837 research outputs found

    The Water Properties of the Site in Capo Passero using the LED Beacon of the Prototype Tower

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    In that work we study the scattering parameters of the water on the KM3Net site in Capo Passero. To this purpose we compare the real data from the time calibration runs of the detector to the results of a simulations of the light emission, propagation and detection according to the expeimental apparatus

    Treatment of HER2+ metastatic salivary ductal carcinoma in a pregnant woman: a case report

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    Salivary duct carcinoma (SDC) is a rare and aggressive malignancy with a high mortality and poor response to treatment in the advanced setting. Human epidermal growth factor 2 (HER2) can be amplified in a fraction of SDC. We describe the case of HER2+ metastatic SDC of the submandibular gland in a young pregnant woman treated by multimodal treatment (chemotherapy, radiotherapy and targeted therapy). During pregnancy, a 27-year-old woman developed SDC of the left submandibular gland with lung and bone metastases. Given the HER2 overexpression, she was treated with trastuzumab, paclitaxel and cisplatin. Since the tumor had arisen during pregnancy, triptorelin was administered after delivery. A complete remission was observed, and after eight cycles of chemotherapy, radiotherapy was started in association with trastuzumab and triptorelin. A prolonged disease control and complete visceral remission were observed. Multimodal therapy based on patient's tumor characteristics showed good clinical efficacy in the treatment of metastatic SDC

    Modulation of CYP1A1 by PKC Inhibitors and TPA Pre-Treatments in MH1C1 Rat Hepatoma Cells Exposed to 3 -Methylcholanthrene

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    Cytochrome P4501A1 (CYP1A1), an enzyme known to metabolize polycyclic aromatic hydrocarbons, is regulated by the aryl hydrocarbon receptor (AhR). The involvement of protein kinase C (PKC) in the regulation of AhR signal transduction pathway, has been widely studied but the role of specific PKC isoform(s) involved in this process it is not well clarified. To study which PKC isoform(s) is implicated in the regulation of CYP1A1, in the poorly tumorigenic MH1C1 rat hepatoma cells, we examined the effects of some PKC pharmacological inhibitors, Calphostin C (CAL), Staurosporine (STA) and H7, and of 12-0-tetradecanoyl phorbol 13-acetate (TPA), a PKC activator, on basal and 3- methylcholanthrene (MC)-induced CYP1A1 protein expression and mediated ethoxyresorufin O-deethylation (EROD) activity. In parallel, the activities of PKC-α, -βI, -δ and -ε isoforms, the most expressed in MH1C1 cells, were monitored. After pre-treatment with CAL, STA and H7, the MC-induced CYP1A1 protein and EROD activity were rapidly reduced with temporal profile similar to the profile of the activity of α and β1 PKC isoforms. Moreover, TPA pre-treatment induced a biphasic effect on EROD activity, and a decline of PKC -βI and -α, in first instance, and -δ and -ε activities later on. These findings clearly show that, in MH1C1 cells, PKC is involved in CYP1A1 regulation and that α and βI classic PKC isoforms play an active role in modulating this process

    Genetic dissection of maize phenology using an intraspecific introgression library

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    Background: Collections of nearly isogenic lines where each line carries a delimited portion of a donor source genome into a common recipient genetic background are known as introgression libraries and have already shown to be instrumental for the dissection of quantitative traits. By means of marker-assisted backcrossing, we have produced an introgression library using the extremely early-flowering maize (Zea mays L.) variety Gasp\ue9 Flint and the elite line B73 as donor and recipient genotypes, respectively, and utilized this collection to investigate the genetic basis of flowering time and related traits of adaptive and agronomic importance in maize.Results: The collection includes 75 lines with an average Gasp\ue9 Flint introgression length of 43.1 cM. The collection was evaluated for flowering time, internode length, number of ears, number of nodes (phytomeres), number of nodes above the ear, number and proportion of nodes below the ear and plant height. Five QTLs for flowering time were mapped, all corresponding to major QTLs for number of nodes. Three additional QTLs for number of nodes were mapped. Besides flowering time, the QTLs for number of nodes drove phenotypic variation for plant height and number of nodes below and above the top ear, but not for internode length. A number of apparently Mendelian-inherited phenotypes were also observed.Conclusions: While the inheritance of flowering time was dominated by the well-known QTL Vgt1, a number of other important flowering time QTLs were identified and, thanks to the type of plant material here utilized, immediately isogenized and made available for fine mapping. At each flowering time QTL, early flowering correlated with fewer vegetative phytomeres, indicating the latter as a key developmental strategy to adapt the maize crop from the original tropical environment to the northern border of the temperate zone (southern Canada), where Gasp\ue9 Flint was originally cultivated. Because of the trait differences between the two parental genotypes, this collection will serve as a permanent source of nearly isogenic materials for multiple studies of QTL analysis and cloning. \ua9 2011 Salvi et al; licensee BioMed Central Ltd

    Advanced Glycation End-Products and Hyperglycemia Increase Angiopoietin-2 Production by Impairing Angiopoietin-1-Tie-2 System

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    The angiopoietin-Tie-2 system plays a crucial role in the maintenance of endothelial integrity. Hyperglycemia and advanced glycation end-products (AGEs) are involved in endothelial cell dysfunction responsible of the pathogenesis of microvascular complications of diabetes. Here, we investigated whether glycated serum (GS) or hyperglycemia (HG) affect the angiopoietin-Tie-2 system in the microvascular endothelial cells HMEC-1. We found that culture for 5 days in the presence of AGEs and HG (alone or in combination) decreased cell proliferation, increased reactive oxygen species (ROS) production, and reduced ratio between the oxidized and the reduced form of glutathione. Since angiopoietin-1 (Ang-1) signaling regulates angiopoietin-2 (Ang-2) expression through inactivation of the forkhead transcription factor FoxO1, we investigated intracellular signaling of Ang-1 and expression of Ang-2. HG and AGEs reduced phosphorylation of Akt and abrogated phosphorylation of FoxO1 induced by Ang-1 without affecting neither Tie-2 expression nor its activation. Furthermore, AGEs and/or HG induced nuclear translocation of FoxO1 and increased Ang-2 production. In conclusion, we demonstrated that both hyperglycemia and AGEs affect the angiopoietin-Tie-2 system by impairing Ang-1/Tie-2 signaling and by increasing Ang-2 expression. These results suggest that therapeutic strategies useful in preventing or delaying the onset of diabetic vascular complications should be aimed to preserve Ang-1 signaling

    Game theory and partner representation in joint action: toward a computational theory of joint agency

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    The sense of agency – the subjective feeling of being in control of our own actions – is one central aspect of the phenomenology of action. Computational models provided important contributions toward unveiling the mechanisms underlying the sense of agency in individual action. In particular, the sense of agency is believed to be related to the match between the actual and predicted consequences of our own actions (comparator model). In the study of joint action, models are even more necessary to understand the mechanisms underlying the development of coordination strategies and how the subjective experiences of control emerge during the interaction. In a joint action, we not only need to predict the consequences of our own actions; we also need to predict the actions and intentions of our partner, and to integrate these predictions to infer their joint consequences. Understanding our partner and developing mutually satisfactory coordination strategies are key components of joint action and in the development of the sense of joint agency. Here we discuss a computational architecture which addresses the sense of agency during intentional, real-time joint action. We first reformulate previous accounts of the sense of agency in probabilistic terms, as the combination of prior beliefs about the action goals and constraints, and the likelihood of the predicted movement outcomes. To look at the sense of joint agency, we extend classical computational motor control concepts - optimal estimation and optimal control. Regarding estimation, we argue that in joint action the players not only need to predict the consequences of their own actions, but also need to predict partner’s actions and intentions (a ‘partner model’) and to integrate these predictions to infer their joint consequences. As regards action selection, we use differential game theory – in which actions develop in continuous space and time - to formulate the problem of establishing a stable form of coordination and as a natural extension of optimal control to joint action. The resulting model posits two concurrent observer-controller loops, accounting for ‘joint’ and ‘self’ action control. The two observers quantify the likelihoods of being in control alone or jointly. Combined with prior beliefs, they provide weighing signals which are used to modulate the ‘joint’ and ‘self’ motor commands. We argue that these signals can be interpreted as the subjective sense of joint and self agency. We demonstrate the model predictions by simulating a sensorimotor interactive task where two players are mechanically coupled and are instructed to perform planar movements to reach a shared final target by crossing two differently located intermediate targets. In particular, we explore the relation between self and joint agency and the information available to each player about their partner. The proposed model provides a coherent picture of the inter-relation of prediction, control, and the sense of agency in a broader range of joint actions

    Mapping genetic factors for resistance to Soil-borne cereal mosaic virus (SBCMV) in durum wheat

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    Article first published online: 8 FEB 2014OBJECTIVE: In an unselected group of women with signs of preterm labour, maintenance tocolysis is not effective in the prevention of preterm birth and does not improve neonatal outcome. Among women with signs of preterm labour, those who are fetal fibronectin positive have an increased risk of preterm birth. We investigated whether maintenance tocolysis with nifedipine would delay delivery and improve neonatal outcome in women with threatened preterm labour and a positive fetal fibronectin status. STUDY DESIGN: Women with a singleton pregnancy in threatened preterm labour (24(+0) to 33(+6)  weeks) with a positive fetal fibronectin test were randomised to nifedipine or placebo. Study medication was continued until 36 completed weeks' gestation. The primary endpoint was prolongation of pregnancy of seven days. Secondary endpoints were gestational age at delivery and length of NICU admission. RESULTS: Of the 60 participants, 29 received nifedipine and 31 placebo. Prolongation of pregnancy by >7 days occurred in 22/29 (76%) in the nifedipine group and 25/31 (81%) in the placebo group (relative risks, RR 0.94 [0.72-1.2]). Gestational age at delivery was 36.1 ± 5.1 weeks for nifedipine and 36.8 ± 3.6 weeks for placebo (P = 0.027). Length of NICU admission [median (interquartile ranges, IQR)] was 27 (24-41) days and 16 (8-37) days in nifedipine and placebo groups, respectively (P = 0.17). CONCLUSION: In women with threatened preterm labour who are fetal fibronectin positive, maintenance tocolysis with nifedipine does not seem to prolong pregnancy, nor reduce length of NICU admission.Emma Parry, Carolien Roos, Peter Stone, Lynsey Hayward, Ben Willem Mol and Lesley McCowa

    Management of prostate cancer radiotherapy during the COVID-19 pandemic: A necessary paradigm change

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    Purpose: To adapt the management of prostate malignancy in response to the COVID-19 pandemic. Methods: In according to the recommendations of the European Association of Urology, we have developed practical additional document on the treatment of prostate cancer. Results: Low-Risk Group Watchful Waiting should be offered to patients >75 years old, with a limited life expectancy and unfit for local treatment. In Active Surveillance (AS) patients re-biopsy, PSA evaluation and visits should be deferred for up to 6 months, preferring non-invasive multiparametric-MRI. The active treatment should be delayed for 6–12 months. Intermediate-Risk Group AS should be offered in favorable-risk patients. Short-course neoadjuvant androgen deprivation therapy (ADT) combined with ultra-hypo-fractionation radiotherapy should be used in unfavorable-risk patients. High-Risk Group Neoadjuvant ADT combined with moderate hypofractionation should be preferred. Whole-pelvis irradiation should be offered to patients with positive lymph nodes in locally advanced setting. ADT should be initiated if PSA doubling time is < 12 months in radio-recurrent patients, as well as in low priority/low volume of metastatic hormone sensitive prostate cancer. If radiotherapy cannot be delayed, hypo-fractionated regimens should be preferred. In high priority class metastatic disease, treatment with androgen receptor-targeted agents should be offered. When palliative radiotherapy for painful bone metastasis is required, single fraction of 8 Gy should be offered. Conclusions: In Covid-19 Era, the challenge should concern a correct management of the oncologic patient, reducing the risk of spreading the virus without worsening tumor prognosis
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