I soggetti valutatori

Il contributo ha ad oggetto l'analisi di commento delle disposizioni del d.lg. 25 maggio 2017, n. 74, che disciplinano la figure dei soggetti che si occupano di svolgere la funzione di valutazione dele performance dei dipendenti nell'ambito delle pubbliche amministrazioni. Dall'Anac, al Dipartimento della funzione pubblica, all' organismo indipendente di valutazione (Oiv), all’organo di indirizzo politico-amministrativo, ai dirigenti, lo studio riflette l'inquadramento sistematico nell'ambito dell'ordinamento giuridico ponendo in evidenza, nel corso della trattazione, l'ambiguo rapporto tra politica e amministrazione

Planck LFI flight model feed horns

this paper is part of the Prelaunch status LFI papers published on JINST: http://www.iop.org/EJ/journal/-page=extra.proc5/jinst The Low Frequency Instrument is optically interfaced with the ESA Planck telescope through 11 corrugated feed horns each connected to the Radiometer Chain Assembly (RCA). This paper describes the design, the manufacturing and the testing of the flight model feed horns. They have been designed to optimize the LFI optical interfaces taking into account the tight mechanical requirements imposed by the Planck focal plane layout. All the eleven units have been successfully tested and integrated with the Ortho Mode transducers.Comment: This is an author-created, un-copyedited version of an article accepted for publication in JINST. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The definitive publisher authenticated version is available online at 10.1088/1748-0221/4/12/T1200

Translating History or Romance? Historical Romantic Fiction and Its Translation in a Globalised Market

Popular romance literature has long been neglected and underestimated in the global literary context and little research on the translation of this genre has been carried out so far. Even taking into account its \u201cpopular connotation\u201d, romantic fiction seems to occupy the lower shelf in the literary polysystem compared with other popular genres. The discrepancy between the importance of this genre in the publishing industry and the scarce attention given to it by traditional scholars means that little is known about the textual practices and processes that accompany its production and circulation, including translation. In this paper, we deal with the issue of translating romantic fiction, focusing on the specific translation of historical romances, one of its most popular subgenres. In particular, through the analysis of a specific case study, the novel Outlander by American author Diana Gabaldon, we suggest that the double filiation of historical romances, i.e. their connection to both popular and canonical traditions, may have consequences at the textual level as when such books are translated, their ambiguous generic labelling tends to be resolved, favouring either the romantic or the historical component, thus resulting in a stronger generic identity

Repetitive low-frequency stimulation reduces epileptiform synchronization in limbic neuronal networks.

Deep-brain electrical or transcranial magnetic stimulation may represent a therapeutic tool for controlling seizures in patients presenting with epileptic disorders resistant to antiepileptic drugs. In keeping with this clinical evidence, we have reported that repetitive electrical stimuli delivered at approximately 1 Hz in mouse hippocampus-entorhinal cortex (EC) slices depress the EC ability to generate ictal activity induced by the application of 4-aminopyridine (4AP) or Mg2+-free medium (Barbarosie, M., Avoli, M., 1997. CA3-driven hippocampal–entorhinal loop controls rather than sustains in vitro limbic seizures. J. Neurosci. 17, 9308–9314.). Here, we confirmed a similar control mechanism in rat brain slices analyzed with field potential recordings during 4AP (50 μM) treatment. In addition, we used intrinsic optical signal (IOS) recordings to quantify the intensity and spatial characteristics of this inhibitory influence. IOSs reflect the changes in light transmittance throughout the entire extent of the slice, and are thus reliable markers of limbic network epileptiform synchronization. First, we found that in the presence of 4AP, the IOS increases, induced by a train of electrical stimuli (10 Hz for 1 s) or by recurrent, single-shock stimulation delivered at 0.05 Hz in the deep EC layers, are reduced in intensity and area size by low-frequency (1 Hz), repetitive stimulation of the subiculum; these effects were observed in all limbic areas contained in the slice. Second, by testing the effects induced by repetitive subicular stimulation at 0.2–10 Hz, we identified maximal efficacy when repetitive stimuli are delivered at 1 Hz. Finally, we discovered that similar, but slightly less pronounced, inhibitory effects occur when repetitive stimuli at 1 Hz are delivered in the EC, suggesting that the reduction of IOSs seen during repetitive stimulation is pathway dependent as well as activity dependent. Thus, the activation of limbic networks at low frequency reduces the intensity and spatial extent of the IOS changes that accompany ictal synchronization in an in vitro slice preparation. This conclusion supports the view that repetitive stimulation may represent a potential therapeutic tool for controlling seizures in patients with pharmacoresistant epileptic disorders

The Planck-LFI flight model composite waveguides

The Low Frequency Instrument on board the PLANCK satellite is designed to give the most accurate map ever of the CMB anisotropy of the whole sky over a broad frequency band spanning 27 to 77 GHz. It is made of an array of 22 pseudo-correlation radiometers, composed of 11 actively cooled (20 K) Front End Modules (FEMs), and 11 Back End Modules (BEMs) at 300K. The connection between the two parts is made with rectangular Wave Guides. Considerations of different nature (thermal, electromagnetic and mechanical), imposed stringent requirements on the WGs characteristics and drove their design. From the thermal point of view, the WG should guarantee good insulation between the FEM and the BEM sections to avoid overloading the cryocooler. On the other hand it is essential that the signals do not undergo excessive attenuation through the WG. Finally, given the different positions of the FEM modules behind the focal surface and the mechanical constraints given by the surrounding structures, different mechanical designs were necessary. A composite configuration of Stainless Steel and Copper was selected to satisfy all the requirements. Given the complex shape and the considerable length (about 1.5-2 m), manufacturing and testing the WGs was a challenge. This work deals with the development of the LFI WGs, including the choice of the final configuration and of the fabrication process. It also describes the testing procedure adopted to fully characterize these components from the electromagnetic point of view and the space qualification process they underwent. Results obtained during the test campaign are reported and compared with the stringent requirements. The performance of the LFI WGs is in line with requirements, and the WGs were successfully space qualified.Comment: this paper is part of the Prelaunch status LFI papers published on JINST: http://www.iop.org/EJ/journal/-page=extra.proc5/jins

A discussion of the market and policy failures associated with the adoption of herbicide-tolerant crops

Weed control in the U.S. Midwest has become increasingly herbicide-centric due to the adoption of herbicide-tolerant (HT) crops in the 1990s. The scarcity of the use of integrated weed management (IWM) practices, including biological and mechanical controls, is concerning for two reasons. First, herbicides create negative health and environmental externalities. Second, weed resistance to some herbicides is increasing, which creates incentives to use additional herbicides. However, it seems certain that weeds will develop resistance to those herbicides as well, so applying “herbicide upon herbicide” is socially problematic. In this context, we develop an economic framework to clarify the interplay among the different market failures that either contribute to the herbicidal “lock-in” or make it problematic. We then analyze the evidence for and perceptions of these market failures based on twenty-four semistructured interviews with farmers and experts conducted in 2017, as well as discussions in the academic literature. To this end, we put into perspective the possible self-reinforcing effects in the adoption path of HT crops, such as increasing farm size, changes in farm equipment, increasing incentives for simplified crop rotations, and the loss of practical knowledge of IWM practices

A Feasibility Study on Cancer Stem Cells Sensitivity Assay

A recent hypothesis is that cancer is driven by a small subpopulation of cells called “cancer stem cells” (CSCs) with an unlimited proliferative potential. These cells are thought to be responsible for the development of the tumor representing the only cell population able to sustain tumor growth and progression. In the present study we investigated whether CSCs could be isolated in patients with metastatic lung cancer (LC), breast cancer (BC) and colorectal cancer (CRC) and whether in vitro CSCs sensitivity assay could identify an effective treatment. The study was conducted in NSCLC patients with metastatic disease progressing after standard therapies. CSCs were isolated from effusions or fresh cancer tissue from primary tumor or metastasis. CSCs were cultivated in vitro and tested against different chemotherapy or targeted agents. The drug or the drugs combination leading to the highest CSC mortality rate was further administered to the patient. A total of 23 patients were included onto the study. Main characteristics were: median age 66 years (range 42-85), male sex in 14 cases (60%), with LC in 18 cases (78%), CRC in 3 cases (13%), other gastrointestinal adenocarcinoma in 2 cases (9%). CSCs were obtained from liver metastases in 6 cases (25%), pleural lung nodule excision in 2 cases (8%), lymphnode excision in 3 cases (12,5%) and by pleural or peritoneal effusion in 13 cases (54%). CSCs were successfully isolated in 15 patients (65%). Main reasons for CSCs isolation failure included inadequate material (6 cases), contamination (1 case) or delivery problems. CSC sensitivity assay was performed in 7 cases (29%), with a median of 15 drugs or combinations tested (range 5-28). The median time between cancer tissue collection and sensitivity assay result was 51 days (range 37-95). Our preliminary data indicate that CSCs isolation and in vitro sensitivity assay are feasible in patients with metastatic NSCLC

Evaluación de un sistema <i>ex vivo</i> para el estudio del transporte de la hormona plasmática ghrelina a través de la barrera sangre-líquido cefalorraquídeo

La ghrelina es una hormona peptídica octanoilada secretada principalmente por las células endocrinas del estómago (Kojima et al., 1999). La ghrelina actúa a través de un receptor acoplado a la proteína G, denominado receptor de ghrelina o receptor de secretagogos de la hormona del crecimiento (GHSR), que se encuentra altamente expresado en la hipófisis y el cerebro (Zigman et al., 2006). La ghrelina actúa en el sistema nervioso central, donde regula la secreción de la hormona del crecimiento, la ingesta de alimentos, la homeostasis de la glucosa en la sangre y las respuestas al estrés, entre otras funciones (Yanagi et al., 2018). Dado que la ghrelina accede al cerebro desde la sangre (Cabral et al., 2017), debe ocurrir un transporte de la hormona desde el compartimiento plasmático al cerebro para que pueda acceder a sus blancos neuronales. El cerebro contiene múltiples núcleos sensibles a la ghrelina bien caracterizados; sin embargo, la accesibilidad de la ghrelina plasmática al cerebro es sorprendentemente baja (Cabral et al., 2015; Perello et al., 2018). Para acceder al cerebro, la ghrelina podría cruzar la barrera hematoencefálica, difundir a través de los capilares fenestrados en los órganos circunventriculares (OCV) o cruzar la barrera de sangre-líquido cefalorraquídeo (LCR) (Perello et al., 2018). El transporte de ghrelina desde la sangre al cerebro a través de la barrera hematoencefálica es muy bajo en condiciones normales (Banks et al., 2002). La ghrelina plasmática extravasa pasivamente de los capilares fenestrados de los OCV, como la eminencia media del hipotálamo (ME) y el área postrema (AP) (Cabral et al., 2014, 2017; Schaeffer et al., 2013). Sin embargo, este mecanismo de entrada limita la acción de la ghrelina a los objetivos neuronales ubicados en la cercanía de los capilares fenestrados. En particular, la ghrelina plasmática puede difundir desde los capilares fenestrados de la ME, que se ramifican a la región ventromedial del núcleo arcuato vecino (ARC), y actúan sobre las neuronas orexigénicas, o desde capilares fenestrados de la AP, donde activa neuronas que expresan GHSR (Cabral et al., 2014, 2017; Schaeffer et al., 2013). De relevancia para este plan es el hecho que nuestro laboratorio recientemente mostró que la ghrelina plasmática se puede transportar selectivamente a través de la barrera sangre-LCR y alcanzar el LCR (Uriarte et al., 2019). Debido a que la monocapa de células ependimales que recubren la mayoría de los ventrículos cerebrales carece de uniones estrechas (Mullier et al., 2010), la ghrelina del LCR puede difundir al parénquima cerebral periventricular y alcanzar conjuntos adicionales de neuronas que expresan GHSR que no son fácilmente accesibles por difusión simple desde el plasma. Por lo tanto, la barrera sangre-LCR parece jugar un papel clave para las acciones centrales de la ghrelina. La barrera sangre-LCR está formado por los plexos coroideos y los tanicitos tipo β hipotalámicos. Los plexos coroideos están formados por una capa de células epiteliales cuboidales que rodea un lecho de capilares fenestrados en los ventrículos cerebrales y produce LCR. Los tanicitos hipotalámicos de tipo β son células ependimales bipolares especializadas que recubren el piso del tercer ventrículo y comunican el LCR con el espacio extracelular ventral de la EM. La barrera sangre-LCR no permite la difusión libre de ghrelina plasmática al LCR, como lo indica el hecho de que los niveles de ghrelina en el LCR son significativamente más pequeños que los niveles de ghrelina plasmática (Grouselle et al., 2008; Uriarte et al., 2019). Por otra parte, existen evidencias experimentales que indican que la barrera sangre-LCR transporta selectivamente la ghrelina circulante hacia el cerebro (Perello et al., 2018). En ovejas, los niveles de ghrelina en LCR muestran un perfil pulsátil, con aproximadamente la mitad de los picos en el LCR observados después de los picos en los niveles plasmáticos (Grouselle et al., 2008). En ratones, la ghrelina fluorescente inyectada periféricamente se encuentra internalizada en ambos tipos de células de la barrera sangre-LCR, y el análisis de tiempo-respuesta mostró que el trazador inyectado sistémicamente alcanza rápidamente el ARC ventromedial, y luego más lentamente accede al parénquima hipotalámico adyacente al tercer ventrículo (Uriarte et al., 2019). Además, los estudios en ratones mostraron que los niveles de ghrelina en el LCR aumentan después de la administración sistémica de la hormona, y que el efecto orexigénico de la ghrelina administrada periféricamente se reduce parcialmente por el inmunobloqueo de la ghrelina en el LCR (Uriarte et al., 2019). Los mecanismos moleculares por los cuales la barrera sangre-LCR transporta la ghrelina al cerebro siguen siendo inciertos. Un estudio in vitro que utilizó cultivos primarios de tanicitos de rata encontró que estas células internalizan la ghrelina fluorescente a través de una vía dependiente de clatrina (Collden et al., 2015). Sorprendentemente, un estudio reciente encontró que el transporte de ghrelina a través de la barrera hematoencefálica no requiere la presencia de GHSR (Rhea et al., 2018). Aquí, se realizan algunos estudios ex vivo para probar la hipótesis de que el transporte de ghrelina a través de la barrera sangre-LCR se produce de una manera dependiente de GHSR.Tutora: Maia Uriarte DonatiFacultad de Ciencias Exacta