728 research outputs found

    Complexity in Work Identifications: the Case of the H-1B Worker in the United States

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    The H-1B visa program allows for United States employers to supplement their workforce with high-skilled foreign workers. Issues arise for these workers when transitioning their lives to the U.S because they have to adapt to a new culture and are exposed to a constantly changing work environment. This exploratory study addresses how these individuals identify with their employing organization and their clients. The findings show that the H-1B contract workers identify more with the client organization as opposed to the employer, who was viewed by the majority as the “payroll department.” Primary factors of such client identification include treatment and relationships with colleagues and managers. Personal factors include motivation and goals. Daily interaction with the client as well as a positive corporate culture had an impact on client identification as well. This study has important implications for both research and practice of management. Furthermore, this study is beneficial to employers seeking to ease the stress of employees joining their organization

    Tecnologías apropiadas para desinfección de agua.

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    La desinfección de agua es una necesidad de primer orden en las emergencias. Reseñamos una investigación sobre una tecnología con este objetivo que se adapta al contexto ambiental, social y económico, además de resultar sencilla en la aplicación y manejo, a escala reducida; no tiene impacto ambiental, es de bajo costo, implica la participación de las comunidades y utiliza materiales fáciles de encontrar. Ello la hace apropiada para la zona de Colombia donde se trabaja, ya que sufre bloqueo económico.Peer Reviewe

    NKAIN2 functions as a novel tumor suppressor in prostate cancer

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    We thank Orchid, Prostate Cancer UK, National Natural Science Foundation of China (No. 81328017), and Guangdong Provincial Science and Technology Projects of China (2013B051000050 and 2014A020212538) for funding support

    The MRN complex is transcriptionally regulated by MYCN during neural cell proliferation to control replication stress

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    The MRE11/RAD50/NBS1 (MRN) complex is a major sensor of DNA double strand breaks, whose role in controlling faithful DNA replication and preventing replication stress is also emerging. Inactivation of the MRN complex invariably leads to developmental and/or degenerative neuronal defects, the pathogenesis of which still remains poorly understood. In particular, NBS1 gene mutations are associated with microcephaly and strongly impaired cerebellar development, both in humans and in the mouse model. These phenotypes strikingly overlap those induced by inactivation of MYCN, an essential promoter of the expansion of neuronal stem and progenitor cells, suggesting that MYCN and the MRN complex might be connected on a unique pathway essential for the safe expansion of neuronal cells. Here, we show that MYCN transcriptionally controls the expression of each component of the MRN complex. By genetic and pharmacological inhibition of the MRN complex in a MYCN overexpression model and in the more physiological context of the Hedgehog-dependent expansion of primary cerebellar granule progenitor cells, we also show that the MRN complex is required for MYCN-dependent proliferation. Indeed, its inhibition resulted in DNA damage, activation of a DNA damage response, and cell death in a MYCN- and replication-dependent manner. Our data indicate the MRN complex is essential to restrain MYCN-induced replication stress during neural cell proliferation and support the hypothesis that replication-born DNA damage is responsible for the neuronal defects associated with MRN dysfunctions.Cell Death and Differentiation advance online publication, 12 June 2015; doi:10.1038/cdd.2015.81

    Identificazione in carica di frammenti nucleari nell'esperimento FOOT

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    Uno degli obiettivi dell’esperimento FOOT (FragmentatiOn Of Target) è quello di acquisire e analizzare dati sui processi di frammentazione in modo da rendere l’adroterapia un trattamento il più sicuro ed efficace possibile. In questa tesi ho analizzato i dati acquisiti ai laboratori del GSI relativi all’interazione tra un fascio di ioni 16O a 400 MeV/u e un bersaglio di grafite, concentrandomi sull’identificazione in carica dei frammenti prodotti nell’interazione. L’analisi ha evidenziato che gran parte delle particelle rivelate (≃90%) risultano essere ioni ossigeno del fascio primario che non hanno subito processi di frammentazione. Questo importate risultato iniziale permette di stimare la probabilità cumulativa di frammentazione dell’ossigeno su carbonio. Al fine di constatare la validità dell’analisi ho stimato la risoluzione con la quale è stato possibile ricostruire la carica delle particelle e ho verificato che soddisfacesse i requisiti dell’esperimento di una risoluzione del 2-3% sulla carica. Ho ottenuto risultati compatibili per la risoluzione sulla carica delle particelle con Z ≥2, ma non del protone, per il quale ho stimato una risoluzione ≃1

    Mitografia e storia dei plebisciti di unificazione nelle due Sicilie

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    Il saggio indaga in modo critico origini e fortune (anche recenti) del discorso di delegittimazione dei plebisciti di unificazione svoltisi il 21 e 22 ottobre 1860 nelle Due Sicilie, con particolare attenzione al caso di studio delle province continentali dell’ex Regno borbonico. L’intento è quello di considerare queste pratiche di voto come un modo storicamente peculiare di apprendistato politico e mobilitazione popolare, dal profilo tanto partecipativo e inclusivo (anche verso soggetti normativamente esclusi dal corpo elettorale come donne e minori) quanto olistico, a-deliberativo e marcato da una personalizzazione della politica che si incarna in figure monocratiche e carismatiche. Un’adeguata comprensione del plebiscito meridionale non può, infatti, prescindere, in primo luogo, da un’analisi che lo collochi nel contesto delle coeve e successive analoghe esperienze europee (e più in generale delle dinamiche elettorali democratizzate fra XVIII e XIX secolo); secondariamente, da una lettura alla luce del lungo e articolato processo di “civilizzazione elettorale”, ovvero della definizione di tecnologie e pratiche del suffragio intese a forcludere la violenza politica, incanalando e ordinando normativamente l’esercizio, altrimenti scomposto, della sovranità popolare.The paper is a critical investigation of the origins and fortunes (including recent developments) of the discourse of delegitimisation of the unification plebiscites carried out on the 21st and 22nd October 1860 in the Two Sicilies. It pays particular attention to the case study of the mainland provinces of the ex-Bourbon Reign. The intent is to consider these voting practices as an historically unique method of political apprenticeship and mobilisation of the popular classes. The profile of these practices was as much participative and inclusive (including subjects who were normally excluded from the electoral body, such as women and minors) as it was holistic, nondeliberative and marked by a personalisation of politics that was incarnated in monocratic and charismatic figures. An adequate understanding of the southern plebiscite must not ignore, firstly, an analysis that is positioned in the context of the coeval and subsequent analogue experiences in Europe (and more generally the democratised electoral dynamics between the 18th and 19th centuries). Secondly, it must be read from the perspective of the long and articulated process of “electoral civilisation”, that is, the definition of the technology and practices of suffrage intended to preclude political violence, channelling and ordering the otherwise broken exercise of popular sovereignty

    The "Preeclampsia and Hypertension Target Treatment" ("PYTT") study: a multicenter prospective study to evaluate the effectiveness of the antihypertensive therapy based on maternal hemodynamic findings

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    Background: Despite major advances in the pharmacological treatment of hypertension in the non-pregnant population, treatments for hypertension in pregnancy have remained largely unchanged over the years. There is recent evidence that a more adequate control of maternal blood pressure is achieved when the first given antihypertensive drug is able to correct the underlying hemodynamic disorder of the mother beside normalizing the blood pressure values. Objective: to compare the blood pressure control in women receiving an appropriate or inappropriate antihypertensive therapy in accordance with the baseline hemodynamic findings STUDY DESIGN: prospective multicenter study including a population of women with de novo diagnosis of HDP. A noninvasive assessment of the following maternal parameters was done upon the hospital admission by means of USCOM (Ultrasound Cardiac Output Monitor) before any antihypertensive therapy was given: Cardiac Output (CO), Heart Rate (HR), Systemic Vascular Resistance (SVR), Stroke Volume (SV). The clinician who prescribed the antihypertensive therapy was blinded to the hemodynamic evaluation and based on his preferences or on the local protocols used as 1st line a vasodilator (nifedipine or alpha methyldopa) or a beta-blocker (labetalol). The 1st line pharmacological treatment was retrospectively considered hemodynamically appropriate in either of the following circumstances: 1) Women with a hypodynamic profile (defined as low cardiac output [CO≤5L/min] and/or high systemic vascular resistance [SVR≥1300 dynes*s*cm]) who were administered oral nifedipine or alpha methyldopa. 2) Women with a hyperdynamic profile (defined as normal or high cardiac output [CO >5 L/min] and/or low systemic vascular resistances [SVR<1300 dynes*s*cm-]) who were administered oral labetalol. The primary outcome of the study was to compare the occurrence of severe hypertension between the women who were found to be treated with a hemodynamically appropriate or inappropriate therapy. Results: A total of 152 women with HDP were included in the final analysis. Of these the majority displayed a hypodynamic profile (114 or 75.0%) and received a hemodynamically appropriate treatment (116 or 76.3%). The occurrence of severe hypertension prior to delivery was significantly lower in the group receiving an appropriate therapy compared with those inappropriately treated (6.0% vs. 19.4%; p= 0.02). Moreover, the number of women who achieved target values of BP within 48-72h from the treatment start was higher in the group who received an appropriate treatment (70.7% vs. 50.0%; p=0.02). Conclusion: In pregnant individuals with de novo HDP, a lower occurrence of severe hypertension is observed when the first line antihypertensive agent is tailored to the correct maternal hemodynamic profile

    Un laboratoire pour les pratiques plébiscitaires contemporaines: les libres votes constitutionnels et les «appels au silence» dans l’Italie révolutionnaire et napoléonienne (1797-1805)

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    Entre la fin du XVIIIe siècle et le début du XIXe siècle, la péninsule italienne est un laboratoire des pratiques plébiscitaires modernes en parallèle avec la France. Partant de l’analyse des «libres votes» constitutionnels qui ont lieu dans les républiques sœurs italiennes et des appels au peuple qui se tiennent à Gênes et Lucques en 1805, cette contribution focalise l’attention sur trois points. D’abord, le rôle pivot de la figure de Bonaparte constituant et père des nouvelles patries par lui-même inventées dans les discourses ainsi que dans les pratiques de vote en 1797. En second lieu, la symmétrie entre l’impératif de l’elargissement, le plus grand possible, du corps électoral (qui dessine une «citoyenneté exceptionnelle de ratification») et la raréfation progressive de l’espace déliberatif qui caractérise les libres votes constitutionnels de 1797-98 tout en gardant le suffrage en assemblée. Enfin, la médiatisation et la correction des résultats électoraux en 1797-98 jusqu’à l’introduction officielle en 1805 du principe du «silence assentiment». SUMMARY Between the late eighteenth century and early nineteenth century , the Italian peninsula is a laboratory of modern plebiscitary practices in parallel with France. Based on the analysis of "free votes " constitutional taking place in the Italian republi

    News on immune checkpoint inhibitors as immunotherapy strategies in adult and pediatric solid tumors

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    Immune checkpoint inhibitors (ICIs) have shown unprecedented benefits in various adult cancers, and this success has prompted the exploration of ICI therapy even in childhood malignances. Although the use of ICIs as individual agents has achieved disappointing response rates, combinational therapies are likely to promise better results. However, only a subset of patients experienced prolonged clinical effects, thus suggesting the need to identify robust bio-markers that predict individual clinical response or resistance to ICI therapy as the main challenge. In this review, we focus on how the use of ICIs in adult cancers can be translated into pediatric malignances. We discuss the physiological mechanism of action of each IC, including PD-1, PD-L1 and CTLA-4 and the new emerging ones, LAG-3, TIM-3, TIGIT, B7-H3, BTLA and IDO-1, and evaluate their prognostic value in both adult and childhood tumors. Furthermore, we offer an overview of preclinical models and clinical trials currently under investigation to improve the effectiveness of cancer immunotherapies in these patients. Finally, we outline the main predictive factors that influence the efficacy of ICIs, in order to lay the basis for the development of a pan-cancer immunogenomic model, able to direct young patients towards more specific immunotherapy

    Identification of Conserved and HLA Promiscuous DENV3 T-Cell Epitopes

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    Anti-dengue T-cell responses have been implicated in both protection and immunopathology. However, most of the T-cell studies for dengue include few epitopes, with limited knowledge of their inter-serotype variation and the breadth of their human leukocyte antigen (HLA) affinity. In order to expand our knowledge of HLA-restricted dengue epitopes, we screened T-cell responses against 477 overlapping peptides derived from structural and non-structural proteins of the dengue virus serotype 3 (DENV3) by use of HLA class I and II transgenic mice (TgM): A2, A24, B7, DR2, DR3 and DR4. TgM were inoculated with peptides pools and the T-cell immunogenic peptides were identified by ELISPOT. Nine HLA class I and 97 HLA class II novel DENV3 epitopes were identified based on immunogenicity in TgM and their HLA affinity was further confirmed by binding assays analysis. A subset of these epitopes activated memory T-cells from DENV3 immune volunteers and was also capable of priming naïve T-cells, ex vivo, from dengue IgG negative individuals. Analysis of inter- and intra-serotype variation of such an epitope (A02-restricted) allowed us to identify altered peptide ligands not only in DENV3 but also in other DENV serotypes. These studies also characterized the HLA promiscuity of 23 HLA class II epitopes bearing highly conserved sequences, six of which could bind to more than 10 different HLA molecules representing a large percentage of the global population. These epitope data are invaluable to investigate the role of T-cells in dengue immunity/pathogenesis and vaccine design. © 2013 Nascimento et al
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