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Thirteen benzylethylenearyl ureas and one carbamate have been designed, synthesized and biologically evaluated as regards their antiproliferative activity on tumor cell lines HEK-293 and A-549 and on the immune and endothelial Jurkat T cells and HMEC-1, respectively. A relationship between the structure of the synthetic compounds and their antiproliferative activity has been established. Compounds C.1, C.3, C.12 and C.14 were chosen for further biological studies in order to determine their potential as oncoimmunomodulating agents. Some compounds exhibited significant inhibitory effects on both total PD-L1 and VEGFR-2 in HT-29 cell line, showing urea C.12 active against both targets. Some compounds could reduce more than 50% of cancer living cells, compared to non-treated ones, when assessed in co-cultures using HT-29 and THP-1 cells. In addition, these compounds showed no effect on the immune cell viability and significantly reduce CD11b expression, which is a promising target for immune modulation in anti-cancer therapies.

Due to the outstanding characteristics of LiDAR imaging systems, they seem essential for the consolidation of novel applications related to computer vision, in fields such as autonomous vehicles, outdoor recognition, and surveillance. However, the final technology implementation still has some uncertainties and needs in-depth work for its use in these real-world applications. Under the presence of adverse weather conditions, for example in fog, LiDAR performance is heavily influenced and the quality of the detection becomes severely degraded. The range is reduced due to the dispersion of the media and the sensor could be saturated due to backscattering or deliver a very limited range. Light propagation modeling through turbid media is used as a tool to understand and study these phenomena. Mie Theory allows the characterization of the optical media and light-particle interactions. Monte-Carlo methods are used to solve the radiative transfer problem related to these situations. When working with those models, the results obtained are in accordance with the ones shown in experimental tests, and it is possible to predict the necessities and problems of the designed systems.

Fog, haze, or smoke are usual atmospheric phenomena that dramatically compromise the overall visibility of any scene, critically affecting features such as illumination, contrast, and contour detection of objects. The decrease in visibility compromises the performance of computer vision algorithms such as pattern recognition and segmentation, some of them very relevant for decision-making for the security or autonomous vehicle industries. Several dehazing methods have been proposed, however, to the best of our knowledge, all proposed metrics compare the defogged image to its ground truth for evaluation of the defogging algorithms, or need to estimate parameters through physical models. This fact hinders progress in the field as obtaining proper ground truth images is costly and time-consuming, and physical parameters greatly depend on the scene conditions. This paper aims to tackle this issue by proposing a contour-based metric for image defogging evaluation that does not need a ground truth image. The proposed metric only requires the original hazy RGB image and the RGB image after the defogging procedure. A comparison of the proposed metric with metrics currently used in the NTIRE 2018 defogging challenge is performed to prove its effectiveness in a general situation, showing comparable results to conventional metrics.

This review summarizes the current knowledge on biofluids and the main flow sensing techniques applied in healthcare today. Since the very beginning of the history of medicine, one of the most important assets for evaluating various human diseases has been the analysis of the conditions of the biofluids within the human body. Hence, extensive research on sensors intended to evaluate the flow of many of these fluids in different tissues and organs has been published and, indeed, continues to be published very frequently. The purpose of this review is to provide researchers interested in venturing into biofluid flow sensing with a concise description of the physiological characteristics of the most important body fluids that are likely to be altered by diverse medical conditions. Similarly, a reported compilation of well-established sensors and techniques currently applied in healthcare regarding flow sensing is aimed at serving as a starting point for understanding the theoretical principles involved in the existing methodologies, allowing researchers to determine the most suitable approach to adopt according to their own objectives in this broad field. This research was supported by the Consejo Nacional de Ciencia y Tecnología (CONACYT) of México through Ph.D. grant 472102 and by the Ministerio de Economía y Competitividad through grant FIS2017-89850R.

Thirteen benzylethoxyaryl ureas have been synthesized and biologically evaluated as multitarget inhibitors of VEGFR-2 and PD-L1 proteins to overcome resistance phenomena offered by cancer. The antiproliferative activity of these molecules on several tumor cell lines (HT-29 and A549), on the endothelial cell line HMEC-1, on immune cells (Jurkat T) and on the non-tumor cell line HEK-293 has been determined. Selective indexes (SI) have been also determined and compounds bearing p-substituted phenyl urea unit together with a diaryl carbamate exhibited high SI values. Further studies on these selected compounds to determine their potential as small molecule immune potentiators (SMIPs) and as antitumor agents have been performed. From these studies, we have concluded that the designed ureas have good tumor antiangiogenic properties, exhibit good inhibition of CD11b expression, and regulate pathways involved in CD8 T-cell activity. These properties suggest that these compounds could be potentially useful in the development of new cancer immune treatments.

We present a generalized mathematical model and algorithm for the multi-cavity self-mixing phenomenon based on scattering theory. Scattering theory, which is extensively used for travelling wave is exploited to demonstrate that the self-mixing interference from multiple external cavities can be modelled in terms of individual cavity parameters recursively. The detailed investigation shows that the equivalent reflection coefficient of coupled multiple cavities is a function of both attenuation coefficient and the phase constant, hence propagation constant. The added benefit with recursively model is that it is computationally very efficient to model large number of parameters. Finally, with the aid of simulation and mathematical modelling, we demonstrate how the individual cavity parameters such as cavity length, attenuation coefficient, and refractive index of individual cavities can be tuned to get a self-mixing signal with optimal visibility. The proposed model intends to leverage system description for biomedical applications when probing multiple diffusive media with distinct characteristics, but could be equally extended to any setup in general.

The ELT M1 Local Coherencer is a non-contact metrology system aimed to simultaneously measure the relative pistons on the six sides of a target M1 segment with respect to neighboring ones (reference segments) with an accuracy below 300nm in a range of ±250µm. This measurement shall be performed while the Local Coherencer is supported by the M1 Segment Manipulator hanging from the M1 Segment Crane. IDOM has developed for the M1 Local Coherencer a lean, compact and robust solution featuring: - Six lightweight and compact Sensing Modules whose main system is a partially coherent light interferometer for the piston measurements that hugely simplifies image processing and avoids any ambiguity in the measurements. - Comprehensive and robust alignment detection and alignment compensation systems that ensure proper positioning and prevent apparent (bias) piston measurement errors. - A lean embodiment in which all the subsystems, including control and safety elements, are mounted on a single support structure and enclosed in the specified design volume, with no need to use the space reserved in the M1 Segment Manipulator - A solution largely based on small COTS and simple electronics, which account for ease of use, high reliability, easy replaceability and high durability of the system.

This article intends to provide all the experimental insights and analyze the best polarimetric calibration method for a division of aperture polarimetric imager considering the different implications it has on the experimental set-up and its performance. Polarimetric cameras require careful calibration for the correct measurement of polarization information. The calibration methods are introduced, intermediate results are presented, and the ability of the set-up to estimate Stokes vectors and Mueller matrices of the samples in passive and active imaging modes is evaluated. Polarization information recovery achieves accuracy errors below the 10% for all polarization modes when the Data Reduction Matrix or the Eigenvalue Calibration Method are used. Such performance, however, degrades significantly when using the Polarizer Calibration Method. To the best of our knowledge, this is the first time such a detailed comparison of calibration methods is presented in the literature, and it is also the first time the Polarizer Calibration Method is applied to a division of aperture polarimeter. Ministerio de Ciencia e Innovación (PDC2021-121038-I00, PID2020-119484RB-I00); Agència de Gestió d’Ajuts Universitaris i de Recerca (2020FI_B2 00068); European Social Fund; Universitat Politècnica de Catalunya; Banco Santander.

This paper focuses on exploring ways to improve the performance of LiDAR imagers through fog. One of the known weaknesses of LiDAR technology is the lack of tolerance to adverse environmental conditions, such as the presence of fog, which hampers the future development of LiDAR in several markets. Within this paper, a LiDAR unit is designed and constructed to be able to apply temporal and polarimetric discrimination for detecting the number of signal photons received with detailed control of its temporal and spatial distribution under co-polarized and cross-polarized configurations. The system is evaluated using different experiments in a macro-scale fog chamber under controlled fog conditions. Using the complete digitization of the acquired signals, we analyze the natural light media response, to see that due to its characteristics it could be directly filtered out. Moreover, we confirm that there exists a polarization memory effect, which, by using a polarimetric cross-configuration detector, allows improvement of object detection in point clouds. These results are useful for applications related to computer vision, in fields like autonomous vehicles or outdoor surveillance where many variable types of environmental conditions may be present. Agència de Gestió d’Ajuts Universitaris i de Recerca (2021FI_B2 00068, 2021FI_B2 00077); DSTL (DSTLX1000145661); Ministerio de Ciencia e Innovación (PDC2021-121038-I00, PID2020-119484RB-I00).

We compare conventional intensity imaging against different modes of polarimetric imaging by evaluating the image contrast of images taken in a controlled foggy environment. A small-scale fog chamber has been designed and constructed to create the necessary controlled foggy environment. A division-of-focal-plane camera of linear polarization and a linearly polarized light source has been used for performing the experiments with polarized light. In order to evaluate the image contrast of the different imaging modes, the Michelson contrast of samples of different materials relative to their background has been calculated. The higher the image contrast, the easier it is to detect and segment the targets of interest that are surrounded by fog. It has been quantitatively demonstrated that polarimetric images present an improvement in contrast compared to conventional intensity images in the situations studied. This research was funded by MICINN project PID2020-119484RB-I00, and by AGAUR Grants 2020FI_B1 00185 and 2020FI_B2 00068, supported by the Secretaria d’Universitats i Recerca de la Generalitat de Catalunya and the Fons Social Europeu (FSE).

Currently, in CD6, a new line of research devoted to polarimetric imaging is being developed. The use of polarization adds new information that is not reachable using other conventional imaging modes. In addition, recent literature explores the capability of using polarized illumination and detection to extend the range and enhance image contrast in turbid media such as fog, dust or smoke. Different computational and experimental tools are presented, in order to study polarized light behavior when propagating through foggy media. This work was supported by the Secretary of Universities and Research from the Generalitat of Catalunya and the European Social Fund under the grant 2019FI-B-00543 and partially supported by the Spanish Ministry of Economy and Competitiveness (MINECO) under the project FIS2017-89850R.

The CD6 has recently developed a powerful line of research on polarimetric imaging. This field covers several applications in which the addition of polarization properties enables to enhance the contrast in detection. Moreover, recent literature states the possibility of using polarization illumination and detection to improve the range detection in turbid media such as fog, dust or smoke. This paper addresses the optical engineering behind the detection of polarization imaging and sets the basis of using polarization as a tool in detecting through fog. This work was supported by the Secretary of Universities and Research from the Generalitat of Catalunya and the European Social Fund under the grant 2018FI-B-00868 and partially supported by the Spanish Ministry of Economy and Competitiveness (MINECO) under the project FIS2017- 89850R.

Acoustic waves (AW) has been used for the testing of static and dynamic structures. They contain the signature about the performance of rotary machines such as cyclic fatigue, friction, turbulence and cavitation. Thus has been extensively used in the condition monitoring and material characterization. In this paper, we present an algorithm based on wavelets to process the transient AW in time and frequency domain both simultaneously to extract its the temporal (e.g. time duration) and spectral properties (e.g. emission frequency). Further, optical method based on optical feedback (OF) is presented for detection of AW providing powerful non-contact, non-destructive diagnostic capabilities, which is safe, efficient, cost-effective and potential to be used in harsh conditions.

This paper presents a novel calibration method for solid-state LiDAR devices based on a geometrical description of their scanning system, which has variable angular resolution. Determining this distortion across the entire Field-of-View of the system yields accurate and precise measurements which enable it to be combined with other sensors. On the one hand, the geometrical model is formulated using the well-known Snell&rsquo, s law and the intrinsic optical assembly of the system, whereas on the other hand the proposed method describes the scanned scenario with an intuitive camera-like approach relating pixel locations with scanning directions. Simulations and experimental results show that the model fits with real devices and the calibration procedure accurately maps their variant resolution so undistorted representations of the observed scenario can be provided. Thus, the calibration method proposed during this work is applicable and valid for existing scanning systems improving their precision and accuracy in an order of magnitude.

A family of dipeptidyl enoates has been prepared and tested against the parasitic cysteine proteases rhodesain, cruzain and falcipain-2 related to sleeping sickness, Chagas disease and malaria, respectively. They have also been tested against human cathepsins B and L1 for selectivity. Dipeptidyl enoates resulted to be irreversible inhibitors of these enzymes. Some of the members of the family are very potent inhibitors of parasitic cysteine proteases displaying k2nd (M−1s−1) values of seven orders of magnitude. In vivo antiprotozoal testing was also performed. Inhibitors exhibited IC50 values in the micromolar range against Plasmodium falciparum, Trypanosoma brucei, Trypanosoma cruzi and even more promising lower values against Leishmania donovanii.

We present experimental results of a low-emission self-mixing interferometer that uses a coupled interferometric effect to improve the signal produced by a vibrating target. This method is intended to be useful in applications where the target is prone to be damaged by high-intensity laser sources. The beam of a Fabry-Perot laser diode is split and ~21% of the original emission is used to measure the harmonic micro-displacements of the target using the self-mixing effect. A portion of the residual beam, which also carries the interferometric information related to the target displacement, is reinjected back into the laser cavity by means of a fixed reflector, causing a second interferometric phenomenon that improves the signal-to-noise ratio of the measurement by up to ~13 dB. A theoretical description of the phenomena is also proposed. Further, we apply this technique to the two most common self-mixing sensing schemes: internal photodiode and junction voltage. The reported results show good agreement with theory and prove the capability of the method to enhance the SNR in SMI schemes. Consejo Nacional de Ciencia y Tecnología (472102); Ministerio de Economía y Competitividad (FIS2017-89850R).

We propose a new confocal device for flow profiling in microcapillaries. A viewfinder system is developed using a visible light microscope, allowing focusing with high precision an 830 nm Fabry-Perot laser diode on a microchannel. By means of a novel confocal approach, the Doppler shift produced by the particles of a turbid liquid moving in the focal plane can be measured in real time using the well-known self-mixing effect. The resolution of this device is characterized in function of the full width at half maximum of the Gaussian frequency peak related to the self-mixing signal in the frequency domain. Velocity measurements for flow rates from 0.2 to 1.6 mL/min are presented, and the results demonstrate that the method reduces the phase noise and the effects of the out-of-focus particles, allowing straightforward flow profiling in microchannel structures

We demonstrate a novel method that makes an efficient use of laser nonlinear dynamics when subject to optical self-injection for subwavelength displacement sensing purposes. The proposed methodology combines two different phenomena taking place inside the laser cavity: optical self-injection, which results in optical feedback interference, and laser continuous wave frequency modulation, giving rise to a wavelength sweeping effect in the laser’s emission. We present a combination of these phenomena to measure vibration amplitudes below $\lambda /2$ with the resolutions of a few nanometers, bandwidth dependent upon the distance of external target, amplitude, and frequency of current modulation. The basic theoretical details and a mathematical model are presented for the developed measurement principle. Experimental results with the system working as a vibrometer to measure a target vibration of amplitude ${\lambda }/{5}$ (137.5 nm) with a mean peak-to-peak error of 2.4 nm just by pointing the laser diode onto the target and applying some signal processing are also demonstrated.

Nowadays, taking advantage of polarization allows enhancing the contrast of a detected object and extending the information of the scene compared to conventional intensity imagery, as the information added by polarimetric images is complementary to intensity ones. Using polarization has a wide interest in space exploration, earth remote sensing, Machine vision and biomedical diagnosis, and is extending its use to several applications. Here, we present a basic imaging polarimeter which measures the full Stokes vector of the scene based on a division of time structure, based on a consumer CMOS camera. The polarization state of partially or fully polarized light can be represented by means of the Stokes vector, which is the goal of the measurement. However, due to its nature, the components of the Stokes vector cannot be measured directly, as they must be recovered from a set of intensity measurements. In the paper the results show the measured intensity at 632nm and the recovered Stokes data produced by the determined data reduction matrix at six reference polarization states, as well as the theoretical and recovered Stokes parameters from the calibration experiment. The root mean square (RMS) errors are below 10% . Therefore, this system can provide a well-conditioned data reduction matrix for noise immunity and the spectral range can be widened by using white light and a monochrome camera.

Aryl-aldehydes containing ortho-substituted propiolate fragments react with hydroxylamine to afford carbinolamine intermediates that undergo intramolecular aza-conjugate addition reactions to afford N-hydroxy-2.3-dihydro-isoindolin-1-ones that can be reduced to their corresponding isoindolin-1-ones and isoindoles.

Dipeptidyl enoates were prepared through a high-yielding two-step synthetic route. They have a dipeptidic structure with a 4-oxoenoate moiety as a warhead with multiple reactive sites. Dipeptidyl enoates were screened against rhodesain and human cathepsins B and L, and were found to be potent and selective inhibitors of rhodesain. Among them (S,E)-ethyl 5-((S)-2-{[(benzyloxy)carbonyl]amino}-3-phenylpropanamido)-7-methyl-4-oxooct-2-enoate (6) was the most potent, with an IC50 value of 16.4 nm and kinact/Ki=1.6×106 m−1 s−1 against rhodesain. These dipeptidyl enoates display a reversible mode of inhibition at very low concentrations and an irreversible mode at higher concentrations. Inhibition kinetics data, supported by docking studies, suggest a dual mode of action via attack of cysteine thiolate at two reactive positions. The authors thank Serveis Centrals d′Instrumentació Científica at Universitat Jaume I for technical support. S.R. thanks the Generalitat Valenciana for a postdoctoral research grant under the VALi+d Program. T.S. thanks the Deutsche Forschungsgemeinschaft (DFG) (SFB630) for financial support.