Mid-infrared tunable filter based on a femtosecond-written silica volume Bragg grating.

A silica volume Bragg grating (VBG) is used to filter the light of a mid-infrared (mid-IR) supercontinuum laser. The VBG with a 7 µm period was inscribed with 800 nm pulses with a 100 fs duration and the phase-mask technique over a glass thickness of 3 mm. Despite silica's absorption, the VBG allows obtaining a narrowband light source tunable from 2.9 to 4.2 µm with a full width at half maximum (FWHM) of 29 nm. This demonstrates the great potential of using femtosecond-written VBGs as highly tunable, yet selective, spectral filters in the mid-IR.

Necrosulfonamide causes oxidation of PCM1 and impairs ciliogenesis and autophagy.

Centriolar satellites are high-order assemblies, scaffolded by the protein PCM1, that gravitate as particles around the centrosome and play pivotal roles in fundamental cellular processes notably ciliogenesis and autophagy. Despite stringent control mechanisms involving phosphorylation and ubiquitination, the landscape of post-translational modifications shaping these structures remains elusive. Here, we report that necrosulfonamide (NSA), a small molecule known for binding and inactivating the pivotal effector of cell death by necroptosis MLKL, intersects with centriolar satellites, ciliogenesis, and autophagy independently of MLKL. NSA functions as a potent redox cycler and triggers the oxidation and aggregation of PCM1 alongside select partners, while minimally impacting the overall distribution of centriolar satellites. Additionally, NSA-mediated ROS production disrupts ciliogenesis and leads to the accumulation of autophagy markers, partially alleviated by PCM1 deletion. Together, these results identify PCM1 as a redox sensor protein and provide new insights into the interplay between centriolar satellites and autophagy.

Reliability Investigation of Silicide-Based Thermoelectric Modules.

The reliability and failure mechanisms of silicide-based thermoelectric modules (n-type Mg2(Si,Sn)/p-type HMS) were investigated thanks to two types of thermal tests with either a fixed or a cycling thermal gradient, under different atmospheres. The hot interfaces of the thermoelectric modules were analyzed by scanning electron microscopy and X-ray diffraction after the reliability tests. The current thermoelectric modules do not exhibit any failure mechanism under ambient air for a hot side temperature of 250 °C for tests conducted either during 500 h at a fixed temperature gradient or after 1000 thermal cycles. However, when the temperature was increased to 350 °C, pesting phenomena were detected at the hot side of the n-type Mg2(Si,Sn) legs caused by the decomposition/oxidation of the material. These phenomena are strongly slowed down for thermoelectric modules tested under a primary vacuum, highlighting the predominant role of oxygen in the degradation mechanism. Interdiffusion phenomena are the most pronounced at the interface of the hot side of the n-type thermoelectric materials. The formation of a MgO layer, which is an electrical and thermal insulator, has decreased the thermoelectric modules' performances. For thermal cycling tests, cracks are observed on the hot side of the n-type legs. The presence of these cracks drastically increases the thermal and electrical resistances, leading to an overheating of the system and limiting its efficiency and failure by breaking electrical continuity. The interfaces at the hot side temperature of the p-type HMS legs remained intact whatever the test conditions were, indicating a high chemical stability and a good mechanical strength.

Inactivating negative regulators of cortical branched actin enhances persistence of single cell migration.

The Rac1-WAVE-Arp2/3 pathway pushes the plasma membrane by polymerizing branched actin, thereby powering membrane protrusions that mediate cell migration. Here, using knockdown (KD) or knockout (KO), we combine the inactivation of the Arp2/3 inhibitory protein arpin, the Arp2/3 subunit ARPC1A and the WAVE complex subunit CYFIP2, all of which enhance the polymerization of cortical branched actin. Inactivation of the three negative regulators of cortical branched actin increases migration persistence of human breast MCF10A cells and of endodermal cells in the zebrafish embryo, significantly more than any single or double inactivation. In the triple KO cells, but not in triple KD cells, the 'super-migrator' phenotype was associated with a heterogenous downregulation of vimentin (VIM) expression and a lack of coordination in collective behaviors, such as wound healing and acinus morphogenesis. Re-expression of vimentin in triple KO cells largely restored normal persistence of single cell migration, suggesting that vimentin downregulation contributes to the maintenance of the super-migrator phenotype in triple KO cells. Constant excessive production of branched actin at the cell cortex thus commits cells into a motile state through changes in gene expression.

Low temperature reaction kinetics inside an extended Laval nozzle: REMPI characterization and detection by broadband rotational spectroscopy.

Chirped-Pulse Fourier-Transform millimeter wave (CP-FTmmW) spectroscopy is a powerful method that enables detection of quantum state specific reactants and products in mixtures. We have successfully coupled this technique with a pulsed uniform Laval flow system to study photodissociation and reactions at low temperature, which we refer to as CPUF ("Chirped-Pulse/Uniform flow"). Detection by CPUF requires monitoring the free induction decay (FID) of the rotational coherence. However, the high collision frequency in high-density uniform supersonic flows can interfere with the FID and attenuate the signal. One way to overcome this is to sample the flow, but this can cause interference from shocks in the sampling region. This led us to develop an extended Laval nozzle that creates a uniform flow within the nozzle itself, after which the gas undergoes a shock-free secondary expansion to cold, low pressure conditions ideal for CP-FTmmW detection. Impact pressure measurements, commonly used to characterize Laval flows, cannot be used to monitor the flow within the nozzle. Therefore, we implemented a REMPI (resonance-enhanced multiphoton ionization) detection scheme that allows the interrogation of the conditions of the flow directly inside the extended nozzle, confirming the fluid dynamics simulations of the flow environment. We describe the development of the new 20 K extended flow, along with its characterization using REMPI and computational fluid dynamics. Finally, we demonstrate its application to the first low temperature measurement of the reaction kinetics of HCO with O2 and obtain a rate coefficient at 20 K of 6.66 ± 0.47 × 10-11 cm3 molec-1 s-1.

Chromatically Corrected Multicolor Multiphoton Microscopy.

Simultaneous imaging of multiple labels in tissues is key to studying complex biological processes. Although strategies for color multiphoton excitation have been established, chromatic aberration remains a major problem when multiple excitation wavelengths are used in a scanning microscope. Chromatic aberration introduces a spatial shift between the foci of beams of different wavelengths that varies across the field of view, severely degrading the performance of color imaging. In this work, we propose an adaptive correction strategy that solves this problem in two-beam microscopy techniques. Axial chromatic aberration is corrected by a refractive phase mask that introduces pure defocus into one beam, while lateral chromatic aberration is corrected by a piezoelectric mirror that dynamically compensates for lateral shifts during scanning. We show that this light-efficient approach allows seamless chromatic correction over the entire field of view of different multiphoton objectives without compromising spatial and temporal resolution and that the effective area for beam-mixing processes can be increased by more than 1 order of magnitude. We illustrate this approach with simultaneous three-color, two-photon imaging of developing zebrafish embryos and fixed Brainbow mouse brain slices over large areas. These results establish a robust and efficient method for chromatically corrected multiphoton imaging.

MiniBAR/GARRE1 is a dual Rac and Rab effector required for ciliogenesis.

Cilia protrude from the cell surface and play critical roles in intracellular signaling, environmental sensing, and development. Reduced actin-dependent contractility and intracellular trafficking are both required for ciliogenesis, but little is known about how these processes are coordinated. Here, we identified a Rac1- and Rab35-binding protein with a truncated BAR (Bin/amphiphysin/Rvs) domain that we named MiniBAR (also known as KIAA0355/GARRE1), which plays a key role in ciliogenesis. MiniBAR colocalizes with Rac1 and Rab35 at the plasma membrane and on intracellular vesicles trafficking to the ciliary base and exhibits fast pulses at the ciliary membrane. MiniBAR depletion leads to short cilia, resulting from abnormal Rac-GTP/Rho-GTP levels and increased acto-myosin-II-dependent contractility together with defective trafficking of IFT88 and ARL13B into cilia. MiniBAR-depleted zebrafish embryos display dysfunctional short cilia and hallmarks of ciliopathies, including left-right asymmetry defects. Thus, MiniBAR is a dual Rac and Rab effector that controls both actin cytoskeleton and membrane trafficking for ciliogenesis.

Synthesis of α-Chloroarylacetic Acid via Electrochemical Carboxylation of α,α-Dichloroarylmethane Derivatives.

The electrocarboxylation of α,α-dichloroarylmethane derivatives in the presence of CO2 was achieved, providing several α-chloroarylacetic acid derivatives with modest yields but high selectivity (chlorinated vs. non-chlorinated or dicarboxylic acid products). The obtained products were then involved in several chemical transformations, underlining their potential as versatile intermediates in synthetic chemistry. A mechanism was also proposed based upon a control experiment and cyclic voltammetry (CV) study.

Ultradifferentiable classes of entire functions.

We study classes of ultradifferentiable functions defined in terms of small weight sequences violating standard growth and regularity requirements. First, we show that such classes can be viewed as weighted spaces of entire functions for which the crucial weight is given by the associated weight function of the so-called conjugate weight sequence. Moreover, we generalize results from M. Markin from the so-called small Gevrey setting to arbitrary convenient families of (small) sequences and show how the corresponding ultradifferentiable function classes can be used to detect boundedness of normal linear operators on Hilbert spaces (associated with an evolution equation problem). Finally, we study the connection between small sequences and the recent notion of dual sequences introduced in the Ph.D. thesis of J. Jiménez-Garrido.

The world around us and the picture(s) in our heads: The effects of news media use on belief organization.

Since Converse [1964. The nature of belief systems in mass publics. Critical Review, 18(1-3), 1 - 74 https://doi.org/10.1080/08913810608443650] asked "What goes with what?", research tries to answer this question. How individuals perceive the world around them depending on media use has been an endeavor of studying societal beliefs of societal issues separately. Building upon literature on cognitive architecture, we study how media use shapes the formation and stability of belief structures across issues in public opinion reflected in groups of individuals. Using a three-wave panel study, we found (1) that individuals' perceptions of different issues are interconnected, (2) translating into aggregate-stable, concurring groups in public opinion, and that (3) differential media use affects the formation and stability of these groups.

Thermal Stability of Mg2Si0.6Sn0.4 under Oxidation Conditions.

The use of Mg2Si0.6Sn0.4 under air in thermoelectric modules in the mid-temperature range of 400-600 °C is linked to its ability to resist oxidation. In this study, oxidation experiments performed at 400 °C under air evidenced the stability of the material, either under static conditions (up to 100 h) or under severe heating-cooling cyclic conditions (up to 400 cycles), showing its ability to be used in a reliable way at this temperature. By combining thermogravimetry, scanning electron microscopy, temperature X-ray diffraction analysis, and mechanical and thermodynamic considerations, a mechanism is proposed explaining how Mg2Si0.6Sn0.4 further undergoes decomposition with time under air when treated above 500 °C. The presence of Sn and the formation of various oxides are the key parameters of the material's degradation.

Diferencia en la expresión del ligando de receptor activador para el factor nuclear K B, en tejido tumoral frente a la infección por diferentes patógenos periodontales / Difference in receptor activator of nuclear factor K B expression in tumoral tissue by different periodontal pathogens

La enfermedad periodontal es una de las principales causas de pérdida dentaria. Clínicamente, esta patología, mediada por la desregulación del sistema inmune producto de una disbiosis ocurrida en el surco gingival, inicia con la inflamación de la encía y evoluciona con el daño irreversible de los tejidos que rodean el diente. El hueso alveolar es uno de los tejidos afectados esta patología, esto debido a la activación de osteoclastos por la sobreexpresión de la proteína RANKL en el huésped. El propósito de este trabajo es determinar el nivel de sobreexpresión de RANKL, en un modelo de células tumorales U2OS, frente a la infección con Porphyromonas gingivalis y Prevotella intermedia. Para identificar el nivel de RANKL, se definieron cuatro grupos: Un grupo control, no tratado; Grupo PG, tratado con P. gingivalis; Grupo PI, tratado con P. Intermedia; y un grupo PG+PI, tratado con ambas bacterias. El nivel relativo de la proteína RANKL fue determinado en el sobrenadante y en los extractos celulares de manera independiente, mediante la técnica Western blot. En sobrenadantes, el grupo PG mostró mayores niveles de RANKL comparados con PI (p < 0,05). En extractos celulares los niveles fueron mayores en el grupo PG+PI (p < 0,05). El grupo PI mostró los niveles más bajos de RANKL. La infección polimicrobiana resulta en una mayor expresión de RANKL en células tumorales U2OS, mientras que frente a la infección P. gingivalis, se observó mayor cantidad de RANKL soluble.

SUMMARY: Periodontal disease is one of the main causes of tooth loss. Clinically, this pathology, mediated by the deregulation of the immune system due to a dysbiosis occurred in the gingival sulcus, begins with the inflammation of the gum and evolves with the irreversible damage of the tissues that surround the tooth. Alveolar bone is one of the most affected tissues by this disease, due to the activation of osteoclasts by the upregulation of RANKL in the host. The aim of this study is to determine the increase of RANKL, in a U2OS tumor cells model, inoculated with Porphyromonas gingivalis and Prevotella intermedia. To identify the level of RANKL, four groups were defined: A control group, not treated; PG group, treated with P.gingivalis; PI group, treated with P. intermedia; and a PG+PI group, treated with both bacteria. The relative level of RANKL was determined in the supernatant and cell extracts independently, using the Western blot technique. In supernatants, the PG group showed higher RANKL levels compared to PI (p < 0.05). In cell extracts the levels were higher in the PG+PI group (p < 0.05.). The PI group showed the lowest levels of RANKL.Polymicrobial infection results in a greater expression of of soluble RANKL was observed.

Label-free imaging of red blood cells and oxygenation with color third-order sum-frequency generation microscopy.

Mapping red blood cells (RBCs) flow and oxygenation is of key importance for analyzing brain and tissue physiology. Current microscopy methods are limited either in sensitivity or in spatio-temporal resolution. In this work, we introduce a novel approach based on label-free third-order sum-frequency generation (TSFG) and third-harmonic generation (THG) contrasts. First, we propose a novel experimental scheme for color TSFG microscopy, which provides simultaneous measurements at several wavelengths encompassing the Soret absorption band of hemoglobin. We show that there is a strong three-photon (3P) resonance related to the Soret band of hemoglobin in THG and TSFG signals from zebrafish and human RBCs, and that this resonance is sensitive to RBC oxygenation state. We demonstrate that our color TSFG implementation enables specific detection of flowing RBCs in zebrafish embryos and is sensitive to RBC oxygenation dynamics with single-cell resolution and microsecond pixel times. Moreover, it can be implemented on a 3P microscope and provides label-free RBC-specific contrast at depths exceeding 600 µm in live adult zebrafish brain. Our results establish a new multiphoton contrast extending the palette of deep-tissue microscopy.

Guidance by followers ensures long-range coordination of cell migration through α-catenin mechanoperception.

Morphogenesis, wound healing, and some cancer metastases depend upon the migration of cell collectives that need to be guided to their destination as well as coordinated with other cell movements. During zebrafish gastrulation, the extension of the embryonic axis is led by the mesendodermal polster that migrates toward the animal pole, followed by the axial mesoderm that undergoes convergence and extension. Here, we investigate how polster cells are guided toward the animal pole. Using a combination of precise laser ablations, advanced transplants, and functional as well as in silico approaches, we establish that each polster cell is oriented by its immediate follower cells. Each cell perceives the migration of followers, through E-cadherin/α-catenin mechanotransduction, and aligns with them. Therefore, directional information propagates from cell to cell over the whole tissue. Such guidance of migrating cells by followers ensures long-range coordination of movements and developmental robustness.

Efficacy and safety of endoscopic papillectomy: a multicenter, retrospective, cohort study on 227 patients.

Background: Endoscopic papillectomy is a minimally invasive treatment for benign tumors of the ampulla of Vater or early ampullary carcinoma. However, reported recurrence rates are significant and risk factors for recurrence are unclear. Objective: The aims of this study were to evaluate the efficacy and safety of endoscopic papillectomy and to identify risk factors for recurrence and adverse events. Methods: All patients who underwent endoscopic papillectomy at five tertiary referral centers between January 2008 and December 2018 were included. Recurrence was defined as the detection of residue on one of the follow-up endoscopies. Treatment success was defined as the absence of tumor residue on the last follow-up endoscopy. Results: A total of 227 patients were included. The resections were en bloc in 64.8% of cases. The mean lesion size was 20 mm (range: 3-80) with lateral extension in 23.3% of cases. R0 resection was achieved in 45.3% of cases. The recurrence rate was 30.6%, and 60.7% of recurrences were successfully treated with additional endoscopic treatment. Finally, treatment success was achieved in 82.8% of patients with a median follow-up time of 22.3 months. R1 resection, intraductal invasion, and tumor size > 2 cm were associated with local recurrence. Adverse events occurred in 36.6% of patients and included pancreatitis (17.6%), post-procedural hemorrhage (11.0%), perforation (5.2%), and biliary stenosis (2.6%). The mortality rate was 0.9%. Conclusion: Endoscopic papillectomy is an effective and relatively well-tolerated treatment for localized ampullary tumors. In this series, R1 resection, intraductal invasion, and lesion size > 2 cm were associated with local recurrence.

Patients' Perceptions of Pharmacogenetic Testing and Access to Their Results: State of the Art in Spain and Systematic Review.

The process of clinical pharmacogenetics implementation depends on patients' and general population's perceptions. To date, no study has been published addressing Spanish patients' opinions on pharmacogenetic testing, the availability of the results, and the need for signing informed consent. In this work, we contacted 146 patients that had been previously genotyped at our laboratory and 46 healthy volunteers that had participated in a bioequivalence clinical trial at the Clinical Pharmacology Department of Hospital Universitario de La Princesa and consented to pharmacogenetic testing for research purposes. From the latter, 108 and 34, respectively, responded to the questionnaire (i.e., a response rate of 74%); Participants were scheduled for a face-to-face, telephone, or videoconference interview and were asked a total of 27 questions in Spanish. Great or almost complete acceptance of pharmacogenetic testing was observed (99.3%), age and university education level being the main predictors of acceptance rates and understanding (multivariate analysis, p = 0.004, R2 = 0.17, age being inversely proportional to acceptance rates and understanding and university level being related to higher acceptance rates and understanding compared to other education levels). Mixed perceptions were observed on the requirement of written informed consent (55.6% in favor); therefore, it seems recommendable to continue requesting it for the upcoming years until more perceptions are collected. The majority of participants (95.8%) preferred storing pharmacogenetic results in medical records rather than in electronic sources (55.6%) and highly agreed with the possibility of carrying their results on a portable card (91.5%). Patients agreed to broad genetic testing, including biomarkers unrelated to their disease (93.7%) or with little clinically relevant evidence (94.4%). Patients apparently rely on clinician's or pharmacogeneticist's interpretation and seem, therefore, open to the generation of ethically challenging information. Finally, although most patients (68.3%) agreed with universal population testing, some were reluctant, probably due to the related costs and sustainability of the Spanish Health System. This was especially evident in the group of patients who were older and with a likely higher proportion of pensioners.

Live 3D imaging and mapping of shear stresses within tissues using incompressible elastic beads.

To investigate the role of mechanical constraints in morphogenesis and development, we have developed a pipeline of techniques based on incompressible elastic sensors. These techniques combine the advantages of incompressible liquid droplets, which have been used as precise in situ shear stress sensors, and of elastic compressible beads, which are easier to tune and to use. Droplets of a polydimethylsiloxane mix, made fluorescent through specific covalent binding to a rhodamin dye, are produced by a microfluidics device. The elastomer rigidity after polymerization is adjusted to the tissue rigidity. Its mechanical properties are carefully calibrated in situ, for a sensor embedded in a cell aggregate submitted to uniaxial compression. The local shear stress tensor is retrieved from the sensor shape, accurately reconstructed through an active contour method. In vitro, within cell aggregates, and in vivo, in the prechordal plate of the zebrafish embryo during gastrulation, our pipeline of techniques demonstrates its efficiency to directly measure the three dimensional shear stress repartition within a tissue.

Nonlinear Conditions for Ultradifferentiability.

A remarkable theorem of Joris states that a function f is C ∞ if two relatively prime powers of f are C ∞ . Recently, Thilliez showed that an analogous theorem holds in Denjoy-Carleman classes of Roumieu type. We prove that a division property, equivalent to Joris's result, is valid in a wide variety of ultradifferentiable classes. Generally speaking, it holds in all dimensions for non-quasianalytic classes. In the quasianalytic case we have general validity in dimension one, but we also get validity in all dimensions for certain quasianalytic classes.

Deep and Spatially Controlled Volume Ablations using a Two-Photon Microscope in the Zebrafish Gastrula.

Morphogenesis involves many cell movements to organize cells into tissues and organs. For proper development, all these movements need to be tightly coordinated, and accumulating evidence suggests this is achieved, at least in part, through mechanical interactions. Testing this in the embryo requires direct physical perturbations. Laser ablations are an increasingly used option that allows relieving mechanical constraints or physically isolating two cell populations from each other. However, many ablations are performed with an ultraviolet (UV) laser, which offers limited axial resolution and tissue penetration. A method is described here to ablate deep, significant, and spatially well-defined volumes using a two-photon microscope. Ablations are demonstrated in a transgenic zebrafish line expressing the green fluorescent protein in the axial mesendoderm and used to sever the axial mesendoderm without affecting the overlying ectoderm or the underlying yolk cell. Cell behavior is monitored by live imaging before and after the ablation. The ablation protocol can be used at different developmental stages, on any cell type or tissue, at scales ranging from a few microns to more than a hundred microns.

Direct Measurements of Electroviscous Phenomena in Nafion Membranes.

Investigation of electroviscous effects is of interest to technologies that exploit transport of ions through ion exchange membranes, charged capillaries, and porous media. When ions move through such media due to a hydrostatic pressure difference, they interact with the fixed charges, leading to an increased hydraulic resistance. Experimentally this is observed as an apparent increase in the viscosity of the solution. Electroviscous effects are present in all electrochemical membrane-based processes ranging from nanofiltration to fuel-cells and redox flow batteries. Direct measurements of electroviscous effects varying the applied ionic current through Nafion membranes have, to the best of the authors' knowledge, not yet been reported in literature. In the current study, electroviscous phenomena in different Nafion ion exchange membranes are measured directly with a method where the volume permeation is measured under constant trans-membrane pressure difference while varying the ion current density in the membrane. The direct measurement of the electroviscous effect is compared to the one calculated from the phenomenological transport equations and measured transport coefficients. Within the experimental uncertainty, there is a good agreement between the two values for all membranes tested. We report here an electroviscous effect for all Nafion membranes tested to be κH?κH-1=1.15-0.052+0.035.