PROBLEMI DI CLUSTERING CON VINCOLI: ALGORITMI E COMPLESSIT\uc0

This thesis introduces and studies the problem of 1-dimensional bounded clustering: for any fixed p 65 1, given reals x1, x2\u2026, xn, and integers k1, k2.., km, determine the partition (A1, A2\u2026 Am) of {1, 2, ..., n} with |A1| = k1, |A2| = k2 , \u2026 , |Am| = km which minimizes \u3a3k \u3a3i\uf0ce Ak |xi - \u3bck |p where \u3bck is the p-centroid of Ak First, we prove that the optimum partition is contiguous (String Property), that is if i,j \uf0ce Ak, and xi < xs < xj, then s \uf0ce Ak . As a consequence, we determine an efficient algorithm for bi-clustering (if p is an integer); however, we show that the general problem is NP-complete, while a relaxed version of it admits a polynomial-time algorithm. When p is not an integer, we prove that the problem of deciding if the centroid \u3bc is less than a given integer is in the Counting Hierarchy CH. As an application, the relaxed clustering algorithm used as a step for solving a problem in the field of Bioinformatics: the Localization of promoter regions in genomic sequences. The results are compared with those obtained through another methodology (MADAP)

Effect of dietary nitrogen level and source on mRNA expression of urea transporters in the rumen epithelium of fattening bulls

This paper aims to study the effect of the dietary treatments on mRNA expression of urea transporter B (UT-B) and some aquaporins (AQP) in rumen epithelium of Italian Simmental young bulls. Eighty animals allocated to 16 pens were fed from about 500 to 650&nbsp;kg body weight with four experimental diets, which resulted from the combination of two crude protein levels (125 and 110&nbsp;g/kg dry matter, diets M and L, respectively) and two nitrogen sources (soybean meal (SBM) or SBM partly replaced by an isonitrogenous mixture of corn and urea; diets −U and +U, respectively). At slaughtering samples of blood and rumen epithelium were collected from six bulls for each diet. Blood samples were analysed for haematological parameters and quantitative PCR was carried out on the mRNA extracted from the rumen epithelium samples. The bulls fed diets M had lower plasma concentrations of aspartate aminotransferase than those receiving diets L (78.9 vs. 88.3&nbsp;U/l, p&nbsp;=&nbsp;0.04). Plasma urea was higher (p&nbsp;=&nbsp;0.03) for diets M and lower for diets +U (2.0 vs. 2.5 and 1.73 vs. 2.00&nbsp;mmol/l, respectively, in M and L diets, p&nbsp;=&nbsp;0.04). The effect of dietary treatments on rumen UT expression were limited to AQP3, which was down regulated (p&nbsp;=&nbsp;0.01) in diets +U. Finally, a high positive correlation (R2&nbsp;=&nbsp;0.871) between the expressions of AQP7 and AQP10 was found. In conclusion, the AQP3 appears very responsive to dietary treatments and therefore it is a candidate to be further studied in rumen metabolism experiments. The close relationship between mRNA expression of AQP7 and AQP10 indicates a similar function of these two proteins

Aflatoxin occurrence in goat milk and supplied concentrate feed in farms of Veneto, Trentino and Friuli Venezia Giulia

Aflatoxin M1 (AFM1) is a probable human hepatocarcinogen (IARC, monographs on the evaluation of carcinogenic risks to human. Vol. 56, 1993) found in milk of animals that consume feeds contaminated with aflatoxin B1 (AFB1), produced by fungi of genus Aspergillus. There is little information about goat milk: the aim of this study was to examine the level of contamination of milk, and related concentrate feed, in goat farms of Veneto, Trentino and Friuli Venezia Giulia. In 2005 and 2006, during the lactation period, 79 samples of total daily milk and 125 concentrate feed samples (principally maize and concentrate feeds), collected in 17 goat farms of Triveneto, were analysed for the content of AFM1 and AFB1 respectively, by HPLC technique. Concerning the milk samples, only one-third of total samples exceed the analytical reliability level (3 ppt), 14 of which were positioned under the value of 9 ppt and only 1 sample was over the value of 27 ppt.With regard to the feed samples, the two-thirds of total samples exceed the analytical reliability level (0.1 ppb), 54 of which had a value lower than 1 ppb and only 1 had a value higher than 10 ppb. The relation between levels of aflatoxin in milk and feeds was also considered: there is a significant correlation that confirms the role of feeds in the contamination of milk. All the samples had values lower than the maximum limit established by Italian law concerning the content of aflatoxins in milk for human diet and the content of aflatoxin in the concentrates for the goat diet (AFM1: 50 ppt; AFB1: 20 ppb), showing a general situation of absence of risk for animal and human health, with only few cases to keep under control. The results are in accordance with the situation found in other regions of North Italy (Regione Lombardia, 2003-2005), where, also in the dairy cow sector, there was a reduction of aflatoxin contamination risk in 2005 after two years of high levels of contamination of the maize and of the milk

Effect of heat stress on dairy cow performance and on expression of protein metabolism genes in mammary cells

The aim of this study was to assess the effect of heat stress on dairy cow performance and on the expression of selected genes involved in milk protein metabolism. Eight Italian Holstein Friesian cows were kept under thermoneutral conditions (temperature\u2013humidity index (THI) 0.05), CSN3 (p > 0.05), HSPA8 (p > 0.05), and STAT5B (p > 0.05) mRNA. Mild heat stress reduced the performance of dairy cows without affecting the expression of genes coding for caseins

Ataxia with oculomotor apraxia type 2: a clinical, pathologic, and genetic study

BACKGROUND: Ataxia with oculomotor apraxia type 2 (AOA2) is characterized by onset between age 10 and 22 years, cerebellar atrophy, peripheral neuropathy, oculomotor apraxia (OMA), and elevated serum alpha-fetoprotein (AFP) levels. Recessive mutations in SETX have been described in AOA2 patients. OBJECTIVE: To describe the clinical features of AOA2 and to identify the SETX mutations in 10 patients from four Italian families. METHODS: The patients underwent clinical examination, routine laboratory tests, nerve conduction studies, sural nerve biopsy, and brain MRI. All were screened for SETX mutations. RESULTS: All the patients had cerebellar features, including limb and truncal ataxia, and slurred speech. OMA was observed in two patients, extrapyramidal symptoms in two, and mental impairment in three. High serum AFP levels, motor and sensory axonal neuropathy, and marked cerebellar atrophy on MRI were detected in all the patients who underwent these examinations. Sural nerve biopsy revealed a severe depletion of large myelinated fibers in one patient, and both large and small myelinated fibers in another. Postmortem findings are also reported in one of the patients. Four different homozygous SETX mutations were found (a large-scale deletion, a missense change, a single-base deletion, and a splice-site mutation). CONCLUSIONS: The clinical phenotype of oculomotor apraxia type 2 is fairly homogeneous, showing only subtle intrafamilial variability. OMA is an inconstant finding. The identification of new mutations expands the array of SETX variants, and the finding of a missense change outside the helicase domain suggests the existence of at least one more functional region in the N-terminus of senataxin

Novel mutation of SACS gene in a Spanish family with autosomal recessive spastic ataxia

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an inherited neurodegenerative disorder characterized by early-onset, spastic ataxia and peripheral neuropathy. It was originally described in an inbred population of Quebec and later in some other countries. We report a new missense SACS mutation (7848C>T) in a Spanish family whose phenotype is similar to that of the previously described ARSACS patients. 7848C>T is the first SACS mutation reported in Spain confirming worldwide distribution of the disease. (c) 2005 Movement Disorder Society

Body mass index in HER2-negative metastatic breast cancer treated with first-line paclitaxel and bevacizumab

The evidence emerged from the TOURANDOT trial encourages evaluating the role of anthropometric determinants on treatment outcomes in HER2-negative metastatic breast cancer patients treated with bevacizumab-including regimens. We thus analyzed data from a subgroup of these patients from a larger cohort previously assessed for treatment outcomes. Patients were included in the present analysis if body mass index values had been recorded at baseline. Clinical benefit rates, progression free survival and overall survival were assessed for the overall study population and subgroups defined upon molecular subtype. One hundred ninety six patients were included (N:196). Body mass index showed no impact on clinical benefit rates in the overall study sample and in the luminal cancer subset (p = 0.12 and p = 0.79, respectively), but did so in the triple negative subgroup, with higher rates in patients with body mass index ≥25 (p = 0.03). In the overall study sample, body mass index did no impact progression free or overall survival (p = 0.33 and p = 0.67, respectively). Conversely, in triple negative patients, progression free survival was significantly longer with body mass index ≥25 (6 vs 14 months, p = 0.04). In this subset, overall survival was more favorable (25 vs 19 months, p = 0.02). The impact of the molecular subtype was confirmed in multivariate models including the length of progression free survival, and number of metastatic sites (p &lt; 0.0001). Further studies are warranted to confirm our findings in more adequately sized, ad hoc, prospective studies

Growth hormone- and pressure overload-induced cardiac hypertrophy evoke different responses to ischemia-reperfusion and mechanical stretch.

Objective. To compare the molecular, histological, and functional characteristics of growth hormone (GH)- and pressure overload-induced cardiac hypertrophy, and their responses to ischemia-reperfusion and mechanical stretch. Design. Four groups of male Wistar rats were studied: aortic banding (n = 24, AB) or sham (n = 24, controls) for 10 weeks, and GH treatment (n = 24; 3.5 mg/kg/day, GH) or placebo (n = 24, controls) for 4 weeks. At 13 weeks, the rats were randomly subjected to: (i) assessment of basal left ventricular mRNA expression of sarcoplasmic reticulum calcium-ATPase (SERCA-2), phospholamban (PLB), and Na+-Ca2+ exchanger (NCX) and collagen volume fraction (CVF) (Protocol A, 8 rats in each group); (ii) left ventricular no-flow ischemia with simultaneous evaluation of intracellular Ca2+ handling and ATP, phosphocreatine (PCr) and inorganic phosphate (Pi) content (Protocol B, 12 rats in each group),- or (iii) left ventricular mechanical stretch for 40 min with assessment of tumor necrosis-alpha (TNF-alpha) mRNA (Protocol C, 4 rats in each group). Protocol B and C were carried out in a Langendorff apparatus. Results. In Protocol A. no difference was found as to myocardial mRNA content of Ca2+ regulating proteins and CVF in GH animals vs controls. In contrast. in the AB group, myocardial mRNA expression of SERCA-2 and PLB was downregulated while that of NCX and CVF were increased vs. controls (p < 0.05). In Protocol B, recovery of left ventricular function was significantly decreased in AB vs GH goups and controls and this was associated with 1.6-fold increase in intracellular Ca2+ overload during reperfusion (p < 0.05). Baseline ATP content was similar in the four study groups, whereas PCr and Pi was lower in AB vs GH rats and controls. However, the time courses of high-energy phosphate metabolic changes did not differ during ischemia and reperfusion in the four study groups. In Protocol C, no detectable TNF-alpha mRNA level was found in the left ventricular myocardium of GH treated rats and controls at baseline, while a modest expression was noted in AB animals. Mechanical stretch resulted in de novo myocardial TNF-a mRNA expression in GH group and controls, which was dramatically increased in AB animals (approximate to 5-fold above baseline, p < 0.001). Conclusions. The data show that cardiac hypertrophy activated by short-term GH treatment confers cardioprotection compared with pressure overload with regard to molecular and histological characteristics, and responses to ischemia-reperfusion and mechanical stretch

Dimethyl fumarate dosing in humans increases frataxin expression: A potential therapy for Friedreich's Ataxia.

Friedreich’s Ataxia (FA) is an inherited neurodegenerative disorder resulting from decreased expression of the mitochondrial protein frataxin, for which there is no approved therapy. High throughput screening of clinically used drugs identified Dimethyl fumarate (DMF) as protective in FA patient cells. Here we demonstrate that DMF significantly increases frataxin gene (FXN) expression in FA cell model, FA mouse model and in DMF treated humans. DMF also rescues mitochondrial biogenesis deficiency in FA-patient derived cell model. We further examined the mechanism of DMF's frataxin induction in FA patient cells. It has been shown that transcription-inhibitory R-loops form at GAA expansion mutations, thus decreasing FXN expression. In FA patient cells, we demonstrate that DMF significantly increases transcription initiation. As a potential consequence, we observe significant reduction in both R-loop formation and transcriptional pausing thereby significantly increasing FXN expression. Lastly, DMF dosed Multiple Sclerosis (MS) patients showed significant increase in FXN expression by ~85%. Since inherited deficiency in FXN is the primary cause of FA, and DMF is demonstrated to increase FXN expression in humans, DMF could be considered for Friedreich's therapy.Friedreich’s ataxia Research Alliance (FARA