Role of Antenna Modes and Field Enhancement in Second Harmonic Generation from Dipole Nanoantennas

We study optical second harmonic generation from metallic dipole antennas with narrow gaps. Enhancement of the fundamental-frequency field in the gap region plays a marginal role on conversion efficiency. In the symmetric configuration, i.e., with the gap located at the center of the antenna axis, reducing gap size induces a significant red-shift of the maximum conversion efficiency peak. Either enhancement or inhibition of second-harmonic emission may be observed as gap size is decreased, depending on the antenna mode excited at the harmonic frequency. The second-harmonic signal is extremely sensitive to the asymmetry introduced by gap’s displacements with respect to the antenna center. In this situation, second-harmonic light can couple to all the available antenna modes. We perform a multipolar analysis that allows engineering the far-field SH emission and find that the interaction with quasi-odd-symmetry modes generates radiation patterns with a strong dipolar component

IDO1 involvement in mTOR pathway: A molecular mechanism of resistance to mTOR targeting in medulloblastoma

Medulloblastoma (MB) is the most common malignant brain tumor in children. Despite therapeutic advancements, high-risk groups still present significant mortality. A deeper knowledge of the signaling pathways contributing to MB formation and aggressiveness would help develop new successful therapies. The target of rapamycin, mTOR signaling, is known to be involved in MB and is already targetable in the clinical setting. Furthermore, mTOR is a master metabolic regulator able to control cell growth versus autophagy decisions in conditions of amino-acid deprivation that can be due to IDO1 enzymatic activity. IDO1 has been also implicated in the regulation of inflammation, as well as of T cell-mediated immune responses, in a variety of pathological conditions, including brain tumors. In particular, IDO1 induces expansion of regulatory T-cells (Treg), preventing immune response against tumor cells. Analysis of 27 MB tissue specimens for the expression of both mTOR and IDO1 showed their widespread expression in all samples. Testing their cooperation in vitro, a significant involvement of IDO1 in mTOR immunogenic pathway was found, able to counteract the aim of rapamycin treatment. In MB cell lines, inhibition of mTOR strongly induced IDO1 expression and activity, corroborating its ability to recruit Treg cells in the tumor microenvironment. The mTOR/IDO1 cross talk was found to be strictly specific of MB cells. We demonstrated that mTOR pathway cross talks with IDO1 pathway to promote MB immune escape, possibly contributing to failure of mTOR- targeted therapy

Les entrepreneurs italiens, leurs organizations et le Conseil supérieur du travail (1902-1923)

The paper examines the relationships and the concerns among business association, workers' organizations and ministerial bureaucracy at the beginning of XXth century: in particular it analyzes the activity of the Consiglio Superiore del Lavoro (the Superior Council for Labour, hereafter CSL) with regard of the issues of working conditions and social legislation. The CSL, established in 1902 by Zanardelli-Giolitti's government and suppressed in 1923 by Mussolini, should have been the first example of official participation of “social movements” to a job policy by institutions. The Italian administrative system followed the Napoleonic experience and the CSL was realized on the same French model. The life of CSL was in an intensive phase of national history: the “reformism” of Giolitti's era and the complex postwar, with a deep social crisis until the end of liberal system and the birth of the first Mussolini’s government. The CSL was mainly involved in programs of job organization and in social legislation (legislative discipline of work, collective contracts, arbitration, legal recognition of unions) with the involvement of economic and social leaders (e.g. Filippo Turati, leader of Socialist Party or Giovanni Montemartini, supporter of public utilities). Many reports of CSL didn't find a real application. In several cases, on the basis of pressure from the business system, the government and in particular the Prime Minister Giolitti did not accept the proposals made by the Committee of CSL and officials of the Ministry of Agriculture, Industry and Commerce. These projects were evaluated too favorable to the positions of Unions. Moreover, in the pre-war phase the action of lobbying on the government seems to be more linked to the initiative of individual industrial than to the formal action of BIAs. So far, Italian historians have studied the CSL on social and trade union issues as well as in political matters for the transformation of the liberal state. Scholars studied the political context of the CSL project, from the topic of child labour to the public utilities and, at the same time, they described the “hard path” and the gradual decline of this structure of the Savoy state. The historians discussed on the alternative perspectives of the CSL, too. According to the “liberal class” the Council was a device to enlarge the social partnership with a state action while socialist politicians planned an institution in competition with the others of the State. The essential feature was the disappearance of the separation between political and administrative organisms while the bureaucratic power had direct political goals.Furthermore, the administrative cooperation was among associations with different identities and goals and – and above all for the CSL - between the conflicting interests of capital and labor. Moreover, the relation of entrepreneurs with the administrative apparatus of the Ministry was in a phase where there was no distinction between political bodies and technical bodies, so the high bureaucracy also had functions concerning the political framework. On the basis of the reports of the CSL, the paper discusses that the representatives of business organizations in the CSL should have an “antagonistic attitude”. Before the WWI, the industrial lobby in the Council wanted to introduce rules to reduce conflict in the workplace but also had a refusal to dialogue for social legislation made by trade unions and the Socialist Party. The first objective of entrepreneurs was the restraint of the public interference on productive activities. At the same time, the representatives of the manufacturing class consolidated their relations with the administrative system sharing solutions of mediation which later liberal governments blocked. In this sense, a more detailed analysis shows the hope by employers for a regulation of the labor market that did not reduce the powers of the entrepreneur in the management of the factory and this interpretation was similar to the proposals of the Ministry. At the same time, the BIAs supported the social spending that is covered in large part by public finance instead of the world of firms and work. Compared to these positions, the connection was with the trade unions, while the ministerial bureaucracy was attentive to the needs of the state budget. The paper debates if the work of delegates of business organizations in the CSL remains connected to a “mainstream view”: the main element of this overview was the efficient organization of labor and capital than the decrease of social conflict. The ministerial bureaucracy agreed with this “overview” and firstly took care of social order. Meanwhile the paper assesses the statement that, before WWI, the alliances between companies, partneships, consortiums, and last the formation of trusts were more important than the “collective action” (the consultation between social partners) and, furthermore, the protection of the interests of enterprises was mainly realized by the support of the government with a direct relationship between entrepreneurs and ministerial bureaucracy

Glutathione S-transferase homozygous deletions and relapse in childhood acute lymphoblastic leukemia: a novel study design in a large Italian AIEOP cohort

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Genetic predisposition to hemophagocytic lymphohistiocytosis: Report on 500 patients from the Italian registry.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disease affecting mostly children but also adults and characterized by hyperinflammatory features. A subset of patients, referred to as having familial hemophagocytic lymphohistiocytosis (FHL), have various underlying genetic abnormalities, the frequencies of which have not been systematically determined previously. OBJECTIVE: This work aims to further our understanding of the pathogenic bases of this rare condition based on an analysis of our 25 years of experience. METHODS: From our registry, we have analyzed a total of 500 unselected patients with HLH. RESULTS: Biallelic pathogenic mutations defining FHL were found in 171 (34%) patients; the proportion of FHL was much higher (64%) in patients given a diagnosis during the first year of life. Taken together, mutations of the genes PRF1 (FHL2) and UNC13D (FHL3) accounted for 70% of cases of FHL. Overall, a genetic diagnosis was possible in more than 90% of our patients with FHL. Perforin expression and the extent of degranulation have been more useful for diagnosing FHL than hemophagocytosis and the cytotoxicity assay. Of 281 (56%) patients classified as having "sporadic" HLH, 43 had monoallelic mutations in one of the FHL-defining genes. Given this gene dosage effect, FHL is not strictly recessive. CONCLUSION: We suggest that the clinical syndrome HLH generally results from the combined effects of an exogenous trigger and genetic predisposition. Within this combination, different weights of exogenous and genetic factors account for the wide disease spectrum that ranges from HLH secondary to severe infection to FHL.Supported by grants from Associazione Italiana Ricerca Istiocitosi (AIRI), Associazione Ciemmeesse-Girotondo per il Meyer, Ministero della Salute (Bando Malattie Rare RF-TOS-2008-1219488), and the Seventh Framework Programme (FP7) of the European Commission (“FIGHT-HLH” Project no. 306124 to M.A.). Disclosure of potential conflict of interest: D. Pende receives royalties paid to her institution. G. M. Griffiths has received research support from the Wellcome Trust. L. Luzzatto is on the Alexion Pharmaceuticals SAB and has received consultancy fees from GlaxoSmithKline.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.jaci.2015.06.04

Ewing Sarcoma of the Bone in Children under 6 Years of Age

BACKGROUND: Ewing Sarcoma Family Tumours (ESFT) are rare in early childhood. The aim of this study was to report the clinical characteristics and outcome of children under 6 years of age affected by ESFT of the bone in Italy. METHODS: The records of all the children diagnosed with osseous ESFT in centres members of the Associazione Italiana di Ematologia ed Oncologia Pediatrica (AIEOP) from 1990 to 2008 were reviewed. The Kaplan-Meier method was used for estimating overall and progression-free survival (OS, PFS) curves; multivariate analyses were performed using Cox proportional hazards regression model. RESULTS: This study includes 62 patients. An axial primary localization was present in 66% of patients, with the primary site in the chest wall in 34%. Fourteen (23%) patients presented metastatic disease. The 5-year OS and PFS were 73% (95% confidence interval, CI, 58-83%) and 72% (95% CI 57-83%) for patients with localized disease and 38% (95% CI 17-60%) and 21% (95% CI 5-45%) for patients with metastatic disease. Metastatic spread, skull/pelvis/spine primary localization, progression during treatment and no surgery predicted worse survival (P<0.01), while patients treated in the last decade had better survival (P = 0.002). In fact, the 5-year OS and PFS for patients diagnosed in the period 2000-2008 were 89% (95% CI 71-96%) and 86% (95% CI 66-94%), respectively. CONCLUSION: The axial localization is the most common site of ESFT in pre-scholar children. Patients treated in the most recent period have an excellent outcome

Quantitative Anatomic Comparison of Endoscopic Transnasal and Microsurgical Transcranial Approaches to the Anterior Cranial Fossa

BACKGROUND: Several microsurgical transcranial approaches (MTAs) and endoscopic transnasal approaches (EEAs) to the anterior cranial fossa (ACF) have been described. OBJECTIVE: To provide a preclinical, quantitative, anatomic, comparative analysis of surgical approaches to the ACF. METHODS: Five alcohol-fixed specimens underwent high-resolution computed tomography. The following approaches were performed on each specimen: EEAs (transcribriform, transtuberculum, and transplanum), anterior MTAs (transfrontal sinus interhemispheric, frontobasal interhemispheric, and subfrontal with unilateral and bilateral frontal craniotomy), and anterolateral MTAs (supraorbital, minipterional, pterional, and frontotemporal orbitozygomatic approach). An optic neuronavigation system and dedicated software (ApproachViewer, part of GTx-Eyes II-UHN) were used to quantify the working volume of each approach and extrapolate the exposure of different ACF regions. Mixed linear models with random intercepts were used for statistical analyses. RESULTS: EEAs offer a large and direct route to the midline region of ACF, whose most anterior structures (ie, crista galli, cribriform plate, and ethmoidal roof) are also well exposed by anterior MTAs, whereas deeper ones (ie, planum sphenoidale and tuberculum sellae) are also well exposed by anterolateral MTAs. The orbital roof region is exposed by both anterolateral and lateral MTAs. The posterolateral region (ie, sphenoid wing and optic canal) is well exposed by anterolateral MTAs. CONCLUSION: Anterior and anterolateral MTAs play a pivotal role in the exposure of most anterior and posterolateral ACF regions, respectively, whereas midline regions are well exposed by EEAs. Furthermore, certain anterolateral approaches may be most useful when involvement of the optic canal and nerves involvement are suspected