Selectable Nanopattern Arrays for Nanolithographic Imprint and Etch-Mask Applications

A parallel nanolithographic patterning method is presented that can be used to obtain arrays of multifunctional nanoparticles. These patterns can simply be converted into a variety of secondary nanopatterns that are useful for nanolithographic imprint, plasmonic, and etch-mask applications

Efficacy and safety of trabectedin in metastatic uterine leiomyosarcoma: A retrospective multicenter study of the Spanish ovarian cancer research group (GEICO)

Objective: We assessed trabectedin in patients with advanced uterine leiomyosarcoma (uLMS) in real-life clinical practice given according to the marketing authorization. Methods: Thirty-six women from 11 tertiary hospitals across Spain who received trabectedin after anthracycline-containing regimen/s were retrospectively analyzed. The primary endpoint was progression-free survival (PFS). Results: Median PFS and overall survival (OS) since starting trabectedin treatment were 5.4 (95%CI: 3.5–7.3) and 18.5 months (95%CI: 11.5–25.6), respectively. Median OS was significantly higher (P = 0.028) in patients receiving trabectedin in = 2nd line (25.3 months) than in = 3rd (15.1 months) and with ECOG performance status = 1 at trabectedin start (19.8 months) than ECOG 2–3 (6.0 months, P = 0.013). When calculating OS since diagnosis, patients had longer OS with localized disease at diagnosis (87.4 months) vs. locally advanced (30.0 months) or metastatic (44.0 months, P = 0.041); and patients who received adjuvant therapy (87.4 months) compared with those who did not (30.0 months, P = 0.003), especially when receiving radiochemotherapy (106.7 months, P = 0.027). One patient (2.8%) had a complete response (CR) and nine patients (25.0%) achieved a partial response (PR) for an objective response rate of 27.8% with median response duration of 11 months (range: 4–93). Eighteen patients (50.0%) had disease stabilization for a disease control rate (DCR) of 77.8%. More patients receiving trabectedin in 1st-line of advanced disease achieved CR (16.7%) and PR (50.0%) than those in = 2nd line/s (0.0% and 20.0%), whereas the DCR was similar across treatment lines. Reversible neutropenia was the most common grade 3/4 laboratory abnormality (19.4%). Conclusions: Trabectedin confers clinical benefit in patients with recurrent/metastatic uLMS, given after failure to an anthracycline-based regimen being comparable to those reported in clinical trials and with a manageable safety profile

Stochastic Resonance in Nonpotential Systems

We propose a method to analytically show the possibility for the appearance of a maximum in the signal-to-noise ratio in nonpotential systems. We apply our results to the FitzHugh-Nagumo model under a periodic external forcing, showing that the model exhibits stochastic resonance. The procedure that we follow is based on the reduction to a one-dimensional dynamics in the adiabatic limit, and in the topology of the phase space of the systems under study. Its application to other nonpotential systems is also discussed.Comment: Submitted to Phys. Rev.

Mission and system architecture for an operational network of earth observation satellite nodes

Nowadays, constellations and distributed networks of satellites are emerging as clear development trends in the space system market to enable augmentation, enhancement, and possibilities of new applications for future Earth Observation (EO) missions. While the adoption of these satellite architectures is gaining momentum for the attaining of ever more stringent application requirements and stakeholder needs, the efforts to analyze their benefits and suitability, and to assess their impact for future programmes remains as an open challenge to the EO community. In this context, this paper presents the mission and system architecture conceived during the Horizon 2020 ONION project, a European Union research activity that proposes a systematic approach to the optimization of EO space infrastructures. In particular, ONION addressed the design of complementary assets that progressively supplement current programs and took part in the exploration of needs and implementation of architectures for the Copernicus Space Component for EO. Among several use cases considered, the ONION project focused on proposing system architectures to provide improved revisit time, data latency and image resolution for a demanding application scenario of interest: Marine Weather Forecast (MWF). A set of promising system architectures has been subject of a comprehensive assessment, based on mission analysis expertise and detailed simulation for evaluating several key parameters such as revisit time and data latency of each measurement of interest, on-board memory evolution and power budget of each satellite of the constellation, ground station contacts and inter-satellite links. The architectures are built with several heterogeneous satellite nodes distributed in different orbital planes. Each platform can embark different instrument sets, which provide the required measurements for each use case. A detailed mission analysis has then been performed to the selected architecture for the MWF use case, including a refined data flow analysis to optimize system resources; a refined power budget analysis; a delta-V and a fuel budget analysis considering all the possible phases of the mission. This includes from the correction of launcher injection errors and acquisition of nominal satellite position inside the constellation, orbit maintenance to control altitude, collision avoidance to avoid collision with space debris objects and end-of-life (EOL) disposal to comply with EOL guidelines. The relevance of the system architecture selected for the MWF has been evaluated for three use cases of interest (Arctic sea-ice monitoring, maritime fishery pressure and aquaculture, agricultural hydric stress) to show the versatility and the feasibility of the chosen architecture to be adapted for other EO applications.This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 687490

Efficacy and safety of trabectedin in metastatic uterine leiomyosarcoma: A retrospective multicenter study of the Spanish ovarian cancer research group (GEICO)

Objective: We assessed trabectedin in patients with advanced uterine leiomyosarcoma (uLMS) in real-life clinical practice given according to the marketing authorization. Methods: Thirty-six women from 11 tertiary hospitals across Spain who received trabectedin after anthracyclinecontaining regimen/s were retrospectively analyzed. The primary endpoint was progression-free survival (PFS). Results: Median PFS and overall survival (OS) since starting trabectedin treatment were 5.4 (95%CI: 3.5–7.3) and 18.5 months (95%CI: 11.5–25.6), respectively. Median OS was significantly higher (P = 0.028) in patients receiving trabectedin in ≤ 2nd line (25.3 months) than in ≥ 3rd (15.1 months) and with ECOG performance status ≤ 1 at trabectedin start (19.8 months) than ECOG 2–3 (6.0 months, P = 0.013). When calculating OS since diagnosis, patients had longer OS with localized disease at diagnosis (87.4 months) vs. locally advanced (30.0 months) or metastatic (44.0 months, P = 0.041); and patients who received adjuvant therapy (87.4 months) compared with those who did not (30.0 months, P = 0.003), especially when receiving radiochemotherapy (106.7 months, P = 0.027). One patient (2.8%) had a complete response (CR) and nine patients (25.0%) achieved a partial response (PR) for an objective response rate of 27.8% with median response duration of 11 months (range: 4–93). Eighteen patients (50.0%) had disease stabilization for a disease control rate (DCR) of 77.8%. More patients receiving trabectedin in 1st-line of advanced disease achieved CR (16.7%) and PR (50.0%) than those in ≥ 2nd line/s (0.0% and 20.0%), whereas the DCR was similar across treatment lines. Reversible neutropenia was the most common grade 3/4 laboratory abnormality (19.4%). Conclusions: Trabectedin confers clinical benefit in patients with recurrent/metastatic uLMS, given after failure to an anthracycline-based regimen being comparable to those reported in clinical trials and with a manageable safety profile

Genetic noise control via protein oligomerization

Gene expression in a cell entails random reaction events occurring over disparate time scales. Thus, molecular noise that often results in phenotypic and population-dynamic consequences sets a fundamental limit to biochemical signaling. While there have been numerous studies correlating the architecture of cellular reaction networks with noise tolerance, only a limited effort has been made to understand the dynamic role of protein-protein interactions. Here we have developed a fully stochastic model for the positive feedback control of a single gene, as well as a pair of genes (toggle switch), integrating quantitative results from previous in vivo and in vitro studies. We find that the overall noise-level is reduced and the frequency content of the noise is dramatically shifted to the physiologically irrelevant high-frequency regime in the presence of protein dimerization. This is independent of the choice of monomer or dimer as transcription factor and persists throughout the multiple model topologies considered. For the toggle switch, we additionally find that the presence of a protein dimer, either homodimer or heterodimer, may significantly reduce its random switching rate. Hence, the dimer promotes the robust function of bistable switches by preventing the uninduced (induced) state from randomly being induced (uninduced). The specific binding between regulatory proteins provides a buffer that may prevent the propagation of fluctuations in genetic activity. The capacity of the buffer is a non-monotonic function of association-dissociation rates. Since the protein oligomerization per se does not require extra protein components to be expressed, it provides a basis for the rapid control of intrinsic or extrinsic noise

Atypical Neurogenesis in Induced Pluripotent Stem Cells From Autistic Individuals

BACKGROUND: Autism is a heterogeneous collection of disorders with a complex molecular underpinning. Evidence from postmortem brain studies have indicated that early prenatal development may be altered in autism. Induced pluripotent stem cells (iPSCs) generated from individuals with autism with macrocephaly also indicate prenatal development as a critical period for this condition. But little is known about early altered cellular events during prenatal stages in autism. METHODS: iPSCs were generated from 9 unrelated individuals with autism without macrocephaly and with heterogeneous genetic backgrounds, and 6 typically developing control individuals. iPSCs were differentiated toward either cortical or midbrain fates. Gene expression and high throughput cellular phenotyping was used to characterize iPSCs at different stages of differentiation. RESULTS: A subset of autism-iPSC cortical neurons were RNA-sequenced to reveal autism-specific signatures similar to postmortem brain studies, indicating a potential common biological mechanism. Autism-iPSCs differentiated toward a cortical fate displayed impairments in the ability to self-form into neural rosettes. In addition, autism-iPSCs demonstrated significant differences in rate of cell type assignment of cortical precursors and dorsal and ventral forebrain precursors. These cellular phenotypes occurred in the absence of alterations in cell proliferation during cortical differentiation, differing from previous studies. Acquisition of cell fate during midbrain differentiation was not different between control- and autism-iPSCs. CONCLUSIONS: Taken together, our data indicate that autism-iPSCs diverge from control-iPSCs at a cellular level during early stage of neurodevelopment. This suggests that unique developmental differences associated with autism may be established at early prenatal stages

Use of rivaroxaban and acetylsalicylic acid as a combined treatment for peripheral arterial disease in Central Military Hospital

Background: The objective of this research was to evaluate the behavior of 3 risk indicators for peripheral arterial disease in patients under oral treatment with rivaroxaban 2.5 mg every 12 hours plus, acetylsalicylic acid 100 mg every 24 hours. It was hypothesized that the oral combination of rivaroxaban and acetylsalicylic acid presents a therapeutic advantage over other treatments.Methods: A prospective longitudinal and non-randomized study of a single center was performed. 59 patients with peripheral arterial disease were included and treated with acetylsalicylic acid + rivaroxaban. Peak systolic velocity, ankle-brachial index and C reactive protein index were evaluated.Results: Significant changes were found at month 1 and 3 of follow-up in maximum systolic velocity, ankle-arm index and C-reactive protein index. The baseline peak systolic velocity (PSV) in the anterior tibial artery had significant differences after one month of treatment (p=0.001) and after 3 months (p=0.001). The baseline PSV in the posterior tibial artery had significant differences compared to the values found at the month of treatment (p=0.001) and 3 months (p=0.001). In the ankle-brachial index a baseline median of 0.790 was found, one month after the treatment of 0.795 (p=0.147) and 3 months after 0.800 (p=0.019). The mean baseline C-reactive protein obtained was 73.142 mg/l, at one month 87.233 mg/l (p=0.001) and at 3 months at 79.009 mg/l (p=0.294) with a standard deviation of 67.18, 74.78 and 69.69 respectively.Conclusions: The combined use of acetylsalicylic acid and rivaroxaban allows a clinical improvement in patients with peripheral arterial disease