5,306 research outputs found
Design of the first Italian roundabout with jointed plain concrete pavement
This work presents the results of the overall design of the first Italian roundabout with jointed plain concrete pavement. The examined case study complies with current international standards and practices for geometry of roundabouts and road pavements. The construction of a concrete pavement in an urban roundabout will better manage and slow down fast vehicular flows, and increase traffic fluidity in an important junction, trafficked by heavy vehicles, where maintenance works should be reduced to avoid queues. The design of the roundabout involved several competences for: defining the geometry of the four-arm junction, designing the thickness of the jointed plain concrete pavement both on the circular crown and the arms, studying the mix design of a high resistance concrete. As regard to the pavement, the result of the study was an un-dowelled concrete pavement composed of square slabs laid on a cement concrete subbase and a granular layer. The shape of the slabs has been designed to optimize the structural performance of their material, which is a high strength concrete mix derived from an extensive laboratory test work. In general, the results summarized approaches typical of different design conditions: urban ones for traffic flow and safety needs; high-traffic ones for the chosen pavement type; airport ones for the absence of dowel and tie bars at the joints. Indeed, the article has highlighted that the design process of a concrete roundabout requires multiple analyses to consider various features and correctly re-design anexistingurbanjunction. Its geometrical design,the structural design of the concrete pavement and the theoretical and experimental design of the concrete mix were the main phases of this process and they needed different competences to conduct comprehensive and appropriate analyses
LA VALUTAZIONE ECONOMICO-FINANZIARIA DEL BRAND.IL CASO TRE MARIE
Prima di procedere con la brand valuation è necessario definire con chiarezza cosa si intende per brand, quindi qual è l'oggetto della valutazione; le ragioni che muovono la valutazione; l'approccio che vogliamo seguire nel processo di stima. A seconda dei vantaggi che il brand può apportare all'azienda, sarà seguito un approccio ai costi, al mercato oppure ai redditi
Changes in total choline concentration in the breast of healthy fertile young women in relation to menstrual cycle or use of oral contraceptives: a 3-T 1H-MRS study
BACKGROUND:
To evaluate changes in total choline (tCho) absolute concentration ([tCho]) in the breast of healthy fertile women in relation to menstrual cycle (MC) or use of oral contraceptives (OC).
METHODS:
After institutional review board approval, we prospectively evaluated 40 healthy fertile volunteers: 20 with physiological MC, aged 28 ± 3 years (mean ± standard deviation; nOC group); 20 using OC, aged 26 ± 3 years (OC group). Hormonal assays and water-suppressed single-voxel 3-T proton magnetic resonance spectroscopy (1H-MRS) were performed on MC days 7, 14, and 21 in the nOC group and only on MC day 14 in the OC group. [tCho] was measured versus an external phantom. Mann-Whitney U test and Spearman coefficient were used; data are given as median and interquartile interval.
RESULTS:
All spectra had good quality. In the nOC group, [tCho] (mM) did not change significantly during MC: 0.8 (0.3-2.4) on day 7, 0.9 (0.4-1.2) on day 14, and 0.4 (0.2-0.8) on day 21 (p = 0.963). In the OC group, [tCho] was 0.7 (0.2-1.7) mM. The between-groups difference was not significant on all days (p ≥ 0.411). All hormones except prolactin changed during MC (p ≤ 0.024). In the OC group, [tCho] showed a borderline correlation with estradiol (r = 0.458, p = 0.056), but no correlation with other hormones (p ≥ 0.128). In the nOC group, [tCho] negatively correlated with prolactin (r = -0.587, p = 0.006) on day 7; positive correlation was found with estradiol on day 14 (r = 0.679, p = 0.001).
CONCLUSIONS:
A tCho peak can be detected in the normal mammary gland using 3-T 1H-MRS. The [tCho] in healthy volunteers was 0.4-0.9 mM, constant over the MC and independent of OC use
Depletion of ATP-citrate lyase (ATPCL) affects chromosome integrity without altering histone acetylation in Drosophila mitotic cells
The Citrate Lyase (ACL) is the main cytosolic enzyme that converts the citrate exported from mitochondria by the SLC25A1 carrier in Acetyl Coenzyme A (acetyl-CoA) and oxaloacetate. Acetyl-CoA is a high-energy intermediate common to a large number of metabolic processes including protein acetylation reactions. This renders ACL a key regulator of histone acetylation levels and gene expression in diverse organisms including humans. We have found that depletion of Drosophila ATPCL, the fly ortholog of human ACL, reduced levels of Acetyl CoA but, unlike its human counterpart, does not affect global histone acetylation and gene expression. Nevertheless, reduced ATPCL levels caused evident, although moderate, mitotic chromosome breakage suggesting that this enzyme plays a partial role in chromosome stability. These defects did not increase upon X-ray irradiation, indicating that they are not dependent on an impairment of DNA repair. Interestingly, depletion of ATPCL drastically increased the frequency of chromosome breaks associated to mutations in scheggia, which encodes the ortholog of the mitochondrial citrate carrier SLC25A1 that is also required for chromosome integrity and histone acetylation. Our results indicate that ATPCL has a dispensable role in histone acetylation and prevents massive chromosome fragmentation when citrate efflux is altered
Marked efficacy of Rituximab in multifocal motor neuropathy associated with chronic lymphocytic leukemia
The authors describe a patient who presented a multifocal motor neuropathy (MMN) associated with a high anti-ganglioside antibody (anti-GM1 and anti-GD1) titer at the clinical onset of a B-cell chronic lymphocytic leukemia (B-CLL). Immunomodulation (IVIg plus cyclosporine) resulted in a neurological improvement and reduced anti-ganglioside antibody titers, both of which remained stable for at least six years. After this period, the patient had a severe relapse of the neuropathy, which was independent of the clinical course of the B-CLL. Both IVIg and cyclophosphamide were ineffective, and the patient became tetraplegic within six months; in the meantime, the patient displayed an increased antiganglioside antibody titer. Treatment with rituximab (RTX), which is designed to selectively inhibit B cell function, resulted in a dramatic, prompt and long-lasting neurological improvement as well as a reduced anti-ganglioside antibody titer. Although there are no previous reports of MMN in patients with B-CLL, the efficacy of RTX in the treatment of MMN in this patient may be considered remarkable. The expansion of B-cell clones may be a prerequisite for RTX effectiveness in MMN, and in dysimmune neuropathies in general
Marked efficacy of rituximab in multifocal motor neuropathy associated with chronic lymphocytic leukemia
The authors describe a patient who presented a multifocal motor neuropathy (MMN) associated with a
high anti-ganglioside antibody (anti-GM1 and anti-GD1) titer at the clinical onset of a B-cell chronic
lymphocytic leukemia (B-CLL). Immunomodulation (IVIg plus cyclosporine) resulted in a neurological
improvement and reduced anti-ganglioside antibody titers, both of which remained stable for at least six
years. After this period, the patient had a severe relapse of the neuropathy, which was independent of the
clinical course of the B-CLL. Both IVIg and cyclophosphamide were ineffective, and the patient became
tetraplegic within six months; in the meantime, the patient displayed an increased antiganglioside
antibody titer. Treatment with rituximab (RTX), which is designed to selectively inhibit B cell function,
resulted in a dramatic, prompt and long-lasting neurological improvement as well as a reduced antiganglioside
antibody titer. Although there are no previous reports of MMN in patients with B-CLL, the
eficacy of RTX in the treatment of MMN in this patient may be considered remarkable. The expansion of
B-cell clones may be a prerequisite for RTX effectiveness in MMN, and in dysimmune neuropathies in
general
Guilt Aversion: Eve versus Adam
Our study contributes to a large literature in experimental economics that explores gender differences in how people are motivated. We focus on guilt aversion (GA), a surprisingly rather unexplored issue. Our experiment supports the idea that men are more GA than women. Our results also support different rationales in explaining observed similar behaviors, e.g., promise keeping. We provide a potential intuition for our findings, which is based on the pregnancy-related biological asymmetry between genders
Animal models of tic disorders: A translational perspective
Tics are repetitive, sudden movements and/or vocalizations, typically enacted as maladaptive responses to intrusive premonitory urges. The most severe tic disorder, Tourette syndrome (TS), is a childhood-onset condition featuring multiple motor and at least one phonic tic for a duration longer than 1 year. The pharmacological treatment of TS is mainly based on antipsychotic agents; while these drugs are often effective in reducing tic severity and frequency, their therapeutic compliance is limited by serious motor and cognitive side effects.
The identification of novel therapeutic targets and development of better treatments for tic disorders is conditional on the development of animal models with high translational validity. In addition, these experimental tools can prove extremely useful to test hypotheses on the etiology and neurobiological bases of TS and related conditions. In recent years, the translational value of these animal models has been enhanced, thanks to a significant re-organization of our conceptual framework of neuropsychiatric disorders, with a greater focus on endophenotypes and quantitative indices, rather than qualitative descriptors.
Given the complex and multifactorial nature of TS and other tic disorders, the selection of animal models that can appropriately capture specific symptomatic aspects of these conditions can pose significant theoretical and methodological challenges. In this article, we will review the state of the art on the available animal models of tic disorders, based on genetic mutations, environmental interventions as well as pharmacological manipulations. Furthermore, we will outline emerging lines of translational research showing how some of these experimental preparations have led to significant progress in the identification of novel therapeutic targets for tic disorders
The Drosophila Citrate Lyase Is Required for Cell Division during Spermatogenesis
The Drosophila melanogaster DmATPCL gene encodes for the human ATP Citrate Lyase (ACL) ortholog, a metabolic enzyme that from citrate generates glucose-derived Acetyl-CoA, which fuels central biochemical reactions such as the synthesis of fatty acids, cholesterol and acetylcholine, and the acetylation of proteins and histones. We had previously reported that, although loss of Drosophila ATPCL reduced levels of Acetyl-CoA, unlike its human counterpart, it does not affect global histone acetylation and gene expression, suggesting that its role in histone acetylation is either partially redundant in Drosophila or compensated by alternative pathways. Here, we describe that depletion of DmATPCL affects spindle organization, cytokinesis, and fusome assembly during male meiosis, revealing an unanticipated role for DmATPCL during spermatogenesis. We also show that DmATPCL mutant meiotic phenotype is in part caused by a reduction of fatty acids, but not of triglycerides or cholesterol, indicating that DmATPCL-derived Acetyl-CoA is predominantly devoted to the biosynthesis of fatty acids during spermatogenesis. Collectively, our results unveil for the first time an involvement for DmATPCL in the regulation of meiotic cell division, which is likely conserved in human cells
Dolphin Morbillivirus in Eurasian Otters, Italy
We report biomolecular evidence of dolphin morbillivirus in 4 wild Eurasian otters (Lutra lutra) from southern Italy; 2 animals showed simultaneous immunohistochemical reactivity against morbilliviral antigen. These cases add further concern and support to the progressively expanding host range of dolphin morbillivirus in the western Mediterranean Sea
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