The ErbB2 receptor in gastric cancer. the quick-change artist

The ErbB family of receptors is providing the oncogenic signals necessary to cells to become transformed. In gastric cancer (GC) the ErbB2 (HER2) expression is associated with a poor prognosis, but addition of ErbB-targeted therapeutics to chemotherapy has produced unsatisfactory results with moderate improved outcomes for patients. The ToGA trail has revolutionized the treatment of GC, introducing the use of trastuzumab and changing the poor prognosis of these patients. However, this study reported only a modest prolongation of progression-free survival (PFS) and overall survival (OS) in patients with high expression of ErbB2 protein, with a large percentage of initially good responders, then becoming refractory to therapy within one year. These findings indicate the occurrence of resistant phenotypes arising from diverse adaptive and genetic changes. Due to the promiscuity of ErbB2 in the EGFR family signaling network, the use of ErbB targeted mono-therapies certainly contributes to a redistribution of the stoichiometry among receptors leading to the activation of compensatory pathways, suggesting that survival of cancer cells is sustained, at least in part, by the network of the ErbB receptors and their ligands. For these reasons, the use of combination therapies is becoming the most logical strategy for any type of cancer treatment, including GC. In this review we summarize information regarding mechanisms, pathways and molecules involved in the resistance to ErbB-targeted molecules with the intent to provide rational guidelines for developing more efficient therapeutic approaches

Patterns, causes, and consequences of connectivity within a coral reef fish metapopulation

Population connectivity influences virtually all ecological and evolutionary processes within metapopulations including population dynamics, persistence, and divergence. A comprehensive analysis of connectivity must consider the exchange of both individuals and alleles among populations, representing demographic and genetic connectivity, respectively. For many marine species, connectivity is driven by larval dispersal. However, despite the widespread recognition that dispersal is key to predicting metapopulation dynamics and effectively managing networks of marine reserves, empirical data are scarce due to the methodological challenges of tracking larvae. This dissertation is an integrative study of the patterns, causes, and consequences of marine connectivity using the sponge-dwelling reef fish Elacatinus lori as a study system. I begin by describing the distribution and abundance patterns of E. lori and its host sponge on the Belize barrier reef. Next, I study demographic connectivity by using genetic parentage analysis to quantify dispersal. I conduct an intra-population study to identify self-recruiting dispersal trajectories and develop a method to approximate a dispersal kernel based on the distribution of habitat patches. I then complete a large-scale parentage analysis to produce the first statistically-robust marine dispersal kernel. I find that dispersal declines exponentially with respect to distance in E. lori, with no dispersal events exceeding 16.2 km. Notably, dispersal probabilities are unrelated to the number of days an individual spends in the larval phase and other biological variables. Finally, to elucidate the long-term microevolutionary consequences of genetic connectivity, I investigate spatial genetic structure in the Belizean metapopulation. In a preliminary study based on mitochondrial and microsatellite data, I find high levels of pairwise genetic differentiation between sites separated by only 20 km. In a follow-up study, I use a high-throughput multiplex approach to resolve fine-scale patterns of genetic structure throughout the species' range. Seascape genetic analyses reveal that genetic connectivity is consistent with the shape of the dispersal kernel. Collectively, this dissertation generates novel insights regarding the spatial scale at which marine fish populations are connected. Given the alarming rate of population declines on coral reefs globally, these results have important and time-sensitive conservation implications

The formation of marine kin structure : effects of dispersal, larval cohesion, and variable reproductive success

Author Posting. © The Author(s), 2018. This is the author's version of the work. It is posted here under a nonexclusive, irrevocable, paid-up, worldwide license granted to WHOI. It is made available for personal use, not for redistribution. The definitive version was published in Ecology 99 (2018): 2374-2384, doi:10.1002/ecy.2480.The spatial distribution of relatives has profound e ects on kin interactions, inbreeding, and inclusive tness. Yet, in the marine environment, the processes that generate patterns of kin structure remain understudied because larval dispersal on ocean currents was historically assumed to disrupt kin associations. Recent genetic evidence of co-occurring siblings challenges this assumption and raises the intriguing question of how siblings are found together after a (potentially) disruptive larval phase. Here, we develop individual based models to explore how stochastic processes operating at the individual level a ect expected kinship at equilibrium. Speci cally, we predict how limited dispersal, sibling cohesion, and variability in reproductive success di erentially a ect patterns of kin structure. All three mechanisms increase mean kinship within populations, but their spatial e ects are markedly di erent. We nd that: (1) when dispersal is limited, kinship declines monotonically as a function of the distance between individuals; (2) when siblings disperse cohesively, kinship increases within a site relative to between sites; and (3) when reproductive success varies, kinship increases equally at all distances. The di erential e ects of these processes therefore only become apparent when individuals are sampled at multiple spatial scales. Notably, our models suggest that aggregative larval behaviors, such as sibling cohesion, are not necessary to explain documented levels of relatedness within marine populations. Together, these ndings establish a theoretical framework for disentangling the drivers of marine kin structure.CCD was supported by a Weston Howland Jr. Postdoctoral Scholarship from WHOI. MGN was supported by a grant from the US NSF (DEB-1558904)

Patterns, causes, and consequences of marine larval dispersal

Quantifying the probability of larval exchange among marine populations is key to predicting local population dynamics and optimizing networks of marine protected areas. The pattern of connectivity among populations can be described by the measurement of a dispersal kernel. However, a statistically robust, empirical dispersal kernel has been lacking for any marine species. Here, we use genetic parentage analysis to quantify a dispersal kernel for the reef fish Elacatinus lori, demonstrating that dispersal declines exponentially with distance. The spatial scale of dispersal is an order of magnitude less than previous estimates—the median dispersal distance is just 1.7 km and no dispersal events exceed 16.4 km despite intensive sampling out to 30 km from source. Overlaid on this strong pattern is subtle spatial variation, but neither pelagic larval duration nor direction is associated with the probability of successful dispersal. Given the strong relationship between distance and dispersal, we show that distance-driven logistic models have strong power to predict dispersal probabilities. Moreover, connectivity matrices generated from these models are congruent with empirical estimates of spatial genetic structure, suggesting that the pattern of dispersal we uncovered reflects long-term patterns of gene flow. These results challenge assumptions regarding the spatial scale and presumed predictors of marine population connectivity. We conclude that if marine reserve networks aim to connect whole communities of fishes and conserve biodiversity broadly, then reserves that are close in space (<10 km) will accommodate those members of the community that are short-distance dispersers.We thank Diana Acosta, Alben David, Kevin David, Alissa Rickborn, and Derek Scolaro for assistance with field work; Eliana Bondra for assistance with molecular work; and Peter Carlson for assistance with otolith work. We are grateful to Noel Anderson, David Lindo, Claire Paris, Robert Warner, Colleen Webb, and two anonymous reviewers for comments on this manuscript. This work was supported by National Science Foundation (NSF) Grant OCE-1260424, and C.C.D. was supported by NSF Graduate Research Fellowship DGE-1247312. All work was approved by Belize Fisheries and Boston University Institutional Animal Care and Use Committee. (OCE-1260424 - National Science Foundation (NSF); DGE-1247312 - NSF Graduate Research Fellowship)Published versio

Electrical, mechanical and electromechanical properties of graphene-thermoset polymer composites produced using acetone-DMF solvents

Recently, graphene-polymer composites gained a central role in advanced stress and strain sensing. A fundamental step in the production of epoxy-composites filled with graphene nanoplatelets (GNPs) consists in the exfoliation and dispersion of expanded graphite in a proper solvent, in the mixing of the resulting GNP suspension with the polymer matrix, and in the final removal of the solvent from the composite before curing through evaporation. The effects of traces of residual solvent on polymer curing process are usually overlooked, even if it has been found that even a small amount of residual solvent can affect the mechanical properties of the final composite. In this paper, we show that residual traces of N,N′-Dimethylformamide (DMF) in vinylester epoxy composites can induce relevant variations of the electrical, mechanical and electromechanical properties of the cured GNP-composite. To this purpose, a complete analysis of the morphological and structural characteristics of the composite samples produced using different solvent mixtures (combining acetone and DMF) is performed. Moreover, electrical, mechanical and electromechanical properties of the produced composites are assessed. In particular, the effect on the piezoresistive response of the use of DMF in the solvent mixture is analyzed using an experimental strain dependent percolation law to fit the measured electromechanical data. It is shown that the composites realized using a higher amount of DMF are characterized by a higher electrical conductivity and by a strong reduction of Young’s Modulus

Low-Terahertz Transparent Graphene-Based Absorber

A new, transparent, metal-free absorber, based on the use of multilayer graphene/dielectric laminates (GLs), is proposed for applications in the low-terahertz frequency range. The designed absorber has a total thickness of around 70 µm and consists of a front matching dielectric layer followed by a GL, a dielectric spacer and a back GL. The laminates are periodic structures constituted of graphene sheets separated by 50-nm-thick polyethylene terephthalate (PET) interlayers, while the matching layer and the spacer are one-quarter-wavelength thick and made of PET. The GLs are modeled as homogeneous-equivalent single layers (ESLs) characterized by their sheet resistances Rs. An innovative analytical method is proposed in order to select Rs values optimizing the electromagnetic wave absorption either in low-gigahertz or low-terahertz frequency range. The frequency spectra of the absorption, reflection and transmission coefficients are computed in the range up to 4 THz by using different values of Rs. Then, realistic Rs values of chemically doped graphene monolayers over PET substrates are considered. The designed absorbers are characterized by an absorption coefficient with a peak value of about 0.8 at the first resonant frequency of 1.1 THz, and a 1.4 THz bandwidth centered at 1.5 THz with reflection coefficient below - 10 dB. Moreover, the optical transmittance of the proposed absorbers are computed by means of the optical matrix theory and it is found to be greater than 86% in all the visible ranges

Gli agguati dello sguardo. Enunciazione della suspense in Jaws

Riferimento imprescindibile dell\u2019invenzione cinematografica contemporanea, le inquadrature \u201cacquatiche\u201d che presagiscono gli agguati dello squalo sono il cuore dell\u2019esperienza che lo spettatore ha compiuto nel 1975 e continua tutt\u2019oggi a compiere di fronte a Jaws. Il film di Steven Spielberg (regia), Verna Fields (montaggio), John Williams (musiche) e Bill Butler (fotografia) sfrutta con grande efficacia le potenzialit\ue0 visive e simboliche dell\u2019acqua, coinvolgendo lo spettatore in una terrorizzante immersione. Da sempre del resto l\u2019acqua nel cinema d\ue0 materia e sostanza ai desideri, ai sogni, alle ossessioni, ai traumi, alle paure consce e inconsce dell\u2019uomo, trasfigurando sullo schermo i miti e gli archetipi dell\u2019immaginario individuale e collettivo. Questo contributo, intitolato Gli agguati dello sguardo. Enunciazione della suspense in Jaws e inserito nello speciale sui 40 anni de Lo squalo curato da Andrea Minuz per la rivista Cinergie (n. 7/2015), si sofferma proprio su alcuni aspetti stilistici e formali del film, in particolare sulle inquadrature \u201cacquatiche\u201d che contraddistinguono la prima met\ue0 del film e che suggeriscono la presenza del mostro e l\u2019imminenza di un suo attacco all\u2019uomo. La tesi fondamentale \ue8 che il gioco di allineamenti e disallineamenti ottici costruito attorno allo sguardo dello squalo e l\u2019insistente sollecitazione della sensibilit\ue0 corporea dello spettatore costituiscano un\u2019originale strategia di costituzione dell\u2019esperienza filmica

Precarious Alternative: Sustaining the Popular Solidarity Economy in Ecuador

Written into the Ecuadorian Constitution in 2008, the Popular Solidarity Economy (PSE) was intended to be an alternative economy that "put people before the market" and was a centrepiece of left-wing President Correa's "21st Century Socialism". Ten years later, staff at the National Institute of Popular Solidarity Economy (IEPS) were uncertain about the future of the PSE and the institute itself. As politics shifted to the right, the place of the PSE and the IEPS appeared to be precarious to everyone involved--government functionaries, academics, NGO staff, and actors in the alternative economy itself. Conducting research with the IEPS, I sought to understand how staff attempted to keep the PSE alive as an economic alternative during a period of waning political interest. While there, I came to see how the many different actors surrounding the PSE experienced precarity in mutually reinforcing ways, whether it was government staff constantly being replaced, NGOs seeking program funding, or PSE actors who were mostly trying to string together livelihoods from multiple unstable income sources. Beyond the precarity experienced by individuals, I use the term 'precarious alternative' to highlight the position of the PSE as a whole. Firstly, with waning interest from both the public and the rest of government, the PSE was in danger of collapsing as a policy framework. Secondly, as the lack of political and economic support pushed the IEPS into encouraging more entrepreneurial strategies among program beneficiaries, the PSE itself risked becoming little different from the rest of the economy--its status as an alternative was also under threat. At the same time, I argue that the very alterity of the PSE created resonances with entrepreneurial logics of disruption. In my analysis, I focus on the labour of IEPS staff. In doing so, I am able to show how experiences of precarity in both their work and careers pushed them to follow economic logics that reinforced the precarity of others. In a context in which having a 'side hustle' appeared sensible, the PSE became a vehicle for promoting micro-entrepreneurialism. What was originally a response to the neoliberalism of the 80s, 90s, and early 2000s in Ecuador became another precarious thread in a patchwork of livelihood strategies. In this thesis, I am making an intervention into the anthropological literature on precarity and bureaucracy. I do this by examining how precarity is ported into and then reinforced by the state, not just through high-level policy decisions, but by the lived experiences of bureaucrats. Economic uncertainty encouraged many staff to have their own 'side hustles'. Entrepreneurial endeavours, however, were not only economic strategies but projects of self-making, with IEPS staff and other PSE proponents using entrepreneurial strategies to remake themselves as affectively engaged bureaucrats. As IEPS staff attempted to sustain both their careers and the PSE under precarious circumstances, they also made the PSE's status as an alternative itself precarious

Eufemismo paradójico : Cambios y creaciones de las artes plásticas en la dictadura militar

En el presente trabajo se desarrollarán las bases teóricas de los cambios y creaciones en las producciones plásticas durante la Dictadura Militar del 76’ en la Argentina, momento en el que varios artistas modificaron su quehacer artístico influenciado por el contexto en el cual se estaba viviendo. En este sentido, algunos artistas crearon un arte hiperrealista que desarrolló los efectos de esta situación, cargada de una retórica sutil que, indirectamente, transitaron el momento de inseguridad y opresión que generó el golpe militar. Sin embargo, otros artistas se replegaron en un estéril academismo, de la abstracción total, el refugio de lo perceptivo en la mente; la máxima posibilidad de abstraerse. Se puede decir entonces, que en este clima se retoma la imagen figurativa, con el Hiperrealismo de los ́70; así como a su vez existió un arte abstracto y geométrico y por último; con la llegada de la democracia, comienzan a darse signos de rebeldía en la llamada Nueva Imagen de los 80’. Esta investigación fue motivada para dar marco teórico a una producción plástica que intenta transmitir la opresión y falta de libertad que se vivía en aquella época, a través de un evento performático que se llevará a cabo en la sala TACEC del Teatro Argentino; esta acción artística será realizada por un cuerpo de baile, específicamente de danza contemporánea. Ésta danza como forma artística, utiliza el cuerpo para inscribir imagen es y señalar la lectura; pues es en el cuerpo entonces donde sucede la acción y por el cual se habla, a pesar de ser una composición subjetivada lo que se busca en la danza-performance es romper lo estático y lo puro visual, del “se mira y no se toca”. Un arte que se mete a través de los sentidos es un arte que se mete en las fisuras del sistema. Esta combinación entre la performance y la danza contemporánea es un cambio en el formato tradicional de estructura definida y acabada, esto es, una estructura distinta de la obra de arte. Para una nueva percepción del contenido y la ruptura con el espacio escénico teatral tradicional, que promueve un canal de intercambio de información entre obra, público y entorno.El video que acompaña a esta tesis de grado puede verse en este enlace.Facultad de Bellas Arte