A Compact raster lensless microscope based on a microdisplay

Lensless microscopy requires the simplest possible configuration, as it uses only a light source, the sample and an image sensor. The smallest practical microscope is demonstrated here. In contrast to standard lensless microscopy, the object is located near the lighting source. Raster optical microscopy is applied by using a single-pixel detector and a microdisplay. Maximum resolution relies on reduced LED size and the position of the sample respect the microdisplay. Contrarily to other sort of digital lensless holographic microscopes, light backpropagation is not required to reconstruct the images of the sample. In a mm-high microscope, resolutions down to 800 nm have been demonstrated even when measuring with detectors as large as 138 μm × 138 μm, with field of view given by the display size. Dedicated technology would shorten measuring time

Individually switchable InGaN/GaN nano-LED arrays as highly resolved illumination engines

GaN-based light emitting diodes (LEDs) have been shown to effectively operate down to nanoscale dimensions, which allows further downscaling the chip-based LED display technology from micro- to nanoscale. This brings up the question of what resolution limit of the illumination pattern can be obtained. We show two different approaches to achieve individually switchable nano-LED arrays. We evaluated both designs in terms of near-field spot size and optical crosstalk between neighboring pixels by using finite difference time domain (FDTD) simulations. The numerical results were compared with the performance data from a fabricated nano-LED array. The outcome underlines the influence of geometry of the LED array and materials used in contact lines on the final illumination spot size and shape

ERK5 Inhibition Induces Autophagy-Mediated Cancer Cell Death by Activating ER Stress

ERK5 kinase; Antitumor drug; ApoptosisKinasa ERK5; Medicament antitumoral; ApoptosiQuinasa ERK5; Medicamento antitumoral; ApoptosisAutophagy is a highly conserved intracellular process that preserves cellular homeostasis by mediating the lysosomal degradation of virtually any component of the cytoplasm. Autophagy is a key instrument of cellular response to several stresses, including endoplasmic reticulum (ER) stress. Cancer cells have developed high dependency on autophagy to overcome the hostile tumor microenvironment. Thus, pharmacological activation or inhibition of autophagy is emerging as a novel antitumor strategy. ERK5 is a novel member of the MAP kinase family that is activated in response to growth factors and different forms of stress. Recent work has pointed ERK5 as a major player controlling cancer cell proliferation and survival. Therefore small-molecule inhibitors of ERK5 have shown promising therapeutic potential in different cancer models. Here, we report for the first time ERK5 as a negative regulator of autophagy. Thus, ERK5 inhibition or silencing induced autophagy in a panel of human cancer cell lines with different mutation patterns. As reported previously, ERK5 inhibitors (ERK5i) induced apoptotic cancer cell death. Importantly, we found that autophagy mediates the cytotoxic effect of ERK5i, since ATG5ˉ/ˉ autophagy-deficient cells viability was not affected by these compounds. Mechanistically, ERK5i stimulated autophagic flux independently of the canonical regulators AMPK or mTORC1. Moreover, ERK5 inhibition resulted in ER stress and activation of the Unfolded Protein Response (UPR) pathways. Specifically, ERK5i induced expression of the ER luminal chaperone BiP (a hallmark of ER stress), the UPR markers CHOP and ATF4, and the spliced form of XBP1. Pharmacological inhibition of UPR with chemical chaperone TUDC, or ATF4 silencing, resulted in impaired ERK5i-mediated UPR, autophagy and cytotoxicity. Overall, our results suggest that ERK5 inhibition induces autophagy-mediated cancer cell death by activating ER stress. Since ERK5 inhibition sensitizes cancer cells and tumors to chemotherapy, future work will determine the relevance of UPR and autophagy in the combined use of chemotherapy and ERK5i to tackle Cancer.This work was supported by the Spanish Ministry of Economy and Competitiveness (MINECO, grant SAF2015-64237-R), the Spanish Ministry of Science and Innovation (Grant PID2019-107561RB-I00), and cofounded by the European Regional Development Fund (ERDF)

Pràctiques de Disseny i Síntesi de Sistemes Digitals - Bus I2C

Aquest document serveix com una guia per a les sessions pràctiques de Disseny i Síntesi de Sistemes Digitals, específicament dissenyada per als alumnes del Grau d'Enginyeria Electrònica de Telecomunicació. Detalla el procés integral de disseny d'un sistema digital, oferint una orientació pas a pas en la creació d'un dispositiu mestre del bus I2C. El document abasta totes les etapes, des de la concepció inicial del disseny fins a la verificació rigorosa i la implementació final en una FPGA, amb l'objectiu específic d'interactuar de manera efectiva amb un sensor. Aquesta guia es presenta com una eina indispensable per a l'assoliment de competències pràctiques en l'àmbit de la síntesi digital

Laboratori de Disseny i Síntesi de Sistemes Digitals

Grau Enginyeria Electrònica de TelecomunicacióGuió del laboratori de l'assignatura Disseny i Síntesis de Sistemes Digitals

The ERK5/NF-κB signaling pathway targets endometrial cancer proliferation and survival

Apoptosis; Endometrial cancer; Map kinaseApoptosis; Cáncer endometrial; Mapa quinasaApoptosi; Càncer d'endometri; Mapa quinasaEndometrial cancer (EC) is the most common type of gynecologic cancer in women of developed countries. Despite surgery combined with chemo-/radiotherapy regimens, overall survival of patients with high-risk EC tumors is poor, indicating a need for novel therapies. The MEK5-ERK5 pathway is activated in response to growth factors and to different stressors, including oxidative stress and cytokines. Previous evidence supports a role for the MEK5-ERK5 pathway in the pathology of several cancers. We investigated the role of ERK5 in EC. In silico analysis of the PanCancer Atlas dataset showed alterations in components of the MEK5-ERK5 pathway in 48% of EC patients. Here, we show that ERK5 inhibition or silencing decreased EGF-induced EC cell proliferation, and that genetic deletion of MEK5 resulted in EC impaired proliferation and reduced tumor growth capacity in nude mice. Pharmacologic inhibition or ERK5 silencing impaired NF-kB pathway in EC cells and xenografts. Furthermore, we found a positive correlation between ERK5 and p65/RELA protein levels in human EC tumor samples. Mechanistically, genetic or pharmacologic impairment of ERK5 resulted in downregulation of NEMO/IKKγ expression, leading to impaired p65/RELA activity and to apoptosis in EC cells and xenografts, which was rescued by NEMO/IKKγ overexpression. Notably, ERK5 inhibition, MEK5 deletion or NF-kB inhibition sensitized EC cells to standard EC chemotherapy (paclitaxel/carboplatin) toxicity, whereas ERK5 inhibition synergized with paclitaxel to reduce tumor xenograft growth in mice. Together, our results suggest that the ERK5-NEMO-NF-κB pathway mediates EC cell proliferation and survival. We propose the ERK5/NF-κB axis as new target for EC treatment.Open Access Funding provided by Universitat Autonoma de Barcelona. The JM Lizcano research group was supported by grants from the Spanish Ministry of Economy and Competitiveness (MINECO, grant SAF2015-64237-R), and the Spanish Ministry of Science and Innovation (grant PID2019-107561RB-I00), and co-funded by the European Regional Development Fund (ERDF)

Exploring Potentialities and Limitations of Stapled o- Oligo(PhenyleneEthynylene)s (o-OPEs) as Efficient Circularly Polarized Luminescence Emitters

In this paper we have studied the chiroptical properties of a family of o-OPE derivatives with different steric hindrance. Experimental results show high dissymmetry factors (gabs and glum up to 1.1x10-2) and very similar ECD and CPL for all the derivatives, that makes this basic o-OPE scaffold a robust pure organic emitter. VCD spectra are used to characterize conformational properties in solution. DFT and TD-DFT calculations support experimental results also proving that ECD and CPL are almost exclusively linked to helical moiety and not to size or conformation of substituents. As chiroptical properties of these emitters are independent of substituents, this OPE scaffold can be used as basic skeleton for the design of sensing probes with high CPL efficiencies.We thank MICINN (CTQ2014-53598-R) and Junta de Andalucía (FQM1484) for financial support. Computing Center CINECA Via Magnanelli 6/3 40033 – Casalecchio di Reno (Bologna) Italy and Regione Lombardia for the LISA Grant No. “ChiPhyto: HPL13POZE1” is acknowledged for access to computational facilities. P. Reiné thanks MICINN for a FPU fellowship

Pursuing the diffraction limit with nano-led scanning transmission optical microscopy

Recent research into miniaturized illumination sources has prompted the development of alternative microscopy techniques. Although they are still being explored, emerging nano-light-emitting-diode (nano-LED) technologies show promise in approaching the optical resolution limit in a more feasible manner. This work presents the exploration of their capabilities with two different prototypes. In the first version, a resolution of less than 1 µm was shown thanks to a prototype based on an optically downscaled LED using an LED scanning transmission optical microscopy (STOM) technique. This research demonstrates how this technique can be used to improve STOM images by oversampling the acquisition. The second STOM-based microscope was fabricated with a 200 nm GaN LED. This demonstrates the possibilities for the miniaturization of on-chip-based microscopes.This work was partially supported by the European Union’s Horizon 2020 research and innovation program under grant agreement No. 737089—ChipScope

The ERK5/NF-κB signaling pathway targets endometrial cancer proliferation and survival

Endometrial cancer (EC) is the most common type of gynecologic cancer in women of developed countries. Despite surgery combined with chemo-/radiotherapy regimens, overall survival of patients with high-risk EC tumors is poor, indicating a need for novel therapies. The MEK5-ERK5 pathway is activated in response to growth factors and to different stressors, including oxidative stress and cytokines. Previous evidence supports a role for the MEK5-ERK5 pathway in the pathology of several cancers. We investigated the role of ERK5 in EC. In silico analysis of the PanCancer Atlas dataset showed altera- tions in components of the MEK5-ERK5 pathway in 48% of EC patients. Here, we show that ERK5 inhibition or silencing decreased EGF-induced EC cell proliferation, and that genetic deletion of MEK5 resulted in EC impaired proliferation and reduced tumor growth capacity in nude mice. Pharmacologic inhibition or ERK5 silencing impaired NF-kB pathway in EC cells and xenografts. Furthermore, we found a positive correlation between ERK5 and p65/RELA protein levels in human EC tumor samples. Mechanistically, genetic or pharmacologic impairment of ERK5 resulted in downregulation of NEMO/ IKKγ expression, leading to impaired p65/RELA activity and to apoptosis in EC cells and xenografts, which was rescued by NEMO/IKKγ overexpression. Notably, ERK5 inhibition, MEK5 deletion or NF-kB inhibition sensitized EC cells to standard EC chemotherapy (paclitaxel/carboplatin) toxicity, whereas ERK5 inhibition synergized with paclitaxel to reduce tumor xenograft growth in mice. Together, our results suggest that the ERK5-NEMO-NF-κB pathway mediates EC cell prolifera- tion and survival. We propose the ERK5/NF-κB axis as new target for EC treatment.The online version contains supplementary material available at 10.1007/s00018-022-04541-

Pursuing the diffraction limit with Nano-LED scanning transmission optical microscopy

Recent research into miniaturized illumination sources has prompted the development of alternative microscopy techniques. Although they are still being explored, emerging nano-light-emitting-diode (nano-LED) technologies show promise in approaching the optical resolution limit in a more feasible manner. This work presents the exploration of their capabilities with two different prototypes. In the first version, a resolution of less than 1 µm was shown thanks to a prototype based on an optically downscaled LED using an LED scanning transmission optical microscopy (STOM) technique. This research demonstrates how this technique can be used to improve STOM images by oversampling the acquisition. The second STOM-based microscope was fabricated with a 200 nm GaN LED. This demonstrates the possibilities for the miniaturization of on-chip-based microscopes