perturbare a motilităţii tractului gastrointestinal superior, cu retropulsia conţinutului gastric/intestinal în esofag, şi decurge cu diverse simptome (esofagiene şi extraesofagiene). Simptomele tipice sunt consecinţe ale agresiunii chimice esofagiene şi faringiene şi cuprind pirozisul, regurgitaţia, eruciaţia, sialoreea şi odinofagia. Simptomele atipice (extraesofagiene) sunt cel mai frecvent extradigestive se întâlnesc la aproape o treime dintre bolnavii cu BRGE şi sunt obişnuit expresia complicaţiilor extradigestive ale BRGE. Manifestările ORL semnifică iritaţia orofaringiană sau tulburări reflexe esofago- şi faringoglotice. Disfonia „idiopatică”, răguşeala inexplicabilă sunt adesea simptomele relevante. Faringitele cronice pot exprima şi alte manifestări ale BRGE. Manifestările pulmonare ale BRGE pot fi întâlnite atunci când refluxul se manifestă trenant. Tusea cronică, fără suport aparent, “surprinzătoare” uneori prin caracterul nocturn, poate releva BRGE. Hemoptiziile se pot asocia în acest cadru simptomatic. Pneumopatiile acute recurente reprezintă o altă formă de manifestare a bolii de reflux gastroesofagian. Astmul bronşic simptomatic BRGE şi-a dobândit un statut legitim, fiind acceptat ca o realitate autonomă şi diferită de cea a agravării evoluţiei clinice a afecţiunii în contextul BRGE. Toate acestea justifică demersuri diagnostice complexe şi responsabile

An Integrated Approach to the Prediction of Chemotherapeutic Response in Patients with Breast Cancer

BACKGROUND: A major challenge in oncology is the selection of the most effective chemotherapeutic agents for individual patients, while the administration of ineffective chemotherapy increases mortality and decreases quality of life in cancer patients. This emphasizes the need to evaluate every patient's probability of responding to each chemotherapeutic agent and limiting the agents used to those most likely to be effective. METHODS AND RESULTS: Using gene expression data on the NCI-60 and corresponding drug sensitivity, mRNA and microRNA profiles were developed representing sensitivity to individual chemotherapeutic agents. The mRNA signatures were tested in an independent cohort of 133 breast cancer patients treated with the TFAC (paclitaxel, 5-fluorouracil, adriamycin, and cyclophosphamide) chemotherapy regimen. To further dissect the biology of resistance, we applied signatures of oncogenic pathway activation and performed hierarchical clustering. We then used mRNA signatures of chemotherapy sensitivity to identify alternative therapeutics for patients resistant to TFAC. Profiles from mRNA and microRNA expression data represent distinct biologic mechanisms of resistance to common cytotoxic agents. The individual mRNA signatures were validated in an independent dataset of breast tumors (P = 0.002, NPV = 82%). When the accuracy of the signatures was analyzed based on molecular variables, the predictive ability was found to be greater in basal-like than non basal-like patients (P = 0.03 and P = 0.06). Samples from patients with co-activated Myc and E2F represented the cohort with the lowest percentage (8%) of responders. Using mRNA signatures of sensitivity to other cytotoxic agents, we predict that TFAC non-responders are more likely to be sensitive to docetaxel (P = 0.04), representing a viable alternative therapy. CONCLUSIONS: Our results suggest that the optimal strategy for chemotherapy sensitivity prediction integrates molecular variables such as ER and HER2 status with corresponding microRNA and mRNA expression profiles. Importantly, we also present evidence to support the concept that analysis of molecular variables can present a rational strategy to identifying alternative therapeutic opportunities

Copy number variation of microRNA genes in the human genome

<p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRNAs) are important genetic elements that regulate the expression of thousands of human genes. Polymorphisms affecting miRNA biogenesis, dosage and target recognition may represent potentially functional variants. The functional consequences of single nucleotide polymorphisms (SNPs) within critical miRNA sequences and outside of miRNA genes were previously demonstrated using both experimental and computational methods. However, little is known about how copy number variations (CNVs) affect miRNA genes.</p> <p>Results</p> <p>In this study, we analyzed the co-localization of all miRNA <it>loci </it>with known CNV regions. Using bioinformatic tools we identified and validated 209 copy number variable miRNA genes (CNV-miRNAs) in CNV regions deposited in Database of Genomic Variations (DGV) and 11 CNV-miRNAs in two sets of CNVs defined as highly polymorphic. We propose potential mechanisms of CNV-mediated variation of functional copies of miRNAs (dosage) for different types of CNVs overlapping miRNA genes. We also showed that, consistent with their essential biological functions, miRNA <it>loci </it>are underrepresented in highly polymorphic and well-validated CNV regions.</p> <p>Conclusion</p> <p>We postulate that CNV-miRNAs are potential functional variants and should be considered high priority candidate variants in genotype-phenotype association studies.</p

Epigenetic regulation of prostate cancer

Prostate cancer is a commonly diagnosed cancer in men and a leading cause of cancer deaths. Whilst the underlying mechanisms leading to prostate cancer are still to be determined, it is evident that both genetic and epigenetic changes contribute to the development and progression of this disease. Epigenetic changes involving DNA hypo- and hypermethylation, altered histone modifications and more recently changes in microRNA expression have been detected at a range of genes associated with prostate cancer. Furthermore, there is evidence that particular epigenetic changes are associated with different stages of the disease. Whilst early detection can lead to effective treatment, and androgen deprivation therapy has a high response rate, many tumours develop towards hormone-refractory prostate cancer, for which there is no successful treatment. Reliable markers for early detection and more effective treatment strategies are, therefore, needed. Consequently, there is a considerable interest in the potential of epigenetic changes as markers or targets for therapy in prostate cancer. Epigenetic modifiers that demethylate DNA and inhibit histone deacetylases have recently been explored to reactivate silenced gene expression in cancer. However, further understanding of the mechanisms and the effects of chromatin modulation in prostate cancer are required. In this review, we examine the current literature on epigenetic changes associated with prostate cancer and discuss the potential use of epigenetic modifiers for treatment of this disease

RESEARCH REGARDING THE USE OF COLD IN CEREALS STORAGE

This paper addresses to one of the main problems faced by 21st century farmers, namely to cut the cost of storing cereal products, in order to get the most profit from after marketing the product. The purpose of the paper was to make a comparison between the various methods of grain storage so as to reduce as much as possible the expenses related to the storage of the cereals

Polimorphism screening using a vntr molecular marker system in romanian resident bison individuals

Genomic DNA isolated from the blood sampled from 14 individuals of Bison bonasus was used in order to obtain a molecular fingerprint and based on that, to obtain a dendrogram exhibiting the phylogentic relationship among those individuals. By using the PCR technique and an VNTR ( Variabile Number of Tandem Repeats molecular markers system: ISSR (Inter simple sequence repeats) was used in this study for establish set of DNA fingerprints. Based on molecular data a common binary matrix was developed. By using DendroUPGMA software, based on Jaccard coefficient the similarity indices and the genetic distances were calculated. Based on those data set a dendrogram containig the phylogenetic relationship among bison exemplars, was generated. By analyzing the molecular data it was observed that the degree of polymorphism was either absent or very low especially in this case, our recorded data suggest that among Romanian resident Bison exemplars, there is a high level of genetic similarity meaning that the individuals are most probably close blood relatives