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La activación de BIM es esencial para la apoptosis desencadenada por el inhibidor de la tirosina quinasa (TKI) del receptor del factor de crecimiento epidérmico (EGFR) en el cáncer de pulmón de células no pequeñas (CPCNP) con mutación de EGFR. Una deleción en el intrón dos del gen BIM da como resultado la generación de isoformas empalmadas alternativamente que alteran su respuesta apoptótica a los TKI, lo que confiere a las células de NSCLC una resistencia intrínseca a estos medicamentos. Los pacientes con ambas alteraciones tienen mala evolución clínica. El estudio actual tuvo como objetivo investigar la eficacia clínica y la tolerabilidad de EGFR-TKI más bevacizumab (Bev) versus EGFR-TKI solos como tratamiento de primera línea en pacientes con NSCLC avanzado con mutaciones de EGFR y deleciones BIM (BIMdel). MATERIALES Y MÉTODOS Se realizó un análisis retrospectivo. BIMdel se detectó mediante análisis de reacción en cadena de la polimerasa y secuenciación directa de ADN. La expresión de la proteína BIM se investigó mediante inmunohistoquímica y los niveles de ARNm de BIM mediante la reacción en cadena de la polimerasa con transcriptasa inversa. Se compararon las características clínicas, la supervivencia general, la supervivencia libre de progresión (PFS), la tasa de respuesta general (ORR) y los eventos adversos relacionados con el tratamiento entre ambos grupos. RESULTADOS Se incluyeron 33 pacientes; 15 recibieron EGFR-TKI y 18 recibieron EGFR-TKI más Bev. La mediana de edad fue de 63 años, con una mayoría de pacientes mujeres reclutadas. Todos los individuos incluidos tenían una puntuación de rendimiento del Grupo Oncológico Cooperativo del Este de 2 o menos. La adición de Bev resultó en un ORR significativamente más alto (94,4 % versus 40 %, P > 0,001). La mediana de SLP fue más larga con el uso de la terapia combinada (11,12 frente a 7,87 meses; P = 0,001). La mediana de supervivencia general tendió a ser más prolongada en los inhibidores de la tirosina quinasa con EGFR más Bev (30,9 frente a 25,4 meses; P = 0,06), pero no alcanzó significación estadística. La respuesta en términos de PFS parcial y completa, así como en general, se vio afectada favorablemente. CONCLUSIÓN Los EGFR-TKI más Bev confirieron una ORR y una SLP significativamente más altas en pacientes con NSCLC avanzado con mutación de EGFR y BIMdel. Se necesitan más estudios prospectivos para validar estos hallazgos. BIM activation is essential for epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI)–triggered apoptosis in EGFR-mutant non–small-cell lung cancer (NSCLC). A deletion in the intron two of the BIM gene results in generation of alternatively spliced isoforms that impairs their apoptotic response to TKIs, conferring the NSCLC cells intrinsic resistance to these medications. Patients with both alterations have poor clinical evolution. The current study aimed to investigate the clinical efficacy and tolerability of EGFR-TKIs plus bevacizumab (Bev) versus EGFR-TKIs alone as first-line treatment in advanced NSCLC patients with EGFR mutations and BIM deletions (BIMdel). MATERIALS AND METHODS A retrospective analysis was conducted. BIMdel was detected using polymerase chain reaction analysis and direct sequencing of DNA. BIM protein expression was investigated by immunohistochemistry, and BIM mRNA levels by reverse transcriptase-polymerase chain reaction. Clinical characteristics, overall survival, progression-free survival (PFS), overall response rate (ORR), and treatment-related adverse events were compared between both groups. RESULTS Thirty-three patients were included; 15 received EGFR-TKIs, and 18 received EGFR-TKIs plus Bev. The median age was 63 years, with a majority of recruited female patients. All included individuals had an Eastern Cooperative Oncology Group performance score of 2 or less. The addition of Bev resulted in a significantly higher ORR (94.4% v 40%, P > .001). Median PFS was longer with the use of the combination therapy (11.12 v 7.87 months; P = .001). Median overall survival tended to be longer in the EGFR-TKIs plus Bev (30.9 v 25.4 months; P = .06) but failed to reach statistical significance. Response in terms of both partial and complete as well as overall favorably affected PFS. CONCLUSION EGFR-TKIs plus Bev conferred a significantly higher ORR and PFS in advanced NSCLC patients with EGFR mutation and BIMdel. Further prospective studies are needed to validate these findings.

Highlights • The identification of the KRAS G12C mutation in non-small cell lung cancer is relevant with new molecules being introduced for treatment. • The variation of mutation prevalence among different regions indicate that certain populations are more prone to develop KRAS G12C mutations among lung cancer than others. • Using genomic markers traditionally employed for the identification of individuals we managed to construct a model that was predictive for KRAS G12C mutational incidence, further indicating that appearance of KRAS G12C follows population substructures., Background The KRAS exon 2 p. G12C mutation in patients with lung adenocarcinoma has been increasing in relevance due to the development and effectiveness of new treatment medications. Studies around different populations indicate that regional variability between ethnic groups and ancestries could play an essential role in developing this molecular alteration within lung cancer. Methods In a prospective and retrospective cohort study on samples from lung adenocarcinoma from 1000 patients from different administrative regions in Colombia were tested for the KRAS p.G12C mutation. An analysis of STR populations markers was conducted to identify substructure contributions to mutation prevalence. Results Included were 979 patients with a national mean frequency for the KRAS exon 2 p.G12C mutation of 7.97% (95%CI 6.27–9.66%). Variation between regions was also identified with Antioquia reaching a positivity value of 12.7% (95%CI 9.1–16.3%) in contrast to other regions such as Bogota DC (Capital region) with 5.4% (2.7–8.2%) and Bolivar with 2.4% (95%CI 0–7.2%) (p-value = 0.00262). Furthermore, Short tandem repeat population substructures were found for eight markers that strongly yielded association with KRAS exon 2 p.G12C frequency reaching an adjusted R2 of 0.945 and a p-value of < 0.0001. Conclusions Widespread identification of KRAS exon 2 p.G12C mutations, especially in cases where NGS is not easily achieved is feasible at a population based level that can characterize regional and national patterns of mutation status. Furthermore, this type of mutation prevalence follows a population substructure pattern that can be easily determined by population and ancestral markers such as STR.

Human papilloma virus (HPV) has been associated with the development and modulation of response in a series of neoplasms. In the case of lung adenocarcinoma, its role in etiology and pathogenesis is still controversial. Considering that this infection brings foreign epitopes, it could be of prognostic significance in patients with lung adenocarcinoma treated with immunotherapy.In a retrospective cohort study we evaluated the presence of HPV genomic material in lung adenocarcinoma primary lesions with the INNO-LiPA platform. Viral replication was also evaluated by detecting the presence of oncoprotein E6/E7 messenger RNA (mRNA) by quantitative RT-PCR. To confirm possible hypotheses regarding viral oncogenesis, vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 (HIF1) were evaluated with stromal fibrosis and immunoscore.A total of 133 patients were included in the analysis, of whom 34 tested positive for HPV, reaching an estimated prevalence of 25.6% [95% confidence interval (CI) 18.2% to 32.9%]. E6/7 mRNA was identified in 28 out of the 34 previously positive cases (82.3%). In immune checkpoint inhibitor (ICI)-treated patients, the median overall survival reached 22.3 months [95% CI 19.4 months- not reached (NR)] for HPV-negative and was not reached in HPV-positive (HPV+) ones (95% CI 27.7-NR; P = 0.008). With regard to progression-free survival, HPV- patients reached a median of 9.2 months (95% CI 7.9-11.2 months) compared to 14.3 months (95% CI 13.8-16.4 months) when HPV was positive (P = 0.001). The overall response rate for HPV+ patients yielded 82.4% compared to 47.1% in negative ones. No differences regarding programmed death-ligand 1, VEGF, HIF1, stromal fibrosis, or immunoscore were identified.In patients with HPV+ lung adenocarcinoma, a significant benefit in overall response and survival outcomes is observed.

We propose an optical method to estimate the average velocity of a liquid fluid circulating through a square pipe with transparent walls. The velocity is obtained from the photovoltage data measured in a semiconductor crystal when is illuminated with a single intensity modulated laser beam, transmitted through the pipe in a perpendicular direction of the moving fluid. Experimental results considering parameters as wavelength, modulation frequency, particles concentration and fluid speed were obtained, and a comparative statistical analysis considering additional measurements obtained by Laser Doppler Anemometry (LDA) as a reference, was performed too.

e21566 Background: Several histopathological markers have been associated with immune system activity and its relationship with clinical outcomes in lung cancer. Determination of tumor infiltrating lymphocytes as well as specific subpopulations could reveal cytotoxic potential. Additionally, changes in stromal composition and fibrosis could also reflect potential cellular interactions with the tumor lesions. In this study we validate these two findings as potential prognostic factors. Methods: A retrospective cohort analysis of patients with advanced lung adenocarcinoma treated in a reference center in Bogota, Colombia was conducted. Demographic as well as treatment variables were collected between January 2018 and December 2019. In addition to clinical outcomes, the percentage of stromal fibrosis and immunoscore were estimated for all biopsy samples by a trained oncological pathologist. Results: A total of 133 patients were included. Male predominance (51.1%) with Karnofsky performance scores (KPS) greater than 80 and 19% of prior cigarette exposure (26 patients) was identified in the cohort. Median overall survival of the cohort was 27.1 months (95%CI 22.1-NA) and progression free survival of 19.4 months (95%CI 18-24.5 months). Percentage of fibrous stroma and immunoscore were associated with a benefit in both OS and PFS. For patients who presented with a low stromal fibrosis, defined as harboring less than 10%, OS reached a median of 25.1 months (95%CI 21.5- 40.5 months) compared to 38.7 months for patients with high fibrosis (95%CI 27.7 months – NA), (p = 0.02). In terms of immunoscore, values under 40% were associated with a longer median OS (38.7 months, [95%CI 31.3- 58.6 months] vs 22.1 months [95%CI19.8- 42.3 months], p < 0.001). Immunoscore and stromal fibrosis were not codependent variables (p < 0.001), suggesting that these markers offer independent prognostic value with regards to OS. Conclusions: Stromal fibrosis and immunoscore serve as prognostic factors that could be easily interpreted and evaluated in order to offer prognostic classification of patients with metastatic adenocarcinoma of the lung.

A copolymer of 3-hexylthiophene and thiophene functionalized with disperse red 1, poly(3-HT-co-TDR1), was synthesized. Chemical structure, molecular weight distribution, optical and thermal properties of this copolymer were characterized by NMR, FT-IR, UV–vis, GPC and DSC–TGA. An optical nonlinear analysis by Z-scan method was also performed for both continuous wave (CW) and pulsed laser pumping. In the CW regime the nonlinearities were evaluated in solid films, and a negative nonlinear refractive index in the range 2.7–4.1 × 10−4 cm2/W was obtained. These values are notoriously high and allowed to observe self-defocusing effects at very low laser intensities: below 1 mW. Further, nonlinear self-phase modulation patterns, during laser irradiation, were also observed. In the pulsed excitation the nonlinear response was evaluated in solution resulting in large two-photon absorption cross section of 5725 GM for the whole copolymer chain and with a value of 232 GM per repeated monomeric unit.

The substrate treatment dependent formation of different micro-morphologies of zinc oxide over PS substrate has been reported. Effect of substrate oxidation and annealing has been studied. Changes in the structural properties were seen in the form of labyrinth patterns developed on the surface and were studied with the help of scanning electron microscope (SEM), atomic force microscope (AFM). X-ray diffraction (XRD) along with UV–visible absorption and photoluminescence (PL) spectroscopy were performed for characterizing the zinc oxide film and the hybrid structure. A relatively flat film of nanostructured zinc oxide particles is found to form on the oxidized substrate as compared to the nanostructured labyrinth patterns formed on the un-oxidized substrate with enhanced aspect ratio. Such micromorphologies can be very promising for fabricating highly sensitive gas sensors.

In this work a brief experimental investigation of velocity changes on a fluid flow by means of a non-contactive optical method based on the Non-steady-state photo-electromotive force (P-EMF) effect is presented. Evidence of linear dependence of P-EMF signal on fluid flow for low velocities as compared with a Laser Doppler Anemometry test is shown and discussed.

This current paper gives a short overview on the results of the study we have conducted to illustrate the operability and reliability properties of CSP plants based on the experience acquired during the first operation year of the CSP generation unit with thermal energy storage (TES) Andasol 3. Andasol 3 was commissioned in autumn 2011 under the leadership of the company “Marquesado Solar S.L.” and is the third of Solar Millennium developed parabolic trough power plants. The plant is located near Guadix in Andalusia, Spain and has an installed capacity of 49.9 MWe and a thermal storage tank with a capacity of 7.5 hours at full load. The power station was designed to reach a net annual energy production of 165 GWh at typical meteorological year conditions. Andasol 3 as well as other solar power plants with TES, are not only providers of environmentally friendly solar electricity, but also power sources with operational capabilities that have the potential to support the continued reliability of the electric power system. Furthermore, the flexibility given by TES allows this type of plants to shift electricity generation meeting capacity needs and peak demand resulting in a rise of utility value due to increased revenues. In order to demonstrate the properties mentioned above and to present the experience gained during the first operational year, Andasol 3 conducted a study based on actual economic and technical data collected during the period past. Our first priority was to explore several operating modes aiming to maximize the economic benefits of the plant and to gain an experience-based foundation that contributes to further developments. For this purpose several operational tests were conducted and anomalies owing to external and internal influence conditions were analyzed and evaluated.

In this work an application of digital holographic microscopy as a tool for oxide layer growth monitoring onto a copper sample, as well as determination of corrosion products formation rate and corrosion type taking place (localized corrosion or uniform corrosion) is presented.

Using electron microscopy and X-ray microanalysis, the formation of tracks by laser processing of AlN:Y 2 O 3 ceramic surfaces was investigated. The main process of channel formation is the decomposition of aluminum nitride (AlN). Due to aluminothermic reduction of Y 2 O 3 , the metallization of channel surfaces occurs. The main products of ablation are Al 2 O 3 , AlN, and AlON.

The use of Information and Communication Technology (ICT)-based power system applications increases continually which poses new engineering challenges regarding the development, validation and management of both - the applications and the intertwined infrastructures. In this paper the need for a joint analysis of power and ICT systems for evaluating smart grid applications is discussed and a systematic validation approach is proposed. After reviewing state of the art validation techniques, a newly developed Wide-Area Monitoring, Protection and Control (WAMPAC) system is introduced. Its extensive use of wide-area communication and the combination of centralized and decentralized decision making stress the complexity of such a cyber-physical system, where the interdependency between the power system and the ICT domains are challenging to validate. Deduced from these requirements, a validation concept is proposed that comprises (i) the usage of a comprehensive smart grid reference model, (ii) a systematic and objectively verifiable generation of scenarios, and (iii) a single and multi-domain validation process using analytical, simulative and experimental techniques. For the latter, a composition of analyses using co-simulation, Hardware-in-the-Loop (HiL) simulations and an empirical test bed is outlined.

The parallel pixel acquisition inherent in wide-field coherence-gated imaging techniques offers the possibility of high-frame-rate imaging and volumetric imaging, including through scattering media. We discuss photorefractive holography using sensitive, dynamic photorefractive multiple quantum well (PRQW) films as a promising approach and, after reviewing the factors that determine the sensitivity of this technique, we demonstrate that high-frame-rate wide-field coherence gated imaging is possible at 830 frames per second with PRQW devices using a non-intensified camera to record the diffracted signal.

Non-steady-state photocurrents are generated in reduced iron-doped lithium niobate crystals. Dependences on spatial frequency and on modulation amplitude are well described by the existing theory and a Debye screening length of 19 nm is determined. The non-steady-state photocurrents strongly decrease for frequencies above 2 Hz. The technique might be useful for material characterization and for convenient active stabilization of holographic setups against mechanical vibrations.

The photoconductivity response time in Bi12SiO20 grows 3 orders of magnitude when the temperature changes from 350 to 200 K. We attribute this to the influence of shallow traps with activation energy 0.4 eV. For low temperatures, the time of holographic grating formation is determined by the time of shallow-level filling.

Measurements of non-steady-state photocurrents and of time-modulated conductivities for homogeneous illumination of varying intensity are performed with a photorefractive iron-doped barium–calcium titanate crystal of the congruently melting composition (Ba 0.77 Ca 0.23 TiO 3 , BCT). The diffraction efficiency and the two-beam coupling gain are determined from conventional holographic experiments. Debye screening and diffusion lengths are found to be of the order of 0.1 μm. The response-time of the material is 2 s (light intensity 0.2 W/cm 2 , wavelength 514 nm) and the dark storage time is 6 s. The measured refractive index changes are only one third of the values, which are expected from the known electrooptic coefficients and space-charge fields.

Measurements of non-steady-state holographic photocurrents and conventional modulated photocurrents are performed with a n-type photorefractive strontium-barium niobate crystal at light wavelength of 532 nm. The effective charge carrier density and the photocarrier diffusion lengths for two orthogonal directions in the crystal are deduced. A ratio of the photoelectron mobilities along the c and a axis of 2.4 is obtained. The dependence of the photocurrent signals on the modulation frequency points to an essential contribution of shallow traps to the charge transport.

It has been recently shown that application of Michelson interferometry, is suitable for monitoring of oxide layers growing in metallic structures during preliminary states of oxidation processes in aqueous solutions, without any physical contact with the sample. The qualitative and quantitative interpretation of the observed interferograms allows evaluation of important physical parameters related to specific corrosion processes [1]. Although the using of aluminum samples with surfaces polished to certain optical quality is a necessary requirement to obtain well-built interferograms, it complicates further applications for diffused surfaces typical of industrial conditions. In this work we present preliminary qualitative results obtained by using a simple experimental setup based on Digital Speckle Pattern Interferometry (DSPI) [2], as a proposal to solve this difficulty and on the other hand, to use the benefits of certain powerful tools like low-coherence optical techniques for further applications on monitoring of corrosion through turbid media.

In this work, implementation of a system-on-chip in a field programmable gate array (FPGA) is described. This system analyzes temporal phase-shift in a pattern of interference fringes, in order to measure displacements in real-time. The interferograms images are introduced to the FPGA through a charge coupled device (CCD). A pipeline architecture is used to the stages of phase analysis and display of the results. The system consumes just 2030 slices of an XC2V3000 and it runs at 65 MHz clock frequency.

Microwave reflection resonator sensors have been developed to monitor the complex, dynamic, in situ real and imaginary dielectric permittivity (ε* = ε'd - jε"d) of thermoset polymer matrix composites and thermoplastics. These reusable and noninvasive sensors are conformably mounted in the autoclave mold in such a manner that the EM fields are strongly coupled to the resin. Tracking of (ε'd, ε" d) during the cure provides in formation about the chemical kinetics, resin viscosity, rigidity, porosity and relative cure index. The sensor is readily adjustable for optimum coupling to the type of material being tested. The existing sensor is rated for temperatures up to 250°C (480°F), but this can be extended to higher temperatures. The technique has been beta-tested in a commercial laboratory over a 9-month period, and is complementary to other analysis techniques such as Differential Scanning Calorimetry (DSC) and Dynamic Mechanical Analysis (DMA). A prototype software and electronics package has been developed to support the sensor. This paper focuses on the testing of neat epoxy resins.

Oscillating photocurrents are generated in a photorefractive iron-doped barium calcium titanate crystal (Ba0.77Ca0.23TiO3; BCT) by illumination with an oscillating interference pattern. Non-steady-state photocurrents arise usually from the interaction of a space-charge field with an oscillating photoconductivity pattern. However, a second-harmonic signal of the oscillating photocurrents is observed in BCT, which is present without any space-charge field. The main features of the new effect can be explained by consideration of a dynamic, i.e., time-dependent, bulk photovoltaic effect. The effect might be useful for optically addressed memories or optical correlators.