Invasive micropapillary carcinoma of the breast overexpresses MUC4 and is associated with poor outcome to adjuvant trastuzumab in HER2-positive breast cancer

Invasive micropapillary carcinoma of the breast (IMPC) is a histological tumor variant that occurs with low frequency characterized by an inside-out formation of tumor clusters with a pseudopapillary arrangement. IMPC is an aggressive tumor with poor clinical outcome. In addition, this histological subtype usually expresses human epidermal growth factor receptor 2 (HER2) which also correlates with a more aggressive tumor. In this work we studied the clinical significance of IMPC in HER2-positive breast cancer patients treated with adjuvant trastuzumab. We also analyzed mucin 4 (MUC4) expression as a novel biomarker to identify IMPC.Fil: Mercogliano, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Inurrigarro, Gloria. Sanatorio Mater Dei Hermanas de María de Schoenstatt; ArgentinaFil: de Martino, Mara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Venturutti, Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Rivas, Martin Alfredo. Cornell University; Estados UnidosFil: Cordo Russo, Rosalia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Proietti Anastasi, Cecilia Jazmín. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Fernandez, Elmer Andres. Universidad Católica de Córdoba; ArgentinaFil: Frahm, Isabel. Sanatorio Mater Dei Hermanas de María de Schoenstatt; ArgentinaFil: Barchuk, Sabrina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos ; ArgentinaFil: Allemand, Daniel H.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos ; ArgentinaFil: Figurelli, Silvina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos ; ArgentinaFil: Gil Deza, Ernesto. Instituto Oncológico Henry Moore; ArgentinaFil: Ares, Sandra. Instituto Oncológico Henry Moore; ArgentinaFil: Gercovich, Felipe G.. Instituto Oncológico Henry Moore; ArgentinaFil: Cortese, Eduardo. Ministerio de Defensa. Fuerza Aérea Argentina. Hospital Aeronáutico Central ; ArgentinaFil: Amasino, Matías. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Guzmán, Pablo. Universidad de La Frontera; ChileFil: Roa, Juan C.. Universidad de La Frontera; ChileFil: Elizalde, Patricia Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Schillaci, Roxana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin

Adverse prognostic and predictive significance of low DNA-dependent protein kinase catalytic subunit (DNA-PKcs) expression in early-stage breast cancers

Background: DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a serine threonine kinase belonging to the PIKK family (phosphoinositide 3-kinase-like-family of protein kinase), is a critical component of the non-homologous end joining (NHEJ) pathway required for the repair of DNA double strand breaks. DNA-PKcs may be involved in breast cancer pathogenesis. Methods: We evaluated clinicopathological significance of DNA-PKcs protein expression in 1161 tumours and DNA-PKcs mRNA expression in 1950 tumours. We correlated DNA-PKcs to other markers of aggressive phenotypes, DNA repair, apoptosis and cell cycle regulation. Results: Low DNA-PKcs protein expression was associated with higher tumour grade, higher mitotic index, tumour de-differentiation and tumour type (ps<0.05). Absence of BRCA1, low XRCC1/SMUG1/APE1/Polβ were also more likely in low DNA-PKcs expressing tumours (ps<0.05). Low DNA-PKcs protein expression was significantly associated with worse breast cancer specific survival (BCCS) in univariate and multivariate analysis (ps<0.01). At the mRNA level, low DNA-PKcs was associated with PAM50.Her2 and PAM50.LumA molecular phenotypes (ps<0.01) and poor BCSS. In patients with ER positive tumours who received endocrine therapy, low DNA-PKcs (protein and mRNA) was associated with poor survival. In ER negative patients, low DNA-PKcs mRNA remains significantly associated with adverse outcome. Conclusions: Our study suggests that low DNA-PKcs expression may have prognostic and predictive significance in breast cancers

Designing AI Interfaces for Children with Special Needs in Educational Contexts

The IDC research community has a growing interest in designing AI interfaces for children with special educational needs. Nonetheless, little research has explored the research and design issues, rationale, challenges, and opportunities in this field. Therefore, we propose to host a half-day workshop to bring together researchers and practitioners from the Learning & Education, Accessibility, and Intelligent User Interfaces sub-fields to discuss and identify existing design issues, challenges, and collaboration barriers, to establish consensus on the design of a pragmatic framework, as well as explore future innovation and research opportunities. We aim to foster mutual unders

Evidence of topological superconductivity in planar Josephson junctions

Majorana zero modes are quasiparticle states localized at the boundaries of topological superconductors that are expected to be ideal building blocks for fault-tolerant quantum computing. Several observations of zero-bias conductance peaks measured in tunneling spectroscopy above a critical magnetic field have been reported as experimental indications of Majorana zero modes in superconductor/semiconductor nanowires. On the other hand, two dimensional systems offer the alternative approach to confine Ma jorana channels within planar Josephson junctions, in which the phase difference {\phi} between the superconducting leads represents an additional tuning knob predicted to drive the system into the topological phase at lower magnetic fields. Here, we report the observation of phase-dependent zero-bias conductance peaks measured by tunneling spectroscopy at the end of Josephson junctions realized on a InAs/Al heterostructure. Biasing the junction to {\phi} ~ {\pi} significantly reduces the critical field at which the zero-bias peak appears, with respect to {\phi} = 0. The phase and magnetic field dependence of the zero-energy states is consistent with a model of Majorana zero modes in finite-size Josephson junctions. Besides providing experimental evidence of phase-tuned topological superconductivity, our devices are compatible with superconducting quantum electrodynamics architectures and scalable to complex geometries needed for topological quantum computing.Comment: main text and extended dat

MagiBricks: Fostering Intergenerational Connectedness in Distributed Play with Smart Toy Bricks

Playing together is crucial to the unique and invaluable bond between grandparents and grandchildren. However, co-located interactions and play can be limited due to time, distance, or pandemic-related restrictions. To facilitate distributed play, we developed MagiBricks, a system comprised of 3D-printed smart toy bricks and baseplates that provide feedback regarding their placement. The familiarity and appeal of toy bricks to both older adults and children make them ideal for intergenerational play. We conducted a within-subjects study with six grandparent-grandchildren pairs. We compared the interactions and perceived connectedness of the pairs while playing over a distance with either i) MagiBricks or ii) identical regular toy bricks. We found that MagiBricks affected communication dynamics, role taking, nature of play, and perception of connectedness during playtime compared to regular bricks, and were unanimously preferred. We contribute design implications for future systems leveraging (smart) tangibles and fostering intergenerational connectedness

MagiBricks: Fostering Intergenerational Connectedness in Distributed Play with Smart Toy Bricks

Playing together is crucial to the unique and invaluable bond between grandparents and grandchildren. However, co-located interactions and play can be limited due to time, distance, or pandemic-related restrictions. To facilitate distributed play, we developed MagiBricks, a system comprised of 3D-printed smart toy bricks and baseplates that provide feedback regarding their placement. The familiarity and appeal of toy bricks to both older adults and children make them ideal for intergenerational play. We conducted a within-subjects study with six grandparent-grandchildren pairs. We compared the interactions and perceived connectedness of the pairs while playing over a distance with either i) MagiBricks or ii) identical regular toy bricks. We found that MagiBricks affected communication dynamics, role taking, nature of play, and perception of connectedness during playtime compared to regular bricks, and were unanimously preferred. We contribute design implications for future systems leveraging (smart) tangibles and fostering intergenerational connectedness

Multiparametric monitoring of chemotherapy treatment response in locally advanced breast cancer using quantitative ultrasound and diffuse optical spectroscopy

Purpose: This study evaluated pathological response to neoadjuvant chemotherapy using quantitative ultrasound (QUS) and diffuse optical spectroscopy imaging (DOSI) biomarkers in locally advanced breast cancer (LABC). Materials and Methods: The institution’s ethics review board approved this study. Subjects (n = 22) gave written informed consent prior to participating. US and DOSI data were acquired, relative to the start of neoadjuvant chemotherapy,at weeks 0, 1, 4, 8 and preoperatively. QUS parameters including the mid-band fit (MBF), 0-MHz intercept (SI), and the spectral slope (SS) were determined from tumor ultrasound data using spectral analysis. In the same patients, DOSI was used to measure parameters relating to tumor hemoglobin and composition. Discriminant analysis and receiver-operating characteristic (ROC) analysis was used to classify clinical and pathological response during treatment and to estimate the area under the curve (AUC). Additionally, multivariate analysis was carried out for pairwise QUS/DOSI parameter combinations using a logistic regression model. Results: Individual QUS and DOSI parameters, including the (SI), oxy-haemoglobin (HbO2), and total hemoglobin (HbT) were significant markers for response after one week of treatment (p < 0.01). Multivariate (pairwise) combinations increased the sensitivity, specificity and AUC at this time; the SI + HbO2 showed a sensitivity/ specificity of 100%, and an AUC of 1.0. Conclusions: QUS and DOSI demonstrated potential as coincident markers for treatment response and may potentially facilitate response-guided therapies. Multivariate QUS and DOSI parameters increased the sensitivity and specificity of classifying LABC patients as early as one week after treatment

Doped Fountain Coding for Minimum Delay Data Collection in Circular Networks

This paper studies decentralized, Fountain and network-coding based strategies for facilitating data collection in circular wireless sensor networks, which rely on the stochastic diversity of data storage. The goal is to allow for a reduced delay collection by a data collector who accesses the network at a random position and random time. Data dissemination is performed by a set of relays which form a circular route to exchange source packets. The storage nodes within the transmission range of the route's relays linearly combine and store overheard relay transmissions using random decentralized strategies. An intelligent data collector first collects a minimum set of coded packets from a subset of storage nodes in its proximity, which might be sufficient for recovering the original packets and, by using a message-passing decoder, attempts recovering all original source packets from this set. Whenever the decoder stalls, the source packet which restarts decoding is polled/doped from its original source node. The random-walk-based analysis of the decoding/doping process furnishes the collection delay analysis with a prediction on the number of required doped packets. The number of doped packets can be surprisingly small when employed with an Ideal Soliton code degree distribution and, hence, the doping strategy may have the least collection delay when the density of source nodes is sufficiently large. Furthermore, we demonstrate that network coding makes dissemination more efficient at the expense of a larger collection delay. Not surprisingly, a circular network allows for a significantly more (analytically and otherwise) tractable strategies relative to a network whose model is a random geometric graph

Flux coupled tunable superconducting resonator

We present a design and implementation of frequency-tunable superconducting resonator. The resonance frequency tunability is achieved by flux-coupling a superconducting LC-loop to a current-biased feedline; the resulting screening current leads to a change of the kinetic inductance and shift in the resonance frequency. The thin film aluminum resonator consists of an interdigitated capacitor and thin line inductors forming a closed superconducting loop. The magnetic flux from the nearby current feedline induces Meissner shielding currents in the resonator loop leading to change in the kinetic part of the total inductance of the resonator. We demonstarte continuous frequency tuning within 160 MHz around the resonant frequency of 2.7 GHz. We show that: (1) frequency upconversion is achieved when kHz AC modulation signal is superimposed onto the DC bias resulting in sidebands to the resonator tone; (2) three-wave mixing is attained by parametrically pumping the nonlinear kinetic inductance using a strong RF pump signal in the feedline. The simple architecture is amenable to large array multiplexing and on-chip integration with other circuit components. The concept could be applied in flux magnetometers, upconverters, and parametric amplifiers operating above 4 Kelvin cryogenic temperatures when alternative high critical temperature material with high kinetic inductance is used

Left-induced model structures and diagram categories

We prove existence results a la Jeff Smith for left-induced model category structures, of which the injective model structure on a diagram category is an important example. We further develop the notions of fibrant generation and Postnikov presentation from Hess, which are dual to a weak form of cofibrant generation and cellular presentation. As examples, for k a field and H a differential graded Hopf algebra over k, we produce a left-induced model structure on augmented H-comodule algebras and show that the category of bounded below chain complexes of finite-dimensional k-vector spaces has a Postnikov presentation. To conclude, we investigate the fibrant generation of (generalized) Reedy categories. In passing, we also consider cofibrant generation, cellular presentation, and the small object argument for Reedy diagrams.Comment: 33 pages; v2 fixes an error in the construction of the Postnikov presentation in section 3 and contains several minor improvements suggested by the referee. To appear in the Proceedings of the August 2013 "Women in Topology" workshop at BIRS, which will be published by Contemporary Mathematic