A simply connected surface of general type with p_g=0 and K^2=2

In this paper we construct a simply connected, minimal, complex surface of general type with p_g=0 and K^2=2 using a rational blow-down surgery and Q-Gorenstein smoothing theory.Comment: 19 pages, 6 figures. To appear in Inventiones Mathematica

Pancreatic transplant surgery and stem cell therapy: Finding the balance between therapeutic advances and ethical principles

The latest achievements in the field of pancreas transplantation and stem cell therapy require an effort by the scientific community to clarify the ethical implications of pioneering treatments, often characterized by high complexity from a surgical point of view, due to transplantation of multiple organs at the same time or at different times, and from an immunological point of view for stem cell therapy. The fundamental value in the field of organ transplants is, of course, a solidarity principle, namely that of protecting the health and life of people for whom transplantation is a condition of functional recovery, or even of survival. The nature of this value is that of a concept to which the legal discipline of transplants entrusts its own ethical dignity and for which it has ensured a constitutional recognition in different systems. The general principle of respect for human life, both of the donor and of the recipient, evokes the need not to put oneself and one's neighbor in dangerous conditions. The present ethical reflection aims to find a balance between the latest therapeutic advances and several concepts including the idea of the person, the respect due to the dead, the voluntary nature of the donation and the consent to the same, the gratuitousness of the donation, the scientific progress and the development of surgical techniques, and the policies of health promotion

Impaired implicit learning of syntactic structure in children with developmental language disorder:Evidence from syntactic priming

Background and aims Implicit learning mechanisms associated with detecting structural regularities have been proposed to underlie both the long-term acquisition of linguistic structure and a short-term tendency to repeat linguistic structure across sentences (structural priming) in typically developing children. Recent research has suggested that a deficit in such mechanisms may explain the inconsistent trajectory of language learning displayed by children with Developmental Learning Disorder. We used a structural priming paradigm to investigate whether a group of children with Developmental Learning Disorder showed impaired implicit learning of syntax (syntactic priming) following individual syntactic experiences, and the time course of any such effects. Methods Five- to six-year-old Italian-speaking children with Developmental Learning Disorder and typically developing age-matched and language-matched controls played a picture-description-matching game with an experimenter. The experimenter’s descriptions were systematically manipulated so that children were exposed to both active and passive structures, in a randomized order. We investigated whether children’s descriptions used the same abstract syntax (active or passive) as the experimenter had used on an immediately preceding turn (no-delay) or three turns earlier (delay). We further examined whether children’s syntactic production changed with increasing experience of passives within the experiment. Results Children with Developmental Learning Disorder’s syntactic production was influenced by the syntax of the experimenter’s descriptions in the same way as typically developing language-matched children, but showed a different pattern from typically developing age-matched children. Children with Developmental Learning Disorder were more likely to produce passive syntax immediately after hearing a passive sentence than an active sentence, but this tendency was smaller than in typically developing age-matched children. After two intervening sentences, children with Developmental Learning Disorder no longer showed a significant syntactic priming effect, whereas typically developing age-matched children did. None of the groups showed a significant effect of cumulative syntactic experience. Conclusions Children with Developmental Learning Disorder show a pattern of syntactic priming effects that is consistent with an impairment in implicit learning mechanisms that are associated with the detection and extraction of abstract structural regularities in linguistic input. Results suggest that this impairment involves reduced initial learning from each syntactic experience, rather than atypically rapid decay following intact initial learning. Implications Children with Developmental Learning Disorder may learn less from each linguistic experience than typically developing children, and so require more input to achieve the same learning outcome with respect to syntax. Structural priming is an effective technique for manipulating both input quality and quantity to determine precisely how Developmental Learning Disorder is related to language input, and to investigate how input tailored to take into account the cognitive profile of this population can be optimised in designing interventions

Del Pezzo surfaces with 1/3(1,1) points

We classify del Pezzo surfaces with 1/3(1,1) points in 29 qG-deformation families grouped into six unprojection cascades (this overlaps with work of Fujita and Yasutake), we tabulate their biregular invariants, we give good model constructions for surfaces in all families as degeneracy loci in rep quotient varieties and we prove that precisely 26 families admit qG-degenerations to toric surfaces. This work is part of a program to study mirror symmetry for orbifold del Pezzo surfaces.Comment: 42 pages. v2: model construction added of last remaining surface, minor corrections, minor changes to presentation, references adde

Helichrysum stoechas (L.) Moench reduces body weight gain and modulates mood disorders via inhibition of silent information regulator 1 (SIRT1) by arzanol

The prevalence of obesity is steadily rising, making safe and more efficient anti-obesity treatments an urgent medical need. Growing evidence correlates obesity and comorbidities, including anxiety and depression, with the development of a low-grade inflammation in peripheral and central tissues. We hypothesized that attenuating neuroinflammation might reduce weight gain and improve mood. We investigated the efficacy of a methanolic extract from Helichrysum stoechas (L.) Moench (HSE), well-known for its anti-inflammatory properties, and its main constituent arzanol (AZL). HPLC-ESI-MS2 and HPLC-UV were used to characterize the extract. HSE effects on mood and feeding behavior was assessed in mice. The mechanism of action of HSE and AZL was investigated in hippocampus samples and SH-SY5Y cells by western blotting and immunofluorescence. Oral administration of HSE for 3 weeks limited weight gain with no significant decrease in food intake. HSE produced an anxiolytic-like and antidepressant-like phenotype comparable to diazepam and amitriptyline, respectively, in the absence of locomotor and cognitive impairments and induced neuroprotective effects in glutamate-exposed SH-SY5Y cells. A dose-dependent reduction of SIRT1 expression was detected in SH-SY5Y cells and in hippocampal samples from HSE-treated mice. The inhibition of the SIRT1-FoxO1 pathway was induced in the hypothalamus. Molecular docking studies proposed a mechanism of SIRT1 inhibition by AZL, confirmed by the evaluation of inhibitory effects on SIRT1 enzymatic activity. HSE limited weight gain and comorbidities through an AZL-mediated SIRT1 inhibition. These activities indicate HSE an innovative therapeutic perspective for obesity and associated mood disorders

Improving the Potency of N-Aryl-2,5-dimethylpyrroles against Multidrug-Resistant and Intracellular Mycobacteria

A series of N-phenyl-2,5-dimethylpyrrole derivatives, designed as hybrids of the antitubercular agents BM212 and SQ109, have been synthesized and evaluated against susceptible and drug-resistant mycobacteria strains. Compound 5d, bearing a cyclohexylmethylene side chain, showed high potency against M. tuberculosis including MDR-TB strains at submicromolar concentrations. The new compound shows bacteriostatic activity and low toxicity and proved to be effective against intracellular mycobacteria too, showing an activity profile similar to isoniazid

Novel ester and acid derivatives of the 1,5-diarylpyrrole scaffold as anti-inflammatory and analgesic agents. Synthesis and in vitro and in vivo biological evaluation.

A new generation of selective cyclooxygenase-2 (COX-2) inhibitors (coxibs) was developed to circumvent the major side effects of cyclooxygenase-1 (COX-1) and COX-2 inhibitors (stomach ulceration and nephrotoxicity). As a consequence, coxibs are extremely valuable in treating acute and chronic inflammatory conditions. However, the use of coxibs, such as rofecoxib (Vioxx), was discontinued because of the high risk of cardiovascular adverse events. More recent clinical findings highlighted how the cardiovascular toxicity of coxibs could be mitigated by an appropriate COX-1 versus COX-2 selectivity. We previously reported a set of substituted 1,5-diarylpyrrole derivatives, selective for COX-2. Here, we describe the synthesis of new1,5-diarylpyrroles along with their inhibitory effects in vitro, ex vivo, and in vivo toward COX isoenzymes and their analgesic activity. Isopropyl-2-methyl-5-[4- (methylsulfonyl)phenyl]-1-phenyl-1H-pyrrole-3-acetate (10a), a representative member of the series, was selected for pharmacokinetic and metabolic studies